Staphylococcus aureus

Biophys Chem, 1996 Jun 11, 60(3), 99 - 110
Simulation of voltage-dependent interactions of alpha-helical peptides with lipid bilayers; Biggin PC et al.; Pore formation in lipid bilayers by channel-forming peptides and toxins is thought to follow voltage-dependent insertion of amphipathic alpha-helices into lipid bilayers . We have developed an approximate potential for use within the CHARMm molecular mechanics program which enables one to simulate voltage-dependent interaction of such helices with a lipid bilayer . Two classes of helical peptides which interact with lipid bilayers have been studied: (a) delta-toxin, a 26 residue channel-forming peptide from Staphylococcus aureus; and (b) synthetic peptides corresponding to the alpha 5 and alpha 7 helices of the pore-forming domain of Bacillus thuringiensis CryIIIA delta-endotoxin . Analysis of delta-toxin molecular dynamics (MD) simulations suggested that the presence of a transbilayer voltage stabilized the inserted location of delta-toxin helices, but did not cause insertion per se . A series of simulations for the alpha 5 and alpha 7 peptides revealed dynamic switching of the alpha 5 helix between a membrane-associated and a membrane-inserted state in response to a transbilayer voltage . In contrast the alpha 7 helix did not exhibit such switching but instead retained a membrane associated state . These results are in agreement with recent experimental studies of the interactions of synthetic alpha 5 and alpha 7 peptides with lipid bilayers.

Ugeskr Laeger, 1996 Jun 10, 158(24), 3471 - 2
{Spread of an imported multiresistant Staphylococcus aureus to other hospitals via secondary colonized patients}; Haahr V et al.; A secondary spread of an imported methicillin-resistant Staphylococcus aureus strain (MRSA) to two other patients occurred within a Danish surgical ward in spite of isolation of a multitraumatized index-patient immediately after arrival from a hospital in the Mediterranean area . The two other colonized patients were later transferred to other hospitals in Denmark where it became apparent that they had developed serious infections with the MRSA strain . In conclusion: to prevent spread of imported MRSA within Danish hospitals, strict adherence to isolation procedures and a high level of general hygiene is essential not only when patients are transferred from hospitals situated in endemic areas of MRSA abroad, but also when admitted from Danish hospital wards where known cases of colonisation or infection with MRSA exist.

Clin Exp Immunol, 1996 Jun, 104(3), 432 - 8
IL-10-driven immunoglobulin production by B lymphocytes from IgA-deficient individuals correlates to infection proneness; Friman V et al.; In search for a possible explanation of the phenotypic heterogeneity in IgA deficiency, we studied the function of B cells from IgA-deficient (IgAd) individuals . Two groups of IgAd individuals, one frequently infected and one clinically apparently healthy, as well as normal controls, were studied . Peripheral blood mononuclear cells (PBMC) and B cells from IgAd individuals and controls were cultured with Staphylococcus aureus Cowan I strain and with anti-CD40 MoAb presented on the CD32-transfected fibroblast cell line in the presence of IL-10 . In this experimental system PBMC and B cells from the infection-prone IgAd individuals produced only minute amounts of IgA . In contrast, PBMC and B cells from healthy IgAd subjects secreted significantly more IgA1 and IgA2 in comparison with infection-prone IgAd patients (P < 0.05) . These data suggest that the abnormalities of B cell differentiation in IgAd could be of heterogeneous origin . Thus, whereas in healthy IgAd subjects IgA production may be efficiently up-regulated in vitro by addition of IL-10 to CD40-activated B cell culture, the corresponding B cell differentiation does not occur in infection-prone IgAd patients . These observations provide a conceptual framework for phenotypic heterogeneity in IgAd subjects.

In Vitro Cell Dev Biol Anim, 1996 Jun, 32(6), 372 - 7
Efficient production of IgG human monoclonal antibodies by lymphocytes stimulated by lipopolysaccharide, pokeweed mitogen, and interleukin 4; Yoshinari K et al.; Extensive screening of the mitogens lipopolysaccharide (LPS), pokeweed mitogen (PWM), and Staphylococcus aureus Cowan I (SAC I), alone and in combination and with and without interleukin (IL) was performed for in vitro activation of regional lymph node lymphocytes from lung cancer patients for the production of human IgG, IgM, and IgA . As assessed by electrofusion of the lymphocytes following their exposure to these agents with mouse myeloma cells and incubation of the fused hybridoma, a remarkable stimulatory effect was shown by LPS and particularly by LPS plus IL-4, which was substantially greater than that of either SAC I or PWM with or without various IL . Optimization studies indicated that the addition of PWM to LPS and IL-4 in the culture medium further stimulated the human antibody (Ab) production, and that the optimal formulation for stimulation of human IgG production was a culture medium containing 20 micrograms/ml of LPS, 1/500 of PWM, and 100 u/ml of IL-4.

Eur J Clin Microbiol Infect Dis, 1996 Jun, 15(6), 499 - 503
Staphylococcal scalded skin syndrome in an immunocompromised adult; Roeb E et al.; Staphylococcal scalded skin syndrome, a generalized exfoliative dermatitis complicating infections by exfoliative toxin-producing strains of Staphylococcus aureus, is rarely observed in adults . In contrast to mortality in infants, mortality in adults is usually high . A case of generalized staphylococcal scalded skin syndrome in an immunocompromised woman is reported . Culture of skin biopsy and pleural fluid yielded identical strains of staphylococcus aureus belonging to phage group II . Exfoliative toxins A and B were detected in both isolates . As far as can be determined, this is the first reported case of generalized staphylococcal scalded skin syndrome in an adult with detection of exfoliate toxins A and B in which the patient was treated successfully.

Eur J Clin Microbiol Infect Dis, 1996 Jun, 15(6), 437 - 45
Clinical spectrum of ventilator-associated pneumonia caused by methicillin-sensitive Staphylococcus aureus; Bergmans D et al.; The incidence of tracheal colonization and its association with ventilator-associated pneumonia caused by methicillin-sensitive Staphylococcus aureus (MSSA) was studied prospectively in 530 consecutively admitted mechanically ventilated patients in a general intensive care unit . Furthermore, the clinical spectrum, outcome, and microbiological results of 27 cases of staphylococcal ventilator-associated pneumonia (SVAP) were examined . Ventilator-associated pneumonia was diagnosed by protected specimen brush and/or bronchoalveolar lavage . On admission, 7% of the patients were colonized with MSSA in the trachea . Acquired tracheal colonization was demonstrated in 10% of the patients and occurred less frequently in patients with a hospital stay of > 48 h before ICU admission compared to patients admitted directly to the ICU (6% vs . 15%, p < 0.001) . Moreover, colonization was acquired more frequently among trauma and neurological/neurosurgical patients (22%) as compared to surgical and medical patients (7%) (p < 0.0001) . Twenty-one patients (4%) developed SVAP, the incident being higher in patients colonized in the trachea with MSSA than in those not colonized (21% vs . 1%), p < 0.00001) . Staphylococcal ventilator-associated pneumonia developed more often in trauma and neurological/neurosurgical patients as compared to surgical and medical patients (8% vs . 3%, p < 0.05) . Moreover, patients with a hospital stay of < 48 h before admission to the ICU had a higher incidence of SVAP as compared to those with a longer hospital stay before ICU admission (7% vs . 2%, p < 0.01) . Crude infection-related mortality was 26% . Preceding colonization with MSSA in the trachea appears to be an important risk factor for the development of SVAP, and patients with a short duration of hospitalization before intensive care unit admission have the highest incidence of ventilator-associated pneumonia caused by MSSA.

Zentralbl Bakteriol, 1996 Jun, 284(1), 58 - 66
Selection of subpopulations resistnat to amikacin and netilmicin of gentamicin-resistant clinical strains of Staphylococcus aureus and Staphylococcus epidermidis; Torres Garcia M et al.; Recently we have found several strains of Staphylococcus aureus and Staphylococcus epidermidis, which in spite of containing aminoglycoside-modifying enzymes (AMEs) remained susceptible to antibiotics such as netilmicin (NET) and amikacin (AN) . Assuming an interest in this agent from a clinical point of view, the aim of this study was to determine if these strains became resistant after prolonged contact with such antibiotics . We found that minimal inhibitory concentrations (MICs) of the bacterial strains not only increased when using these two agents, but also when using other aminoglycosides such as gentamicin (GM), tobramycin (TM), amikacin (AN) and isepamicin (ISE) . In order to see the effect of prolonged use of NET on enzyme production, three strains containing AMEs were selected and we could observe an increase in the enzyme levels after successive passages through media containing NET.

J Antimicrob Chemother, 1996 Jun, 37(6), 1171 - 5
Activity of glycylcyclines CL 329998 and CL 331002 against minocycline-resistant and other strains of methicillin-resistant Staphylococcus aureus; Hamilton-Miller JM et al.; Two glycylcyclines have been tested against 191 strains of methicillin-resistant Staphylococcus aureus, 72 of which were resistant to minocycline, isolated from many parts of the world . MICs of CL 329998 ranged from 0.06 to 4 mg/L, with MIC50 and MIC90 0.5 and 2 mg/L, respectively . CL 331002 was slightly less potent, having an MIC range 0.12-16 mg/L and MIC50 and MIC90 values of 1 and 4 mg/L, respectively.

J Antimicrob Chemother, 1996 Jun, 37(6), 1077 - 89
Antimicrobial activity of cecropins; Moore AJ et al.; The lytic peptides, cecropins, were originally isolated from the haemolymph of the giant silk moth, Hyalophora cecropia and possess antibacterial and anticancer activity in vitro . This study investigated the antimicrobial activity of these peptides against human pathogens using standardised assay techniques, and the activity of cecropin B on outer and inner bacterial membranes . From a panel of 15 organisms, Gram-negative bacteria were generally more sensitive to cecropins than Gram-positive organisms, especially the lipopolysaccharide defective mutant, Escherichia coli BUE55 . Cecropins B and P1 shared similar MIC values whereas Shiva-1, a cecropin B analogue, was less active . Through combination studies with hydrophobic antibiotics and electron microscopy, cecropin B was shown to disrupt the bacterial outer membrane . Protoplasts of Staphylococcus aureus and Staphylococcus epidermidis were resistant to cecropin B, suggesting that the cytoplasmic membranes of Gram-positive organisms were inherently more resistant to the peptide.

J Dairy Sci, 1996 Jun, 79(6), 1021 - 6
Staphylococcus aureus invasion of bovine mammary epithelial cells; Almeida RA et al.; Staphylococcus aureus is a frequent cause of mastitis in dairy cows . However, pathogenesis of the infection has not been completely defined . We report the invasion of two strains of S . aureus into a bovine mammary epithelial cell line and a bovine mammary epithelial cell primary culture . Invasion of S . aureus into bovine mammary cells was time-dependent . Transmission electron microscopy of bovine mammary cells invaded by S . aureus showed intracellular replication of the bacterium within membrane-bound vacuoles . Invasion was reduced significantly when bovine mammary epithelial cells were treated with inhibitors of F-actin microfilament polymerization but not when these cells were treated with inhibitors of microtubule formation . Results indicated that S . aureus is capable of invading and replicating inside bovine mammary epithelial cells . Data also suggested that S . aureus invasion of bovine mammary epithelial cells requires active participation of specific components of the cytoskeleton of the epithelial cell.

J Neurosci Nurs, 1996 Jun, 28(3), 155 - 62
Shunt infections in children: presentation and management; Williams DG et al.; Since the earliest attempt at surgical management of hydrocephalus, infection has been a significant complication . For better assessment and care the neuroscience nurse needs to be aware of the signs and management of this condition . A retrospective review of 68 infections in 61 children was undertaken . Results showed an increased incidence of infection in the first nine months after surgery . Gram positive organisms (Staphylococcus epidermidis and Staphylococcus aureus) were most frequent; Propionobacter acnes was a significant pathogen in adolescence . Presenting symptoms included fever (26%), abdominal pain (19%), wound changes (22%) and indicators of shunt malfunction (33%) . Elevated white blood cells (WBCs) in spinal fluid from shunt tap and positive cultures were most reliable laboratory data . Culturing of causative organism was sometimes difficult . A value regulated system for ventricular drainage which allows greater mobility for the patient is described.

J Antimicrob Chemother, 1996 Jun, 37 Suppl C, 21 - 35
Influence of immunosuppression on the pharmacokinetics and pharmacodynamics of azithromycin in infected mouse tissues; Girard D et al.; Azithromycin has been shown to preferentially distribute to infection loci . Due to the potential contribution of phagocytes as transporters of drug to these sites, there has been some concern that immunosuppression of the cellular arm of the host defence system would greatly reduce the delivery of azithromycin to sites of infection and hence impair efficacy . Therefore, we evaluated the pharmacokinetics and pharmacodynamics of azithromycin in a Staphylococcus aureus intramuscular infection model in normal and immunosuppressed mice, employing therapeutic and prophylactic regimens . Immunosuppression was induced by daily doses of cyclophosphamide that culminated in leucopenia with an underlying granulocytopenic condition, with circulating peripheral granulocytes numbering from < or = 0.1-0.3 x 10(9)/L . Azithromycin tissue levels were not reduced in infection loci in granulocytopenic mice but moderate increases in Cmax and AUC values were observed, relative to similar tissues from normal mice . The tissue half-life of azithromycin in infected tissues in a therapeutic mode (75 h) was three-fold longer than in a prophylactic mode (25 h); this correlated with the degree of inflammation (therapy was withheld until inflammation was evident; i.e., prophylaxis reduced inflammation) . Histological examination of infected tissues from normal and leucopenic mice was indistinguishable despite a 70%-85% reduction in circulating granulocytes . Compared with untreated infected controls, bactericidal activity was noted following prophylaxis with azithromycin and bacteraemia was suppressed in mice receiving azithromycin therapeutically . In summary, these data indicate that azithromycin delivery and efficacy in a moderately immunosuppressed animal model are unimpaired.

J Dermatol Sci, 1996 Jun, 12(2), 132 - 9
Adhesion of Staphylococcus aureus to horny layer: role of fibrinogen; Kanzaki H et al.; Staphylococcus aureus cells attach to and invade the epidermis more easily under conditions of abrasion or occlusion or in the presence of irritant dermatitis than when the epidermis is intact . This fact strongly suggests that exuded plasma components may play an important role in the adherence of S . aureus cells to the horny layer . S . aureus cells (Cowan 1 strain, Wood 46 strain, and the protein A-deficient mutant, C7 strain, which was isolated from the Cowan 1 strain) were epicutaneously inoculated on the backs of mice . Biopsy specimens were taken from the mice at 1 h, 3 h, and 6 h after inoculation and examined using immunoelectron microscopy . Gold particles for fibrinogen gathered in a time-dependent manner at the interfaces of S . aureus cells and horny material in the lesions inoculated with the Cowan 1 and C7 strains but not in the lesions inoculated with the Wood 46 strain . These results suggest that fibrinogen plays a role in the binding of S . aureus cells to the horny layer.

Acta Med Okayama, 1996 Jun, 50(3), 131 - 7
Purification and characterization of a 39kDa apurinic/apyrimidinic endonuclease from mouse ascites sarcoma cells; Wakabayashi H et al.; We purified an apurinic/apyrimidinic (AP) endonuclease from mouse ascites sarcoma (SR-C3H/He) cells . The enzyme showed nicking activity on acid-depurinated DNA but not on untreated, intact DNA . It also showed priming activity for DNA polymerase on both acid-depurinated and bleomycin-damaged DNA . The priming activity on bleomycin-damaged DNA was two times higher than that on an acid-depurinated DNA . The enzymatic properties indicate that the enzyme is a class II AP endonuclease having DNA 3' repair diesterase activity . The purified enzyme has a molecular weight of 39,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis . The optimal pH for AP endonuclease activity was 8.0 in 50 mM Tris-HCl buffer . The AP endonuclease activity depended on divalent cation such as Mg2+ and Co2+ ions, and was inhibited by 2 mM EDTA with no addition of the divalent cation . An appropriate concentration of sodium or potassium salt stimulated the activity . Partial digestion of the AP endonuclease with Staphylococcus aureus V8 protease produced 4 major peptide fragments which may be used for protein sequencing.

Infect Control Hosp Epidemiol, 1996 Jun, 17(6), 372 - 4
Trends in the prevalence of methicillin-resistant Staphylococcus aureus associated with discontinuation of an isolation policy; Fazal BA et al.; The number of patients with methicillin-resistant Staphylococcus aureus (MRSA) before and after discontinuing placement of patients into private rooms was determined . The mean monthly number of patients with MRSA decreased from 34 to 22, and the proportion of S aureus isolates that were MRSA decreased from 34% to 20% . We found no evidence that failure to isolate patients with MRSA resulted in an increased prevalence of MRSA.

J Epidemiol, 1996 Jun, 6(2), 69 - 73
Incidence of methicillin-resistant Staphylococcus aureus (MRSA) isolation in a skilled nursing home: a third report on the risk factors for the occurrence of MRSA infection in the elderly; Washio M et al.; A case control study was carried out in order to evaluate the various factors which may influence the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) infections in a skilled nursing home . From April 1991 to March 1994, bacterial cultures were performed in 55 out of 102 residents in a nursing home based on various clinical aspects . We divided 102 residents into following three groups; (1) the MRSA group (n = 10), residents whose materials for bacterial culture were positive for MRSA, (2) the non-MRSA group (n = 45), residents whose specimens were negative for MRSA but positive for other bacteria, (3) the control group (n = 47), residents who did not have to undergo a bacterial culture because they were free from moderate and severe infectious diseases . Compared with the control group, the activities of daily living score and the serum albumin level were significantly lower in the MRSA group and the non-MRSA group at the beginning of the study . In contrast, the number of antibiotics used prior to the bacterial culture and the proportion of hospitalization within 6 months prior to the bacterial culture were significantly larger in the MRSA group than in either the non-MRSA group, or the control group . These results thus suggest that a low activities of daily living score, the use of many kinds of antibiotics and a recent previous hospitalization may be risk factors of MRSA infection in a nursing home environment.

Appl Environ Microbiol, 1996 Jun, 62(6), 2006 - 12
Investigation of the effect of combined variations in temperature, pH, and NaCl concentration on nisin inhibition of Listeria monocytogenes and Staphylococcus aureus; Thomas LV et al.; Gradient plates were used to investigate the effects of varying temperature, pH, and sodium chloride (NaCl) concentration on nisin inhibition of Staphylococcus aureus and Listeria monocytogenes, Nisin was incorporated into the plates of 0, 50, 100, 250, and 500 IU ml -1 . Gradients of pH (3.7 to 7.92) at right angles to NaCl concentration (2.1 to 7% {wt/vol}) were used for the plates, which were incubated at 20, 25, 30 and 35 degrees C . Growth on the plates were recorded by eye and by image analysis . The presence of viable but nongrowing cells was revealed by transfer to nongradient plates . Lower temperatures and greater NaCl concentrations increased the nisin inhibition of S . aureus synergistically . Increasing the NaCl concentration potentiated the nisin action against L . monocytogenes; the effect of temperature difference was not so apparent . Between pH 7.92 and ca . pH 5, a fall pH appeared to increase nisin's effectiveness against both organisms . At more acid pH values (ca . pH 4.5 to 5), the organisms showed resistance to both nisin and NaCl at 20 and 25 degrees C . Similar results were obtained with one-dimensional liquid cultures.

Cardiovasc Surg, 1996 Jun, 4(3), 389 - 92
Prophylaxis against Staphylococcus epidermidis vascular graft infection with rifampicin-soaked, gelatin-sealed Dacron; Sardelic F et al.; An animal model was used to assess the efficacy of rifampicin-impregnated, gelatin-sealed Dacron in the prevention of vascular graft infections caused by Staphylococcus epidermidis . Under a general anaesthetic an interposition graft was placed into sheep carotid artery . On completion of the operation 1 ml of normal saline containing 10(8) colony forming units (cfu) of a slime-producing S . epidermidis was inoculated directly onto the graft . After 3 weeks the graft was harvested . Swabs were taken of perigraft tissues, and of external and internal aspects of the graft . A 3-5-mm segment of the graft was incubated in broth medium and a second segment was ground for 5 min and incubated in broth medium . The presence of abscess formation and anastomotic disruption was assessed . Ten sheep received a gelatin-sealed Dacron graft (control), while nine received the same graft impregnated with rifampicin at a concentration of 1.2 mg/ml (treated) . Eight of 10 control grafts were infected, with 30 of 50 possible cultures positive, compared with four of nine treatment grafts infected (P = 0.13) and 13 of 45 cultures positive (P = 0.004) . The control group had four abscesses and two anastomotic disruptions; the treatment group had no abscesses (P = 0.05) or anastomotic disruptions (P = 0.26) . Other organisms were isolated from nine of the 12 infected grafts, most commonly Staphylococcus aureus . There was no development of resistance to rifampicin . Rifampicin-impregnated, gelatin-sealed Dacron is successful at reducing the incidence of S . epidermidis vascular graft infection.

Burns, 1996 Jun, 22(4), 283 - 6
Effective control of methicillin-resistant Staphylococcus aureus in a burn unit; Matsumura H et al.; Methicillin-resistant Staph, aureus (MRSA) colonization and infection was studied in 231 patients who were admitted to our burn unit and remained for 3 days or more between 1986 and 1994 (patients with inhalation injury only and no burn wound were excluded) . The study was divided into two periods: from 1988 to 1989 and from 1990 to 1994 . MRSA was found in 80 patients . They increased from 1986 to 1988, slightly decreasing thereafter . In 1994 the incidence of MRSA was 4.3 per cent . The number of strains of MRSA isolated from burn wounds was significantly reduced in the later period . Comparing the two periods, isolation of patients from MRSA, prevention of contamination during care, and reduction in the number of patients initially given second- or third-generation cephem antibiotics were performed more strictly in the later period . The effectiveness of these measures was confirmed . Moreover, the first operation was carried out significantly earlier in the later period . Early excision and early closure of the wound was more effective in preventing and controlling MRSA colonization and infection.

Jpn J Antibiot, 1996 Jun, 49(6), 658 - 62
{Studies on cerebrospinal fluid penetration of cefpirome in adult with meningitis}; Munemoto S et al.; A patient with intracerebral hematoma suffered from postoperative bacterial meningitis . Staphylococcus aureus was found from CSF . The organism was multiple drug resistant and refractory to antibiotics including piperacillin (PIPC), cephalexin (CEX), cefotaxime (CTX), ceftazidime (CAZ) and latamoxef (LMOX) . It was susceptible to cefpirome (CPR) . Treatment with CPR resulted in clinical improvement associated with clearing of the organism from CSF . Serum level of CPR was high enough and CPR penetration into the CSF was satisfactory . The results suggest that CPR is an extremely effective antibiotic for meningitis caused by CPR-susceptible bacteria . Evaluation of the CPR penetration into the CSF of adult meningitis was rarely reported . The result we obtained was important in the treatment for the adult meningitis.

J Formos Med Assoc, 1996 Jun, 95(6), 458 - 63
Infectious spondylitis: MRI characteristics; Huang YC et al.; Magnetic resonance imaging (MRI) scans of 24 patients with clinically proven infectious spondylitis were retrospectively evaluated . Evaluation was made of abnormal signal and enhancement patterns within vertebral bodies, intervening disks, and epidural and paraspinal abscesses . The causative organisms included Mycobacterium tuberculosis, fungi and pyogenic bacteria . Staphylococcus aureus was the predominant causative organism among pyogentic bacteria . Decreased signal intensity of vertebral marrow on T1-weighted images was more extensive in pyogenic infections . Multilevel involvement (more than two) was observed in six of the 24 patients . Contiguous multilevel involvement was observed only in patients with tuberculous spondylitis . Noninvolvement of the intervertebral disk space was observed in two patients with pyogenic spondylitis . Epidural abscess was found in 15 patients, most of whom had dense, homogeneous enhancement . Paraspinal abscess was found in 18 patients . Diffuse patchy enhancement without obvious abscess formation in the paraspinal compartment was found in those patients with pyogenic infections . "Rice bodies" were found in paraspinal abscesses in only three patients with tuberculous spondylitis . It was difficult to differentiate candidal from tuberculous spondylitis on MRI . Compared with pyogenic infection, tuberculous spondylitis had a predilection for spinal deformity, subligamentous spread, contiguous multilevel involvement, presence of signal voids in paraspinal abscesses on T2WT and a lesser extent of marrow edema.

Am J Physiol, 1996 Jun, 270(6 Pt 1), G962 - 8
Differential effects of GTP gamma S on acid and pepsinogen secretion by permeable gastric glands; Miller MD et al.; Gastric glands isolated from rabbit stomach were permeabilized with Staphylococcus aureus alpha-toxin . Acid secretion by parietal cells, as measured by the accumulation of weak base, was inhibited by incubation with alpha-toxin but could be restored by addition of exogenous ATP (1 mM) . The permeable glands were found to retain acid secretory responses to receptor-linked secretagogues, histamine and carbachol, as well as to intracellular mediators, forskolin and 8-bromoadenosine 3',5'-cyclic monophosphate, indicating the presence of intact, functional intracellular coupling mechanisms . Both basal and stimulated acid secretion by the permeable glands were blocked by the Mg2+ chelator, trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (CDTA; 5 mM), whereas CDTA had no effect on nonpermeabilized glands . These results are interpreted to show that alpha-toxin permeabilizes parietal cells to moderate sized molecules without causing a loss of critical intracellular components . The acid secretory responses to histamine and carbachol persisted in media containing low ( < 50 nM) levels of free Ca2+ buffered by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (0.5 mM), indicating that changes in bulk Ca2+ are not required for these responses . Inclusion of the nonhydrolyzable analogue of GTP, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S; 100 microM), resulted in inhibition of spontaneous acid secretion, blocked responses to all agents tested, and inhibited stimulated acid secretion . GTP gamma S had no effect on nonpermeabilized glands . No effects on acid secretion by either permeable or nonpermeable glands were observed with GTP, guanosine diphosphate, or guanosine 5'-O-(2-thiodiphosphate) . GTP gamma S had no effect on H+ gradient formation by gastric membrane vesicles, showing that it does not inhibit the gastric H(+)-K(+)-adenosinetriphosphatase directly . These results are interpreted to show that GTP gamma S interacts at a postreceptor site to inhibit or reverse a critical step in stimulus-secretion coupling in parietal cells . In contrast to the effect on parietal cells, GTP gamma S was found to stimulate pepsinogen secretion by alpha-toxin-permeabilized chief cells . The differential effects of GTP gamma S on acid and pepsinogen secretions suggest unique roles for GTP binding proteins in these two secretory processes . The use of alpha-toxin-permeabilized gastric glands should prove useful in defining the stimulus-secretion coupling mechanisms involved in both acid and pepsinogen secretions.

J Laryngol Otol, 1996 Jun, 110(6), 547 - 50
Evaluation of the microbiology of chronic sinusitis; Sener B et al.; Chronic sinusitis is one of the most common diseases treated in outpatient centres . In this prospective study, 49 patients with the diagnosis of chronic maxillary sinusitis were evaluated microbiologically by using sinus swab, irrigation fluid and sinus mucosal tissue specimens obtained during endoscopic sinus surgery . There was no bacterial growth in seven cases . In the remaining 42 cases a total of 89 bacteria were isolated, 28 of them being classical pathogens and 61 being non-classical pathogens . Among the classical pathogens Staphylococcus aureus was the most common one . The correlation between the isolates obtained from maxillary sinus and isolates obtained from throat, nose and nasopharynx did not have a predictive value . Since the overall rate of classical pathogen isolation from patients with chronic sinusitis was not significantly high, the possible role of factors other than bacterial growth should be identified in the pathogenesis of chronic sinusitis.

J R Coll Surg Edinb, 1996 Jun, 41(3), 182 - 3
Pyomyositis: an unusual infection due to staphylococcus aureus; Das I et al.; Pyomyositis is a primary pyogenic infection of skeletal muscle, leading to the formation of intramuscular abscesses . Although common in tropical climates, it is infrequent in temperate zones . We report a patient who developed the condition without travelling to tropical areas.

Nippon Kyobu Geka Gakkai Zasshi, 1996 Jun, 44(6), 814 - 9
{A case report of mediastinitis due to methicillin resistant Staphylococcus aureus after total aortic arch replacement}; Asano S et al.; A 78-year-old man underwent total aortic arch replacement for ruptured aortic arch aneurysm . Two weeks after the surgery, high fever and leucocytosis developed . He was placed on a regimen of antibiotics . However, mediastinitis eventually ensued five weeks later with the pus draining from the sternotomy wound . The culture revealed a Methicillin resistant staphylococcus aureus . The infected tissue was debrided from the mediastinal cavity 40 days postoperatively . The cavity was kept open and was intermittently irrigated with 2% Providone-iodine for three days . Subsequently, an omental graft was placed . The infection successfully subsided gradually and the patient has been well for a year and a half after the initial surgery . The procedure is considered to be extremely effective for the management of a drastic infection involving thoracic aortic prosthesis.

J Clin Microbiol, 1996 Jun, 34(6), 1502 - 5
Typing of Staphylococcus aureus by PCR for DNA sequences flanked by transposon Tn916 target region and ribosomal binding site; Cuny C et al.; The continuous intra- and interhospital spread of multiresistant Staphylococcus aureus demands a rapid molecular typing system . This study describes the fingerprinting of S . aureus by PCR amplification of DNA sequences flanked by the target site for transposon Tn916 and the ribosomal binding site and neighboring nucleotides (target 916-Shine-Dalgarno PCR {tar 916-shida PCR}) . Both starting points for PCR are known to be randomly distributed on the S . aureus chromosome . By use of SmaI-macrorestriction patterns as the reference method it was shown that this PCR genotyping discriminates among strains of the major clonal groups of the species S . aureus (strains with phage patterns 29, +, 94, 96, and 95 as well as group II and group III patterns) and identifies the six epidemic methicillin-resistant S . aureus strains prevalent in German hospitals . All of the investigated strains including methicillin-sensitive . S . aureus were typeable . Tar 916-shida patterns are stable during the dissemination of epidemic methicillin-resistant S . aureus among different hospitals.

J Clin Microbiol, 1996 Jun, 34(6), 1364 - 72
Genomic fingerprinting for epidemiological differentiation of Staphylococcus aureus clinical isolates; Smeltzer MS et al.; We used genomic fingerprinting to investigate an outbreak of methicillin-resistant Staphylococcus aureus in the neonatal intensive care units (NICUs) of two hospitals . The hospitals are located in the same city and are part of the same medical care system . Fingerprinting was done by Southern blot hybridization with DNA probes for the genes encoding the S . aureus collagen adhesin (cna), fibronectin-binding proteins (fnbA and fnbB), and beta-toxin (hlb) . Genomic DNA was digested with HaeIII (cna and fnbA-fnbB probes) or HindIII (hlb probe) . Hybridization patterns could be distinguished on the basis of (i) the presence or absence of cna, (ii) the size of the restriction fragment containing the cna gene, (iii) restriction fragment length polymorphisms within fnbA and fnbB, (iv) the presence of a lysogenic phage within hlb, and (v) the sizes of the restriction fragments containing the phage-bacterial DNA junction fragments . Over a period of 4 months we examined a total of 46 isolates obtained from various wards within each hospital . Among these 46 isolates, we observed a total of 4 cna patterns, 11 fnbA-fnbB patterns, and 11 hlb patterns . Southern blots with HaeIII-digested genomic DNA and a combination of all three gene probes revealed a total of 16 clearly distinguishable patterns . A total of 22 of the 46 isolates were identical with respect to every genomic marker examined . A total of 21 of these 22 isolates were obtained from patients within an NICU . Nineteen of 21 isolates also exhibited identical antibiotic resistance profiles (antibiogram) . Although 5 of the remaining 24 strains exhibited an antibiogram identical to those of the NICU isolates, all 24 strains could be distinguished from the NICU isolates by at least one genomic marker . These results suggest that the NICU isolates had a common origin and that genomic fingerprinting with the cna, fnbA, fnbB, and hlb gene probes can provide an important epidemiological tool for the identification of clinical isolates of S . aureus.

Ophthal Plast Reconstr Surg, 1996 Jun, 12(2), 131 - 5
Draining cutaneous fistula associated with infection of hydroxyapatite orbital implant; Glasgow BJ et al.; The implantation of an orbital hydroxyapatite implant was complicated by conjunctival dehiscence, cutaneous fistula formation, and infection with Staphylococcus aureus . Pathologic examination of the sphere 2 years after its implantation revealed reduction in the size of the implant, peripheral lamellar bone formation and central necrosis . This is the first report of this constellation of complications with hydroxyapatite spheres positioned in the orbit . The 2-year interval between implantation and removal of the sphere is the longest reported in a case with histopathologic analysis.

Ophthal Plast Reconstr Surg, 1996 Jun, 12(2), 121 - 6
Adverse effects of bone wax in surgery of the orbit; Katz SE et al.; The goal of this article is to establish the incidence and scope of adverse reactions to bone wax in a large orbital surgical series . We report two patients with bone wax granulomas of the orbit as a remote surgical complication . These are the first reported cases of adverse reactions to bone wax in the ophthalmic literature . A chart review was conducted on all patients from the University of British Columbia Orbit Clinic that had surgery with temporary or permanent removal of orbital bone . Two patients with bone wax granulomas were identified . In one case, intraoperative cultures grew Staphylococcus aureus, confirming that the wax may indeed act as a nidus for infection . No cases of pseudoarthrosis have occurred . This syndrome of chronic granulomatous giant cell foreign body inflammation has characteristic clinical, radiologic, and histopathologic features . The literature regarding adverse reactions to bone wax is reviewed, and specific implications for orbital surgery are discussed.

Antimicrob Agents Chemother, 1996 Jun, 40(6), 1534 - 5
Vancomycin-gentamicin synergism revisited: effect of gentamicin susceptibility of methicillin-resistant Staphylococcus aureus; Mulazimoglu L et al.; Vancomycin monotherapy of deep-seated staphylococcal infection may be associated with poor bacteriological response . We evaluated 24 unique patient isolates of methicillin-resistant Staphylococcus aureus (MRSA) for vancomycin-gentamicin synergism by determining time-kill curves for vancomycin at 10 micrograms/ml and gentamicin at 1 microgram/ml . Nine MRSA strains showed high-level gentamicin resistance (HLGR) (MIC, > 500 micrograms/ml), and 15 did not . Vancomycin-gentamicin demonstrated synergism against none of the HLGR strains . For the non-HLGR strains, gentamicin agar dilution MICs ranged from 0.5 to > 128 micrograms/ml . Vancomycin-gentamicin demonstrated synergism against six of these strains and indifference against nine of them . There was no relationship between the agar dilution MIC of gentamicin and the occurrence of synergism against non-HLGR strains . We conclude that a gentamicin MIC of > 500 micrograms/ml predicts a lack of vancomycin-gentamicin synergism for strains of MRSA . For non-HLGR strains, synergism is not predictable from the gentamicin MIC.

Antimicrob Agents Chemother, 1996 Jun, 40(6), 1498 - 503
Effect of exogenous glycine on peptidoglycan composition and resistance in a methicillin-resistant Staphylococcus aureus strain; de Jonge BL et al.; A highly homogeneously methicillin-resistant Staphylococcus aureus strain was grown in the presence of various concentrations of exogenous glycine . Increasing concentrations of glycine in the medium resulted in a decrease in methicillin resistance and the appearance of a heterogeneous resistance phenotype . Parallel to the gradual changes in resistance was an alteration in the muropeptide composition of peptidoglycan . Increasing concentrations of glycine in the medium resulted in peptidoglycan in which muropeptides with a D-alanyl-D-alanine terminus were replaced with D-alanyl-glycine-terminating muropeptides . The disappearance of D-alanyl-D-alanine-terminating muropeptides in peptidoglycan and the concomitant decrease in resistance indicate a central role for D-alanyl-D-alanine-terminating precursors in methicillin resistance.

Antimicrob Agents Chemother, 1996 Jun, 40(6), 1432 - 7
Antibiotic-impregnated heart valve sewing rings for treatment and prophylaxis of bacterial endocarditis; Cimbollek M et al.; Prosthetic heart valve sewing rings were impregnated with gentamicin crobefat (EMD 46217), a poorly soluble gentamicin salt, gentamicin sulfate, and clindamycin palmitate to prevent early prosthetic endocarditis . MICs and MBCs of gentamicin and/or clindamycin were tested against several pathogens of early prosthetic endocarditis . The combination of gentamicin and clindamycin was found to be effective against most relevant bacterial pathogens . With an in vitro pharmacokinetic model, the antibacterial activity of gentamicin and clindamycin was tested against Staphylococcus aureus and Escherichia coli . High gentamicin levels over the first 24 h were required for a strong reduction of bacterial counts of both strains . Equal amounts of gentamicin and clindamycin sustained the antibacterial effect and prevented regrowth . The most effective release curves of gentamicin and clindamycin found with an in vitro model were used for monitoring release profiles of these antibiotics from impregnated sewing rings by investigating combinations of gentamicin sulfate, gentamicin crobefat, and clindamycin palmitate . Sewing rings impregnated with 4 mg of gentamicin sulfate, 14 mg of gentamicin crobefat, and 20 mg of clindamycin palmitate gave an initial gentamicin burst and afterwards yielded a lower sustained release of gentamicin and clindamycin palmitate . These in vitro release kinetics were confirmed in vivo by pharmacokinetic analysis after intramuscular implantation of impregnated sewing ring segments . Gentamicin and active clindamycin palmitate metabolites were obtained at the implantation site for at least 2 weeks in concentrations of 3 and 5 micrograms per g of muscle, respectively . The investigated method of impregnation holds promise for revision implants after prosthetic valve endocarditis . It may also serve as a prophylactic tool for routine use against this disease.

Antimicrob Agents Chemother, 1996 Jun, 40(6), 1403 - 7
Variation in postantibiotic effect of clindamycin against clinical isolates of Staphylococcus aureus and implications for dosing of patients with osteomyelitis; Xue IB et al.; Initial measurements of postantibiotic effect (PAE) were made by a standard laboratory method (exposure to 1 mg of clindamycin per liter for 1 h) . The range of PAE for 21 strains of Staphylococcus aureus isolated from osteomyelitis patients was 0.4 to 3.9 h, which markedly exceeded the coefficient of variation for the method (6 to 19%) . Exposure of S . aureus to three doses of clindamycin at 8-h intervals had no consistent effect on either PAE or MIC . The PAE was dependent on both concentration and duration of exposure to clindamycin: for example, the PAEs for one strain were 1.7 h after exposure to 1 mg/liter for 1 h, 2.4 h after exposure to 4 mg/liter for 1 h, and 5.9 h after exposure to 4 mg/liter for 3 h . Pharmacokinetic simulations showed that the dose required to maintain free serum clindamycin concentrations above the MIC was 300 mg 6 hourly after oral administration (95% confidence interval, 243 to 301 mg) and 1.2 g 6 hourly (95% confidence interval, 305 to 1,145 mg) after intravenous (i.v.) administration . The duration of PAE would have to be at least 2.4 h to allow an increase in the oral dose interval to 8 h or to allow i.v . administration of 300 mg 6 hourly . Additional PAE experiments were performed with the three strains for which PAEs are the shortest after exposure to 1 mg/liter for 1 h (0.4 to 1.2 h) . The PAE for these three strains increased markedly to 4.4 to 6.7 h following exposure to 2 mg/liter for 6 h (to mimic the area under the concentration-time curve from 0 to 6 h after a 300-mg dose) . These data suggest that oral clindamycin could be administered at 300 mg 8 hourly in the treatment of S . aureus infection, whereas the i.v . dose interval should be 6 h . These suggestions should be confirmed by performing clinical trials.

Microbiology, 1996 Jun, 142 ( Pt 6), 1491 - 7
Proline is biosynthesized from arginine in Staphylococcus aureus; Townsend DE et al.; Staphylococcus aureus NCTC 8325 exhibited a long lag phase (11 h) when inoculated into defined medium lacking proline, that could be shortened by increasing the concentration of arginine in the medium, or by supplying ornithine . Radioactivity from L-{14C}arginine, but not L-{14C}glutamate was incorporated into a spot with the chromatographic mobility of {14C}proline in the pool metabolites fraction . Selection for transposon Tn917-lacZ mutants impaired in arginine catabolism yielded four proline auxotrophs . Enzyme assays and precursor feeding experiments suggested that the major pathway for proline biosynthesis in S . aureus was from arginine via ornithine and delta'-pyrroline 5-carboxylate, rather than from glutamate . Strain 8325 Pro+, a proline prototrophic variant obtained by cultivation of 8325 in the absence of proline, accumulated L-{14C}arginine from the medium at about eight times the rate of strain 8325, suggesting its response to proline starvation was to increase arginine uptake.

J Appl Bacteriol, 1996 Jun, 80(6), 577 - 82
Quantification of Staphylococcus aureus and Escherichia coli in the liquid medium by fluorimetry and its use in phagocytosis assay; Fang W; A fluorimetric technique was compared with the plate counting method for quantification of viable cells of Staphylococcus aureus and Escherichia coli in the liquid medium . The fluorimetric assay measures the release of fluorogenic 4-methylumbelliferone (4-MU) from 4-methylumbelliferyl phosphate by the bacterial phosphatases . The increase in fluorescence was dependent on the size of bacterial inocula . Setting the fluorescence threshold at the middle of the logarithmic growth phase resulted in good linear relationship between bacterial counts and fluorescence (r = 0.99 for both Staph . aureus and E . coli) . There was also an excellent correlation between the fluorimetric assay and the plate counting method in quantifying viable bacteria in saline (r = 0.99) . Both methods were further compared for evaluation of extracellular bacteria following phagocytosis . The fluorimetric technique, in general, gave a higher percentage of phagocytosis than the plate counting method with statistical significance for E . coli.

J Leukoc Biol, 1996 Jun, 59(6), 902 - 7
Killing of phagocytosed Staphylococcus aureus by human neutrophils requires intracellular free calcium; Wilsson A et al.; The mobilization of intracellular calcium plays an important role in regulating neutrophil activation . With this in mind we investigated the effect of intra- and extracellular calcium on the ability of human neutrophils to kill complement-opsonized Staphylococcus aureus . We found that a rise in intracellular calcium is necessary for efficient killing of phagocytosed S . aureus . In the presence of extracellular calcium, killing of ingested bacteria in calcium-buffered neutrophils compared with normal cells was slightly reduced . Calcium buffering had no effect on phagocytic uptake by the neutrophils, but did decrease the generation of toxic oxygen metabolites, measured as chemiluminescence (CL) . In nondepleted and calcium-depleted cells, removal of extracellular calcium did not affect ingestion but did cause a marked decrease in the ability to kill the bacteria . In parallel, the CL response was substantially reduced or completely blocked . These data show that calcium is not a prerequisite for phagocytosis of S . aureus by human neutrophils, but does play a vital role in the post-ingestion killing of the bacteria by regulating the generation of toxic oxygen metabolites.

J Exp Med, 1996 Jun 1, 183(6), 2675 - 80
Protection against lethal toxic shock by targeted disruption of the CD28 gene; Saha B et al.; Toxic shock syndrome (TSS) is a multi system disorder resulting from superantigen-mediated cytokine production . Nearly 90% of the clinical cases of TSS arise due to an exotoxin, toxic shock syndrome toxin-1 (TSST-1), elaborated by toxigenic strains of Staphylococcus aureus . It is clearly established that besides antigen-specific signals a variety of costimulatory signals are required for full T cell activation . However, the nature and potential redundancy of costimulatory signals are incompletely understood, particularly with regards to superantigen-mediated T cell activation in vivo . Here we report that CD28-deficient mice (CD28-/-) are completely resistant to TSST-1-induced lethal TSS while CD28 (+/-) littermate mice were partially resistant to TSST-1 . The mechanism for the resistance of the CD28 (-/-) mice was a complete abrogation of TNF-alpha accumulation in the serum and a nearly complete (90%) impairment of IFN-gamma secretion in response to TSST-1 injection . In contrast, the serum level of IL-2 was only moderately influenced by the variation of CD28 expression . CD28 (-/-) mice retained sensitivity to TNF-alpha as demonstrated by equivalent lethality after cytokine injection . These findings establish an essential requirement for CD28 costimulatory signals in TSST-1-induced TSS . The hierarchy of TSST-1 resistance among CD28 wild-type (CD28+/+), CD28 heterozygous (CD28+/-), and CD28-/- mice suggests a gene-dose effect, implying that the levels of T cell surface CD28 expression critically regulate superantigen-mediated costimulation . Finally, as these results demonstrate the primary and non-redundant role of CD28 receptors in the initiation of the in vivo cytokine cascade, they suggest therapeutic approaches for superantigen-mediated immunopathology.

J Immunol, 1996 Jun 1, 156(11), 4107 - 13
Inability to produce IL-6 is a functional feature of human germinal center B lymphocytes; Burdin N et al.; In response to Ag encounter, B lymphocytes undergo a complex maturation process yielding phenotypically distinct subpopulations that are located in highly organized compartments of secondary lymphoid organs . This study describes the patterns of cytokine secretion of naive, memory, and germinal center (GC) human tonsillar B lymphocytes, activated either through CD40 or B cell receptor or with Staphylococcus aureus Cowan I particles . The three B cell subpopulations produced comparable levels of IL-10 and TNF-alpha, regardless of the stimulation pathway . Interestingly, activated GC B lymphocytes fail to express IL-6, as determined both at mRNA and at protein levels, whereas both naive and memory B cells can be induced to secrete IL-6 . Likewise, naive B lymphocytes undergoing dual ligation of CD40 and B cell receptor fail to express IL-6, since they acquire a GC-like phenotype . IL-6 receptors are up-regulated on both ex vivo-purified GC B lymphocytes and in vitro generated GC-like B cells, following CD40 activation . Consistent with this, addition of exogenous IL-6 sustains growth of CD40-stimulated GC B lymphocytes . Taken together, these results demonstrate that loss of IL-6 secretion is a functional characteristic of human GC B lymphocytes . The swap from an autocrine to a paracrine IL-6 response may permit a better control of B cell growth and differentiation during the germinal center reaction.

Epidemiol Infect, 1996 Jun, 116(3), 319 - 22
Nasal carriage of enterotoxin-producing Staphylococcus aureus among restaurant workers in Kuwait City; al Bustan MA et al.; Enterotoxin-producing Staphylococcus aureus is a common cause of staphylococcal food poisoning . To determine the incidence of carriage of enterotoxin-producing S . aureus in a sample of the healthy population in Kuwait city, restaurant workers in the city were screened for nasal carriage of S . aureus . 26.6% of 500 workers studied carried S . aureus and 86.6% of the S . aureus produced staphylococcal enterotoxins . 28% produced enterotoxin A, 28.5% produced enterotoxin B, 16.4% produced enterotoxin C and 3.5% produced enterotoxin D . Ten isolates produced both enterotoxins A and B or A and C . 73% of the isolates were untypeable with standard phages . However, 17.1%, 3% and 6% belonged to phage groups I, II and III respectively . The results demonstrated a high level of enterotoxigenic S . aureus carriage among restaurant workers which although lower than that reported for the general population and hospital workers may be important in the restaurant industry.

World J Surg, 1996 Jun, 20(5), 613 - 7
Tropical pyomyositis; Ansaloni L; Tropical pyomyositis (TP), a suppurative disease caused predominantly by Staphylococcus aureus, is responsible for 3% to 4% of surgical admissions in some hospitals in certain tropical countries . This study describes the clinical features of 35 patients with TP (20 males, 15 females; mean +/- SD age 28.3 +/- 14.1 years) admitted to our hospital during a 1-year period and analyzes the causal association between ancylostomiasis, human immunodeficiency virus (HIV) infection, and TP . Concerning the supposed etiologic association between Ancylostoma duodenale infection and TP, among the 35 patients with TP the stool examination of 22 (62.8%) revealed the presence of eggs of A . duodenale . In a control group of 100 asymptomatic subjects the prevalence of ancylostomiasis was 55% . The Odds ration between the two groups is 1.38 (exact 95% confidence limits = 0.59 < OR < 3.34) . Furthermore, the pus from all TP abscesses (41 in 35 patients) was carefully collected and examined microscopically, but nematode larvae were not detected in any of the specimens . Hence these results do not support an association between ancylostomiasis and TP . With the aim of correlating TP with HIV infection, I carried out a case-control comparison of HIV seroprevalence among the patients affected by TP and an age- and sex-matched control group of healthy subjects . Eleven patients with TP were HIV antibody-positive (seroprevalence 31.42%), as were two controls (seroprevalence 5.71%) . The matched analysis produced a Mantel-Haenszel matched Odds ratio of 5.50 and a maximum likelihood estimate of OR (MLE) of 5.50 (exact 95% confidence limits for MLE: 1.20 < OR < 51.07) . Among the 11 patients HIV-seropositive, 9 (81.8%) fulfilled the World Health Organization clinical case definition (CCD) for AIDS, compared with 1 of 24 (4.1%) HIV-negative subjects . The chi-square test for difference in fulfilling the CCD for AIDS between patients with TP seropositive and seronegative result was statistically significant (p < 0.0001) . It is concluded that TP is a bacterial infection highly significantly associated with HIV infection and thus must be considered a strong sign of stage III-IV of HIV disease.

J Bacteriol, 1996 Jun, 178(11), 3362 - 4
Identification and characterization of the pckA gene from Staphylococcus aureus; Scovill WH et al.; The Staphylococcus aureus pckA gene was identified and characterized . A pckA mutant lacked detectable phosphoenolpyruvate carboxykinase activity and grew poorly in the absence of glucose . Both enzymatic activity and pckA promoter activity in wild-type cells grown in the absence of glucose were at least 22-fold greater than activities in cells grown in the presence of glucose.

Arthritis Rheum, 1996 Jun, 39(6), 959 - 67
In situ hybridization analysis of synovial and systemic cytokine messenger RNA expression in superantigen-mediated Staphylococcus aureus arthritis; Zhao YX et al.; OBJECTIVE: To investigate patterns of synovial and systemic cytokine messenger RNA (mRNA) expression in mice with superantigen-mediated Staphylococcus aureus arthritis . METHODS: Mice were inoculated intravenously with 1 x 10(7) colony-forming units of toxic shock syndrome toxin-1-producing S aureus LS-1 . Synovial tissues and spleens were obtained at varying time intervals after bacterial inoculation, and examined for mRNA expression of interleukin-1beta (IL-1beta), IL-4, IL-10, IL-12, tumor necrosis factor alpha (TNFalpha), TNFbeta, interferon-gamma (IFN-gamma), transforming growth factor beta, and perforin, by an in situ hybridization technique . RESULTS: In situ hybridization revealed early synovial up-regulation of TNFalpha and IL-1 beta mRNA expression . Peak frequencies of these proinflammatory cytokines were observed at the second and third week of the infection . Expression of T cell-derived cytokine mRNAs was detected later, and in a relatively low frequency . Notably, induction and peak numbers of Th2 cytokine (IL-4 and IL-10) mRNA expression preceded Th1 cytokine (IFNgamma and TNFbeta) mRNAs . In comparison with synovial tissues, peak spleen cytokine mRNA expression of IL-1beta, TNFalpha, TNFbeta, IL-12, and IFNgamma occurred earlier, but displayed a clearly lower magnitude of expression . CONCLUSION: These findings demonstrate synovial and systemic up-regulation of cytokine mRNA expression during S aureus arthritis, indicating that both monocyte/macrophage and T cell-derived products are involved in the pathogenesis of this disease.

Ann Otol Rhinol Laryngol, 1996 Jun, 105(6), 476 - 80
Effect of SC-41930, a potent selective leukotriene B4 receptor antagonist, in the guinea pig model of middle ear inflammation; Sutbeyaz Y et al.; Arachidonic acid metabolites such as prostaglandins and leukotrienes have been shown to play an important role in the pathogenesis of otitis media (OM) . Among these mediators, leukotriene B4 (LTB4) is one of the most potent inducers of inflammatory processes . SC-41930 has been shown to be a specific LTB4 receptor antagonist both in vitro and in vivo . In this study, anti-inflammatory effects of SC-41930 were investigated in a guinea pig model of OM induced by middle ear (ME) inoculation of killed Staphylococcus aureus . Outcome of treatment was determined by measurement of myeloperoxidase activity in the samples of ME mucosa, evaluation of temporal bone histopathology, and presence of ME fluids . Myeloperoxidase activity in the SC-41930-treated group was found to be significantly lower than that in the control group . Histopathology of temporal bones indicated decreased inflammation in the treated group as compared to the controls . In addition, ME fluids were absent in four out of six treated animals . These results demonstrate that SC-41930 can produce significant anti-inflammatory effects in this model of OM.

J Med Microbiol, 1996 Jun, 44(6), 496 - 9
True identity of control Staphylococcus aureus strains and their performance in the tube coagulase test; Wilcox MH et al.; One hundred laboratories were asked to submit their control Staphylococcus aureus strains to determine the true identity of strains presumed to be S . aureus NCTC 6571, and also to evaluate the performance of those strains being used as controls in the tube coagulase test (TCT) . Of the 60 who replied, 55 laboratories sent at least one strain labelled as S . aureus NCTC 6571 (total of 64 strains) . Of these, 84% were identified as S . aureus, and were indistinguishable from a fresh type strain by a combination of phenotypic methods including biotyping, antibiotic susceptibility testing and phage typing . Six-to-ten strains (9-16%), depending on the degree of stringency, were not identifiable as S . aureus NCTC 6571 . The time since last retrieval from storage ranged from daily to > or = 3 years, but there was no correlation between this duration and the likelihood of differing from S . aureus NCTC 6571 . Forty-seven laboratories submitted 51 strains used as controls in the TCT; these included 31 strains labelled as S . aureus NCTC 6571, eight wild strains, three other NCTC strains and nine strains of uncertain origin . Generally, the S . aureus NCTC 6571 strains produced weaker clots than the remainder . None of the S . aureus NCTC 6571 strains was found to be inoculum dependent but four of the other control strains were . The study demonstrates that some laboratories must improve procedures for ensuring that control S . aureus strains retain their true identity, particularly by avoiding repeated subcultures . Laboratories are divided in their use of strong or weak (S . aureus NCTC 6571) positive controls for the TCT . S . aureus NCTC 6571 is a more stringent control for the TCT than other control strains presently being used and is, therefore, to be preferred.

Biochim Biophys Acta, 1996 May 31, 1301(1-2), 127 - 32
Differential effects of glycero- and sphingo-phospholipolysis on human high-density lipoprotein fluidity; Lottin H et al.; This study investigates the effect of enzymatic modifications of the HDL(3) surface lipid composition on their physical properties . Human HDL(3) (d: 1.125-1.21 g/ml) was treated either by an exogenous phospholipase A(2) from Crotalus adamanteus or by a sphingomyelinase from Staphylococcus aureus in the presence of albumin for various periods of time in order to obtain several degrees of hydrolysis . Glycerophospholipid hydrolysis ranged from 13 to 81% and sphingomyelinase action led to a 31-92% sphingophospholipid degradation . Physical properties of the surface of HDL(3) were examined by two spectroscopic methods: fluorescence polarisation and electron spin resonance . Glycerophospholipolysis treatment of HDL(3) enhanced the fluorescence anisotropy values (6-18%) and both relaxation correlation time (30-100%) and degree of order . All these results indicated a more rigid environment, a decreased mobility and an increased order of the surface lipids . Conversely, treatment of the HDL(3) with sphingophospholipase induced a progressive fluidization: fluorescence polarisation and degree of order decreasing down to 10% and relaxation correlation time down to 35% compared to native HDL(3) . Taken together, all these observations suggest the relative importance of the two major phospholipids to modulate the fluidity and order of the surface of HDL(3) and could account for several recent physiological observations.

J Am Vet Med Assoc, 1996 May 15, 208(10), 1705 - 8
Use of composite milk samples for diagnosis of Staphylococcus aureus mastitis in dairy cattle; Lam TJ et al.; OBJECTIVE--To measure relative sensitivity and relative specificity for use of composite milk samples, compared with that of individual gland milk samples, for diagnosis of Staphylococcus aureus mastitis . ANIMALS--505 cows suspected of having subclinical mastitis . Of these cows, 172 were considered infected with Sta aureus, based on the results from individual gland samples . PROCEDURE--Composite and individual gland milk samples were collected from cows suspected of having subclinical mastitis, and results of bacteriologic culturing of samples from the same cow were compared . Results were interpreted at the cow level . Relative sensitivity and relative specificity for composite samples were computed from 2 x 2 tables, using results from individual gland samples as references . RESULTS--Relative sensitivity for use of composite milk samples in diagnosing Sta aureus mastitis was 0.63 . The relative specificity was 0.98 . Factors influencing the relative sensitivity for composite samples were the number of infected glands per cow, the amount of Sta aureus shedding from infected glands, and the proportion of the composite milk obtained from each gland . CLINICAL IMPLICATIONS--Collecting composite instead of individual gland milk samples increases the number of false-negative results in diagnosing Sta aureus mastitis . By collecting consecutive samples from the same cow or by increasing the inoculum volume at culturing, this problem can be diminished.

J Immunol, 1996 May 15, 156(10), 3932 - 8
Induction of IL-12 p40 messenger RNA expression and IL-12 production of macrophages via CD40-CD40 ligand interaction; Kato T et al.; The mechanism of IL-12 production has been studied by stimulating macrophages or B cell lines with LPS, Staphylococcus aureus, or phorbol diester . However, since IL-12 plays an important role in the activation of T cells interacting with APC, it is important to study the mechanism of IL-12 production induced by T helper cell-APC interaction . We and others have demonstrated that IL-12 is produced in cultures where Th1 cells are stimulated with Ag or APC . In the present experiments, we studied a role of CD40-CD40 ligand (CD40L) interaction in IL-12 production and obtained the following results: 1) incubation of normal Th1 clone with APC in the presence of Ag induced IL-12 p40 and p35 mRNA accumulation and IL-12 production, and the addition of anti-CD40L blocked the p40 mRNA accumulation and IL-12 production but not p35 mRNA accumulation; 2) when Th1 clone from a CD40L-deficient mouse was used in the incubation, p35 mRNA accumulation was induced, but neither p40 mRNA accumulation nor IL-12 production was induced; 3) CD40L+ Th1 clone, or insect cell membrane expressing mouse CD40L, induced p40 mRNA accumulation and IL-12 production but not p35 mRNA accumulation . These results indicate that the CD40-CD40L interaction plays a critical role in IL-12 p40 mRNA accumulation and bioactive IL-12 production and that p35 mRNA accumulation was regulated via a different mechanism than CD40-CD40L interaction . Most of the cells producing IL-12 were Mac-1+ macrophages.

Cancer Lett, 1996 May 15, 103(1), 41 - 7
Antitumour activity of protein A in a mouse skin model of two-stage carcinogenesis; Shukla Y et al.; Protein A (PA) is an immunostimulating glycoprotein (mol . wt . 43,000 kDa) obtained from Staphylococcus aureus cowan I . The antitumour property of PA is well documented in the literature in various transplantable tumours of rats and mice . In the present set of investigations, the antitumour property of PA was tested in Swiss albino mice in a two-stage initiation-promotion mouse skin carcinogenesis model . The animals were initiated topically with a single subcarcinogenic dose (52 microgram) of 7,12-dimethylbenzanthracene (DMBA) . PA was administered intraperitoneally (1 microgram/animal), twice weekly for 2 weeks . Promotion was performed by twice weekly applications of 12-O- tetradecanoyl phorbol-13-acetate (TPA) at a dose of 5 microgram/animal for 32 weeks . The result showed that the treatment schedule can effectively check the onset of tumorigenesis, the cumulative number of tumours and the average number of tumours per mouse . In the PA administered group, 30% of the animals remained tumour free until the termination of the experiments (i.e . 32 weeks of promotion) . Thus the present study proves that protein A can effectively inhibit DMBA initiated and TPA promoted mouse skin carcinogenesis.

J Biol Chem, 1996 May 3, 271(18), 10853 - 8
Molecular expression of the alpha-chemokine rabbit GRO in Escherichia coli and characterization of its production by lung cells in vitro and in vivo; Johnson MC 2nd et al.; GRO proteins are alpha-chemokine cytokines that attract neutrophils and stimulate the growth of a variety of cells . Previously, we observed that rabbit alveolar macrophages transcribe the genes for at least two GRO homologues . In order to study the role of GRO cytokines in lung inflammation, we cloned the predominant rabbit GRO cDNA (RabGRO) from alveolar macrophages, expressed bioactive recombinant protein (rRabGRO) in Escherichia coli, and developed a sensitive and specific enzyme-linked immunosorbent assay for RabGRO protein . We found that rabbit AM express and secrete GRO in vitro in response to both exogenous (e.g . lipopolysaccharide, heat-killed Staphylococcus aureus, and crystalline silica) and endogenous inflammatory stimuli (e.g . tumor necrosis factor-alpha) as determined by both radioimmunoprecipitation and enzyme-linked immunosorbent assay . Biologically significant amounts of GRO are present in vivo in the bronchoalveolar lavage fluid of rabbits with E . coli pneumonia; by in situ hybridization, GRO mRNA is detectable in infiltrating pulmonary leukocytes and bronchial epithelial cells . These results indicate that GRO chemokines are likely to be important mediators of the inflammatory response that accompanies acute infectious processes in the lungs.

Antibiot Khimioter, 1996 May, 41(5), 13 - 8
{Absorption of various actinomycins by Staphylococcus aureus cells}; Polin AN et al.; The absorption of actinomycin D by the cell suspension of Staphylococcus aureus via diffusion linearly depended on the antibiotic concentration in the suspension within the ranges of 2 to 15 micrograms/ml . The absorption of active actinomycins C2, C3 and Au6 was the same as that of actinomycin D . The Staphylococcus intact membranes limited the inlet of the actinomycins to the cells since the membranotropic substances such as gramicidin S and its derivatives and thyrocidin increased their absorption by 30-70 per cent . The absorption of a low active actinomycin D0 and inactive actinomycinic acid even after the exposure to the membranotropic substances was not detectable . These compounds did not form any complexes with DNA . The level of the absorption of the actinomycins by the cells was likely defined by their ability to complex with DNA.

J Nucl Med, 1996 May, 37(5), 863 - 8
Functional upregulation of granulocytes labeled with technetium-99m-HMPAO and indium-111-oxinate; Bertrand-Caix J et al.; Indium-111-oxinate-labeled granulocytes have been used in vivo for several years for the detection of abscesses . Technetium-99-m-hexamethylpropyleneamine oxime (99mTc-HMPAO) labeling has more recently been described . METHODS: The influence of radiolabeling by both radiotracers on adhesion glycoprotein CD11b quantification was studied in quiescent and formyl-methionylleucylphenylalanine (fMLP)-activated neutrophils (PMN) . Adhesion was assessed on human umbilical endothelial cells (HUVEC) as well as the repercussion of the granulocyte labeling on HUVEC viability (neutral red) and metabolic activity (MTT) . Chemotaxis of PMN was evaluated by measuring migration under agarose with fMLP as chemoattractant . We also measured phagocytosis and the production of hydrogen peroxide induced by staphylococcus aureus . RESULTS: Whereas whole functional integrity is maintained after labeling, most of the functions (CD11b expression, adhesion, HUVEC metabolic activity) are up-regulated while chemotaxis is decreased in the presence of both radiotracers . Indium-111-oxinate induces larger alterations than 99mTc-HMPAO . CONCLUSION: These data were obtained in normal volunteers . In patients, alterations due to the in vitro labeling procedure, in addition to potential functional alterations caused by the underlying pathology, should be taken into account during image interpretation.

Head Neck, 1996 May-Jun, 18(3), 292 - 4
Wide reconstruction of the anterior cranial base with bipedicled galeopericranial flap; Terashi H et al.; BACKGROUND . Reconstruction of facial bone fractures complicated by frontal sinus destruction must seal off the cranial cavity from the upper respiratory tract to avoid ascending infections of the intracranial contents . METHODS . We used a bipedicled galeopericranial flap for reconstruction of the extradural and subcutaneous spaces of the frontal region, which were infected with methicillin-resistant Staphylococcus aureus (MRSA) following unsuccessful coverage of the anterior cranial base with an anteriorly based pericranial flap . RESULTS . The patient healed uneventfully without infection . CONCLUSION . Because a bipedicled galeopericranial flap has abundant blood supply, it can be used to cover a wide segment of the anterior cranial base . This is the first report of the application of a bipedicled galeopericranial flap for wide reconstruction of the anterior cranial base.

Curr Microbiol, 1996 May, 32(5), 286 - 90
A phage-mediated transfer of chromosomally integrated tetracycline resistance plasmid in Staphylococcus aureus; Udo EE et al.; The ability of a Staphylococcus aureus isolate WBG7416 to transfer its resistance determinants was studied in conjugation and mixed-culture transfer experiments . It carried plasmid-borne resistance to kanamycin, trimethoprim, chloramphenicol, cadmium, propamidine isethionate, and chromosomal resistance to methicillin, gentamicin, streptomycin, erythromycin, clindamycin, tetracycline, and minocycline . It transferred tetracycline resistance in mixed-culture transfer but not in conjugation experiments . DNA-DNA hybridization of genomic DNA from the tetracycline-resistant transferrants against a labeled tetracycline resistance plasmid, pWBG3, probe revealed the presence of an integrated plasmid in their chromosomes . In contrast, no homology to the probe was detected in the chromosome of a tetracycline-resistant mutant of the recipient strain . The results established a role for a bacteriophage in the transfer of chromosomal tetracycline resistance in WBG7416 besides demonstrating the presence of an integrated tetracycline resistance plasmid in the transferrants . It also offered an insight into the nature of the integrated plasmid.

Plasmid, 1996 May, 35(3), 174 - 88
Characterization of a Staphylococcus aureus transposon, Tn5405, located within Tn5404 and carrying the aminoglycoside resistance genes, aphA-3 and aadE; Derbise A et al.; A new staphylococcal composite transposon, designated Tn5405, carrying the genes aphA-3 and aadE, which encode resistance to aminoglycosides, was partially characterized . The transposon is 12 kb long and is flanked by inverted repeated sequences displaying the characteristic features of an insertion sequence, named IS1182 . This insertion sequence is 1864 bp long and has 23/33-bp imperfect inverted repeats at its ends . One of the IS1182 copies delimiting Tn5405 contains a copy of IS1181 flanked by 8-bp direct repeats . Tn5405 was found in the chromosome of MRSA clinical isolate BM3121, within a Tn552-related transposon, Tn5404 . Tn5404 was previously characterized following its transposition onto a beta-lactamase plasmid harbored by BM3121 . Two forms of the recombinant beta-lactamase-encoding plasmid generated by the inversion of Tn5405 within Tn5404 were detected . IS1182 was not detected in the DNA of 4 of the 17 tested MRSA isolates containing aphA-3 and resistant to streptomycin . Thus, aphA-3 and aadE genes are not disseminated only by Tn5405 or related transposons delimited by IS1182.

FEMS Immunol Med Microbiol, 1996 May, 14(1), 45 - 51
Intramammary immunization with live-attenuated Staphylococcus aureus: microbiological and immunological studies in a mouse mastitis model; Garcia V et al.; Mammary infection was induced in lactating mice by intramammary injection of Staphylococcus aureus . Histopathological analysis revealed infiltration and lesions of varying magnitude that were still apparent 21 days after the challenge . Concomitantly, viable S . aureus was recovered from infected mammary glands . Mice were immunized by the intramammary route with 5 x 10(6) colony forming units of a temperature-sensitive mutant of S . aureus and subsequently received a boosting injection seven days later . On day 14 mice were challenged by the intramammary route with the wild-type strain . Intramammary immunization induced a significant increase in milk IgA (P < 0.05), serum IgG (P < 0.05) and serum IgA (P < 0.05) on the day of the challenge, when compared with non-immunized mice . Immunization decreased significantly (P < 0.01) the number of S . aureus colony forming units recovered 96 h after intramammary challenge . In conclusion, the feasibility of immunizing locally with temperature-sensitive S . aureus to induce immunity in the mouse mammary gland was demonstrated . The mouse model of mastitis is proposed as a useful system for screening temperature-sensitive S . aureus strains to be utilized in the development of a vaccine.

Ger J Ophthalmol, 1996 May, 5(3), 176 - 81
Oculomucocutaneous changes as paraneoplastic syndromes; Kreutzer B et al.; Bullous dermatoses such as erythema exsudativum multiform major (EEMM) and bullous pemphigoid can lead to severe ocular involvement . In rare cases, both diseases develop as paraneoplastic syndromes . The immunopathologic mechanisms are discussed . A 69-year-old woman with non-Hodgkin's lymphoma (NHL) of grade IIIb developed EEMM while under systemic treatment with Fluconazole, Ofloxacin, and/or a combination of sulfamethoxazole and trimethoprim after polychemotherapy . In the eye, conjunctival necrosis with sicca syndrome led to Staphylococcus aureus-induced corneal superinfection, perforation, and consecutive keratoplasty a chaud . The patient died 6 weeks after the first presentation . A 44-year-old man with NHL of grade IVa after polychemotherapy developed a bullous pemphigoid affecting the skin, mucous membranes, and both eyes while under systemic treatment with sulfamethoxazole and trimethoprim . Although the underlying malignancy responded well to chemotherapy, the ocular manifestations of the paraneoplastic systemic syndrome slowed down only on treatment with cyclosporin A but not following therapy with azathioprine and cyclophosphamide . Therapy could not stop cicatrization and keratinization of the conjunctiva and cornea . An occult malignancy should be excluded in acute and chronic oculomucocutaneous syndromes . The prognosis for the eye seems to be poor because of the rapid course and the ineffectiveness of therapy as demonstrated in the present cases.

Acta Derm Venereol, 1996 May, 76(3), 214 - 8
Preferential expression of T-cell receptor V beta-chains in atopic eczema; Neuber K et al.; Chronic skin colonization with Staphylococcus aureus is a characteristic feature of atopic eczema, and about 60% of S . aureus strains isolated from the skin of patients with atopic eczema secrete enterotoxins . T-cell stimulation by staphylococcal enterotoxins is restricted to the V beta-chain of the T-cell receptor . Therefore, the expression of different V beta-chains (V beta 3, 5 a,b,c, 6, 8, 12) on peripheral blood T-cells (CD4+) from patients with atopic eczema was measured by flowcytometry before and after stimulation with staphylococcal enterotoxin B . Lymphocytes from healthy donors served as controls . Additionally, the expression of V beta-chains in normal skin and in lesional skin of patients with atopic eczema was determined by immunofluorescence histology . In atopic eczema, higher numbers of CD4+ T-cells expressed V beta 3, V beta 8 and V beta 12 compared to the control group . No correlation between S . aureus enterotoxin B-stimulated V beta-expression and HLA-haplotypes was found . In lesional skin of patients with atopic eczema most of the infiltrating T-cells were V beta 3+, whereas in normal skin only very few T-cell receptor-expressing cells were detected . To evaluate the significance of these T-cell clones for allergic inflammation, T-cells from patients with atopic eczema and normal donors were stimulated with monoclonal antibodies against V beta 3, 5(c) and 8 . Afterwards, the proliferative response of lymphocytes as well as IL-5 and IFN gamma synthesis were measured . T-cells from patients with atopic eczema showed a significantly higher proliferation and IL-5 secretion than normal donors after stimulation with monoclonal antibodies against V beta 3 and V beta 8 . In contrast, the monoclonal antibodies directed to V beta 5(c) induced a markedly elevated proliferation and IFN gamma production of normal lymphocytes compared to patients with atopic eczema . Our results suggest a preferential expression of certain V beta-subgroups during inflammation in atopic eczema; this may be explained by a selective stimulation of TH2-cells via S . aureus-derived enterotoxins.

Vet Immunol Immunopathol, 1996 May, 51(1-2), 67 - 78
Effects of in vitro supplementation with alpha-tocopherol and selenium on bovine neutrophil functions: implications for resistance to mastitis; Ndiweni N et al.; A low vitamin E/selenium status has been associated with increased vulnerability of dairy cattle to mastitis . Since polymorphonuclear leucocytes (PMN) provide the major cellular defence mechanism within the mammary gland, the effect of in vitro supplementation with vitamin E and selenium on the function of these cells was investigated . Both vitamin E and selenium enhanced the chemotactic and random migration of PMN and increased the production of superoxide following stimulation with phorbol myristate acetate . Vitamin E, but not sodium selenite, was also found to enhance the phagocytosis of opsonised Staphylococcus aureus by PMN . No synergistic effects of the two nutrients were observed . These results obtained in vitro may indicate the potential benefits of in vivo supplementation of dairy cows with vitamin E and selenium in terms of enhancing their natural resistance to mastitis.

Harefuah, 1996 May 1, 130(9), 602 - 3, 655
{Purulent pericarditis}; Evron E et al.; Purulent pericarditis is diagnosed when pus is drained from the pericardial space or when bacteria are cultured from the pericardial fluid . This rare disease is often diagnosed late, when severe hemodynamic compromise develops due to pericardial tamponade . It is usually a complication of pneumonia, especially if there is empyema as well, and often follows chest surgery or chest wall infections . It sometimes appears in patients with septicemia, especially when they are debilitated or immuno-compromised . Diagnosis is aided by echocardiography . Pericardiocentesis and drainage of the pus, as well as prolonged antibiotic treatment, are mandatory . Delay in diagnosis and treatment often results in death . Some surviving patients may develop constrictive pericarditis and require pericardiectomy . We report a 73-year-old man with pulmonary lymphoma who suffered from purulent pericarditis secondary to sepsis with methicillin-resistant Staphylococcus aureus . Pericardial drainage and appropriate antibiotic treatment eventually resulted in complete recovery.

J Dairy Sci, 1996 May, 79(5), 846 - 50
A method for measuring specific antibodies in bovine lacteal secretions during the nonlactating period; Guidry AJ et al.; A large portion of new IMI in dairy cattle occurs during the nonlactating period . Because antibiotic infusions at the beginning of the nonlactating period are only partially effective, attempts have been made to stimulate the production of protective antibodies in lacteal secretions during this period . However, measurement of antibodies in mammary secretions during the nonlactating period has been hampered by the complex, viscous nature of these secretions . This report describes the use of caprylic acid to clarify secretions from the bovine mammary gland during the nonlactating period to provide a more accurate measurement of specific antibody . Six healthy Jersey cows were injected in the area of the supramammary lymph node with an encapsulated strain of Staphylococcus aureus in dextran sulfate at the beginning of the nonlactating period and 15 and 30 d later . Seven healthy unimmunized Jersey cows served as controls . Lacteal secretions taken at the beginning of the nonlactating period; at 15, 30, and 45 d into the nonlactating period; and at calving were treated with caprylic acid prior to assay for specific antibodies using ELISA . Purified S . aureus capsule was used as the antigen in the ELISA . Caprylic acid lowered non-specific binding of IgG1 and IgM in secretions during the dry period from unimmunized control cows and lowered IgM from immunized cows . The most pronounced effect of caprylic acid was an increase in IgG2 binding in secretions from immunized cows . Treatment with caprylic acid more accurately measured specific activity of Ig in mammary secretions during the nonlactating period.

Zh Mikrobiol Epidemiol Immunobiol, 1996 May-Jun, (3), 74 - 7
{The role of the persistent characteristics of a causative agent in determining the protracted course of a suppurative-inflammatory course}; Deriabin DB et al.; An important role of the complex of biological properties of Staphylococcus aureus, including anticomplementary and antilysozyme activity, capacity for the inactivation of the bactericidal component of interferon and the Fc-reception of immunoglobins, in the prolonged character of the purulent inflammatory process induced by this infective agent . The system permitting the prognosis of the unfavorable course of post-injection abscesses, based on the analysis of known informative properties of the infective agent, was developed with the use of the heterogeneous consecutive procedure of sample recognition.

Z Orthop Ihre Grenzgeb, 1996 May-Jun, 134(3), 273 - 82
{Outbreak of infection with methicillin-resistant Staphylococcus aureus (MRSA) in an orthopedic septic care unit--measures for eradication and subsequent colonization studies}; Fruhauf G et al.; An outbreak due to a methicillin-resistant S . aureus (MRSA) strain in an orthopaedic septic care unit was observed . 17 patients developed wound infections . Stronger regime of hygiene and chemotherapy and new technics of operations controlled the outbreak within 5 months . Studies of colonisation were performed at the care unit in march, june and august 1992 . 618 isolates were investigated from patients, personnel and their environment . The frequencies of detected MRSA diminished from 30% in march only to 22% in august 1992 . The long time persistence of endemic MRSA in a care facility was evident from the presence of MRSA even 5 months after the last infection.

Res Microbiol, 1996 May, 147(4), 279 - 86
Anionic properties of beta-lactam-enhancing factor on methicillin-resistant Staphylococcus aureus; Tajima Y et al.; We found a Factor (factor T) in aged mixtures of tungstate and phosphate which greatly enhanced the antibacterial effects of beta-lactams upon methicillin-resistant Staphylococcus aureus (MRSA) . Factor T suppressed penicillinase production and the amount of penicillin-binding protein-2' in the membrane fraction, thus sensitizing MRSA strains to beta-lactams . In addition, Factor T caused a metachromatic reaction and prolonged the blood coagulation time, indicating that it is a heparin-like polyanion . Since Factor T becomes ineffective in the presence of a polycation, a charge interaction may play an important role in the enhancing effect . One possibility is that Factor T non-specifically inhibits several anion-sensitive enzymes . Factor T inhibited several nucleotide-interacting enzymes, but not most serum enzymes.

Res Microbiol, 1996 May, 147(4), 263 - 71
Phenotypic and genotypic (pulsed-field gel electrophoresis) characteristics of enterotoxin-A-producing Staphylococcus aureus strains; Gouloumes C et al.; The phenotypic (antibiotype, serotype, phagetype) and genotypic (SmaI restriction patterns using pulsed-field gel electrophoresis) characters of 162 Staphylococcus aureus epidemiologically unrelated strains were studied . Eighty-two of the isolates produced enterotoxin-A (SEA+), while 80 produced none (SEA-) . None of the phenotypic characters observed were characteristic of SEA+ strains . On the other hand, the electrophoretic profiles revealed a non-random distribution of the SEA+ strains (p < 0.01 in groups PI and PIII, and p < 0.03 in group PII) . It can therefore reasonably be assumed that the enterotoxin-A-producing strains did not constitute a single clone, but rather, seemed to belong to strains derived from at least three clones with distinct genetic organization.

Trans R Soc Trop Med Hyg, 1996 May-Jun, 90(3), 280 - 3
Pyogenic liver abscesses and acute schistosomiasis mansoni: report on 3 cases and experimental study; Teixeira R et al.; Three children with acute schistosomiasis mansoni developed pyogenic liver abscesses . The abscesses were diagnosed by ultrasonography and confirmed during laparotomy . Staphylococcus aureus were the sole bacteria isolated from the abscesses . An experimental study was carried out in mice to establish whether schistosomiasis is a predisposing cause for pyogenic liver abscesses . Seventeen mice (group 1) were infected with 40 Schistosoma mansoni cercariae (LE strain) and 60 d later inoculated intravenously with a strain of Staph . aureus, isolated from a patient with bacteraemia; 17 mice infected with Sch . mansoni (group 2), 19 infected with bacteria alone (group 3), and 18 uninfected mice (group 4), served as controls . Thirteen group 1 mice (77%) developed multiple liver abscesses while none was observed in the controls . These results indicate that acute schistosomiasis mansoni concurrent with Staph . aureus bacteraemia favours the colonization of the liver by bacteria and the development of pyogenic hepatic abscesses.

Jpn J Antibiot, 1996 May, 49(5), 517 - 21
{Transferability of cefozopran to cerebrospinal fluid in rabbits with meningitis caused by Staphylococcus aureus}; Haruta T et al.; The transferability of cefozopran (CZOP) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus . The mean plasma concentration was 293 +/- 17.6 micrograms/ml at 15 minutes after intravenous administration of CZOP at a dose level of 100 mg/kg . The mean concentration in CSF reached its maximum, 16.5 +/- 2.74 micrograms/ml at 60 minutes after administration . Pharmacokinetic parameters calculated from these values were as follows: Cmax (CSF/plasma) 5.72%, AUC (CSF/plasma) 6.61% between 15 and 60 minutes, 9.38% between 15 and 120 minutes and 11.2% between 15 and 180 minutes, T 1/2 for CZOP in CSF: 138 minutes, T 1/2 (CSF/plasma): 2.81 . In comparison to those of beta-lactams that were obtained in the same way, the transferability of CZOP to CSF was moderate but concentration in CSF was high, hence, in consideration of the antimicrobial potency against the main pathogens of meningitis, it appears worthwhile of running clinical trials for CZOP.

Reg Anesth, 1996 May-Jun, 21(3), 239 - 42
Bactericidal activity of clinically used local anesthetics on Staphylococcus aureus; Sakuragi T et al.; BACKGROUND AND OBJECTIVES . The rate of onset of antimicrobial activity of local anesthetics is unknown . Similarly, whether the activity is bactericidal or bacteriostatic is also unknown . The antimicrobial activity of local anesthetics with preservatives has not been studied . This study investigated the rate and potency of the antimicrobial activity of 0.125%, 0.25%, and 0.5% bupivacaine, 2.0% mepivacaine and 2.0% lidocaine with preservatives, and 2.0% lidocaine without preservatives on two strains of methicillin-resistant Staphylococcus aureus . METHODS . The pathogen was exposed to each local anesthetic for 1, 3, 6, 12, and 24 hours at room temperature . The inocula from these suspensions were diluted to 1:1,000 with physiological saline to inactivate the antimicrobial activity of the local anesthetics and then were cultured for 24 hours at 37 degrees C on agar plates . RESULTS . Lower colony counts were observed with a 3-hour or longer exposure to 0.5% bupivacaine in both strains of S . aureus (P < .05) . The 3-hour exposure reduced the count by approximately 60%, the 6-hour exposure by 70%, and the 24-hour exposure by more than 99% . The bactericidal activity was lowest with 0.125% bupivacaine and 2.0% mepivacaine . CONCLUSIONS . Antimicrobial activity was observed shortly after exposure of S . aureus to local anesthetics and appeared to be bactericidal rather than bacteriostatic . However, the observed bactericidal activity, although it developed rapidly, may be insufficient to account for the low incidence of epidural infection related to epidural cannulation.

Biol Pharm Bull, 1996 May, 19(5), 672 - 7
Proteolysis of human tumor necrosis factor (TNF) by endo- and exopeptidases: process of proteolysis and formation of active fragments; Nakamura K et al.; Recombinant human tumor necrosis factor (TNF) was digested with endopeptidases under mild conditions . Incubation of the TNF (155-amino-acid TNF) with trypsin, Staphylococcus aureus V-8 protease or chymotrypsin initially released small peptides derived from the amino (N)-terminal region of TNF, but did not release peptides from the carboxyl (C)-terminal region . The TNF was resistant to carboxypeptidases A and Y under a non-denaturing condition, but in the presence of urea or sodium dodecyl sulfate the C-terminal amino acid was released quantitatively by these peptidases . These results indicate that the N-terminal region of the TNF molecule is accessible to protease, while the C-terminal region is not susceptible to degradation . When the TNF was incubated with seven kinds of endopeptidases, its activity rapidly disappeared . At an early stage of the degradation, one active fragment was detected among the fragments produced with trypsin or pronase P, but no active fragments were detected on the degradation with the other peptidases . The active fragment was a fragment lacking the four N-terminal amino acid residues of the TNF . These results suggest that TNF is initially degraded at the N-terminal region by an endopeptidase and loses its activity as the degradation proceeds.

J Hosp Infect, 1996 May, 33(1), 49 - 53
Consecutive isolation of homologous strains of methicillin-resistant and methicillin-susceptible Staphylococcus aureus from a hospitalized child; Lawrence C et al.; A multiply resistant, methicillin-resistant Staphylococcus aureus was repeatedly isolated from the anterior nares of a premature neonate hospitalized in an intensive-care unit and treated with multiple courses of antibiotics . Two months following cessation of antibiotic therapy, a strain of S . aureus with a similar antibiotic resistance profile, but susceptible to methicillin, was isolated from three consecutive nasal swabs . Total DNA of the methicillin-susceptible and -resistant isolates was digested with SmaI and resolved by pulsed-field gel electrophoresis . The SmaI restriction profile of the susceptible isolate was similar to that of the resistant one except for the replacement of a 207-kb fragment by a 147-kb fragment . In Southern hybridization, a mecA-specific probe hybridized to the 207-kb SmaI fragment of the methicillin-resistant strain but not to DNA of the susceptible strain . These results suggest that loss of the mecA gene can occur in vivo when antibiotic selective pressure is removed.

Nucl Med Commun, 1996 May, 17(5), 430 - 4
Accumulation of 99Tcm-polyclonal immunoglobulin in different stages of infection: an experimental study; Burak Z et al.; In this experimental study, the utility of 99Tc(m)-polyclonal human immunoglobulin (99Tcm-HIG) for localizing acute and chronic phases of inflammatory lesions was investigated . Three groups of rats were inoculated with Staphylococcus aureus in the right thigh . Then, 24 h (group I, n = 12), 48 h (group II, n = 12) and 72 h (group III, n = 12) post-inoculation, the rats received 40 MBq 99Tcm-HIG into the jugular vein . In addition, two control rats were studied at 24 h after inoculation of sterile saline . Both visual and quantitative evaluations were undertaken . The acute and chronic stages of inflammation were determined by pathological examination . The mean ( +/- S.D.) lesion/contralateral uptake ratios at 4 and 24 h after 99Tcm-HIG injection were: group I, 1.22 +/- 0.1 and 2.12 +/- 0.16; group II, 1.15 +/- 0.08 and 2.25 +/- 0.16; group III, 1.06 +/- 0.09 and 2.08 +/- 0.14 . In conclusion, the acute and chronic phases of infection showed non-significant differences in 99Tcm-HIG uptake ratios.

Br J Dermatol, 1996 May, 134(5), 962 - 5
Staphylococcal scalded skin syndrome in an HIV-1 seropositive man; Farrell AM et al.; The staphylococcal scalded skin syndrome (SSSS) is very rare in adults . Renal impairment and immunocompromise are predisposing causes . We report a 38-year-old HIV-1 seropositive intravenous drug abuser who developed SSSS due to staphylococcal pneumonia . An exfoliating toxin-releasing Staphylococcus aureus, phage type II type 3C, was isolated from the sputum and from blood cultures . This is the third case of adult SSSS to be reported in the context of HIV disease.

J Clin Immunol, 1996 May, 16(3), 171 - 9
The effects of retinoic acid on immunoglobulin synthesis: role of interleukin 6; Ballow M et al.; Retinoic acid (RA) and its parent compound, retinol (ROH, vitamin A), have been recognized as important immunopotentiating agents . Previous studies from our laboratory have demonstrated that RA can augment formalin-treated Staphylococcus aureus (SAC)-stimulated immunoglobulin (Ig) synthesis of cord blood mononuclear cells (CBMC) . To determine the mechanism(s) by which RA modulates Ig synthesis, we studied the effects of RA on B cells and cytokine production . The addition of RA (10(-5) to 10(-10) M) to Epstein-Barr virus (EBV)-transformed B-cell clones derived from either adult or cord blood B cells augmented Ig secretion twofold . In contrast, cell proliferation was inhibited as measured by 3H-thymidine incorporation . We evaluated two cytokines known to be constitutively produced by EBV cell lines, IL-1 and IL-6 . While RA had no effect on IL-1 production, IL-6 synthesis was greatly enhanced (20- to 45-fold), which was also reflected by an increase in steady-state mRNA levels for IL-6 but not TNF-alpha or TGF-beta on Northern blot analysis . Polyclonal rabbit anti-IL-6 antibodies were used to block the augmenting effects of RA on Ig synthesis of adenoidal B cells . RA-induced augmentation in IgG and IgA synthesis was blocked 58 and 29%, respectively, by anti-IL-6 antibodies . These studies suggest that the enhancing effects of RA on Ig synthesis are mediated, at least in part, by the autocrine or paracrine effects of IL-6 on B-cell differentiation.

Pediatr Res, 1996 May, 39(5), 835 - 42
Granulocyte functions in children with cancer are differentially sensitive to the toxic effect of chemotherapy; Lejeune M et al.; To analyze the toxicity associated to chemotherapy upon granulocytes, different functional assays were performed, within days of drug exposure and at time of bone marrow recovery, on polymorphonuclear neutrophils (PMN) from children with cancer . There were no significant postchemotherapy changes in the expression of the different receptors studied nor in the phagocytosis of Staphylococcus aureus 42D . By contrast, a significant decrease was observed in H2O2 production in PMN recently exposed to chemotherapy with both cytofluorometric and chemiluminescence assays . There was also a decrease in the production of O2- and in chemotaxis; finally, the intracellular killing of S . aureus 42D and Escherichia coli was reduced . In patients having recovered from drug-induced bone marrow aplasia, PMN functions were found to be normal except for bactericidal activity which was still defective . The observations indicate that, in patients exposed to chemotherapy, some PMN functions are transiently altered, whereas microorganism cell killing is continuously impaired.

Can J Anaesth, 1996 May, 43(5 Pt 1), 471 - 4
Bacterial meningitis and cauda equina syndrome after epidural steroid injections; Cooper AB et al.; PURPOSE: To describe a rare adverse outcome resulting from lumbar epidural steroid injections for the treatment of chronic lower back pain . CLINICAL FEATURES: We report a case of staphylococcus aureus meningitis and cauda equina syndrome following a series of epidural steroid injections for chronic back pain . Although rare, bacterial meningitis following epidural analgesia has been reported, but epidural steroid injections have not been associated with either bacterial meningitis or cauda equina syndrome . The causal relationship between epidural steroid injections, bacterial meningitis, and cauda equina syndrome is discussed . CONCLUSION: A through pre-procedure assessment with attention to the neurologic examination and signs/symptoms of infection is essential.

Antimicrob Agents Chemother, 1996 May, 40(5), 1308 - 10
Treatment of Staphylococcus aureus catheter-related infection and infective endocarditis with granulocyte colony-stimulating factor in the experimental rabbit model; Frank U et al.; The role of granulocyte colony-stimulating factor with and without antibiotics in the treatment of catheter-related infection and infective endocarditis caused by methicillin-susceptible Staphylococcus aureus was assessed in the experimental rabbit model . Granulocyte colony-stimulating factor stimulated leukocytosis in infected animals but did not increase the clearance of methicillin-susceptible S . aureus from peripheral blood, subcutaneous port catheters, intravascular cardiac catheters, or aortic valve vegetations.

Antimicrob Agents Chemother, 1996 May, 40(5), 1301 - 3
50S ribosomal subunit synthesis and translation are equivalent targets for erythromycin inhibition in Staphylococcus aureus; Champney WS et al.; Macrolide antibiotics like erythromycin can prevent the formation of the 50S ribosomal subunit in growing bacterial cells, in addition to their inhibitory effect on translation . The significance of this novel finding has been further investigated . The 50% inhibitory doses of erythromycin for the inhibition of translation and 50S subunit assembly in Staphylococcus aureus cells were measured and were found to be identical . Together they account quantitatively for the observed effects of erythromycin on cell growth rates . There is also a direct relationship between the loss of rRNA from the 50S subunit and its accumulation as oligoribonucleotides in cells . The importance of this second site for erythromycin inhibition of bacterial cell growth is discussed.

Antimicrob Agents Chemother, 1996 May, 40(5), 1219 - 24
Importance of penicillinase production for activity of penicillin alone or in combination with sulbactam in experimental endocarditis due to methicillin-resistant Staphylococcus aureus; Fantin B et al.; The activity of penicillin, alone and in combination with sulbactam, against a heterogeneously methicillin-resistant, penicillinase-producing clinical isolate of Staphylococcus aureus and its penicillinase-negative derivative was investigated in vitro and in a rabbit experimental endocarditis model . Penicillin was significantly more effective than vancomycin against the penicillinase-negative derivative in vivo (P < 0.001), and it sterilized 25% of the vegetations . The combination of penicillin and sulbactam exhibited an in vivo synergistic effect on the penicillinase-producing strain (P < 0.01) but did not produce any advantage over treatment with vancomycin, even when a high dose of sulbactam was used (100 mg/kg of body weight every 6 h) . This combination was significantly less effective against the penicillinase-producing strain than was penicillin alone against the penicillinase-negative derivative (P < 0.03) . In addition, the most resistant subpopulation of the surviving bacteria, which grew on agar containing 16 micrograms of methicillin per ml, was detected in 5 of 6 animals treated with penicillin and a high dose of sulbactam against the penicillinase-producing strain compared with only 1 of 12 animals treated with penicillin alone against the penicillinase-negative derivative (P < 0.01) . We conclude that penicillin is highly effective against penicillinase-negative methicillin-resistant S . aureus and that penicillinase production, rather than methicillin resistance, appears to be the limiting factor for the activity of the penicillin-sulbactam combination against penicillinase-producing, methicillin-resistant S . aureus.

Antimicrob Agents Chemother, 1996 May, 40(5), 1157 - 63
Alterations in the DNA topoisomerase IV grlA gene responsible for quinolone resistance in Staphylococcus aureus; Yamagishi J et al.; A 4.2-kb DNA fragment conferring quinolone resistance was cloned from a quinolone-resistant clinical isolate of Staphylococcus aureus and was shown to possess a part of the grlB gene and a mutated grlA gene . S-80-->F and E-84-->K mutations in the grlA gene product were responsible for the quinolone resistance . The mutated grlA genes responsible for quinolone resistance were dominant over the wild-type allele, irrespective of gene dosage in a transformation experiment with the grlA gene alone . However, dominance by mutated grlA genes depended on gene dosage when bacteria were transformed with the grlA and grlB genes in combination . Quinolone-resistant gyrA mutants were easily isolated from a strain, S . aureus RN4220, carrying a plasmid with the mutated grlA gene, though this was not the case for other S . aureus strains lacking the plasmid . The elimination of this plasmid from such quinolone-resistant gyrA mutants resulted in marked increases in quinolone susceptibility . These results suggest that both DNA gyrase and DNA topoisomerase IV may be targets of quinolones and that the quinolone susceptibility of organisms may be determined by which of these enzymes is most quinolone sensitive.

Kansenshogaku Zasshi, 1996 May, 70(5), 490 - 5
{Two cases of gram-positive sepsis successfully treated with vancomycin in combination with imipenem or cilastatin}; Sakamoto M et al.; Against gram-positive sepsis, vancomycin (VCM) was administered in combination with imipenem or cilastatin (IPM/CS) . Its excellent efficacy was confirmed in 2 cases, one affected with methicillin resistant Staphylococcus aureus and another with Gemella morbillorum . By calculating the FIC index according to a checkerboard technique, the in vitro synergistic effect was also demonstrated . At the present state multi-drug resistant gram-positive infections prevailed, the combination of VCM with IPM/CS can be expected as an effective measure for treating these diseases.

Vet Med (Praha), 1996 May, 41(5), 149 - 53
Survival of model bacterial strains and helminth eggs in the course of mesophilic anaerobic digestion of pig slurry; Juris P et al.; The effect of methanogenesis on the survival of model bacterial strains (Escherichia coli EC 5, Staphylococcus aureus SA 11, Enterococcus faecium CCM 4231) and non-embryonated helminth eggs (Ascaris suum) was investigated in pig slurry . Two pilot-plant experiments were carried out in two anaerobic digesters (800 and 1,000 litre) in a mesophilic thermal range (35-37 degrees C) . The mean hydraulic retention time of the digesters was 20 days . The methanogenesis process was monitored by determining the following chemical parameters: pH, N-NH3, total dry matter (kg/day), organic matter (kg/day) production of methane by supplied and degraded organic matter (m3/kg) . The results obtained allow us to state that the anaerobic stabilization of pig slurry in the mesophilic temperature range resulted in total devitalization of model bacterial strains E . coli EC 5 and Ent . faecium CCM 4231 . St . aureus SA 11 cells, exposed to the above mentioned conditions, were also reduced in their number from 10.04 to 3.27 and from 8.69 to 2.77 log cfu/ml . It is assumed that the longer retention time of excrements in the digester could also result in total devitalization of St . aureus SA 11 cells . From the microbiological point of view, the above mentioned facts indicate a sufficient hygienization effect of the anaerobic fermentation on the contaminated pig excrements . The survival of A . suum eggs was little affected by the 20-day anaerobic mesophilic digestion of pig slurry . Only 17 or 18% (F1, F2) of the non-embryonated A . suum eggs were damaged after the 20-day exposure.

Pflugers Arch, 1996 May, 432(1), 66 - 74
Thermosensitivity is reduced during fever induced by Staphylococcus aureus cells walls in rabbits; Toien O et al.; Thermosensitivity (TS) and threshold core temperature for metabolic cold defence were determined in six conscious rabbits before, and at seven different times after i.v . injection of killed Staphylococcus aureus (8 x 10(7) or 2 x 10(7) cell walls x kg(-1)) by exposure to short periods (5-10 min) of body cooling . Heat was extracted with a chronically implanted intravascular heat exchanger . TS was calculated by regression of metabolic heat production (M) and core temperature, as indicated by hypothalamic temperature . Threshold for cold defence (shivering threshold) was calculated as the core temperature at which the thermosensitivity line crossed preinjection resting M . The shivering thresholds followed the shape of the fever response . TS was significantly reduced (up to 49%) during the time course of fever induced by the highest dose of pyrogen only . At both high and low doses of pyrogen TS correlated negatively with shivering threshold (r = 0.66 and 0.79 respectively) with similar slopes . The reduction in TS during fever was thus associated with the increase in shivering threshold resulting from the pyrogen injection and not by the dose of pyrogen . Model considerations indicate, however, that changes in sensitivity of the thermosensory input to the hypothalamic controller may affect threshold changes but cause negligible TS changes . It is more likely that the reduction in TS is effected in the specific hypothalamic effector pathways.

Am J Med, 1996 May, 100(5), 509 - 16
Nosocomial Staphylococcus aureus bacteremia among nasal carriers of methicillin-resistant and methicillin-susceptible strains; Pujol M et al.; OBJECTIVES: To determine the relevance of nasal carriage of Staphylococcus aureus, either methicillin-sensitive (MSSA) or methicillin-resistant (MRSA), as a risk factor for the development of nosocomial S aureus bacteremia during an MRSA outbreak . PATIENTS AND METHODS: In this prospective cohort study, 488 patients admitted to an intensive care unit (ICU) during a 1-year period were screened with nasal swabs within 48 hours of admission and weekly thereafter in order to identify nasal S aureus carriage . Nasal staphylococcal carriers were observed until development of S aureus bacteremia, ICU discharge, or death . RESULTS: One hundred forty-seven (30.1%) of 488 patients were nasal S aureus carriers; 84 patients (17.2%) harbored methicillin-sensitive S aureus; and 63 patients (12.9%) methicillin-resistant S aureus . Nosocomial S aureus bacteremia was diagnosed in 38 (7.7%) of 488 patients . Rates of bacteremia were 24 (38%) of the MRSA carriers, eight (9.5%) of the MSSA carriers, and six (1.7%) of noncarriers . After adjusting for other predictors of bacteremia by means of a Cox proportional hazard regression model, the relative risk for S aureus bacteremia was 3.9 (95% confidence interval, 1.6-9.8; P = 0.002) for MRSA carriers compared with MSSA carriers . CONCLUSIONS: Among ICU patients, nasal carriers of S aureus are at higher risk for S aureus bacteremia than are noncarriers; in the setting of an MRSA outbreak, colonization by methicillin-resistant strains represents a greater risk than does colonization by MSSA and strongly predicts the occurrence of MRSA bacteremia.

J AOAC Int, 1996 May-Jun, 79(3), 661 - 9
Efficacy of a latex agglutination test for rapid identification of Staphylococcus aureus: collaborative study; Chang TC et al.; Fifteen laboratories completed a collaborative study comparing the efficacy of a latex agglutination kit (Aureus Test) with that of AOAC Official Method 987.09 (coagulase test for identification of Staphylococcus aureus) . Each laboratory analyzed 240 strains of bacteria, including 160 isolates of S . aureus and 80 isolates of other bacteria . Upon receipt of cultures, collaborators subcultured each isolate on both tryptic soy agar (TSA) and Baird-Parker agar medium (BPA) to determine whether the growth medium has any effect on either method . For cultures grown on TSA, the latex test had sensitivity and specificity rates of 99.2 and 97.1%, respectively, whereas the coagulase test had respective rates of 98.4 and 92.5% . For cultures able to grow on BPA, the latex test had sensitivity and specificity rates of 99.2 and 96.6%, respectively, while the coagulase test had respective rates of 98.3 and 91.3% . By using the McNemar pairwise comparison test of the 2 methods, the false-positive and false-negative rates of the latex test were significantly lower (p < 0.01) than those of the coagulase test for strains grown either on TSA or BPA . The latex agglutination test for identification of S . aureus isolated from foods has been adopted by AOAC INTERNATIONAL.

Aust N Z J Surg, 1996 May, 66(5), 287 - 90
Spinal epidural abscess: a report of nine cases and the use of intra-operative ultrasonography; Mak KH et al.; BACKGROUND: Spinal epidural abscess is an uncommon and dangerous lesion . Once neurological complications occur the damage is often irreversible . METHODS: The clinical presentation, operative findings, management and follow up of nine cases of spinal epidural abscess were reported . Four patients were diabetic and four others were intravenous drug addicts . The last patient had a history of a protracted stay in an intensive care unit complicated by pneumonia and pleural effusion . Ultrasonography was used intraoperatively to guide and to assess the adequacy of drainage and decompression of the epidural abscess . RESULTS: Multiple level laminectomy was necessary and Staphylococcus aureus was the most common organism cultured . None of the five patients presenting with acute complete paralysis regained neurological function . Two of the four patients with incomplete paralysis were able to walk with an aid . CONCLUSIONS: Spinal epidural abscess usually presents late and the prognosis is generally poor . Ultrasound may be useful in determining the extent of the abscess during operation to drain the collection.

Aust N Z J Surg, 1996 May, 66(5), 282 - 6
Pyogenic infection of the sacroiliac joint; McGaughey I; BACKGROUND: This review was undertaken to examine a collected series of patients with this uncommon condition . METHOD: Six definite and three possible cases of pyogenic infection of the sacroiliac joint are reported . Their manner of presentation, investigations, management and outcome are discussed in conjunction with a review of the literature . The patients were identified by searching the medical records of three hospitals over a 10 year period and the clinical data were analysed retrospectively . RESULTS: All patients were clinically tender over the involved sacroiliac joint and were experiencing fever . Technetium-99m bone scans demonstrated increased uptake in the sacroiliac joint in all patients, although two scans were initially negative . Plain pelvic radiographs, computed tomography scans and white cell counts were generally unhelpful in initially establishing the diagnosis . Blood cultures were positive in eight cases, and Staphylococcus aureus was isolated . There were four women and five men with an average age of 25 years . Six reported recent respiratory tract or skin infections . Two of these had also reported an episode of minor pelvic trauma in the preceding 2 weeks . A further two patients were intravenous drug users . Treatment was bed rest and antibiotics in all cases and marked initial improvement was seen . The outcome was variable, with a significant proportion reporting discomfort on the affected side after heavy exercise many years after the infection . CONCLUSION: The importance of a thorough clinical assessment and suspicion of the diagnosis of this uncommon illness is emphasized.

Appl Environ Microbiol, 1996 May, 62(5), 1831 - 4
Nisin stimulates oxygen consumption by Staphylococcus aureus and Escherichia coli; Carneiro de Melo AM et al.; Nisin stimulated oxygen consumption by nongrowing, glucose-metabolizing Staphylococcus aureus and Escherichia coli cells, indicating a protonophore mode of action . A similar stimulation in E . coli cells osmotically stressed to disrupt the outer cell membrane confirmed the cytoplasmic membrane as the site of nisin action and showed that nisin uptake was not prevented by the outer membrane.

Scand J Immunol, 1996 May, 43(5), 574 - 82
Inhibition of immunoglobulin production in vitro by IgG and F(ab')2 fragments, but not by the Fc portion; Klaesson S et al.; Antibody-secreting B cells were measured as plaque-forming cells (PFC) in a modified haemolysis-in-gel assay, using protein A coupled sheep erythrocytes as targets . Human lymphocytes from blood (PBL), bone marrow or spleen were stimulated in vitro by various polyclonal B-cell activators and incubated with intravenous immunoglobulin (IVIG) or peptide fragments of IVIG . IgG and IgM production from PBL and bone marrow cells, measured as PFC, was inhibited more than 50% by IVIG 2.5 mg/ml, compared to controls without IVIG . Inhibition of the IgG and IgM response of spleen cells by IVIG varied depending on the stimuli . Using Staphylococcus aureus protein A (SPA), inhibition was almost 90% (P < 0.001) . The inhibition of the IgG and IgM responses to lipopolysaccharide from Escherichia coli (LPS) were 70% (P < 0.01) and 28% (P < 0.05), respectively . IgG stimulation by pokeweed mitogen (PWM) was inhibited by 57% (P < 0.01), but the IgM response was inhibited only by the higher IVIG concentration of 5.0 mg/ml . In mixed lymphocyte cultures of spleen cells, IgG and IgM production were inhibited by more than 60% (P < 0.05) . The effect of IgG, IgG-F(ab')2 and IgG-Fc on LPS or PWM-stimulated spleen cells were compared, using equimolar concentrations of the various preparations . IgG- and IgM-producing PFC were significantly (P < 0.05) inhibited in a dose-dependent fashion by IgG and F(ab')2, but not by Fc . LPS-induced IgG and IgM production was inhibited also when IgG and F(ab')2 were added up to 48 h after the stimulator . A comparison of IgG, F(ab')2 and Fc products from different companies showed that all IgG and F(ab')2 preparations significantly inhibited IgG and IgM production of LPS-stimulated spleen cells . No significant inhibition was obtained with any of the purified Fc products.

Am J Kidney Dis, 1996 May, 27(5), 695 - 700
A randomized trial of Staphylococcus aureus prophylaxis in peritoneal dialysis patients: mupirocin calcium ointment 2% applied to the exit site versus cyclic oral rifampin; Bernardini J et al.; The objective of this study was to compare prophylaxis for Staphylococcus aureus infections in peritoneal dialysis patients using 600 mg cyclic oral rifampin for 5 days every 3 months versus mupirocin calcium ointment 2% applied daily to the exit site . The study design was a prospective randomized trial, controlling for S aureus nasal carriage . Eighty-two continuous ambulatory and continuous cyclic peritoneal dialysis patients (54% male, 71 % white, 34% insulin-dependent, mean prestudy time on peritoneal dialysis 1.2 years) were randomly assigned to cyclic rifampin (n = 41 patients) or daily exit site mupirocin prophylaxis (n = 41 patients) . Mean follow-up was 1 year . S aureus catheter infection rates were 0.13/yr with mupirocin and 0.15/yr with rifampin (P = NS) . Both rates were significantly lower than the center's historical rate (the period between 1983 and 1992) of 0.46/yr prior to the study (P < 0.001) . S aureus peritonitis rates were 0.04/yr with mupirocin and 0.02/yr with rifampin (P = NS), both significantly lower than the center's historical rate of 0.16/yr (P < 0.02) . Catheter loss due to S aureus infections was 0.02/yr with mupirocin and 0/yr with rifampin (P = NS), both significantly lower than the center's historical rate of 0.12/yr (P < 0.001) . There were no side effects in patients using mupirocin, but 12% were unable to continue rifampin due to side effects . We conclude that mupirocin ointment at the exit site and cyclic oral rifampin are equally effective in reducing S aureus catheter infections . In addition, rifampin or mupirocin significantly reduced S aureus peritonitis and catheter loss due to S aureus infections . Mupirocin at the exit site provides an excellent alternative prophylaxis for S aureus infections, particularly in patients who cannot tolerate oral rifampin therapy.

Am J Kidney Dis, 1996 May, 27(5), 687 - 94
Clinical and economic effects of mupirocin calcium on preventing Staphylococcus aureus infection in hemodialysis patients: a decision analysis; Bloom BS et al.; This study was performed to determine the clinical and economic consequences of alternative strategies of preventing Staphylococcus aureus infection in chronic hemodialysis patients by use of intranasal mupirocin calcium to clear nasal carriage of S aureus . Decision analysis evaluated clinical outcomes and cost-effectiveness of three likely management strategies to address S aureus nasal carriage and prevent subsequent infection in chronic ambulatory hemodialysis patients: (1) screen for S aureus nasal carriage every 3 months and treat those with a positive test result with mupirocin calcium; (2) treat all patients weekly with mupirocin calcium; or (3) no prevention strategy, treat infection only . Rates of nasal carriage of S aureus, S aureus infection rates, proportion of infections attributable to nasal carriage, efficacy of mupirocin, natural history of infection, and patient management strategies were derived from the published literature and supplemented by a panel of experts . Actual payments for medical services were obtained from Medicare parts A and B . Incremental cost-effectiveness was calculated from the perspective of Medicare and subjected to sensitivity analyses . Assuming that 75% of S aureus infections are attributable to nasal carriage in hemodialysis patients, eliminating nasal carriage of S aureus with mupirocin calcium (with or without screening) markedly reduces the number of infections (45% to 55%) and also reduces health care expenditures relative to treating infections when they occur . Annual savings to Medicare are $784,000 to $1,117,000 per 1,000 hemodialysis patients, depending on the prevention strategy . Preventing S aureus infection by eradicating nasal carriage in chronic hemodialysis patients reduces morbidity while simultaneously reducing medical care costs . The decision to eliminate nasal carriage on a regular basis or use a screening test to guide antibiotic therapy is dependent on the tradeoff between improved short-term clinical and cost benefits and the potential for bacterial resistance that may arise from widespread use of mupirocin calcium.

J Bacteriol, 1996 May, 178(9), 2605 - 12
Sequence, expression in Escherichia coli, and analysis of the gene encoding a novel intracellular protease (PfpI) from the hyperthermophilic archaeon Pyrococcus furiosus; Halio SB et al.; A previously identified intracellular proteolytic activity in the hyperthermophilic archaeon Pyrococcus furiosus (I . I . Blumentals, A . S . Robinson, and R . M . Kelly, Appl . Environ . Microbiol . 56:1992-1998, 1990) was found to be a homomultimer consisting of 18.8-kDa subunits . Dissociation of this native P . furiosus protease I (PfpI) into a single subunit was seen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) but only after trichloroacetic acid precipitation; heating to 95 degrees C in the presence of 2% SDS and 80 mM dithiothreitol did not dissociate the protein . The gene (pfpI) coding for this protease was located in genomic digests by Southern blotting with probes derived from the N-terminal amino acid sequence . pfpI was cloned, sequenced, and expressed in active form in Escherichia coli as a fusion protein with a histidine tag . The recombinant protease from E . coli showed maximum proteolytic activity at 95 degrees C, and its half-life was 19 min at this temperature . This level of stability was significantly below that previously reported for the enzyme purified by electroelution of a 66-kDa band from SDS-PAGE after extended incubation of cell extracts at 98 degrees C in 1% SDS (>30 h) . The pfpI gene codes for a polypeptide of 166 amino acid residues lacking any conserved protease motifs; no protease activity was detected for the 18.8-kDa PfpI subunit (native or recombinant) by substrate gel assay . Although an immunological relationship of this protease to the eukaryotic proteasome has been seen previously, searches of the available databases identified only two similar amino acid sequences: an open reading frame of unknown function from Staphylococcus aureus NCTC 8325 (171 amino acid residues, 18.6 kDa, 41% identity) and an open reading frame also of unknown function in E . coli (172 amino acid residues, 18.8 kDa, 47% identity) . Primer extension experiments with P . furiosus total RNA defined the 5' end of the transcript . There are only 10 nucleotides upstream of the start of translation; therefore, it is unlikely that there are any pre- or pro-regions associated with PfpI which could have been used for targeting or assembly of this protease . Although PfpI activity appears to be the dominant proteolytic activity in P . furiosus cell extracts, the physiological function of PfpI is unclear.

Infect Immun, 1996 May, 64(5), 1876 - 8
Reconsideration of the role of fibronectin binding in endocarditis caused by Staphylococcus aureus; Flock JI et al.; The adherence characteristics in vivo and virulence of two isogenic strains of Staphylococcus aureus differing in fibronectin binding were compared in a rat model of catheter-induced infective endocarditis . No differences were found between the two strains . The results strongly point to the multifactorial nature of bacterial adherence to damaged heart valves and suggest that other binding functions can compensate for the lack of fibronectin binding in S . aureus.

Infect Immun, 1996 May, 64(5), 1839 - 41
Passive immunization with antiserum to a nontoxic alpha-toxin mutant from Staphylococcus aureus is protective in a murine model; Menzies BE et al.; A nonhemolytic, nonlethal variant of Staphylococcus aureus alpha-toxin constructed via oligonucleotide-directed mutagenesis and containing a single amino acid substitution (H-35 to L) was used to immunize a rabbit . The resulting antiserum was cross-reactive with wild-type alpha-toxin and neutralized its hemolytic activity in vitro . Passive immunization of mice with rabbit antiserum conferred protection against lethal challenge with wild-type alpha-toxin and against acute lethal challenge with a high-alpha-toxin -producing S . aureus strain . H35L alpha-toxin may be useful as a protective immunogen in S . aureus vaccine studies.

Infect Immun, 1996 May, 64(5), 1762 - 9
Human monocyte CD14 is upregulated by lipopolysaccharide; Landmann R et al.; Membrane CD14 is involved in lipopolysaccharide (LPS)-induced monocyte activation; it binds LPS, and antibodies against CD14 block the effects of low-dose LPS . It is unknown how LPS regulates its own receptor CD14 in vitro . Therefore, we investigated the effects of LPS on CD14 mRNA and membrane and soluble CD14 (mCD14 and sCD14, respectively) in human monocytes and macrophages . No changes were observed during the first 3 h of LPS stimulation . After 6 to 15 h, LPS weakly reduced CD14 mRNA and mCD14 and transiently enhanced sCD14 release . A 2-day incubation with LPS caused increases in the levels of CD14 mRNA (2-fold), mCD14 (2-fold), sCD14 (1.5-fold), and LPS-fluorescein isothiocyanate binding (1.5-fold); a 5-h incubation with LPS was sufficient to induce the late effects on mCD14 and sCD14 . The maximal effect on mCD14 and sCD14 was reached with > or = 1 ng of LPS per ml; the proportional distribution of the two sCD14 isoforms was not modified by LPS . Besides rough and smooth LPS, lipid A, heat-killed Escherichia coli, lipoteichoic acid, and Staphylococcus aureus cell wall extract (10 micrograms/ml) caused similar increases of mCD14 . The LPS effect was blocked by polymyxin B but not by anti-tumor necrosis factor alpha, anti-interleukin-6, anti-gamma interferon, and anti-LPS-binding protein . LPS-induced tumor necrosis factor alpha production was abolished after a second 4-h challenge . In contrast, the LPS-induced increases CD14 mRNA, mCD14, and sCD14 were stronger and appeared earlier after a second LPS challenge . In conclusion, CD14 is transcriptionally upregulated by LPS and other bacterial cell wall constituents.

Anesth Analg, 1996 May, 82(5), 948 - 53
Lipoteichoic acid from Staphylococcus aureus depresses contractile function of human arteries in vitro due to the induction of nitric oxide synthase; Tsuneyoshi I et al.; The aim of this study was to clarify the role of Gram-positive organisms in the genesis of sepsis . In the present study, we investigated the effect of lipoteichoic acid (LTA) from the cell wall of Staphylococcus aureus on contractions elicited by norepinephrine (NE) in rings cut from human gastroepiploic arteries . LTA diminished the contractile response to NE . This attenuation began after several hours of exposure, whether or not endothelium was present . The cyclic guanosine monophosphate content of LTA-treated rings was higher than that of control rings, whether there was a functional endothelium . These LTA-mediated responses were reduced significantly by inhibitors of nitric oxide (NO) synthase and guanylate cyclase . All of this indicates that the main underlying cause of the vascular hyporeactivity to NE was a massive generation of No . In addition, cycloheximide, an inhibitor of inducible NO synthase, prevented the attenuation of NE-induced contractions caused by LTA . Thus, our results offer strong supporting evidence that the important factor in the genesis by Gram-positive organisms of a diminished contractile response to pressor drugs is their induction of inducible NO synthase in smooth muscle.

Proc Natl Acad Sci U S A, 1996 Apr 16, 93(8), 3630 - 5
Multidrug resistance proteins QacA and QacB from Staphylococcus aureus: membrane topology and identification of residues involved in substrate specificity; Paulsen IT et al.; The closely related multidrug efflux pumps QacA and QacB, from the bacterial pathogen Staphylococcus aureus, both confer resistance to various toxic organic cations but differ in that QacB mediates lower levels of resistance to divalent cations . Cloning and nucleotide sequencing of the qacB gene revealed that qacB differs from qacA by only seven nucleotide substitutions . Random hydroxylamine mutagenesis of qacB was undertaken, selecting for variants that conferred increased resistance to divalent cations . Both QacA and the QacB mutants capable of conferring resistance to divalent cations contain an acidic residue at either amino acid 322 or 323, whereas QacB contains uncharged residues in these positions . Site-directed mutagenesis of qacA confirmed the importance of an acidic residue within this region of QacA in conferring resistance to divalent cations . Membrane topological analysis using alkaline phosphatase and beta-galactosidase fusions indicated that the QacA protein contains 14 transmembrane segments . Thus, QacA represents the first membrane transport protein shown to contain 14 transmembrane segments, and confirms that the major facilitator superfamily contains a family of proteins with 14 transmembrane segments.

Arch Biochem Biophys, 1996 Apr 15, 328(2), 219 - 26
Purification of the 11- and 5-kDa antibacterial polypeptides from guinea pig neutrophils; Yomogida S et al.; It has been known that neutrophils contain various antimicrobial components in the granules, which contribute to the oxygen-independent host defense mechanism . In this study, we have isolated the two antimicrobial polypeptides from guinea pig neutrophil granules . Urea-SDS-PAGE analysis revealed that the molecular masses of the polypeptides were 11 and 5 kDa under nonreducing conditions . Under reducing conditions, the molecular mass of the 5-kDa polypeptide did not change, whereas the molecular mass of the 11-kDa polypeptide changed to about 5 kDa, suggesting that the 11-kDa polypeptide is a dimer composed of 5-kDa subunits joined with a disulfide bond . The amino acid composition and sequence data indicated that the 5-kDa subunit of the 11-kDa polypeptide contained 9 lysine, 8 arginine, and 1 cysteine residues and that the 11-kDa polypeptide was a homodimer of G1LRKKFRKTRKRIQKLGRKIGKTGRKVWKAWREYGQIPYPCRI43 (4599 Da) joined with one disulfide bond . Amino acid sequence of the 11-kDa polypeptide showed partial homology (19-30%) to the active peptides of rabbit and human cationic antimicrobial proteins of 18 kDa (CAP18), suggesting the 11-kDa polypeptide might be a homologue of CAP18 . In contrast, the amino acid analysis of the 5-kDa antibacterial polypeptide revealed that the polypeptide was composed of 41 amino acids (5007 Da) containing 7 lysine, 10 arginine, and 2 cystine residues . However, sequence analysis indicated that the N-terminus of the 5-kDa polypeptide was likely blocked . The 11- and 5-kDa polypeptides showed almost the same antibacterial activities; ED50 values were 30-35 nM against Escherichia coli and 90-120 nM against Staphylococcus aureus, which were 4- to 20-fold lower than those of defensins . Furthermore, the 11- and 5-kDa polypeptide retained the antibacterial activities even at the physiological concentration of NaCl (0.15 M), although the antibacterial activity of defensin was completely lost in the presence of NaCl.

EMBO J, 1996 Apr 15, 15(8), 1857 - 64
Molecular architecture of a toxin pore: a 15-residue sequence lines the transmembrane channel of staphylococcal alpha-toxin; Valeva A et al.; Staphylococcus aureus alpha-toxin is a hydrophilic polypeptide of 293 amino acids that produces heptameric transmembrane pores . During assembly, the formation of a pre-pore precedes membrane permeabilization; the latter is linked to a conformational change in the oligomer . Here, 41 single-cysteine replacement toxin mutants were thiol-specifically labelled with the polarity-sensitive fluorescent probe acrylodan . After oligomerization on membranes, only the mutants with acrylodan attached to residues in the sequence 118-140 exhibited a marked blue shift in the fluorescence emission maximum, indicative of movement of the fluorophore to a hydrophobic environment . Within this region, two functionally distinct parts could be identified . For mutants at positions 126-140, the shifts were partially reversed after membrane solubilization by detergents, indicating a direct interaction of the label with the membrane lipids . Membrane insertion of this sequence occurred together with the final pre-pore to pore transition of the heptamer . Thus residues 126-140 constitute a transmembrane sequence in the pore . With labelled residues 118-124, pre-pore assembly was the critical event to induce the spectral shifts, which persisted after the removal of membrane lipids and hence probably reflects protomer-protomer contacts within the heptamer . Finally, a derivative of the mutant N121C yielded occluded pores which could be opened by reductive reversal of the modification . Therefore this residue probably lines the lumen of the pore.

Biochem J, 1996 Apr 15, 315 ( Pt 2), 537 - 41
Efficient catalysis by beta-lactamase from Staphylococcus aureus PC1 accompanied by accumulation of an acyl-enzyme; Qi X et al.; The pH- and temperature-dependence of steady-state kinetic parameters for 6-beta-(2-furyl)-acryloylamido-penicillanic acid showed it to be a good substrate of staphylococcal PC1 beta-lactamase, and the viscosity-dependence of K(m)/k(cat) indicated that steps up to the formation of the acyl-enzyme were partially diffusion-limited . In the pH range 4-9, a pre-steady-state transient blue shift in the UV absorption spectrum of the bound furyl-acryloylamido chromophore was of constant amplitude and decayed to the spectrum of the product with a first-order rate constant equal to k(cat) . The spectrum of the isolated denatured acyl-enzyme was similar to that of the methyl ester of furyl-acryloylpenicilloic acid, pointing to non-covalent interactions with the folded protein, possibly associated with the charge on Glu-166, as the source of the blue-shifted spectrum . Taken together, these results point to a rapid acylation and slower deacylation at Ser-70 and imply that ionization of groups affecting enzyme activity at alkaline pH, for which likely candidates are Lys-73 and Lys-234, affect the rate of deacylation.

J Biol Chem, 1996 Apr 12, 271(15), 8655 - 60
Partial C-terminal unfolding is required for channel formation by staphylococcal alpha-toxin; Vecsey-Semjen B et al.; The pore-forming alpha-toxin from Staphylococcus aureus is secreted as a soluble monomeric protein . In order to form a transmembrane channel, the protein has to undergo oligomerization and membrane insertion . Previous studies have shown that channel formation is favored by acidic pH . We have analyzed the effect of pH on the kinetics of channel formation as well as on the conformation of the toxin . Using a variety of spectroscopic probes for protein structure, we have shown that alpha-toxin unfolded upon acidification and that the unfolding process occurred in at least three steps . The various steps could be selectively affected by modifying the salt concentration or the temperature . This unfolding was, however, only partial as the secondary structure remained native-like as witnessed by far UV CD measurements . The first unfolding step, corresponding to a region of the C-terminal half of the toxin, is of particular importance as it coincided with the exposure of hydrophobic patches on the surface of the protein as well as with the onset of channel formation . Our observations strongly suggest that transition of the C-terminal half of alpha-toxin to a molten globule-like state is required for channel formation.

J Biol Chem, 1996 Apr 12, 271(15), 8575 - 81
p-Azidosalicyl-5-amino-6-phenoxybenzimidazole photolabels the N-terminal 63-103 amino acids of Haemonchus contortus beta-tubulin 1; Nare B et al.; Benzimidazoles (BZ) are broad spectrum anthelmintics thought to exert their effects by interacting with and disrupting the functions of microtubules . However, direct biochemical evidence for binding between BZ and tubulin has not been shown nor is it known what sequences in tubulin interact with BZ . In this study, a photoactive analogue of 2-acetamido-5-(3-aminophenoxy)benzimidaz ole that has biological activity similar to other benzimidazoles was synthesized and used to photoaffinity label cell lysates from the parasitic nematode of sheep Haemonchus contortus . The photoactive analogue, 2-acetamido-5-{3-(4-azido-3-125I-salicyl amido)phenoxy}benzimida zol e or 125I-ASA-BZ, was shown to photolabel a 54-kDa protein that was specifically immunoprecipitated with anti-tubulin monoclonal antibodies . Tubulin photoaffinity labeling by 125I-ASA-BZ was also inhibited with molar excess of various BZ analogues and colchicine . Interestingly, 125I-ASA-BZ photoaffinity-labeled the beta- and not the alpha-subunits of tubulin . Proteolytic digestion of 125I-ASA-BZ-labeled tubulin with Staphylococcus aureus V8 proteinase revealed one major peptide with an apparent molecular mass of 3.5 kDa . Exhaustive digestion of 125I-ASA-BZ-labeled beta-tubulin with trypsin resulted in two fractions containing radioactive peptides . Protein sequencing of the high performance liquid chromatography-purified tryptic ASA-BZ-photolabeled peptides identified the N-terminal 63-77 and 78-103 sequences as the BZ binding domain.

Front Biosci, 1996 Apr 01, 1, a25 - 33
Phagocytosis and intracellular killing of serum-opsonized Staphylococcus aureus by mouse fibroblasts expressing human Fcgamma receptor type IIa (CD32); Nibbering PH et al.; Phagocytes bear more than one class of receptors for the Fc domain of IgG (FcgammaR) . In addition the same ligand can interact with different classes of FcgammaR . This complexity makes it difficult to study the contribution of the various classes of FcgammaR to antimicrobial functions . To circumvent this difficulty, in the present study mouse 3T6 fibroblasts transfected with cDNA encoding for human FcgammaR type IIa (FcgammaRIIa-expressing cells) were used to determine the role of this receptor in phagocytosis and intracellular killing of serum-opsonized Staphylococcus aureus . Experiments using microbiological and fluorescent techniques to discriminate between cell-adherent and intracellular bacteria revealed that serum-opsonized bacteria are phagocytized by FcgammaRIIa-expressing cells, but not by parental fibroblasts . Non-opsonized bacteria were poorly internalized by FcgammaRIIa-expressing as well as parental fibroblasts . Furthermore, incubation of FcgammaRIIa-expressing cells with opsonized bacteria at 4oC and incubation of FcgammaRIIa-expressing cells with cytochalasin E prior to addition of opsonized bacteria inhibited the phagocytosis of these bacteria almost completely . Phagocytosis of opsonized bacteria by FcgammaRIIa-expressing cells was partly inhibited by selective inhibition of protein tyrosine kinases (PTK) . FcgammaRIIa cross-linking initiated transient tyrosine phosphorylation of various proteins in FcgammaRIIa-expressing cells . These data indicate that activation of PTK is involved in the FcgammaRIIa-mediated phagocytosis of opsonized S . aureus by transfected fibroblasts . Human serum from normal individuals and agammaglobulinemic patients triggered the intracellular killing of S . aureus by FcgammaRIIa-expressing fibroblasts . Surprisingly, heat-inactivated human serum, IgG and incubation with anti-FcgammaRII antibodies followed by a bridging secondary antibody did not stimulate the killing process . The possibility that these ligands did not interact with FcgammaRIIa on the cells can be excluded since they induced tyrosine phosphorylation of cellular proteins . The serum factor that stimulates the intracellular killing of bacteria by FcgammaRIIa-expressing cells is not yet identified . Oxygen-independent mechanisms are thought to be responsible for the killing of intracellular bacteria by these cells since the NADPH oxidase inhibitor diphenylene iodonium did not affect the serum-stimulated intracellular killing of S . aureus and no reactive oxygen and nitrogen intermediates were produced by FcgammaRIIa-expressing cells after appropiate stimulation . Taken together, these data show that phagocytosis but not intracellular killing of S . aureus is mediated via FcgammaRIIa on cells expressing this receptor.

Rev Med Chil, 1996 Apr, 124(4), 465 - 8
{Subacute thyroiditis and concurrent suppurative thyroiditis in one case}; Foncea L et al.; We report a 41 years old man admitted with a tender goiter, fever, thyrotoxic manifestations and atrial fibrillation . Laboratory confirmed the diagnosis of subacute thyroiditis and treatment with aspirin and propranolol was started, obtaining a rapid relief of symptoms and normalization of heart rate . On the tenth day after admission, severe dysphagia, dysphonia, irritative cough and further enlargement of the neck mass developed . Fine needle aspiration of the mass and thyroid ultrasound lead to the diagnosis of a thyroidal abscess, which was surgically excised, draining 250 ml of purulent material . Cultures were positive for Staphylococcus aureus . Patient was treated during 21 with cloxacilyn and discharged with normal thyroid function . Long term follow up has been uneventful.

Indian J Med Res, 1996 Apr, 103, 212 - 5
The spectrum of antimicrobial resistance among methicillin resistant Staphylococcus aureus (MRSA) in a tertiary care centre in India; Pulimood TB et al.; Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen globally, including India . Staph . aureus strains isolated from pus or blood of patients during January 1993 to November 1994 were tested for antimicrobial susceptibility using Kirby-Bauer disc diffusion technique . Among 1382 isolates of Staph . aureus, 332 (24%) were MRSA . Among the latter, 97 per cent were resistant to trimethoprim-sulphamethoxazole; 85.5 per cent to gentamicin and 45 per cent to amikacin . While over 90 per cent were resistant to norfloxacin and ciprofloxacin, only 53 per cent were resistant to ofloxacin . Fifty seven per cent were susceptible to rifampicin and 87 per cent to netilmicin . All tested strains were susceptible to vancomycin . Therefore, when antimicrobials other than vancomycin are considered for therapy, their choice requires the results of in vitro susceptibility testing of every isolate of MRSA.

Infect Control Hosp Epidemiol, 1996 Apr, 17(4), 236 - 48
Nosocomial infection caused by antibiotic-resistant organisms in the intensive-care unit; Flaherty JP et al.; Resistance to antimicrobial agents is an evolving process, driven by the selective pressure of heavy antibiotic use in individuals living in close proximity to others . The intensive care unit (ICU), crowded with debilitated patients who are receiving broad-spectrum antibiotics and being cared for by busy physicians, nurses, and technicians, serves as an ideal environment for the emergence of antibiotic resistance . Problem pathogens presently include multiply resistant gram-negative bacilli, methicillin-resistant Staphylococcus aureus, and the recently emerged vancomycin-resistant enterococci . The prevention of antimicrobial resistance in ICUs should focus on recognition via routine unit-based surveillance, improved compliance with handwashing and barrier precautions, and antibiotic-use policies tailored to individual units within hospitals.

Infect Control Hosp Epidemiol, 1996 Apr, 17(4), 227 - 31
Control of methicillin-resistant Staphylococcus aureus in a neonatal intensive-care unit: use of intensive microbiologic surveillance and mupirocin; Back NA et al.; OBJECTIVE: To describe the epidemiology and the interventions used to control two methicillin-resistant Staphylococcus aureus (MRSA) epidemics involving 46 infants with two fatalities in a neonatal intensive care unit (NICU) . SETTING: A 50-bed, level III NICU in a university hospital . INTERVENTIONS: After traditional interventions failed to stop the first epidemic, an intensive microbiologic surveillance (IMS) program was developed . Cultures were obtained on all infants each week, and those colonized with MRSA were isolated . When an infant was found to be colonized with MRSA, cultures immediately were obtained on all surrounding infants . This was continued until no MRSA-colonized infants were found in the area . During the first epidemic, mupirocin was used in an attempt to eradicate the organism from the unit . RESULTS: All infants, colonized and noncolonized, and parents of and personnel working with colonized infants were treated simultaneously with 5 days of mupirocin . This failed to eradicate MRSA in colonized infants . The spread of MRSA ceased in the unit, but a second epidemic occurred 4 months later . This time, IMS alone was successful in quickly containing the epidemic, and MRSA disappeared from the unit after all colonized infants were discharged . Plasmid analysis demonstrated that the same strain was responsible for both outbreaks . CONCLUSIONS: IMS and isolation are effective in containing the spread of MRSA in an NICU . The use of mupirocin failed to eradicate the organism.

Cardiovasc Surg, 1996 Apr, 4(2), 200 - 4
Prophylaxis of graft infection with rifampicin-bonded Gelseal graft: 2-year follow-up of a prospective clinical trial . Italian Investigators Group; D'Addato M et al.; Between March 1991 and June 1992, 600 patients were treated with mono-, bifemoral or iliofemoral arterial graft revascularization for occlusions and/or aneurysms . The patients were divided into two groups: group A (n = 296) received a Gelseal Vascutek graft immersed for 15 min before implant in a solution containing 1 mg/ml rifampicin; group B (n = 304) received an untreated Gelseal Vascutek graft . Both groups received perioperative antibiotic treatment with cephalosporins . Clinical follow-up was performed at 1, 6, 12 and 24 months after surgery to exclude signs of graft infection . Statistical analysis (X(2)) of pre-, intra- and postoperative risk factors showed both groups to be well matched . Among 600 patients treated, the 2-year follow-up showed 12 cases of graft infection (2.0%): five in group A (1.7%) and seven in group B (2.3%) (P = n.s.) . All cases of graft infection originated in the groin and Staphylococcus aureus was isolated in 50% of cases . Statistical analysis (Mann-Whitney U test) showed a significant prevalence of lymphatic complications and immediate redo surgery in patients with graft infection . Of the 12 cases with infection, one was lost to follow-up, three were treated with total graft removal, six with partial graft removal and two with conservative therapy: there were no deaths . In spite of the relatively limited series and follow-up, no statistically significant difference emerged from the clinical use of vascular grafts pretreated with antibiotics.

J Appl Bacteriol, 1996 Apr, 80(4), 387 - 94
Antibacterial activity of anacardic acid and totarol, alone and in combination with methicillin, against methicillin-resistant Staphylococcus aureus; Muroi H et al.; The inhibitory and bactericidal activities of anacardic acid and totarol, alone and in combination with methicillin, were investigated against methicillin-resistant Staphylococcus aureus (MRSA) . The growth of two MRSA strains was inhibited by 6 x 25 microg ml-1 of anacardic acid and 0 x 78 microg ml-1 of totarol . The time-kill curve study showed that these two compounds were bactericidal against MRSA . Anacardic acid killed MRSA cells more rapidly than totarol, and no viable cells were detected after being exposed to 6 x 25 microg ml-1 of anacardic acid for 6 h . Anacardic acid showed bactericidal activity against MRSA at any stage of growth, and also even when cell division was inhibited by chloramphenicol . In the combination studies, the minimal inhibitory concentration (MIC) of methicillin was lowered from 800 to 1 x 56 microg ml-1 for MRSA ATCC 33591, and from 800 to 6 x 25 microg ml-1 for MRSA ATCC 33592, by combining with 1/2 x MIC of anacardic acid . The time-kill curves demonstrated synergistic bactericidal activities for these combinations.

Antimicrob Agents Chemother, 1996 Apr, 40(4), 992 - 8
Clinical strain of Staphylococcus aureus inactivates and causes efflux of macrolides; Wondrack L et al.; Searching through a collection of 124 Staphylococcus aureus clinical strains, we found one isolate, strain 01A1032, that inactivates 14- and 16-membered macrolides . The products of inactivation were purified from supernatant fluids of cultures exposed to erythromycin for 3 h and were found to be identical to products of inactivation from Escherichia coli strains that encode either an EreA or EreB esterase . Further, strain 01A1032 was shown to be resistant to azithromycin, a 15-membered macrolide, by an alternate mechanism, efflux . Thus, strain 01A1032 harbors determinants encoding an esterase activity that hydrolyzes 14- and 16-membered macrolides and a macrolide efflux system.

Antimicrob Agents Chemother, 1996 Apr, 40(4), 924 - 9
Characterization of IS1272, an insertion sequence-like element from Staphylococcus haemolyticus; Archer GL et al.; We have previously shown (G . L . Archer, D . M . Niemeyer, J . A . Thanassi, and M . J . Pucci, Antimicrob . Agents Chemother . 38:447-454, 1994) that some methicillin-resistant staphylococcal isolates contain a partial deletion of the genes (mecR1 and mecI) that regulate the transcription of the methicillin resistance structural gene (mecA) . When a fragment of DNA inserted at the point of the mecR1 deletion was used as a probe, hybridization with multiple bands was detected for Staphylococcus haemolyticus genomic DNA . In the present study, DNA sequencing of four unique clones recovered from a lambda library of S . haemolyticus revealed identical 1,934-bp elements . Each element, designated IS1272, contained 16-bp terminal inverted repeats (sequence identity, 15 of 16 bp) and two open reading frames of 819 and 687 bp; there were no flanking target site duplications . Database searches yielded amino acid homology with proteins predicted to be encoded by open reading frames from a putative insertion sequence element from Enterococcus hirae . DNA probes from each end and the middle of IS1272 were hybridized with restriction endonuclease-digested genomic DNA from clinical S . haemolyticus, Staphylococcus epidermidis, and Staphylococcus aureus isolates . Each of the 20 or more copies of the element found in S . haemolyticus isolates was intact, and copies were found in most chromosomal SmaI fragments . S . aureus and S . epidermidis isolates contained mostly incomplete fragments of the element, and there were many more hybridizing fragments in methicillin-resistant than in methicillin-susceptible isolates . IS1272, which appears to be primarily resident in S . haemolyticus, has disseminated to multiple staphylococcal species and is prevalent in multiresistant isolates.

Antimicrob Agents Chemother, 1996 Apr, 40(4), 1060 - 2
GyrB mutations in Staphylococcus aureus strains resistant to cyclothialidine, coumermycin, and novobiocin; Stieger M et al.; The sequence of the gyrase B subunit gene from Staphylococcus aureus strains resistant to the gyrase B subunit inhibitors cyclothialidine, coumermycin, and novobiocin has been determined . The residues altered in the resistant gyrase B subunits map to the ATP-binding region, suggesting that the drugs inhibit ATP binding and hydrolysis . The pattern of cross-resistances indicates that the detailed binding mode of the compounds differs.

Rinsho Byori, 1996 Apr, 44(4), 367 - 72
{Methicillin-resistant Staphylococcus aureus infection in the Akita University Hospital: surveillance and microbiology data}; Tobita M et al.; In order to control the nosocomial infections by methicillin-resistant Staphylococcus aureus (MRSA) in the Akita University Hospital, the systematic surveillance for MRSA-infection has been done since October in 1991 . We reviewed MRSA-isolation numbers, MRSA-detected patient numbers, risk factors of nosocomial infection and patient's basic diseases with the data of a total 336 cases, and then examined the microbiological characteristics of MRSA strains which had been isolated in our hospital in 1986 approximately 1994 . The results obtained are as follows; 1) MRSAs were isolated at 13 per month on the average and the detection rate was 0.81 to 1,000 inpatients per day . 2) MRSAs were isolated more in the surgical ward . 3) Patients with 0 year old and more than 60 years old were more infected . 4) MRSA was isolated more from the immunocompromised patients with underlying diseases such as malignant tumors but half of the diseases were not affected by MRSA . 5) Seventy percent of patients had the risk factors of MRSA-transmission such as surgical operation and IVH-cathetering . 6) All isolates of MRSA strains in our hospital showed type II in coagulase type analysis and resistance to minocycline and ofloxacin . 7) It was suggested that one strain expanded throughout the hospital by several DNA analysis with the mecA gene in MRSA . These surveillance and microbiology data will be useful for our nosocomial mecA gene in MRSA . These surveillance and microbiology data will be useful for our nosocomial infection control.

Diagn Microbiol Infect Dis, 1996 Apr, 24(4), 221 - 3
A case of carbuncle caused by a catalase-negative strain of staphylococcus aureus; Lee N et al.; A gram-positive coagulase-positive coccus was isolated from purulent drainage from the carbuncle of a pediatric patient . It shows characteristics typical of Staphylococcus aureus with the exception that catalase activity could not be found.

Eur J Epidemiol, 1996 Apr, 12(2), 163 - 9
Comparison of an improved RAPD fingerprinting with different typing methods for discriminating clinical isolates of Staphylococcus spp; Damiani G et al.; Different epidemiological markers were used to characterize 2 Staphylococcus epidermidis and 8 Staphylococcus aureus strains isolated from patients with severe infections . We compared random amplified polymorphic DNA (RAPD) fingerprints, biotypes, antibiotic assays, plasmid profiles and chromosomal DNA restriction endonuclease analysis (REA) . Data analysis based on numerical taxonomy methods indicates that RAPD and REA give similar results allowing a good discrimination of the two species and of each isolate . The RAPD method is easier and faster than REA, but the reproducibility of RAPD fingerprints obtained in independent experiments can be problematic . We have found simple technical devices to improve the reproducibility of the RAPD procedure which is therefore a very useful tool in epidemiology for identification and characterization of Staphylococcus spp.

Eur J Clin Microbiol Infect Dis, 1996 Apr, 15(4), 340 - 3
Types of methicillin-resistant Staphylococcus aureus associated with high mortality in patients with bacteremia; Nada T et al.; Forty-seven strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from 47 patients with bacteremia were analyzed by chromosomal DNA digestion pattern using pulsed-field gel electrophoresis and evaluated for serological coagulase type, enterotoxin type, and toxic shock syndrome toxin-1 production . The mortality rate was significantly higher in the older patients (> or = 51 years of age) than in the younger patients (< or = 50 years of age) (50% vs . 4%, p = 0.0007) . Methicillin-resistant Staphylococcus aureus strains of serological coagulase type II were more likely to be associated with mortality in older patients than were strains of the other types (p = 0.037).

Arch Mal Coeur Vaiss, 1996 Apr, 89(4), 471 - 5
{Pulmonary valve replacement for endocarditis . Apropos of 2 cases}; Chatel D et al.; The authors report two cases of pulmonary valve endocarditis which required emergency surgical treatment . A 74 year old patient with trivalvular endocarditis (pulmonary, aortic, mitral), due to Sptreptococcus D bovis, developed cardiogenic shock with acute pulmonary oedema and underwent double aortic and pulmonary valve replacement with Carpentier-Edwards prostheses and simple resection of a mitral valve vegetation . Another 36 year old drug addict developed isolated pulmonary valve endocarditis due to Staphylococcus aureus infection complicated by pulmonary regurgitation with right ventricular failure and by septic pulmonary embolism with persistent sepsis: he underwent pulmonary valve replacement with a Bravo 300 bioprosthesis . The postoperative course was uncomplicated in both cases, with interruption of the infection and normalisation of the haemodynamic status . The insidious and severe nature of pulmonary valve endocarditis is demonstrated by these two cases, confirming previous reports which have underlined the poor prognosis of this condition . Surgery has been shown to be effective and well tolerated and should be integrated early in the therapeutic strategy, the results being all the better when an aggressive attitude is taken.

J Hosp Infect, 1996 Apr, 32(4), 305 - 17
Comparison of DNA fingerprinting by PFGE and PCR-RFLP of the coagulase gene to distinguish MRSA isolates; Nada T et al.; Staphylococcus aureus isolates were collected from epidemiologically unrelated clinical sources in Japan between 1991 and 1993 . A total of 40 isolates, five each of eight coagulase types, were analysed by polymerase chain reaction (PCR) of the coagulase gene, PCR-restriction fragment length polymorphism (RFLP) after AluI digestion, and pulsed-field gel electrophoresis (PFGE) of chromosomal DNA after SmaI digestion . The efficiency of discrimination among the isolates increased in the order of PCR < PCR-RFLP < PFGE, yielding five, 13 and 31 different types, respectively . To assess the clinical use of these methods, 42 additional methicillin-resistant S . aureus (MRSA) isolates collected from 27 inpatients in a hospital were analysed . PFGE and PCR-RFLP were able to discriminate 11 and four types, respectively . PFGE analysis detected cross-infection between four postoperative patients in an intensive-care unit, and in six neonates in intensive care . We conclude that of the three methods tested, PFGE analysis currently allows the most effective discrimination of MRSA strains.

J Hosp Infect, 1996 Apr, 32(4), 257 - 66
Blanket use of intranasal mupirocin for outbreak control and long-term prophylaxis of endemic methicillin-resistant Staphylococcus aureus in an open ward; Mayall B et al.; In December 1992, a thoracic ward in a Melbourne teaching hospital experienced an increase in patients infected with methicillin-resistant Staphylococcus aureus (MRSA) . It was decided to attempt to control the outbreak by cohorting positive patients (infected and colonized), as well as nurse cohorting, emphasis on handwashing, and use of intranasal mupirocin initially three times a day for three days, then thrice weekly, for all patients in the ward (with or without MRSA) . The campaign comprised for phases of 53, 45, 92 and 365 days, respectively . Patient and nurse cohorting stopped at the end of phase I . In phases I and II, surveillance nose swabs were taken on admission, then twice weekly; in phase III, on admission and weekly and in phase IV, on admission until the end of 1993 . In phases I and II (98 days), only one patient acquired MRSA . When the frequency of mupirocin prophylaxis was decreased to once weekly (phase III), two patients acquired MRSA in 92 days (no significant difference): thrice weekly administration resumed (phase IV), during which there were three acquisitions in 365 days . The rates of nose colonization of admissions were 6.4%, 6.3%, 9.7% and 3.1% in phase I-IV, respectively . Only three patients were treated with vancomycin between July 1993 and June 1994 (significantly lower than historical rates, P = 0.0086) . No mupirocin resistance was seen in MRSA isolates from this ward during phases I, II and III . In areas of low-level endemic MRSA, the blanket use of thrice-weekly intranasal mupirocin may be effective in decreasing serious infections with MRSA, and does not necessarily elicit mupirocin resistance.

Zentralbl Bakteriol, 1996 Apr, 283(4), 529 - 42
Frequency, clonal heterogeneity and antibiotic resistance of methicillin-resistant Staphylococcus aureus (MRSA) isolated in 1992-1994; Schneider C et al.; Since 1992, the proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolated from patients of the University Hospital of Frankfurt/Main and six community hospitals increased to a level of 11% and has remained constant during the following two years . MRSA and methicillin-sensitive Staphylococcus aureus (MSSA) were distributed equally among almost all specimens except blood . There was evidence of a diminished potency of MRSA to cause bacteremia . All MRSA strains were susceptible to glycopeptides and mupirocin . Resistance rates to other non-beta-lactam antibiotics were low for fusidic acid (7.1%), fosfocin (8.3%), amikacin (11.4%) and cotrimoxazole (18.3%) and high for gentamicin (90.7%), ofloxacin (94.3%) and erythromycin (95.5%) . Among 378 MRSA strains originating from 180 individuals, macrorestriction analysis of chromosomal DNA revealed 39 different genotypes . These could be divided into 14 epidemic strains isolated from 155 patients and 25 sporadic strains isolated from single patients . As most of the sporadic strains emerged in close local proximity to epidemic strains, we suppose a horizontal genetic transfer from MRSA to MSSA leading to the appearance of novel MRSA genotypes . Upon repeated isolation of MRSA strains from the same individuals, resistance rates and genotypes remained stable . Resistance patterns of the non-beta-lactams correlated poorly with macrorestriction analysis, whereas several MRSA genotypes could be distinguished by particular MICs of methicillin.

J Vet Pharmacol Ther, 1996 Apr, 19(2), 95 - 103
Pharmacokinetic-pharmacodynamic model for spiramycin in staphylococcal mastitis; Renard L et al.; Simultaneous pharmacokinetic-pharmacodynamic (PK/PD) modelling for spiramycin in staphylococcal infections of the mammary gland of cows was used to predict the efficacy of spiramycin . A differential equation derived from the Zhi model was fitted to an in vitro killing curve and post-antibiotic effect determination . A seven-compartment PK model, in which 4 compartments representing each quarter of the mammary gland which was considered to be the effect compartment, was included . The PD model linked to the PK model was able to describe the in vivo spiramycin effect against Staphylococcus aureus . The parameters calculated from in vitro data predicted a rapid decrease for the first 12-24 h, and regrowth within 72 h following the treatment, whereas in vivo the bacterial effect was much less after 24 h than that predicted by the in vitro data . PK/PD modelling permitted the simulation of various doses to optimize the efficacy of the antibiotic, taking into account such dynamic parameters as bacterial growth rate constant, bacterial killing rate constant and the Michaelis-Menten type saturation constant . An optimal dosage regimen of 20000 IU/kg per day for 3 days was predicted for the treatment of Staphylococcus aureus mastitis.

Trends Microbiol, 1996 Apr, 4(4), 162 - 6
The prospects for developing a vaccine against Staphylococcus aureus; Lee JC; Staphylococcus aureus is an important bacterial pathogen with multiple virulence factors . The prevalence of antibiotic resistance among clinical isolates means that new vaccine strategies to prevent staphylococcal infections are needed . An ideal vaccine would induce antibodies to prevent bacterial adherence, promote opsonophagocytic killing by leukocytes and neutralize toxic secreted proteins.

Leuk Lymphoma, 1996 Apr, 21(3-4), 281 - 91
Expression and production of cytokines by heterohybrids and their parental B cells in CLL; Diaw L et al.; Three hybrids derived from CD5+ B cell chronic lymphocytic leukemia (B-CLL) and their parental B cells were studied for phenotypic evolution, immunoglobulin (Ig), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) secretion . When phenotypic evolution was examined, hybrids showed the loss of classical B cell markers, indicating that they follow the same pattern of phenotypic differentiation as normal B cells . Hybrids displayed spontaneous high Ig secretion, which did not appear to be modified through stimulation by phorbol 12-myristate 13-acetate (PMA), recombinant interferon-gamma (rIFN-gamma) and Staphylococcus aureus Cowan I (SAC) . Parental cells secreted minimal amounts of Ig spontaneously or through IFN-gamma and SAC stimulation, whereas PMA succeeded in increasing this secretion . An opposite pattern was observed when TNF-alpha and IL-6 secretion an expression at the mRNA level were assessed in hybrids and parental cells . TNF-alpha and IL-6 were spontaneously secreted by parental cells and this secretion was increased after PMA and SAC stimulation, both cytokine secretion and expression at the mRNA level were negative in hybrid cells . The absence of expression of these cytokines could be explained either by chromosomal loss or by down regulation . These results indicate that when parental CLL cells are induced to differentiate in the heterohybrid model, they acquire high spontaneous secretion of Ig, lose the classical B cell phenotypic markers and down regulate the expression of the cytokines studied.

Jpn Circ J, 1996 Apr, 60(4), 258 - 61
Reconstruction of the mitral annulus with porcine pericardium--report of a case with mitral annular disruption due to staphylococcal endocarditis; Aoyagi S et al.; A 60-year-old man was admitted to our hospital for investigation of dyspnea and disorientation with right hemiplegia . Echocardiography showed thickened mitral valve leaflets with vegetations and severe mitral regurgitation . Blood cultures grew Staphylococcus aureus . During the operation, perforation and destruction of the mitral valve leaflets and vegetations were confirmed . Debridement of the infected tissues resulted in segmental disruption of the posterior mitral fibrous annulus . Reconstruction of the mitral annulus with porcine pericardium treated with glutaraldehyde and mitral valve replacement were successful . The patient's postoperative course was complicated with metastatic cerebral and splenic abscesses . After splenectomy on the 8th postoperative day, he gradually recovered without major neurologic sequelae . We believe that reconstruction of the mitral valve annulus with pericardium, especially autologous pericardium, is reliable and useful for the treatment of patients with disruption of the mitral valve annulus.

J Am Soc Nephrol, 1996 Apr, 7(4), 536 - 42
Antibiotic-resistant endocarditis in a hemodialysis patient; Vijayvargiya R et al.; A chronic dialysis patient developed persistent bacteremia as a result of infection with Enterococcus faecium . During the patient's illness, resistance to ampicillin, gentamicin, vancomycin, and teicoplanin developed . Despite arteriovenous (AV) graft removal and an extensive but inconclusive search for the source of the infection, bacteremia persisted . On autopsy, the patient was found to have had aortic-valve endocarditis . Endocarditis is a well-known complication in dialysis patients . Multidrug-resistant organisms are becoming more prevalent in hospitalized patients as well . Risk factors for the development of endocarditis in dialysis patients include catheters, AV grafts, and calcific valvular disease, all in conjunction with frequent access to the circulation . Avoidance of temporary catheter use by prompt placement of AV fistulas or grafts and consideration of their early use, the meticulous care of catheters once in place, and treatment of the nasal carriage of Staphylococcus aureus may lower the incidence of bacteremia and therefore endocarditis in dialysis patients . The removal of infected catheters and/or AV grafts if prompt clearing of the blood with antibiotics does not occur is the next step, followed by valve replacement in selected cases . The routine use of vancomycin in the dialysis population should be reevaluated in light of the development of high-level antibiotic-resistant organisms.

Biokhimiia, 1996 Apr, 61(4), 656 - 63
{Bacteriolytic enzyme preparation lysoamidase . Purification and some properties of bacteriolytic peptidase L1}; Stepanaia OA et al.; The bacteriolytic peptidase L1 has been isolated from the enzyme preparation of lysoamidase capable to lyze cell walls of gram-positive bacteria using ion-exchange chromatography and gel filtration . Some physico-chemical properties of the enzyme have been established . The molecular mass of L1 is 21 kDa, the pH optimum for Staphylococcus aureus cell lysis is 7-11 . The optimal concentration of the buffer is 50 mM; the temperature optimum is 70 degrees C; the half-inactivation temperature is 55 degrees C.

J Antimicrob Chemother, 1996 Apr, 37(4), 687 - 96
Use of the coagulase gene typing method for detection of carriers of methicillin-resistant Staphylococcus aureus; Lawrence C et al.; Strains of Staphylococcus aureus can be typed on the basis of the polymorphism of the coagulase gene . DNA fragments generated after amplification by polymerase chain reaction (PCR) of the variable region of this gene and digested with the restriction enzyme HaeIII can be compared by their restriction fragment length polymorphism (RFLP) . Seventy-nine of 86 (91.8%) methicillin-resistant S . aureus (MRSA) strains isolated in various hospitals had a characteristic RFLP pattern . This pattern differed from those of 32 methicillin-susceptible S . aureus (MSSA) . Only one MSSA shared with MRSA the same RFLP pattern . After modification, we applied this method to the rapid detection of MRSA from 255 nasal swabs from patients hospitalized in intensive care units . When screened by plating on Chapman agar, 55 of these samples contained MRSA, whereas 40/55 yielded the expected restriction profile after amplification by PCR . No DNA was amplified by PCR in 9/55 samples and restriction profiles were uninterpretable in six cases . When compared to culture, the positive and negative predictive values of the PCR test were 100% and 93%, respectively . The specificity was 100% and the sensitivity was 72.7% . Since control of spread of MRSA strains in hospitals is based in part on rapid isolation of carriers, this method which allows detection of epidemic MRSA in nasal swabs within a day could be helpful, though culture would still be necessary to confirm the result.

Nippon Jinzo Gakkai Shi, 1996 Apr, 38(4), 185 - 90
{A case of selective IgM deficiency associated with systemic lupus erythematosus}; Tanaka A et al.; We report a case of selective IgM deficiency associated with systemic lupus erythematosus (SLE) . A 34-year-old female suffering from SLE was admitted with proteinuria and general fatigue . Laboratory findings revealed a very low serum IgM level, almost lower than 12 mg/dl . Renal biopsy findings showed diffuse proliferative lupus nephritis (DPLN) . In immunofluorescent microscopy, IgG was the most strongly stained followed by IgA, but IgM staining was only faint . As for the immunophenotype of the T cells, the OKT4/OKT8 ratio was normal . Response to both phytohemagglutinin (PHA) and concanavalin A (ConA) was normal . However, responses of B cells to both pokeweed mitogen (PWM) and Staphylococcus aureus Cowan strain I (SAC) were significantly reduced . Surface IgM-positive B cells were decreased . These results indicate that the patient had B cell dysfunction, involving impairment of B cell differentiation . In this report, we discuss selective IgM deficiency and SLE documented in the literature.

Kansenshogaku Zasshi, 1996 Apr, 70(4), 354 - 9
{Relation between nutrition of patients and methicillin-resistant Staphylococcus aureus (MRSA)}; Takeda S et al.; We respectively evaluated the nutritional state of 31 patients who isolated Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from January to November in 1993 . Because 4 of 31 isolates were not considered to be a causative bacteria, we evaluated the rest 27 cases . Fifteen of 27 cases were diagnosed as MRSA infection and 12 (44%) MRSA colonization . We evaluated the nutritional state of patients with infection and colonization . There was significance (p < 0.01) between two groups as for serum total protein were 5.52 g/dl in infection group and 6.65 g/dl in colonization group . Furthermore there were significance (p < 0.05) for mean serum albumin were 3.04 g/dl v.s . 3.58 g/dl and total cholesterol were 122.3 mg/dl v.s . 162.5 mg/dl . Thus, MRSA was colonized in respiratory patients who were in better nutritional state, suggesting that importance of nutritional improvement for prevention and therapy against MRSA infection . We obtained similar results on Methicillin-sensitive Staphylococcus aureus (MRSA).

Kansenshogaku Zasshi, 1996 Apr, 70(4), 331 - 7
{Drug-resistance patterns and biological properties of MRSA isolated from different geographical areas of Japan}; Kanayama A et al.; One hundred isolates of methicillin-resistant Staphylococcus aureus (MRSA) collected from hospitals located in different geographical areas of Japan were used in the present study . The susceptibilities of the strains to gentamicin (GM), erythromycin (EM), tetracycline (TC) and ofloxacin (OFLX) were determined and classified into twelve groups according to their differences in the patterns of the resistance to the four drugs . Of the 100 strains tested, 75 belonging to the main four groups were investigated for the relationships between their patterns of the drug-resistance and biological properties such as coagulase, enterotoxin and phage types, TSST-1 and beta-lactamase producibilities, and percentages of the strains carrying plasmids of large size (> or = 20,000 bp) . The main four patterns of drug resistance of the 75 strains were as follows: the first group (33 strains resistant to GM, EM, TC and OFLX), the second group (15 strains resistant to EM, TC and OFLX), the third group (11 strains resistant to GM, EM and OFLX) and the fourth group (16 strains resistant to EM and OFLX) and the remaining 25 strains were divided into further groups . A considerable number of the strains in the third group differed markedly in some biological properties from those in the other groups; coagulase typing (III type-50%: the other groups-II type), enterotoxin typing (64%-non-production: the other groups-C type), TSST-1 producibility (36%-production: the other groups-76 to 88%-production) and phage typing (55%-non-typable: the other groups-80 to 97%-non-typable) . In beta-lactamase and plasmids of large size, the first group consisted of the strains with beta-lactamase producibility at the ratio of 50:50, but the other groups consisted of most of the strains with the beta-lactamase producibility . Most of the strains belonging to the second and fourth groups carried large size of plasmids, but 36 and 46% of those belonging to the first and third groups did not carry them . On the other hand, our results of the susceptibility test for the 100 strains showed that a considerable number of strains were susceptible to GM (35%) and TC (42%) at therapeutically significant concentrations.

Biomaterials, 1996 Apr, 17(7), 667 - 78
Physical and biological effects of a surface coating procedure on polyurethane catheters; Francois P et al.; Central venous catheters are widely used in clinical practice; however, complications such as venous thrombosis or infection are frequent . The physical and biological effects of a coating procedure designed to improve the blood-contacting properties of polyurethane central venous catheters (CVCs) were studied . The surface atomic composition of poly(vinyl pyrrolidone) (PVP)-coated or uncoated Pellethane single lumen CVCs was characterized by electron spectroscopy for chemical analysis (ESCA), which confirmed the presence of an oxygen-rich PVP layer on the former material . Topological analysis of both single and triple lumen CVCs by scanning force microscopy (SFM) revealed a very smooth surface in PVP-coated catheters compared to the more frequent surface irregularities found either in uncoated Pellethane or in four additional randomly selected, commercially available triple lumen polyurethane CVCs . The PVP-coated Pellethane showed a strong reduction in either fibrinogen or fibronectin adsorption compared to all other PVP-free polyurethane CVCs . This decreased protein adsorption led to a proportional reduction in protein-mediated adhesion of either Staphylococcus aureus or Staphylococcus epidermidis and in the binding of a monoclonal antibody directed against the cell-binding domain of fibronectin . Increased surface smoothness and hydrophilic properties of polyurethane CVCs might decrease the risk of bacterial colonization and infection.

J Exp Med, 1996 Apr 1, 183(4), 1579 - 86
Localization of the binding site for the monocyte immunoglobulin (Ig) A-Fc receptor (CD89) to the domain boundary between Calpha2 and Calpha3 in human IgA1; Carayannopoulos L et al.; Immunoglobulin (Ig) A serves as the first line of humoral defense at all mucosal surfaces and is present in large quantities of blood . In playing its role in humoral immunity, IgA interacts with a variety of effector molecules present both in serum and on the surfaces of immune and inflammatory cells . To study these interactions, we previously established expression of human IgA1 in insect cells using recombinant baculoviruses and showed that the expressed antibody is a structurally and functionally intact polypeptide useful for examining the molecular properties of IgA . Indeed, since the C alpha 2 N-linked glycosylation site lies near the Fab-distal pole of C alpha 2, the inability of a mutant IgA1 lacking C alpha 2 N-glycosylation to bind its cognate receptor suggested that the monocyte Fc alpha receptor (mFcalphaR) recognizes IgA at a hinge-distal site encompassing the boundary between the C alpha 2 and C alpha 3 domains . In this report, we utilize both domain-swapped IgA/IgG and point-mutated IgA chimeras to verify the above hypothesis . Using an antigen-specific rosetting assay and a mFc alpha R-expressing cell line, we show that (a) C alpha 2 and C alpha 3 together are necessary and sufficient for binding; (b) neither the IgA hinge nor the tailpiece is necessary for binding; (c) mutations away from the interdomain boundary do not affect binding; and (d) mutations located near the three-dimensional boundary between C alpha 2 and C alpha 3 completely disrupt binding . Taken together, these results localize the mFc alpha R recognition site on IgA to the boundary region between the second and third constant domains--a site analogous to that recognized by Staphylococcus aureus protein A on IgG . The use of this hinge-distal site is, to date, unique among Fc receptors of the Ig superfamily.

Can Fam Physician, 1996 Apr, 42, 654 - 9
Staphylococcus aureus and sore nipples; Livingstone VH et al.; OBJECTIVE: To correlate clinical symptoms and signs of sore nipples with the presence of Staphylococcus aureus and to determine the probability of mothers having S aureus-infected nipples when these local symptoms and signs are found . DESIGN: Two cohorts of consecutive patients were enrolled regardless of presenting complaint . A questionnaire was administered to determine the presence and severity of sore nipples . Objective findings on breast examination were documented . A nipple swab was taken for culture and sensitivity . SETTING: Breastfeeding clinic serving patients referred by family physicians, pediatricians, and community health nurses . PATIENTS: A sample of 227 breastfeeding mothers was collected in two cohorts . MAIN OUTCOME MEASURES: Answers to questions about sore nipples, objective findings from physical examination, and results from nipple swabs . RESULTS: Most subjects (51%) had sore nipples, and 45% of subjects had objective findings on examination; 23% of subjects had a positive nipple swab culture; 15% grew S aureus on culture . The risk of having S aureus colonization was 4.8 times greater if nipple pain was moderate or severe rather than mild . A break in nipple integument associated with cracks, fissures, ulcers, or pus gave a 35% chance of having S aureus colonization, five times greater than when the integument was intact . CONCLUSIONS: The study showed that mothers with infants younger than 1 month who complained of moderate to severe nipple pain and who had cracks, fissures, ulcers, or exudates had a 64% chance of having positive skin cultures and a 54% chance of having S aureus colonization.

Blood, 1996 Apr 1, 87(7), 2861 - 9
Expression of granulocyte colony-stimulating factor and granulocyte colony-stimulating factor receptor genes in partially overlapping monoclonal B-cell populations from chronic lymphocytic leukemia patients; Corcione A et al.; B lymphocytes were purified from the peripheral blood of 30 B-cell chronic lymphocytic leukemia (B-CLL) patients and tested for the ability to produce granulocyte colony-stimulating factor (G-CSF) in vitro . Fifteen Staphylococcus aureus Cowan I (SAC)-stimulated, but not unstimulated, B-cell suspensions produced G-CSF in short-term cultures . Accordingly, G-CSF mRNA was detected only in SAC-stimulated B cells . Five CLL B-cell fractions that released G-CSF following exposure to SAC were also incubated with CD40 or anti-mu antibodies in the presence or absence of recombinant (r) interleukin-2 (IL-2) or IL-4 . The 5 cell suspensions produced G-CSF only on culture with CD40 monoclonal antibody in combination with rIL-2 or rIL-4 . CD5+ B lymphocytes, which represent the normal counterparts of most B-CLL proliferations, did not produce G-CSF under any of the above culture conditions . G-CSF produced by leukemic B lymphocytes was biologically active, because conditioned media of SAC-stimulated cells supported the in vitro growth of myeloid colonies from normal bone marrow progenitors . The colony stimulating activity of CLL B-cell supernatants was ascribed to both G-CSF and granulocyte-macrophage colony stimulating factor . G-CSF receptors (G-CSFRs) were detected on freshly isolated B lymphocytes from 7 of 11 B-CLL patients; 5 of these cell suspensions produced G-CSF in culture, whereas 2 did not . rG-CSF rescued 3 of the 7 G-CSFR+ cell fractions from spontaneous apoptosis but had no effect on their in vitro proliferation.

Plast Reconstr Surg, 1996 Apr, 97(4), 801 - 6
Advantages of autologous fascia versus synthetic patch abdominal reconstruction in experimental animal defects; Disa JJ et al.; Although prosthetic patches (i.e., expanded polytetrafluoroethylene) are commonly used to repair abdominal fascial defects, autologous tissue is preferred in the presence of wound contamination . This study was undertaken to discover (1) whether fascial grafts are revascularized and incorporated as living tissue, and (2) whether fascial grafts are more resistant to bacterial contamination than prosthetic patches . In the first experiment, 18 New Zealand White rabbits underwent full-thickness resection of the central abdominal wall preserving only panniculus carnosus and skin . Six control animals had only skin repaired, and all developed large ventral hernias . Twelve animals had the defect repaired with thoracodorsal fascia patches . At 3- and 6-week intervals, no hernias were present and all patches were incorporated with minimal contraction . Fluorescein angiography verified revascularization from the surrounding abdominal wall . Next, 36 rabbits underwent similar resection followed by repair with either autologous fascia (n=18) or expanded polytetrafluoroethylene (n=17) . Six rabbits of each repair group were inoculated with 10(4) Staphylococcus aureus and twelve rabbits with each repair were inoculated with 10(9) S . aureus . All rabbits receiving 10(4) S . aureus were infection-free survivors . Seven of the twelve expanded polytetrafluoroethylene-repaired animals receiving 10(9) S . aureus developed necrotizing wound infections and died . Only 2 of 12 rabbits with autologous fascia repairs died from wound sepsis and 1 died of diarrhea with a healed wound . Differences in wound infection rates achieved statistical significance, whereas survival differences approached significance (Fisher's exact test), suggesting that revascularized fascial grafts may be more resistant to bacterial contamination than expanded polytetrafluoroethylene patches at this concentration (10(9) S . aureus).

Eur J Nucl Med, 1996 Apr, 23(4), 414 - 21
Technetium-99m labelled hydrazinonicotinamido human non-specific polyclonal immunoglobulin G for detection of infectious foci: a comparison with two other technetium-labelled immunoglobulin preparations; Claessens RA et al.; Recently a new linker - hydrazinonicotinate (HYNIC) - was introduced for labelling of proteins and peptides with technetium-99m . HYNIC and other linkers have been used for labelling of human non-specific polyclonal immunoglobulin G (hIgG) with 99mTc for the detection of infections . In this study we compared the tissue distribution of three different 99mTc-hIgG preparations in groups of five Wistar rats with a focal intramuscular infection with Staphylococcus aureus . We compared 99mTc-HYNIC-hIgG with 99mTc-hIgG labelled via the so-called Schwarz method (reduction of disulphide bonds) and with the 99mTc-labelled commercially available Technescan-HIG . Unlike the HYNIC linker, in the two other labelling methods free sulph-hydryl groups are involved in the binding of 99mTc . High-performance liquid chromatography analysis of the labelled preparations and of plasma samples revealed aggregate or polymer formation in all three agents; this was least pronounced in the product labelled by means of the Schwarz method . The tested preparations did not show signs of degradation in vitro . The difference in linker chemistry was reflected in the tissue distribution . Thus the biodistribution of 99mTc-HYNIC-hIgG was significantly different from the distribution of the two other preparations: abscess (1.4%+/-0.2%ID/g), muscle, liver, spleen, plasma, lung, bone marrow, and small intestine concentrations were higher at 24 h p.i.; kidney uptake (1.19%+/-0.08%ID/g) was significantly lower . The abscess-to-plasma and the abscess-to-muscle ratios (0.5 and 11, respectively), however, were in the same range for the three preparations tested . Quantitative analysis of the scintigraphs revealed that the total body clearance of 99mTc-HYNIC-hIgG was significantly slower than for the other agents . The abscess uptake of 99mTc-HYNIC-hIgG as a percentage of the remaining body activity was significantly higher . Based on its high abscess uptake, its low uptake in the kidneys and the high percentage of its abscess uptake in relation to the remaining body activity, we conclude that 99mTc-HYNIC-hIgG seems superior to the two other preparations tested for the detection of infections.

AJR Am J Roentgenol, 1996 Apr, 166(4), 903 - 7
MR appearances of the temporal evolution and resolution of infectious spondylitis; Gillams AR et al.; OBJECTIVE . We undertook this study to document the MR appearances of evolving or resolving infectious spondylitis . MATERIALS AND METHODS . A retrospective review was carried out of all patients with infectious spondylitis who had undergone MR imaging from 1991-1993 at Boston University Hospital and Boston City Hospital Imaging Foundation . The study population consisted of 25 patients (seven females and 18 males) . There was a bimodal age distribution with peaks at 34 and 59 years old (age range, 25-81 years old) . The causative organism was isolated in 20 . Sixteen had Staphylococcus aureus, two had mycobacterium tuberculosis, and two had gram-negative bacilli . Follow-up MR imaging was performed in 20 . Nine had two studies, three had three, five had four, two had five, and one had six . The median length of follow-up was 8 weeks (range, 2-104 weeks) . Follow-up MR appearances were correlated with clinical outcome . RESULTS . Early imaging revealed atypical appearances . Fourteen of 20 (70%) improved; the first sign of response to treatment was a reduction in the inflammatory soft tissue (8/14, 57%) . Changes in the bones or discs concurrently progressed in six of eight patients (75%) including involvement of a new disc level in four (50%) . A definitive sign of healing was a peripheral rim of high T1 signal in bone (5/14, 36%) . Gadolinium enhancement persisted long after resolution of changes in the soft tissues, for up to a median of 17.5 weeks (range, 8-80 weeks) . A subgroup of six IV drug users showed unique radiologic features . CONCLUSION . The early appearances of infectious spondylitis may be atypical . Resolution of soft-tissue change and fat deposition in the bone marrow are reliable signs of healing . Bone or disc changes can progress despite clinical improvement . Gadolinium enhancement can increase and persist after symptom resolution.

J Med Microbiol, 1996 Apr, 44(4), 303 - 10
Epidemiological study of an outbreak of infection with Staphylococcus aureus resistant to lincosamides and streptogramin A in a French hospital; Arpin C et al.; A significant increase in the incidence of isolates of methicillin-resistant Staphylococcus aureus (MRSA), that were also resistant to lincosamides and streptogramin A (LSA-MRSA), was observed in a French university hospital . Twenty-seven isolates from the outbreak were characterised, including 17 isolates from a plastic surgery ward and six control strains of MRSA . The strains were examined by antibiotyping and biotyping, and by three molecular methods: plasmid analysis, ribotyping and insertion sequence (IS) typing with IS256 sequence as a probe . Antibiotyping (five antibiotypes) was discriminatory because of the uncommon resistance phenotype of the epidemic strain . Biotyping (three biotypes), DNA plasmid analysis (four profiles) and ribotyping (two profiles) were poorly sensitive, in contrast to IS-typing (12 profiles) . By the latter method, a coefficient of similarity (percentage similarity) compared to the predominant IS profile was calculated . Strains with a coefficient of similarity > or = to 82% were considered as highly related to the epidemic strain, while those with a coefficient of similarity < or = to 40% were regarded as distant . Results obtained with the five markers confirmed that an outbreak of hospital infection had occurred in the plastic surgery ward, with spread of the epidemic strain throughout the hospital.

J Bacteriol, 1996 Apr, 178(7), 2118 - 26
Cloning of type 8 capsule genes and analysis of gene clusters for the production of different capsular polysaccharides in Staphylococcus aureus; Sau S et al.; Eleven serotypes of capsular polysaccharide from Staphylococcus aureus have been reported . We have previously cloned a cluster of type 1 capsule (cap1) genes responsible for type 1 capsular polysaccharide biosynthesis in S . aureus M . To clone the type 8 capsule (cap8) genes, a plasmid library of type 8 strain Becker was screened with a labelled DNA fragment containing the cap1 genes under low-stringency conditions . One recombinant plasmid containing a 14-kb insert was chosen for further study and found to complement 14 of the 18 type 8 capsule-negative (Cap8-) mutants used in the study . Additional library screening, subcloning, and complementation experiments showed that all of the 18 Cap8- mutants were complemented by DNA fragments derived from a 20.5-kb contiguous region of the Becker chromosome . The mutants were mapped into six complementation groups, indicating that the cap8 genes are clustered . By Southern hybridization analyses under high-stringency conditions, we found that DNA fragments containing the cap8 gene cluster show extensive homology with all 17 strains tested, including type 1 strains . By further Southern analyses and cloning of the cap8-related homolog from strain M, we show that strain M carries an additional capsule gene cluster different from the cap1 gene cluster . In addition, by using DNA fragments containing different regions of the cap8 gene cluster as probes to hybridize DNA from different strains, we found that the central region of the cap8 gene cluster hybridizes only to DNAs from certain strains tested whereas the flanking regions hybridize to DNAs of all strains tested . Thus, the cap8 gene clusters and its closely related homologs are likely to have organizations similar to those of the encapsulation genes of other bacterial systems.

Am J Surg, 1996 Apr, 171(4), 391 - 3
Do topical antibiotics provide improved prophylaxis against bacterial growth in the presence of polypropylene mesh?
Troy MG, Dong QS, Dobrin PB, Hecht D.
BACKGROUND: Herniorrhaphies using a foreign body such as mesh can become infected . An experiment was performed in rabbits to compare three methods of antibiotic treatment to prevent the growth of bacteria in mesh-containing wounds . METHODS: This experiment compared preoperative intravenous antibiotics (cefazolin), topical antibiotics applied intraoperatively (bacitracin), and their combination in preventing the quantitative growth of bacteria in a subcutaneous wound containing a polypropylene mesh inoculated with Staphylococcus aureus . The bacteria were inoculated in doses sufficient to deliberately cause the growth of 130.0 +/- 56.4 x 10(4) bacteria per gram of tissue in saline-treated control animals . Quantitative cultures of the mesh and surrounding tissues were obtained 5 days after insertion of the mesh and inoculation of the wound . RESULTS: Experimental data showed that treatment with systemic intravenous antibiotics, topical powdered antibiotics, or their combination all statistically significantly decreased the quantitative cultures grown from the inoculated tissues as compared with saline-treated controls (P<0.05) . However, there were no statistically significant differences in quantitative growth among the three methods of antibiotic treatment . CONCLUSIONS: Antibiotics reduced the quantitative growth of bacteria in tissues excised from wounds inoculated with bacteria . However, preoperative intravenous antibiotics, topical powdered antibiotics, and their combination all were equally effective.

J Infect Dis, 1996 Apr, 173(4), 914 - 9
Delta APACHE II for predicting course and outcome of nosocomial Staphylococcus aureus bacteremia and its relation to host defense; Yzerman EP et al.; To predict at an early phase the clinical course and outcome of nosocomial Staphylococcus aureus bacteremia, the APACHE II score at onset of bacteremia was calculated in 99 patients . A delta APACHE II score (i.e., the difference between this score and one calculated for the day before the bacteremia) was also determined . This delta APACHE II score was highly significantly correlated with clinical course (P<.001) and outcome (P<.001) . The risk of a complicated clinical course and of dying from S . aureus bacteremia is determined at the very onset of bacteremia, and this risk can best be assessed by calculating the delta APACHE II score . Furthermore, a positive correlation was found between delta APACHE II scores and the level of serum opsonic activity (P=.003) toward S . aureus . Therefore, the complicated clinical course of S . aureus bacteremia is not due to a relative lack of specific opsonins.

Int J Cancer, 1996 Mar 28, 66(1), 98 - 103
Tolerance to the anti-metastatic effect of lipopolysaccharide against liver metastasis in mice; Sato K et al.; We describe the involvement of endotoxin tolerance in the refractoriness of its anti-metastatic effect against murine syngeneic tumors . Three i.v . administrations of LPS at intervals of 4 days after tumor inoculation inhibited liver metastasis of L5178Y-ML25 cells, whereas 3 consecutive i.v . administrations of LPS showed only a slight suppressive effect . Multiple i.v . administrations of LPS, synthetic lipid A, its synthetic derivative DT-5461, Staphylococcus aureus (S . aureus) BioParticles or Staphylococcal enterotoxin B (SEB) on days 1, 5 and 9 after tumor inoculation inhibited liver metastasis of T-lymphoma cells in normal mice . The anti-metastatic effects of LPS, synthetic lipid A or DT-5461 but not S . aureus BioParticles or SEB were diminished in mice injected with LPS at daily intervals for 7 days before tumor inoculation . Mice receiving 3 consecutive i.v . administrations of LPS at daily intervals exhibited suppression of LPS-induced production of endogenous tumor necrosis factor-alpha (TNF-alpha), tumoricidal activity of macrophages, and natural-killer (NK) activity of splenocytes when compared with those of normal mice . Macrophages from mice receiving consecutive daily i.v . administrations of LPS for 3 days showed reduction of LPS-induced tyrosine phosphorylation of several intracellular proteins, including p42(mapk) /ERK2 when compared with that of the cells obtained from normal mice . These data suggest that the LPS-induced anergic state of monocytes/macrophages plays a crucial role in endotoxin tolerance with respect to the metastasis of T lymphoma in the liver.

Biochem Biophys Res Commun, 1996 Mar 27, 220(3), 664 - 9
Production in Escherichia of moricin, a novel type antibacterial peptide from the silkworm, Bombyx mori; Hara S et al.; Moricin is a novel type antibacterial peptide recently isolated from the silkworm, Bombyx mori . Two foreign gene expression systems in Escherichia coli were employed to obtain a large amount of the peptide for further characterization . An artificial moricin gene was chemically synthesized and inserted into two expression vectors, pXa1 and pMAL-c2 . The recombinant moricin was efficiently produced in E . coli as fusion proteins and released by chemical cleavage with cyanogen bromide or o-iodosobenzoic acid . Eleven milligrams of pure recombinant moricin was obtained from 2 L of E . coli culture . The primary structure and molecular mass of the purified recombinant moricin was the same as those of the natural moricin . In addition, the antibacterial activity of the recombinant moricin against E . coli and Staphylococcus aureus was comparable to that of the natural moricin.

Biochem Biophys Res Commun, 1996 Mar 27, 220(3), 569 - 74
Phagocytosis by rat liver: relationships between phagosomes and lysosomes; Wattiaux R et al.; To study the transfer of phagocytosed components from phagosomes to lysosomes, we have investigated phagocytosis by rat liver of killed Staphylococcus aureus labelled with (125)I tyramine cellobiose . Lysosomes were identified by injecting the animals with Triton WR1339, a non ionic detergent that is endocytosed by the liver and accumulates in lysosomes, causing a marked decrease of their density; that allows these organelles to be well separated from other particles in a density gradient . Bacteria were quickly taken up by the liver; their uptake is followed by a slow degradation as ascertained by the increase of acid-soluble radioactivity in the homogenates with time . Triton WR1339 injection does not affect the uptake and the degradation of the particles . Differential centrifugation of homogenates shows that at any time after injection, most of the radioactivity is recovered in the mitochondrial fractions . Distributions of acid precipitable and acid soluble radioactivities amongst subcellular structures present in mitochondrial fractions were studied by isopycnic centrifugation in sucrose gradients, at increasing times after bacteria injection . Results show that: 1) acid-precipitable radioactivity is quasi-exclusively present in gradient fractions of high density, well separated from the fractions where there are recovered lysosomes; 2) with time, acid-soluble radioactivity is more and more associated with lysosomes, however, a significant proportion can be detected for many hours after injection, in gradient fractions where acid-precipitable radioactivity is located . The most plausible explanation of our observations is that phagocytosed particles are degraded in phagosomes and that the degradation products are delivered to lysosomes, probably by a vesicular process.

Med Clin (Barc), 1996 Mar 23, 106(11), 401 - 4
{Infection of sternal wound in heart surgery: analysis of 1000 operations}; Cobo J et al.; BACKGROUND: Sternal wound infection (SWI) is the most important complication in cardiac surgery . The aim of this study was to describe the frequency and clinical and microbiological features of this complication . METHODS: All the cases of SWI which were observed in the authors' hospital in the first 1,000 cardiac surgery operations performed with extracorporeal circulation were retrospectively reviewed . The cases were identified through the Infectious Diseases and Cardiac Surgery Department files and were classified according to the depth of the infection . During the study period neither the prophylaxis against infection nor the surgical techniques were modified . RESULTS: Forty-three patients (4.3%) presented SWI . Fourteen were superficial infections and 29 were deep infections of which 9 were classified as osteomyelitis and 20 as mediastinitis . A progressive decrease was observed in the proportion of SWI over time parallel to an increase in the number of operations performed . Staphylococcus aureus was the agent most frequently isolated (60.4%) . Gram-positive aerobic cocci were found in 66.7% of the total number of isolations, being most frequent in the deep infections (83.3% of the isolations) . The gram-negative aerobic bacilli were isolated more frequently in the superficial infections than in the deep infections (57.8% v.s . 16.7% of the isolations, respectively p < 0.01) . In patients with SWI the predictive value of the positive blood cultures for the diagnosis of mediastinitis was 83.3%, with a sensitivity of 50% and specificity of 91.3% . Three patients with deep infection developed chronic complications and another three died (mortality by mediastinitis 15.0%) . The mean postoperative stay was 52 days for the patients with deep infection and 39 days for those with superficial infection (p = NS) . CONCLUSIONS: The percentage of surgical wound infection during the study period showed a trend to a decrease parallel with an increase in the number of operations . The gram-positive bacteria were responsible for most of the SWI . Although the depth of SWI is difficult to clinically predict, the presence of bacteremia suggests the existence of mediastinitis . Despite their lesser clinical importance, the superficial infections carry a long postoperative stay.

Cell Immunol, 1996 Mar 15, 168(2), 133 - 40
Interleukin-12 stimulates B cell growth by inducing IFN-gamma; Li L et al.; Human interleukin-12 (IL-12) is a 70-kDa polypeptide that activates human natural killer cells . It has been purified from the culture supernatant of a human Epstein-Barr virus-transformed B cell line and cloned . We show that native as well as recombinant IL-12 promoted growth of Staphylococcus aureus Cowan I strain (SAC) or anti-mu antibody-activated B cells in a dose-dependent manner . IL-12 also acted in synergy with IL-2 in growth and differentiation of SAC-activated B cells . Since anti-interferon (IFN)-gamma antibody completely abrogates B-cell growth factor (BCGF) activity of IL-12, the BCGF activity is mediated by IFN-gamma . This conclusion is clearly supported by the results that IL-12 indeed induced IFN-gamma production by activated B cells . These results suggest that the B cell proliferative effect of IL-12 may be mediated by autocrine IFN-gamma.

Cell Immunol, 1996 Mar 15, 168(2), 125 - 32
Inhibition of neutrophil function by human milk; Grazioso CF et al.; Human colostrum, the first product of lactation, has antioxidant properties and inhibits selected enzyme and bactericidal activities of human neutrophils . We examined the subsequent product of lactation, mature human milk, with respect to its antioxidant activities, its effects on neutrophil enzyme activities (myeloperoxidase, beta-glucuronidase, and lysozyme), and its effects on neutrophil bactericidal and phagocytic activities . Mature human milk displayed antioxidant characteristics similar to those of human colostrum, reducing cytochrome c and consuming H2O2 . Mature milk also displayed colostrum-like characteristics in depressing neutrophil myeloperoxidase and beta-glucuronidase activities, but not in altering lysozyme activity . Neutrophil bactericidal activity against Staphylococcus aureus was depressed by both mature milk and colostrum, without dramatic effects on phagocytic activity . These data show that mature milk shares characteristics with human colostrum that may result in anti-inflammatory effects, but the magnitude of these effects is generally smaller.

Ann Intern Med, 1996 Mar 15, 124(6), 539 - 47
A cloud adult: the Staphylococcus aureus-virus interaction revisited; Sheretz RJ et al.; BACKGROUND: Nasal carriage of Staphylococcus aureus is common among health care workers, but outbreaks caused by such carriers are relatively uncommon . We previously reported outbreaks of S . aureus skin infections that affected newborn infants and were attributed to an S . aureus nasal carrier who had had an associated upper respiratory tract infection (UR) during the outbreak period . OBJECTIVE: To investigate the contribution of a nasal methicillin-resistant S . aureus (MRSA) carrier (physician 4) who contracted a URI to an outbreak of MRSA infections that involved 8 of 43 patients in a surgical intensive care unit during a 3-week period . DESIGN: An epidemiologic study of an outbreak of MRSA infections and a quantitative investigation of airborne dispersal of S . aureus associated with an experimentally induced rhinoviral infection . SETTING: A university hospital . PARTICIPANTS: 43 patients in a surgical intensive care unit and 1 physician . MEASUREMENTS: Molecular typing was done, and risk factors for MRSA colonization were analyzed . Agar settle plates and volumeric air cultures were used to evaluate the airborne dispersal of S . aureus by physician 4 before and after a rhinoviral infection and with or without a surgical mask . RESULTS: A search for nasal carriers of MRSA identified a single physician (physician 4); molecular typing showed that the MRSA strain from physician 4 and those from the patients were identical . Multivariate logistic regression analysis identified exposure to physician 4 and duration of ventilation as independent risk factors for colonization with MRSA (P < or = 0.008) . Air cultures showed that physician 4 dispersed little S . aureus in the absence of a URI . After experimental induction of a rhinovirus URI, physician 4's airborne dispersal of S . aureus without a surgical mask increased 40- fold; dispersal was significantly reduced when physician 4 wore a mask (P < or = 0.015) . CONCLUSIONS: Physician 4 became a "cloud adult," analogous to the "cloud babies" described by Eichenwald and coworkers who shed S . aureus into the air in association with viral URIs . Airborne dispersal of S . aureus in association with a URI may be an important mechanism of transmission of S . aureus.

Presse Med, 1996 Mar 2-9, 25(8), 353 - 9
{Bacterial meningitis in adults in the intensive care unit . Clinical analysis and study of prognostic factors}; Milhaud D et al.; OBJECTIVES: Bacterial meningitis frequently leads to hospitalization in the intensive care unit . Despite progress in antibiotics, prognosis remains poor . METHODS: We analyzed the clinical manifestations and complications which occurred in 41 patients admitted to the intensive care unit for bacterial meningitis . A case-control survey was used to determine prognosis factors . RESULTS: All patients required ventilatory assistance and 83% were in a state of coma at admission . Causal germs isolated were: Pneumococci 34%, Listeria 22%, Staphylococcus aureus 17%, and Gram-positive bacilli 12% . Overall mortality was 56% . The main prognosis factors after univariate analysis were age, delay to treatment, presence of septic shock, bacteriemia at admission, low cell count in first lumbar tap, high urea level and low protein level . After multivariate analysis, the following risk factors were retained: low number of leukocytes at first lumbar tap and high urea level . CONCLUSION: The gravity of bacterial meningitis in the intensive care unit appears to be related to the patient's overwhelmed defense system and especially to hemodynamic disorders with acute renal failure and capillary hyperpermeability leading to insufficient cerebral perfusion.

J Antimicrob Chemother, 1996 Mar, 37(3), 545 - 53
Pharmacokinetics of a single dose of teicoplanin in burn patients; Steer JA et al.; Patients with severe burns are susceptible to infection with Gram-positive organisms including methicillin-resistant Staphylococcus aureus, and often require higher antibiotic dosages compared with other patients . This study examined the pharmacokinetics of a single iv dose of teicoplanin (12 mg/kg) in 15 adults and five children with severe burns . Adults were aged 21-82 years with a median total body surface area (TBSA) burn of 30% (range 15-60%) . Children were aged 10 months-l0 years with median TBSA burn of 15% (10-30%) . At 12 h, the median serum teicoplanin concentration was 12.8 mg/L (9.027.1 mg/L) in adults and 7.6 mg/L (6.6-l0.8 mg/L) in children, (P < 0.01); at 24 h, the corresponding values were 8.3 mg/L (4.6-l2.9 mg/L) and 5.2 mg/L (4.2-6.0 mg/L) . Using a three-compartment model, the median terminal half life in adults was 114 h (47-278 h) . Children fitted a two-compartment model with a terminal half-life of 38 h (2l-41 h) . The median concentration of teicoplanin in fluid from the burn wound was 60% of the serum antibiotic concentration . A single iv dose of 12 mg/kg of teicoplanin was sufficient to produce therapeutic serum concentrations in burn patients for 24 h, but monitoring of antibiotic levels in serum may be advisable in those with high total clearance, especially children.

Jpn J Antibiot, 1996 Mar, 49(3), 264 - 72
{In vitro and in vivo antibacterial activities of a new quinolone derivative, FD501}; Imamori K et al.; FD501 is a newly synthesized quinolone derivative with aminoazepine group at the C-7 position . The in vitro and in vivo antibacterial activities of FD501 were investigated comparing with those of norfloxacin, ofloxacin, ciprofloxacin and sparfloxacin . The in vitro antibacterial activities of FD501 against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus, were equal to or higher than those of other quinolones . But its activities against Gram-negative bacteria were equal to or lower than those of other quinolones . Minimum inhibitory concentrations of FD501 against Gram-positive bacteria were similar to that of sparfloxacin . The bactericidal activity may be due to the inhibition of the DNA super-coiling activity of DNA gyrase . The area under the serum concentration-time curve of FD501 in rats following oral administration was larger than norfloxacin and ciprofloxacin and smaller than those of ofloxacin and sparfloxacin.

Eur J Pediatr, 1996 Mar, 155(3), 194 - 9
Demonstration of mother-to-infant transmission of Staphylococcus aureus by pulsed-field gel electrophoresis; Mitsuda T et al.; We assessed mother-to-infant transmission of Staphylococcus aureus . Anterior nares swabs of 466 pregnant women, vaginal swabs of 305 of these women and anterior nares swabs of 305 6-day-old infants were examined for the presence of S . aureus . The results showed that 7.5% of the vaginal swabs from the pregnant women and 10.1% of the anterior nares swabs from the infants were positive for S . aureus . Six of the 466 pregnant women (1.3%) and 12 of the 305 infants (3.9%) carried methicillin-resistant S . aureus (MRSA) in the anterior nares site, but none of the vaginal specimens were positive for MRSA . Analysis of SmaI digested chromosomal DNA analysis using pulsed-field gel electrophoresis (PFGE) showed that methicillin-sensitive S . aureus (MSSA) strains obtained from four pairs of pregnant women and their infants were completely identical, which strongly suggests {correction of suggesting} mother-to-infant transmission of S . aureus . CONCLUSION: This study elucidated the prevalence of S . aureus carriage among pregnant women and newborn infants . Mother-to-infant infection of S . aureus was demonstrated phenotypically and genetically . PFGE is a useful tool to detect infection routes including mother-to-infant infection.

Biol Pharm Bull, 1996 Mar, 19(3), 459 - 65
Synergistic effect of polyoxotungstates in combination with beta-lactam antibiotics on antibacterial activity against methicillin-resistant Staphylococcus aureus; Yamase T et al.; The in vitro antibacterial effect of the combination of various polyoxometalates with beta-lactam antibiotics on methicillin-resistant Staphylococcus aureus (MRSA) strains is investigated by the use of both the National Committee for Clinical Laboratory Standards (NCCLS) disk method and the agar dilution method . Keggin-structural polyoxotungstates such as K7{PTi2W10O40}.6H2O (5) and K7{BVW11O40}.7H2O (8) and their lacunary species formulated by {XW11O39}n- and{XW9O34}n- potentiated the antibacterial activity of beta-lactam antibiotics such as oxacillin, piperacillin and cefazolin on MRSA with high selectivity . The depression of bacterial growth with the coexistence of polyoxotungstates and oxacillin was confirmed by the measurement of the bacterial turbidity at 660nm . Polyoxomolybdates and polyoxovanadates, on the other hand, exhibited hardly any synergistic effect in combination with oxacillin . The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of the membrane proteins separated from MRSA revealed that polyoxotungstates depressed the formation of penicillin-binding protein 2'(PBP2'), an enzyme which is essential for cell wall construction in the MRSA growth . It is concluded that polyoxotungstates make the MRSA strains susceptible to beta-lactam antibiotics.

Br J Pharmacol, 1996 Mar, 117(6), 1163 - 70
Analysis of the signal transduction in the induction of nitric oxide synthase by lipoteichoic acid in macrophages; Kengatharan M et al.; 1 . This study investigates the signal transduction mechanisms leading to the enhanced formation of nitric oxide (NO) due to the induction of NO synthase (iNOS) in murine J774.2 macrophages in culture activated with lipoteichoic acid (LTA), a cell wall component of the gram-positive bacterium Staphylococcus aureus . 2 . LTA (10 microgram ml-1) caused within 24 h an enhanced accumulation of nitrite (an indicator of NO biosynthesis) in the supernatant of J774.2 macrophages which was prevented by the non-selective NOS inhibitor NG-monomethyl-L-arginine (L-NMMA; IC50: 35 microM) or by the iNOS-selective NOS inhibitor, aminoethyl-isothiourea (AE-ITU; IC50: 6 microM) . The inhibition of nitrite formation afforded by these agents was prevented by excess L-arginine (3-30 mM), but not by D-arginine (3-30 mM) . Furthermore, the degree of iNOS inhibition was similar when these NOS inhibitors were added to the macrophages 10 h after LTA . 3 . Pretreatment of J774.2 macrophages with cyclohexamide or dexamethasone prevented the enhanced formation of nitrite caused by LTA . This inhibition did not occur when dexamethasone or cyclohexamide were added to the cells 10 h after LTA . The increase in nitrite formation stimulated by LTA (10 micrograms ml-1) was not affected by polymyxin B (0.05-0.5 microgram ml-1), an agent which binds and inactivates endotoxin . 4 . A specific inhibitor of phosphatidylcholine-phospholipase C (PC-PLC), D609, prevented the increase in nitrite formation (IC50 = 20 micrograms ml-1) caused by LTA . The inhibition afforded by D609 was significantly smaller when this agent was added to the cells 10 h after LTA . 5 . The structurally distinct tyrosine kinase inhibitors, erbstatin, genistein, and tyrphostin AG126 prevented the formation of nitrite caused by LTA . The inhibition afforded by these compounds was significantly attenuated when they were added to the cells 10 h after LTA . In contrast, daidzein or tyrphostin A-1, which are inactive analogues of genistein and tyrphostin (up to a concentration of 10 microM) did not affect the nitrite formation caused by LTA . 6 . Inhibitors of the activation of the nuclear transcription factor NF-kappa B such as pyrrolidine dithiocarbamate (PDTC; an antioxidant and a metal chelator), butylated hydroxyanisole (BHA; an antioxidant), L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK), calpain inhibitor I (both I kappa B-protease inhibitors), or rotenone (an antioxidant which inhibits electron transport) prevented the nitrite formation stimulated by LTA . The inhibition afforded by these agents was significantly smaller when they were added to the macrophages 10 h after LTA . 7 . Incubation of J774.2 cells with LTA over 24 h resulted in the expression of iNOS protein (130 kDa) as identified by Western blot analysis . The expression of iNOS protein by LTA was significantly attenuated by cyclohexamide, D609, tyrphostin AG126, PDTC or by TPCK . 8 . Thus, the signal transduction leading to the expression of iNOS protein and activity caused by LTA in murine J774.2 macrophages involves (i) the activation of PC-PLC, (ii) phosphorylation of tyrosine kinase, and (iii) the activation of the transcription factor NF-kappa B.

J Physiol, 1996 Mar 1, 491 ( Pt 2), 447 - 53
Phospholipase A2 and protein kinase C contribute to myofilament sensitization to 5-HT in the rabbit mesenteric artery; Parsons SJ et al.; 1 . Calcium (Ca2+, 0.1-100 microM) stimulated concentration-dependent contractions in small strips from the rabbit mesenteric artery in which the smooth muscle cells had been permeabilized with Staphylococcus aureus alpha-toxin . 2 . 5-Hydroxytryptamine (5-HT) and phenylephrine, each in the presence of 10 microM guanosine 5'-triphosphate (GTP), concentration-dependently stimulated additional contractions in strips sub-maximally contracted by the presence of a buffered concentration of calcium (0.3 microM) . All the additional contraction was abolished with the selective inhibitor of protein kinase C, Ro 31-8220 (10 microM) . 3 . Quinacrine (10-50 microM), an inhibitor of phospholipase A2, selectively inhibited the sensitization to 5-HT, but did not alter the sensitization to either phenylephrine or GTP . 4 . Myofilament sensitization to calcium was mimicked by exogenous arachidonic acid (300 microM, in the presence of indomethacin, miconazole and BW755c) and the stable analogue of arachidonic acid, 5,8,11,14-eicosatetrayonic acid (ETYA, 100 microM), and in both cases did not require the additional presence of GTP . Ro 31-8220, but not quinacrine, reduced the sensitization to arachidonic acid by around 30% . 5 . These results indicate that G protein-linked myofilament sensitization to calcium in the mesenteric artery that follows the activation of 5-HT receptors, but not alpha 1-receptors, involves phospholipase A2 . The sensitization stimulated by each of these different receptors, and a component of the response to arachidonic acid, also appears to involve the activation of protein kinase C.

Chemotherapy, 1996 Mar, 42 Suppl 1, 33 - 42
Quinolones in everyday clinical practice: respiratory tract infections and nosocomial pneumonia; Marklein G; Currently available fluoroquinolones have established their value in the treatment of lower respiratory tract infections due to gram-negative rods and Staphylococcus aureus . The fact that these drugs are absorbed (and well tolerated) when given orally is a major positive feature . The once daily dosage of fleroxacin {400 mg once daily intravenously (i.v.) for 2-4 days followed by oral doses of 400 mg for up to 10 days} was compared with twice daily ciprofloxacin (400 mg twice daily i.v . for 2-4 days followed by oral doses of 2 x 500 mg for up to 10 days) for treatment of inpatients with pneumonia confirmed by clinical signs and chest X ray . To date, 93 evaluable patients have been enrolled in this study . Clinical cure and improvement rates were 73.3% in the fleroxacin group and 79.2% in the ciprofloxacin group . The rate of adverse clinical or laboratory events was similar in both study groups.

Lett Appl Microbiol, 1996 Mar, 22(3), 192 - 4
Antibiotic sensitivity of Staphylococcus aureus and Staph . intermedius of canine and feline origin; Hoekstra KA et al.; Disc agar diffusion testing was performed on 547 isolates (two common pathogens) to determine if the site of isolation influenced the antimicrobial susceptibility results for a given bacterium . The most statistically significant results (P < 0.05) included cephalothin (ear) against Staphylococcus aureus and cephalothin (ear), lincomycin (ear), trimethoprim sulpha (ear), and amoxycilin and clavulanic acid (nose) against Staph . intermedius . Although the impact of these results (empirical treatment) is unknown, it is hypothesized that the site of isolation of Staph . aureus and Staph . intermedius may influence the choice of antimicrobial therapy in the dog and cat.

J Intraven Nurs, 1996 Mar-Apr, 19(2), 99 - 101
Medicare reimbursement for home infusion therapy: a contributor to the development of community acquired vancomycin-resistant enterococci?
Herbert JR.
Vancomycin is a bacteriocidal antibiotic widely used to treat gram-positive infections, including methicillin-resistant Staphylococcus aureus . During the past 5 years, there have been increasingly frequent reports of infections caused by enterococci species resistant to vancomycin . Until recently, this was a phenomenon limited almost exclusively to the hospital . Presently, there are reports of vancomycin-resistant enterococci developing in the outpatient and home care population . The intent of this article is to present one possible explanation for this trend in the hope that further research will be stimulated.

No Shinkei Geka, 1996 Mar, 24(3), 241 - 5
{Prevention of MRSA spread in the neurosurgical field}; Fujii M et al.; We investigated the distribution of MRSA (methicillin-resistant Staphylococcus aureus) on and around six patients with MRSA infection in our neurosurgical ward . All patients had a disturbance of consciousness and had sputum colonization of MRSA . Samples were obtained from 11 sites (patients' hands, attendances' hands, floors, sidetables, bedclothes, chairs, walls, curtains, door knobs, faucets and disposable gloves) in the patients' rooms by the wiping method . High counts of MRSA were detected on horizontal planes such as floors, sidetables and chairs, but MRSA was not detected on vertical planes such as curtains and walls . The reason why MRSA was detected on the horizontal planes was due to a fall of MRSA spread from sputum in the air . These findings indicate that the disinfection of horizontal planes is important for preventing the spread of MRSA . We also evaluated what disinfectant was useful for floor disinfection and concluded that 0.5% chlorhexidine digluconate (Hibitane) and 0.5% benzalkonium chloride (Osvan) were more effective than the other usually-used disinfectants such as alkyldiaminoethyl glycine (Tego-51).

Antimicrob Agents Chemother, 1996 Mar, 40(3), 812 - 5
Penetration of ceftriaxone (1 or 2 grams intravenously) into mediastinal and cardiac tissues in humans; Martin C et al.; Penetration of ceftriaxone into heart tissues (valves, myocardium, auricles, and pericardium) and mediastinal tissues (fat and sternal bone) was evaluated after two regimens of ceftriaxone administration . Ten patients (group 1) were given 1,000 mg of ceftriaxone intravenously 30 min before anesthesia . Ten other patients (group 2) received the same dose and then a second 1,000-mg dose at the time of initiation of cardiopulmonary bypass . Similar and very satisfactory penetrations of ceftriaxone into tissue were observed for both groups . During opening and closure of the thorax, mean ceftriaxone concentration was in excess of the MIC at which 90% of the potential pathogens were inhibited (> or = 4 micrograms/g) in the thoracic fat, the sternal bone, and the pericardium . No significant differences between the two administration regimens in penetration of ceftriaxone into tissue were observed . During cardiopulmonary bypass, the ceftriaxone concentration was > or = 4 micrograms/g in the myocardium, the endocardium, and the auricle . The regimen of ceftriaxone administration did not significantly influence penetration of the drug into heart tissues . However, for some patients in the two groups and mainly in the sternal bone at the time of thorax closure (6 patients in group 1 and 5 patients in group 2), ceftriaxone levels in tissues were less than the MICs (4 micrograms/g) for some potential pathogens (methicillin-susceptible Staphylococcus aureus and methicillin-susceptible Staphylococcus epidermidis) . During the different steps of the surgical procedures, all (10 of 10) patients in each group had tissue ceftriaxone levels greater than the MICs for gram-negative aerobic bacilli (0.1 microgram/g), except for Pseudomonas spp.

Antimicrob Agents Chemother, 1996 Mar, 40(3), 799 - 801
In vitro activities of oxazolidinone compounds U100592 and U100766 against Staphylococcus aureus and Staphylococcus epidermidis; Kaatz GW et al.; The new oxazolidinone antimicrobial agents U100592 and U100766 demonstrated good in vitro inhibitory activity against clinical strains of Staphylococcus aureus and Staphylococcus epidermidis regardless of methicillin susceptibility . Both agents appeared bacteriostatic by time-kill analysis . Stable resistance to low multiples of the MIC of either drug could be produced only in methicillin-resistant S . aureus.

Antimicrob Agents Chemother, 1996 Mar, 40(3), 795 - 8
Pharmacokinetics in nonhuman primates of a prototype carbapenem active against methicillin-resistant Staphylococcus aureus; Sundelof JG et al.; Pharmacokinetic parameters were determined for imipenem-cilastatin and a carbapenem antibiotic, L-695,256, active against methicillin-resistant Staphylococcus aureus in rhesus monkeys and a chimpanzee . L-695,256 had larger areas under the concentration-time curve than imipenem-cilastatin (30 +/- 5 versus 24 +/- 1 micrograms.h/ml in the rhesus monkeys and 77 versus 60 micrograms.h/ml in the chimpanzee) and a longer half-life at beta phase (1.2 +/- 0.1 versus 0.6 +/- 0.1 h in the rhesus monkeys and 1.0 versus 0.8 h in the chimpanzee) . Resistance to hydrolysis by the renal dehydropeptidase-I allowed L-695,256 to be administered as a single agent.

Antimicrob Agents Chemother, 1996 Mar, 40(3), 701 - 5
Pharmacodynamics of once- or twice-daily levofloxacin versus vancomycin, with or without rifampin, against Staphylococcus aureus in an in vitro model with infected platelet-fibrin clots; Palmer SM et al.; We compared the pharmacodynamic activities of levofloxacin versus vancomycin, with or without rifampin, in an in vitro model with infected platelet-fibrin clots simulating vegetations . Infected platelet-fibrin clots were prepared with human cryoprecipitate, human platelets, calcium, thrombin, and approximately 10(9) CFU of organisms (MSSA 1199 and MRSA 494) per g and then were suspended via monofilament line into the in vitro model containing Mueller-Hinton growth medium . Antibiotics were administered by bolus injection into the model to simulate human pharmacokinetics; the regimens simulated included levofloxacin at dosages of 800 mg every 24 h (q24h) and 400 mg q12h, vancomycin at 1 g q12h, and rifampin at 600 mg q24h . Each model was run in duplicate over a 72-h period . Infected platelet-fibrin clots were removed in duplicate from each model, weighed, homogenized, serially diluted with sterile 0.9% saline, and plated on tryptic soy agar plates and plates containing antibiotics at 3, 6, and 12 times the MIC to evaluate the emergence of resistance . Time-kill curves were constructed by plotting the inoculum size versus time . Residual inoculum at 72 h was used to compare regimens . All levofloxacin regimens were significantly better than vancomycin monotherapy against both isolates (P < 0.002) . Against MSSA 1199, levofloxacin q24h was significantly better than all other regimens, including levofloxacin q12h (P < 0.002); however, no difference between the levofloxacin monotherapy and combination therapy (with rifampin) regimens against MRSA 494 was seen . Killing activity for levofloxacin appeared to correlate better with the peak/MIC ratio than with the area under the curve/MIC ratio . The addition of rifampin significantly enhanced the activity of vancomycin but had little effect upon the activity of levofloxacin . For MRSA 494, vancomycin plus rifampin resulted in the greatest killing (P < 0.05) . Development of resistance was not detected with any regimen . Levofloxacin may be a useful therapeutic alternative in the treatment of staphylococcal endocarditis, and further study with animal models of endocarditis or clinical trials are warranted.

Antimicrob Agents Chemother, 1996 Mar, 40(3), 696 - 700
Comparison of conventional dosing versus continuous-infusion vancomycin therapy for patients with suspected or documented gram-positive infections; James JK et al.; Ten patients were treated with conventional dosing (CD) and continuous-infusion (CI) vancomycin therapy in this prospective, randomized, crossover study . Patients were randomized to receive either CD or CI therapy for 2 consecutive days and then crossed over to receive the opposite regimen for 2 days . CD therapy consisted of 1 g of vancomycin every 12 h . CI therapy consisted of a 500-mg loading dose followed by 2 g infused over 24 h . Ten serum samples were obtained on the second day of each therapy for pharmacokinetic and pharmacodynamic analyses . Two clinical isolates of Staphylococcus aureus, one methicillin sensitive (MSSA 1199) and one methicillin resistant (MRSA 494), were chosen for pharmacodynamic evaluation of both regimens . The patient demographics (means +/- standard deviations {SD}) were as follows: sex, six males, four females; age, 36 +/- 11 years; and serum creatinine, 0.72 +/- 0.18 mg/dl . Mean pharmacokinetic parameters +/- SD for CD therapy were as follows: elimination rate constant, 0.16 +/- 0.07 h-1; half-life, 5.6 +/- 3.5 h; volume of distribution, 33.7 +/- 25 liters, 0.5 +/- 0.2 liters/kg; maximum concentration in serum, 53.4 +/- 19.3 micrograms/ml; and minimum concentration, 8.4 +/- 5.9 micrograms/ml . The steady-state concentration for CI was 20.2 +/- 11.1 micrograms/ml . Overall, both regimens resulted in the MIC being exceeded 100% of the time . The mean CD trough serum bactericidal titer (SBT) was 1:8, and the average CI SBTs were 1:16 for both isolates . Even though there was no statistically significant difference between CD trough and CI SBTs, the CI SBTs remained > 1:8 for 100% of the time versus 60% of the time for CD therapy . During CI therapy, 20 and 40% of the patients maintained SBTs of > 1:32 throughout the dosing interval for MSSA 1199 and MRSA 494, respectively . During CD therapy, however, only 10% of patients maintained SBTs of > 1:32 during the entire dosing interval for both isolates . The mean areas under the bactericidal titer-time curve (AUBC24s) +/- SD for MSSA 1199 were 528 +/- 263 for CD therapy and 547 +/- 390 for CI therapy . The mean AUBC24s +/- SD against MRSA 494 were 531 +/- 247 for CD and 548 +/- 293 for CI therapy . Similar to the AUBC24, the mean area under the concentration-time curve for a 24-h dosing interval divided by the MIC (AUC/MIC24) ratios +/- SD were 550.0 +/- 265.7 for CD and 552.6 +/- 373.4 for CI therapy, respectively . No statistically significant differences were found between any of the pharmacodynamic parameters for CD and CI therapy . In addition, no adverse effects with either CD or CI therapy were observed during the study . We conclude that CI and CD vancomycin therapy demonstrated equivalent pharmacodynamic activities . Although CI therapy was more likely to result in SBTs that remained above 1:8 for the entire regimen, the clinical impact of this result is unknown . Serum drug concentration variability was observed with both treatment regimens but to a lesser extent with CI administration . CI administration of vancomycin should be further evaluated to determine the clinical utility of this method of administration.

J Am Soc Echocardiogr, 1996 Mar-Apr, 9(2), 206 - 8
Transesophageal echocardiographic diagnosis of eustachian valve endocarditis; Georgeson R et al.; A 33-year-old man with a history of intravenous drug abuse was seen with fever, septic pulmonary embolization, and Staphylococcus aureus bacteremia . Transthoracic echocardiography was nondiagnostic . Transesophageal echocardiography showed a large, pedunculated, and highly mobile vegetation attached to the eustachian valve.

Ann Acad Med Singapore, 1996 Mar, 25(2), 270 - 2
Vancomycin-resistant Enterococcus in the Singapore National Burns Centre: a case report; Ang SW et al.; Vancomycin-resistant Enterococcus (VRE) is becoming an important cause of nosocomial infections . An outbreak of VRE in a burns unit, if it ever occurs, will be a catastrophe as vancomycin-resistance can potentially be transferred to other organisms like methicillin-resistant Staphylococcus aureus . We report a case of VRE in our burns centre in which it was detected and the patient isolated from other patients early . Measures to control the occurrence of VRE include the restriction of the use of vancomycin and the practice of other established infection-control measures.

Nutrition, 1996 Mar, 12(3), 195 - 9
High protein diets are associated with increased bacterial translocation in septic guinea pigs; Nelson JL et al.; During sepsis, body protein stores are decreased due to an increase in protein catabolism . The utilization of nutritional support with high-protein diets has been used as a solution to the problem of sepsis-induced protein loss . Work from our laboratory, however, has shown that diets low in protein (5% of total calories) improve survival in septic animals as compared to high protein (20%) diets . The present study investigated the relationship between low-protein diets and improved survival by determining whether septic animals receiving high-protein diets have increased bacterial translocation . Sepsis was induced in guinea pigs by the implantation of an osmotic minipump into the peritoneal cavity containing an equal mixture of Escherichia coli (10(8)) and Staphylococcus aureus (10(8)) or saline . On Day 3 postlaparotomy, the animals were randomized to one of four groups . The groups consisted of septic and nonseptic animals that received a diet with 5 or 20% of total calories as protein . Following 4 days of diet all animals received an instillation of 14C labeled E . coli (10(10)) . Four hours later the animals were sacrificed and blood, mesenteric lymph nodes, spleen, lungs, and liver were removed for determination of radionuclide counts . Results indicated that the septic animals that received the high protein diet had more bacterial translocation, as indexed by higher radionuclide counts in the MLN, liver, lung and blood . These findings suggest that a low protein, enterally fed diet may improve survival in septic patients by decreasing the incidence of bacterial translocation.

Curr Opin Nephrol Hypertens, 1996 Mar, 5(2), 122 - 6
Drugs of abuse and renal disease; Bakir AA et al.; The complications of drug abuse encompass a spectrum of glomerular, interstitial, and vascular diseases . They comprise the heroin-associated nephropathy seen in African-American intravenous drug addicts, which, however, has given way in the 1990s to HIV-associated nephropathy . Infections with methicillin-resistant Staphylococcus aureus may cause acute glomerulonephritis by releasing bacterial superantigens . Hepatitis C has supplanted hepatitis B and may give rise to membranoproliferative glomerulonephritis and cryoglobulinemia . Addicts who inject drugs subcutaneously ('skin popping') may develop amyloidosis . Cocaine causes rhabdomyolysis, severe hypertension, occasionally renal failure in the absence of rhabdomyolysis, and may hasten progression to uremia in patients with underlying renal insufficiency . 'Ecstasy', an amphetamine-like recreational drug, has caused acute renal failure, electrolyte disturbances, and malignant hypertension . In Belgium and some other European countries, women taking Chinese herbs in a slimming regimen have developed a severe and irreversible interstitial fibrosis that is assuming epidemic proportions.

J Pediatr Orthop, 1996 Mar-Apr, 16(2), 231 - 6
Chondroprotective effect of betamethasone in lapine pyogenic arthritis; Stricker SJ et al.; The chondroprotective effect of betamethasone was examined to determine if corticosteroids can decrease articular cartilage injury caused by inflammatory exudate in Staphylococcus aureus gonarthritis in rabbits . Three experimental groups of antibiotic-treated rabbits were created, comparing parenteral versus low-dose intraarticular routes of betamethasone administration . Rabbits that received ceftriaxone plus supplemental parenteral betamethasone (group 2) demonstrated significantly less articular cartilage proteoglycan loss than did rabbits treated with antibiotics alone (group 1) . Supplemental intraarticular betamethasone (group 3) was somewhat less effective in this regard, possibly reflecting the smaller steroid dosage . This animal study introduces histologic and biochemical evidence that betamethasone, administered early and in conjunction with appropriate systemic antibiotics, may help protect infected articular cartilage from proteolytic degradation . Further study is needed to prove safety and efficacy of corticosteroids before recommending their clinical use in the treatment of septic arthritis.

Blood Coagul Fibrinolysis, 1996 Mar, 7 Suppl 1, S39 - 44
Central venous access catheters in children with haemophilia; Blanchette VS et al.; Twenty-five central venous lines (two external 23 subcutaneous ports) were placed in 19 boys with haemophilia A (n = 17) or B (n = 2) . The mean age of the boys was 4.9 years (range 0.2-15.3 years) . The haemophilia was severe (factor level < 1%) in 18 boys and moderate (factor level 3%) in one . Three boys had circulating inhibitors and three were positive for human immunodeficiency virus (HIV)-1 antibody . Central venous lines were placed to facilitate intermittent factor replacement therapy (n = 6), long-term factor prophylaxis (n = 9), induction of an immune tolerance protocol (n = 2) or therapy for acquired immunodeficiency syndrome (AIDS)-related complications (n = 2) . The ports remained in place for 15795 days (mean 687 days, range 11-2059 days) . The frequency of port-related sepsis was 48% (11/23 ports in eight boys) or 0.7 port infections per 1000 patient days . Ports were removed from five boys with an unresolved infection (four with Staphylococcus aureus sepsis and one with Pseudomonas sp . sepsis) . Other complications requiring port removal included a catheter tip placed too high in the venous system (n = 1), severe persistent pain associated with needle access of the port (n = 1) and a subclavian vein thrombosis (n = 1) . Both the benefits and risks of a subcutaneous port should be considered when deciding whether to place this device in a very young child with haemophilia.

Phytochemistry, 1996 Mar, 41(4), 1017 - 22
Primary structure of a Kunitz-type trypsin inhibitor from Enterolobium contortisiliquum seeds; Batista IF et al.; A trypsin inhibitor was isolated from Enterolobium contortisiliquum seeds . Starting with a saline extract, ECTI (E . contortisiliquum trypsin inhibitor) was purified as a homogeneous protein by acetone precipitation, ion-exchange chromatography (DEAE-Sephadex A-50), gel filtration (Sephadex G-75 and Superose 12) and reversed phase HPLC (mu-Bondapak C-18) . The amino acid sequence was determined by automatic degradation and by DABITC/PITC microsequence analysis of the reduced and carboxymethylated protein and also of purified peptides derived from the protein by cleavage with iodosobenzoic acid and by enzymic digestion with trypsin, chymotrypsin and Staphylococcus aureus V8 protease . ECTI contains 174 amino acid residues in two polypeptide chains, an alpha-chain consisting of 134 residues and a beta-chain made up of 40 residues . The inhibitor displays a high degree of sequence identity with other Kunitz-type proteinase inhibitors isolated from the Mimosoideae subfamily . The reactive site was identified (by homology) as the arginine-isoleucine peptide bond at position 64-65 . ECTI inhibits trypsin and chymotrypsin in the stoichiometric ratio of 1:1 and also Factor XIIa, plasma kallikrein and plasmin, but not thrombin and Factor Xa.

Infect Control Hosp Epidemiol, 1996 Mar, 17(3), 178 - 80
Comparative killing kinetics of methicillin-resistant Staphylococcus aureus by bacitracin or mupirocin; Chapnick EK et al.; The in vitro activities of bacitracin and mupirocin were compared for seven different strains of methicillin-resistant Staphylococcus aureus . Six of seven strains showed bacitracin minimum inhibitory concentrations (MICs) of 0.5 to 1.0 units/mL, and all seven had mupirocin MICs of 0.5 to 2 micrograms/mL . Time-kill studies revealed 2.6- to 4.5-log reduction in 24 hours with strains susceptible to bacitracin (4 units/mL) and 0 to 2.2 reduction with mupirocin (16 micrograms/mL) . Bacitracin should be considered further for in vivo studies because of enhanced bacteriocidal effect and lower cost.

Infect Control Hosp Epidemiol, 1996 Mar, 17(3), 165 - 8
Staphylococcus aureus bacteremia: factors predicting hospital mortality; Mylotte JM et al.; Among 89 episodes of Staphylococcus aureus bacteremia, factors identified as independent predictors of hospital mortality were Acute Physiology and Chronic Health Evaluation III score > 60 (odds ratio {OR}, 3.2; 95% confidence interval {CI95}, 1.7 to 5.9) and Lifestyle score > 1 (OR, 2.1; CI95, 1.2 to 3.6) . Future studies of S aureus bacteremia should take into consideration acute severity of illness (as well as treatment and source of infection) when evaluating outcome.

Thromb Haemost, 1996 Mar, 75(3), 432 - 6
Feasibility of using recombinant factor VIIa in continuous infusion; Schulman S et al.; Recombinant factor VIIa (rFVIIa; NovoSeven) is a recent addition to the hemostatic alternatives for the treatment of hemophiliacs with inhibitors . A drawback in the use of rFVIIa has been its half-life of only about 2 h, which necessitates very frequent and punctual injections . We evaluated the stability of reconstituted, but not further diluted, rFVIIa in 3 infusion systems (WalkMed 350 and CADD-Plus minipumps and Meddex 2001 syringe pump) . The factor VII (F VII) activity was maintained for at least 3 days at room temperature with only a minor and clinically insignificant increase in oxidized forms of rFVIIa and minimal leaching of the plastic softeners dibutylphthalate and di-octylphthalate after 24-48 h . Addition of heparin, 5-10 U/ml, to reconstituted rFVIIa caused a loss of about 50% of the activity within 4 h of storage in the infusion system, whereas low molecular weight heparin had no such effect . Repeated samples showed that the infusion systems maintained sterility . Reconstituted rFVIIa did not support bacterial growth when inoculated with Staphylococcus aureus or Escherichia coli to any greater extent than did reconstituted factor VIII, lidocaine in saline or heparin in saline . Two patients were treated with continuous infusion of rFVIIa on 4 occasions (total knee arthroplasty, wound revision, and twice straightening of a 90 degrees contracture of the knee under general anaesthesia) . A preoperative pharmacokinetic evaluation was performed, and the clearance was used to calculate the maintenance dose, aiming at a FVII level of 10 U/ml, which proved to be a hemostatic level . The first patient had no change in the clearance during the two treatment episodes . He suffered from repeated thrombophlebitis at the infusion site . The second patient had a progressive decrease of the clearance from 86.4 to 24.7 ml/h/kg . He received during the first treatment a parallel infusion with heparin (approximately 250 U/24 h) to the same venous access and did not develop thrombophlebitis during 3.5 days of therapy . For the second episode low molecular weight heparin was added directly to the infusion bag, and no adverse effects were observed . Continuous infusion with rFVIIa is thus feasible with the minipumps used by us, eliminates the need for 2 h injections and reduces the total dose of rFVIIa by 50-75%, depending on the behaviour of the clearance.

J Biomed Mater Res, 1996 Mar, 30(3), 281 - 6
Controlled release of antibiotics from coated orthopedic implants; Price JS et al.; Chronic osteomyelitis is one of the most serious complications of orthopedic open fracture treatment . The objective of this study was to develop a biodegradable implant coating with impregnated antibiotics as an adjunct to current therapy . We used a polylactic-co-glycolic acid copolymer (PLGA) as the biodegradable carrier and gentamicin as the antibiotic . Our objectives were to establish elution characteristics of the antibiotic from the polymer, and determine if the coated orthopedic implants would inhibit bacterial growth in vitro . In the elution study, coated implants were incubated in phosphate buffered saline (PBS) at 37 degrees C and sampled daily for gentamicin levels . The in vitro model consisted of test tubes containing Mueller-Hinton culture broth inoculated with 5 x 10(6) cfu of Staphylococcus aureus and incubated at 37 degrees C . The implants were switched to a new set of inoculated tubes each day . Tubes were sampled for colony counting to determine bactericidal effects . Implant coatings consisted of 40 mg of gentamicin as a 20% mixture with PLGA . The elution curve showed an average level of 138 micrograms/mL over 15 days . This local concentration would be more than adequate to kill susceptible organisms . The in vitro study showed a significant reduction in bacterial growth in the test tubes containing coated implants . Control tubes averaged 2.5 x 10(8) cfu/mL of S.aureus over 24 days . Coated implant tubes averaged 0.9 cfu/mL . This was a reduction of greater than 99.999% (p < 0.0001) . This study showed that a thin biodegradable implant coating can be developed with bactericidal activity against the organisms frequently associated with osteomyelitis in cases of open fractures.

Chemotherapy, 1996 Mar-Apr, 42(2), 133 - 9
Sparfloxacin therapy for experimental endocarditis caused by methicillin-resistant Staphylococcus aureus; Maserati R et al.; Sparfloxacin, a new difluorinated quinolone antibiotic, was employed in the treatment of catheter-induced endocarditis in rabbits infected with a methicillin-resistant strain of Staphylococcus aureus (MRSA) . Animals (n = 12) in the study group received sparfloxacin, 25 mg/kg body weight every 12 h intravenously . Comparison groups were untreated controls (n = 9) and animals injected with vancomycin (n = 13) at the same dosage . MICs and MBCs of the test organism were both 1.56 mg/l for vancomycin and 0.15/0.30 mg/l for sparfloxacin . Antibiotic treatments started 24 h after bacterial challenge and lasted 4 days until sacrifice . In comparison with no treatment, both sparfloxacin and vancomycin significantly reduced the bacterial counts in aortic vegetations, while no significant difference was found between the two antibiotics . Combination of the two antibiotics, tried in a smaller group of rabbits (n = 3) showed no advantages over either single-drug therapy . Our results suggest that sparfloxacin is a potentially useful agent, at least in the rabbit model, for treating MRSA endocardial infections.

Chemotherapy, 1996 Mar-Apr, 42(2), 118 - 32
Immunobiology of methicillin-resistant Staphylococcus aureus: immune response of rabbits and patients to systemic infection; Traub WH et al.; Teichoic acid (TA) and peptidoglycan (PG) extracted from Staphylococcus aureus strains ATCC 25923 and Lafferty as well as formalinized cells of these two strains and several clinical methicillin-resistant S . aureus (MRSA) isolates were immunogenic for New Zealand White rabbits . Rabbits which had recovered from experimental bacteremia due to MRSA seroconverted, i.e . demonstrated raised titers of antibodies against TA and PG of the S . aureus strain Lafferty and against whole cells (WC) and ultrasound cell lysates (UCL) of MRSA isolates No . 1 and 2 (representative of nosocomial MRSA strain I), as determined with enzyme-linked immunosorbent assays . Furthermore, sera from 2 long-term survivor rabbits recognized four polypeptides (apparent molecular weight = 38.9, 33.9, 30.9, and 28.2 kDa) shared by UCL extracts from MRSA isolates No . 1 and 2, as determined with immunoblots . Neither normal nor immune rabbit sera augmented the bactericidal activity of fresh defibrinated human blood (65% v/v) against selected MRSA isolates and S . aureus strain ATCC 25923 . Sera from 12 patients with documented systemic infection due to MRSA outbreak strain I were examined for IgM and IgG antibodies against TA, WC, and UCL antigens . Three patient sera exhibited raised IgM antibodies against TA; 7 of 12 patient sera showed increased IgG anti-TA titers . Only 1 patient had a markedly raised IgM anti-WC titer, whereas 4 and 10 of the patients had increased IgG titers against WC from MRSA isolates No . 1 and 2, respectively . However, all 12 patients had raised IgG titers against UCL from MRSA isolate No.2 versus 4 of 12 patients with elevated IgG titers against UCL from MRSA isolate No.1 . Immunoblots with 3 selected patient sera revealed IgG antibodies to be more multifaceted than IgM antibodies . Sera from 11 of the 12 patients contained antimicrobial drug(s); yet only 5 of these 11 sera (used at 10% v/v in broth) killed inocula of MRSA isolate No . 43 . None of the 12 patient sera (10% v/v) enhanced the bactericidal activity of human blood against selected MRSA isolates . Neither three commercial intravenously applicable IgG preparations nor an IgG anti-alpha-hemolysin formulation (employed at 10% v/v) augmented the bactericidal activity of fresh defibrinated human blood against selected MRSA isolates comprising MRSA outbreak strain I.

J Hosp Infect, 1996 Mar, 32(3), 207 - 16
An unusual source for an outbreak of methicillin-resistant Staphylococcus aureus on an intensive therapy unit; Cotterill S et al.; During a four-month period, six patients on an intensive therapy unit became colonized or infected with methicillin-resistant Staphylococcus aureus (MRSA) . Four of these patients were colonized by the Epidemic MRSA strain 15 (EMRSA 15) . The outbreak was characterized by the fact that all four of these patients were nursed in the same bed on the unit before acquisition of the organism . Investigation of the outbreak led the authors to believe that the source of the MRSA may have been the exhaust ducting of the adjacent isolation room ventilation system which allowed the organisms to enter the unit via a partially open window positioned above that particular bed . The cycle was broken once the ventilation system was repaired and the window above the bed was properly sealed.

Bioorg Khim, 1996 Mar, 22(3), 168 - 74
{An artificial gene, biosynthesis and properties of the recombinant Fc fragment of human immunoglobulin G1}; Efimov VA et al.; Chemicoenzymatic synthesis and cloning of a gene encoding the Fc domain of human immunoglobulin G1 were carried out . The artificial gene was expressed in Escherichia coli cells in plasmid vectors under control of a late T7 promoter . The recombinant protein isolated from the bacterial cells is capable of forming dimers and binding protein A from Staphylococcus aureus.

Res Vet Sci, 1996 Mar, 60(2), 179 - 81
Detection of antibodies to Staphylococcus aureus in water buffalo milk by flow cytometry; D'Apice L et al.; An assay has been developed to detect antibodies to Staphylococcus aureus in water buffalo milk by flow cytometry . The method was the protein A-deficient strain Wood 46 of S aureus incubated with milk samples and fluorescein-labelled rabbit anti-water buffalo antiserum . The assay can detect antibodies when the pathogen is not detectable by bacterial tests and can determine the antibody titre directly on undiluted samples.

Am J Vet Res, 1996 Mar, 57(3), 308 - 12
Role of milk fractions, serum, and divalent cations in protection of mammary epithelial cells of cows against damage by Staphylococcus aureus toxins; Cifrian E et al.; OBJECTIVE--To determine the effect of milk and blood serum constituents on cytotoxicity of Staphylococcus aureus on mammary epithelial cells . DESIGN--In vitro incubation of cells with cytotoxic agents and milk and serum constituents . SAMPLE POPULATION--Mammary cells, milk, and blood obtained from 3 cows . PROCEDURE--Staphylococcal alpha-toxin and culture supernatants from S aureus M60 and an alpha-toxin-negative mutant of M60 were incubated with bovine mammary epithelial cells in the presence of milk fractions, serum, and divalent cations . Propidium iodide fluorescence was used as a measure of cell damage . RESULTS--Skim milk and milk whey inhibited S aureus cytotoxic agents . Skim milk protected against alpha-toxin damage to a greater extent than milk whey . Serum from an adult animal was more protective than was fetal serum . Milk fat and serum albumin had no protective effect . Divalent calcium and Mg2+ were more effective inhibitors of mammary epithelial cell damage caused by alpha-toxin than of damage attributable to M60 culture supernatant . Divalent calcium and Mg2+ at concentrations similar to those of free Ca2+ and Mg2+ in normal bovine milk decreased cytotoxic damage attributable to alpha-toxin . However, concentrations similar to those of total Ca2+ and Mg2+ in normal milk were required to decrease cell damage caused by M60 culture supernatant . The alpha-toxin-negative mutant was less cytotoxic than the M60 parent strain . CONCLUSIONS--Casein, as well as Ca2+ and Mg2+ in bovine milk, inhibit the cytotoxic effect of S aureus on mammary epithelial cells.

J Neuroimmunol, 1996 Mar, 65(1), 21 - 30
Regulation of human B lymphocyte activation by opioid peptide hormones . Inhibition of IgG production by opioid receptor class (mu-, kappa-, and delta-) selective agonists; Morgan EL; Opioid peptides have been reported by many laboratories to modulate in vitro and in vivo cell-mediated and humoral immune responses . However, less attention has been afforded to the class or classes of opioid receptors involved in these immunomodulatory effects . Previous studies by this laboratory indicated that beta-endorphin and methionine-enkephalin were potent inhibitors of Staphylococcus aureus, Cowen strain I (SAC)-induced IgG production by human B lymphocytes . Results obtained from the present studies indicate that, at pharmacological concentrations, mu-, delta-, and kappa-receptor-selective agonists are potent inhibitors of SAC-induced IgG-secreting cells (IgG-ISC) by human B lymphocytes . Moreover, the suppression of IgG-ISC formation was reversed by mu-, delta-, and kappa-receptor class-selective antagonists, {D'Tic}cTAP, ICI 174,864, and nor-BNI, respectively . These findings are in agreement with other studies showing that more than one class of receptors are involved in opioid peptide-mediated immunoregulation . Additional studies indicated that all three class-selective receptor agonists were found to suppress SAC-induced IL-6 production in intact PBMC cultures . As observed for suppression of IgG-ISC formation, inhibition of IL-6 production was found to be reversed by the appropriate receptor class-selective antagonist . These results support the hypothesis that one mechanism of opioid peptide-mediated inhibition of antibody production is via the down regulation of cytokine synthesis.

Infect Immun, 1996 Mar, 64(3), 714 - 8
Interleukins 6 and 11 protect mice from mortality in a staphylococcal enterotoxin-induced toxic shock model; Barton BE et al.; BALB/By mice given doses of D-galactosamine plus Staphylococcus aureus enterotoxin B die within 48 h of administration . The cause of death is a syndrome much like toxic shock syndrome in humans . We used this model to investigate the role of two cytokines, interleukin 6 and interleukin 11, which share the signal transducing subunit, gp130, of their respective receptors . We observed that pretreatment of mice with antibody to interleukin 6 increased mortality from 55% to nearly 90% (P < 0.001), while pretreatment with either cytokine reduced death . The protection was dose dependent; however, interleukin 6 was about 10-fold more potent that interleukin 11 . These data indicate that endogenous interleukin 6 plays a protective role in attenuating acute inflammatory responses; furthermore, interleukin 6 and interleukin 11 can abrogate T-cell activation due to triggering by superantigen . A possible clinical role for these cytokines in the treatment of toxic shock merits further investigation.

Infect Immun, 1996 Mar, 64(3), 1070 - 4
Staphylocidal action of thrombin-induced platelet microbicidal protein is not solely dependent on transmembrane potential; Koo SP et al.; Thrombin-induced platelet microbicidal protein (tPMP) is a small, cationic, antimicrobial peptide released from rabbit platelets when stimulated with thrombin . We studied the relationship between staphylococcal transmembrane potential (delta psi) and tPMP staphylocidal activity . A genetically related pair of Staphylococcus aureus strains, 6850 and JB1, which differ in delta psi generation (-143 and -97 mV, respectively) were used . Mutant JB-1 was substantially less susceptible to tPMP than the parental strain, 6850 . Menadione supplementation, which normalized the delta psi of strain JB-1, did not restore JB-1 tPMP susceptibility . These findings suggest that the staphylocidal activities of tPMP require factors other than or in addition to an intact delta psi.

J Med Microbiol, 1996 Mar, 44(3), 179 - 84
Inter-centre comparison of pulsed-field gel electrophoresis for the typing of methicillin-resistant Staphylococcus aureus; Cookson BD et al.; The results of pulsed-field gel electrophoresis (PFGE) of chromosomal DNA of the same 12 methicillin-resistant S . aureus (MRSA) strains of diverse geographical origin, performed in three different laboratories were compared; one laboratory used field-inversion gel electrophoresis (FIGE), one used contour clamped homogenous electrophoresis (CHEF) and one used both (all manufactured by BioRad Laboratories Inc., Hercules, CA, USA) . No single method produced the maximum number of chromosomal fragments from all isolates . In only four instances were the same number of fragments identified by any two techniques . Although there were similar trends in strain identification the results showed many discrepancies even with a three-band difference rule to discriminate between strains . Plasmids in seven of the isolates produced a fragment, but this did not affect discrimination of the study isolates . There is a great need to standardise methodology and produce a standard set of strains to assist in this process.

J Med Microbiol, 1996 Mar, 44(3), 171 - 7
Serum antibody response to Staphylococcus aureus enterotoxins and TSST-1 in patients with septicaemia; Kanclerski K et al.; The prevalence of enterotoxins and toxic shock syndrome toxin (TSST-1) production in strains isolated from patients with Staphylococcus aureus septicaemia, and the serum antibody response in relation to toxin production in vitro of each isolate, were investigated . Among 63 strains of S . aureus isolated from the blood of patients with septicaemia, 51 from patients with superficial wounds and 49 from nasal carriers, 50-60% produced at least one of the enterotoxins A-D or TSST-1 . The most frequent toxins produced were enterotoxins A and C and TSST-1 . Among the 63 patients with staphylococcal septicaemia, 51 (81%) had a significant rise or a high antibody titre, or both, to at least one of the toxins . A positive serological response to toxin A was found in 78%, to enterotoxin B in 83%, to enterotoxin C in 80%, to enterotoxin D in 86% and to TSST-1 in 92% of the patients from whom the isolated strain produced the respective toxin . Antibodies against enterotoxins A, B, C and D and TSST-1 were also seen in 35%, 16%, 32%, 59% and 10%, respectively, in patients infected by strains that did not produce the specific toxin . Immunological cross-reactions between the toxins were demonstrated both in hyperimmune sera obtained from rabbits and in patients' sera, particularly between enterotoxins B and C . It is concluded that these potent toxins with superantigenic properties are produced in vivo during S . aureus septicaemia . No differences with regard to enterotoxin or TSST-1 production or antibody response were noted between patients with complicated versus uncomplicated septicaemia.

J Med Microbiol, 1996 Mar, 44(3), 157 - 64
Clinical and molecular aspects of the pathogenesis of Staphylococcus aureus bone and joint infections; Cunningham R et al.; Staphylococcus aureus is an important cause of bone and joint infections . In recent years, significant changes in the incidence of septic arthritis and osteomyelitis have occurred . Haematogenous osteomyelitis is now less common during childhood, but secondary spread of infection to bone or joint from a contiguous site in adults is increasing in incidence . Infection introduced at the time of surgery or arising by the haematogenous route is a significant complication of prosthetic joint implantation, and the effect of bone cement on local immune function may be important in this setting . ALthough S . epidermis is a more common cause of prosthetic joint infection, S . aureus is more difficult to treat . S . aureus produces a number of extracellular and cell-associated factors, but it is unclear what role these have as virulence factors in vivo . Furthermore, it is difficult in animal models to simulate transient bacteraemia followed by non-fulminating septic arthritis or osteomyelitis, as occurs in the patient . Surface factors which may be important in pathogenesis include the cell wall (activates complement and stimulates cytokine release), capsular polysaccharide (promotes adhesion to host cell surfaces), collagen receptors and fibronectin-binding protein . Staphylococcal toxic shock syndrome toxin (TSST-1) and the enterotoxins are superantigens and have the potential to suppress plasma cell differentiation and antibody responsiveness . TSST-1-positive isolates have been shown to cause more severe joint infection in one animal model, but most other studies to date have focused on in-vitro rather than in-vivo effects . There is little evidence supporting a role for coagulase, lipase and the haemolysins in staphylococcal bone and joint infections . Despite the clinical importance of these infections, surprisingly little is known about pathogenesis at the cellular level . Future research should focus on the role of the host immune system in limiting spread of infection, and the expression of virulence factors in animal or other models incorporating isogenic mutant strains.

J Bacteriol, 1996 Mar, 178(6), 1565 - 71
An autolysin ring associated with cell separation of Staphylococcus aureus; Yamada S et al.; atl is a newly discovered autolysin gene in Staphylococcus aureus . The gene product, ATL, is a unique, bifunctional protein that has an amidase domain and a glucosaminidase domain . It undergoes proteolytic processing to generate two extracellular peptidoglycan hydrolases, a 59-kDa endo-beta-N-acetylglucosaminidase and a 62-kDa N-acetylmuramyl-L-alanine amidase . It has been suggested that these enzymes are involved in the separation of daughter cells after cell division . We recently demonstrated that atl gene products are cell associated (unpublished data) . The cell surface localization of the atl gene products was investigated by immunoelectron microscopy using anti-62-kDa N-acetylmuramyl-L-alanine amidase or anti-51-kDa endo-beta-N-acetylglucosaminidase immunoglobulin G . Protein A-gold particles reacting with the antigen-antibody complex were found to form a ring structure on the cell surface at the septal region for the next cell division site . Electron microscopic examination of an ultrathin section of the preembedded sample revealed preferential distribution of the gold particles at the presumptive sites for cell separation where the new septa had not been completed . The distribution of the gold particles on the surface of protoplast cells and the association of the gold particles with fibrous materials extending from the cells suggested that some atl gene products were associated with a cellular component extending from the cell membrane, such as lipoteichoic acid . The formation of a ring structure of atl gene products may be required for efficient partitioning of daughter cells after cell division.

Am J Epidemiol, 1996 Mar 1, 143(5), 496 - 504
Effectiveness of contact isolation during a hospital outbreak of methicillin-resistant Staphylococcus aureus; Jernigan JA et al.; Contact isolation has been recommended by the Centers for Disease Control and Prevention for the prevention of nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA), but there are few data which prospectively quantitate the effectiveness of contact isolation for this purpose . During an outbreak of MRSA in a neonatal intensive care unit between July 18, 1991 and January 30, 1992, weekly surveillance cultures were performed on all patients . Sixteen of 331 admissions became colonized with MRSA, and 3 (19%) developed infections: bacteremia, conjunctivitis, and dialysis catheter site infection . The isolates from all 16 patients were submitted to plasmid profile analysis and restriction enzyme analysis of whole cell DNA . All of the patients had identical chromosomal patterns and plasmid profiles, which differed from control isolates from other wards, indicating that the outbreak resulted from spread of a unique strain . None of 144 personnel who were cultured after recent contact with newly colonized patients during the outbreak were found to carry MRSA, which suggests that patients were the reservoir for transmission rather than caregivers . The most probable source for each individual transmission was determined based on proximity in time and space and shared exposure to caregivers . The rate of transmission of MRSA from patients on contact isolation was significantly lower (0.009 transmissions per day on isolation) than the rate for patients not on isolation (0.140 transmissions per day unisolated, relative risk = 15.6, 95% confidence interval 5.3-45.6, p < 0.0001) . The authors conclude that the risk of nosocomial transmission of MRSA was reduced 16-fold by contact isolation during the outbreak in this neonatal intensive care unit . These data confirm the results of previous studies which have suggested that contact isolation was effective in controlling the epidemic spread of methicillin-resistant Staphylococcus aureus.

Eur J Immunol, 1996 Mar, 26(3), 659 - 68
Interleukin-12 is produced by dendritic cells and mediates T helper 1 development as well as interferon-gamma production by T helper 1 cells; Heufler C et al.; Interleukin-12 (IL-12), a 70-kDa heterodimeric cytokine composed of covalently linked p35 and p40 chains, is to date the most critical factor for skewing the immune response towards a T helper 1 (Th1) of cytokine profile {high interferon-gamma (IFN-gamma), low IL-4} . Established sources of IL-12 are stimulated macrophages, neutrophils and B cells . As dendritic cells (DC) process antigen in the periphery and then migrate to lymphoid organs to sensitize T cells and induce cell mediated immunity, we reasoned that DC should constitute a critical source of IL-12 . The criteria used to detect IL-12 in DC were the demonstration of p40 and p35 mRNA (semiquantitative polymerase chain reaction, northern blotting, and in situ hybridization) as well as IL-12 protein (p70 enzyme-linked immunosorbent assay, p70 antigen capture followed by IFN-gamma bioassay, free p40 chain radioimmunoassay or immunoprecipitation) . We found that conventional stimuli such as Staphylococcus aureus induced production of IL-12 by murine as well as human DC in amounts comparable to spleen cells, peritoneal macrophages or peripheral mononuclear cells . DC exhibited, however, features that had not been seen with other antigen-presenting cells: they produced bioactive IL-12 upon antigen-specific interaction with T cells without any other stimuli; in an allogeneic mixed leukocyte reaction model, neutralizing anti-IL-12 antibodies showed that DC-derived IL-12 was critical for optimal proliferation and IFN-gamma production by activated Th1 blasts; and finally, the priming of resting, naive allogeneic T cells by DC, followed by restimulation of primed T blasts by DC, skewed the response to Th1 without the need for any exogenous cytokines or stimuli such as microorganisms . This skewing to Th1 cytokine production, which depended on DC-derived IL-12, but did not require anti-IL-4, exogenous IL-12, or microbes, might be a major function of DC.

Clin Immunol Immunopathol, 1996 Mar, 78(3), 215 - 22
Polyethylene glycol-modified IL-2 abrogates superantigen-induced anergy without affecting peripheral clonal deletion in vivo; Gonzalez-Garcia A et al.; As compared with the native molecule, recombinant human interleukin-2 that is modified by covalently attached polyethylene glycol residues (IL-2-PEG) exhibits a markedly enhanced half-life in vivo, thus facilitating its biological evaluation . We have characterized the effect of IL-2-PEG on the Staphylococcus aureus enterotoxin B (SEB)-induced tolerance of peripheral SEB-reactive (V beta 8+) T cells . Treatment with sublethal doses of IL-2-PEG does not modulate (inhibit or enhance) the SEB-triggered apoptosis and deletion of V beta 8+ T cells . In contrast, in vivo treatment with IL-2-PEG partially abolishes the SEB-triggered anergy of V beta 8+ T cells, i.e., the failure to proliferate in response to SEB in vitro . To abolish SEB-triggered anergy, IL-2-PEG must act for an extended period in vivo; short term treatment in vivo (2 days) or exposure of anergic T cells to IL-2 in vitro fails to reconstitute proliferative responses . Moreover, the effect of in vivo treatment with IL-2-PEG on lymphokine production by anergic T cells is partial . IL-2-PEG restores IL-4-dependent autocrine proliferation in response to SEB but does not reestablish defective IL-2 production . These data are compatible with the notion that IL-2 is a regulator of postdeletional rather than deletional T cell tolerance.

Am J Kidney Dis, 1996 Mar, 27(3), 441 - 3
Spontaneous bacterial peritonitis in a patient with nephrogenic ascites during an episode of acute renal transplant rejection; Horn S et al.; Spontaneous bacterial peritonitis (SBP) is a primary infection of asci tes without signs of perforation or penetration . It occurs most often in patients with liver cirrhosis but can also be diagnosed in patients with ascites from other causes . We report a kidney transplant recipient who developed nephrogenic ascites during an episode of acute rejection . The patient complained of fever, abdominal tenderness, and loose stools and showed all of the signs of peritonitis on physical examination . The patient's serum creatinine was elevated, and Duplex sonography of the graft was highly suggestive for acute rejection . Ascites puncture was performed . The ascitic fluid contained 4,000 leukocytes per microliter . No source of infection was detected, so the diagnosis of SBP was made . The patient was treated with ciprofloxacin intravenously and received low-dose steroid pulse therapy . The ascites culture grew Staphylococcus aureus that was highly sensitive to ciprofloxacin . The patient recovered rapidly . We could avoid laparotomy, which is associated with high mortality in patients suffering from SBP . No relapses of SBP occurred . Renal function has improved and remained stable.

J Vasc Surg, 1996 Mar, 23(3), 529 - 33
Endovascular stent infection; Deiparine MK et al.; We report a case of iliac stent infection . Nine days after a 24-hour infusion of urokinase and right iliac artery stent deployment, the patient had fever, in addition to severe groin pain and petechiae isolated to the stented limb . The hospital course was complicated by sepsis, adult respiratory distress syndrome, liver dysfunction, and renal insufficiency . Stent removal and iliac/femoral artery resection, as well as an above-knee amputation, were life-saving . Arterial and stent cultures grew Staphylococcus aureus . Stent infection with arterial necrosis is a devastating, rare endovascular complication . Given its potential seriousness, we would recommend the use of prophylactic antibiotics before stent deployment.

J Vasc Surg, 1996 Mar, 23(3), 472 - 6
Arteries from human beings are less infectible by Staphylococcus aureus than polytetrafluoroethylene in an aortic dog model; Koskas F et al.; PURPOSE: Treatment of aortoiliac prosthetic graft infections includes the removal of the infected material and repeat revascularization if necessary . The risk of infection of the graft material used for the repeat revascularization has been the drawback of its use in situ except with autografts . Good results were obtained in this setting by use of in situ arterial allografts . The purpose of our study was to compare in vivo the infectibility of arteries used as allografts to the infectibility of commercially available prostheses . METHODS: Twelve dogs underwent thoracoabdominal aortic bypass with use of either an artery from a human being (n=6) or an expanded polytetrafluoroethylene (ePTFE) graft (n=6) . One month later, bacteremia was produced with Staphylococcus aureus . One week after bacterial challenge, the animals were killed to recover the grafts . Each graft then underwent bacterial study . RESULTS: None of the arterial grafts grew bacteria, whereas four of the six ePTFE grafts (p < 0.05) did . In addition, none of the fragments of the arterial grafts grew bacteria, whereas 24 of the 60 ePTFE fragments (p < 0.01) did . CONCLUSION: Nonautologous arteries are less infectible than ePTFE in vivo . This decreased infectibility makes the arterial allograft an appealing material when revascularization must be performed in a contaminated field.

Am J Ophthalmol, 1996 Mar, 121(3), 310 - 7
Comparative treatment of experimental Staphylococcus aureus endophthalmitis; Aguilar HE et al.; PURPOSE: To compare treatment strategies for Staphylococcus aureus endophthalmitis, we created an animal model in an aphakic rabbit eye and tested six different approaches to treatment . METHODS: Rabbit eyes were rendered aphakic, and three weeks postoperatively, S . aureus organisms were injected into the vitreous cavity . One group was maintained as a control . Twenty-four hours after bacterial injection, six different treatment groups were created for comparison . Clinical inflammation scores, culture results 48 hours after treatment, histopathologic gradings, and development of total corneal opacity three weeks after treatment were assessed . RESULTS: Injection of vancomycin hydrochloride into the vitreous cavity was more effective than injection of cefazolin sodium (P = .01) in reducing the percentage of eyes that had positive culture results and also resulted in lower inflammation scores . Vitrectomy plus injection of either antibiotic was more effective than injection of the same antibiotic alone in reducing culture-positive results and reducing clinical inflammation scores . addition of systemic corticosteroids to intravitreal antibiotic injection did not improve any measure of outcome . Vitrectomy and injection of intravitreal vancomycin was the most effective strategy to sterilize the vitreous cavity, resulting in the lowest inflammation scores and the smallest percentage of eyes with opaque corneas . CONCLUSION: In an animal model of S . aureus endophthalmitis, the combination of vitrectomy and injection of intraocular vancomycin was the most effective strategy for rapidly controlling the infective process and improving the outcomes measured three weeks after treatment.

FEMS Microbiol Lett, 1996 Feb 15, 136(2), 129 - 36
Suppression of the thermosensitive replication phenotype of the derivative plasmid of pI9789::Tn552 in Staphylococcus aureus may involve integration of the plasmid into the host chromosome; Sohail M et al.; Plasmid-chromosome co-integration was found to be the mechanism of choice to overcome thermosensitivity of replication of the plasmid pS1 in PS80d and RN4220 strains of Staphylococcus aureus . The integration of the plasmid was sometimes accompanied by deletion of a specific section of the plasmid pS1 in PS80d . Growth of bacteriophage on strains containing the integrated plasmid and the subsequent use of the phage in transduction gave transductants containing plasmids that had regained their replication thermosensitivity . These plasmids had not acquired any detectable chromosomal DNA . The 16-kb EcoRI fragment of the PS80d chromosome that hybridizes to pS1 is the target for recombination in many cases, but apparently other sites are also used . This fragment contains sequence homologous to parts of the transposon Tn552 and it is probable that site-specific recombination is involved in the integration . The possible mechanisms for the integrations and the deletions are discussed.

J Immunol, 1996 Feb 15, 156(4), 1392 - 401
Human B cells express IL-5 receptor messenger ribonucleic acid and respond to IL-5 with enhanced IgM production after mitogenic stimulation with Moraxella catarrhalis; Huston MM et al.; The potential for IL-5 to regulate human B cells is controversial despite its well established role as a regulatory factor for murine B cells . We hypothesized that the mechanism by which human B cells were stimulated would, as with murine B cells, determine their potential to respond to IL-5 . Since Staphylococcus aureus Cowan strain I (SAC) and Moraxella catarrhalis (MCat) stimulate human B cells by distinct interactions with cell-surface Ig, we compared their potential to induce an IL-5-responsive state by human B cells purified to homogeneity . Neither SAC alone nor SAC plus IL-5 stimulated Ig production, although microgram quantities of IgM were produced with SAC plus IL-2 . In contrast, MCat induced microgram quantities of IgM by B cells in the absence of exogenous cytokines, and IL-5 significantly increased IgM production over twofold in the majority of donors . Synergism of IL-5 and IL-2 was detected using suboptimal concentrations of IL-2 with MCat-, but not SAC-, stimulated B cells . Donor B cells unresponsive to IL-5 when stimulated with MCat, became IL-5 responsive in the presence of IL-2 . Since message for the IL-5R alpha, IL-5R beta, and soluble IL-5R alpha chains was detected in freshly isolated B cells, we further investigated whether IL-5 responsiveness to MCat, but not SAC, was due to their differential regulation of IL-5R mRNA . Surprisingly, stimulation by either MCat or SAC, without or with IL-2, increased both IL-5R alpha and IL-5R beta mRNA and decreased soluble IL-5R alpha mRNA . These studies demonstrate that, as with murine B cells, human B cells express message for IL-5R but can respond to IL-5 only if appropriately stimulated to undergo terminal differentiation.

Diagn Microbiol Infect Dis, 1996 Feb, 24(2), 93 - 100
Detection of oxacillin-resistance in Staphylococcus aureus by MicroScan MIC panels in comparison to four other methods; Dillard SC et al.; Two hundred fifty-two isolates of Staphylococcus aureus were tested for oxacillin susceptibility by MicroScan Gram positive overnight and rapid MIC panels . Results were compared with nonautomated methods including disk diffusion, MRSA Crystal ID, and Etests using MRSA Screen Agar as reference . One hundred sixty-nine isolates (67.1%) were oxacillin-susceptible and 83 (32.9%) were resistant . All methods agreed for 234 (92.9%) isolates . Very major error rates were 1.2% for disk diffusion, 3.6% for Etest, and 0 for all other methods . Major error rates were 5.3% for MicroScan overnight panels, 3% for rapid panels, 2.4% for disk diffusion, 1.2% for Etest, and 0.6% for MRSA Crystal ID . Nine oxacillin-susceptible isolates with borderline MICs and discrepant results for 1 or more methods were tested for the mec A gene and all were negative . Each was susceptible to beta lactam/beta lactamase inhibitor combinations, suggesting that false resistance may have been due to excessive beta lactamase production . Oxacillin-resistant S . aureus with borderline MICs determined by MicroScan should be confirmed by an alternate method . The most practical and cost-effective means among those we tested is the MRSA Screen Agar.

Vet Microbiol, 1996 Feb, 48(3-4), 187 - 98
Effect of staphylococcal beta toxin on the cytotoxicity, proliferation and adherence of Staphylococcus aureus to bovine mammary epithelial cells; Cifrian E et al.; The effect of staphylococcal beta toxin on the cytotoxicity, proliferation and adherence of S . aureus . to bovine mammary epithelial cells was studied . Bovine erythrocytes and mammary epithelial cells were incubated with purified staphylococcal alpha and beta toxins and with culture supernatants from S . aureus M60 and two mutant strain that are negative for either the production of alpha (DU5789 alpha-) or beta (DU5846 beta-) toxin . Lysis of bovine erythrocytes was due primarily to beta toxin . Alpha toxin increased the lysis of bovine erythrocytes by purified beta toxin, but the presence of alpha toxin in culture supernatants from S . aureus did not increase the lysis of bovine erythrocytes . Purified beta toxin was cytotoxic to mammary secretory epithelial cells, but to a lesser extent than alpha toxin . Together they exhibited an additive effect on mammary epithelial cells . Inactivation of the alpha toxin-gene of S . aureus M60 decreased the cytotoxic effect on mammary epithelial cells to a greater extent than the inactivation of the beta toxin-gene . Also, the relative percentages of DU5789 alpha- and DU5846 beta- adhering to mammary cell monolayers, the number and size of colonies and the number of infected epithelial cells decreased . This in vitro study showed that beta toxin damages bovine mammary secretory epithelial cells, increased the damaging effects of alpha toxin, increases the adherence of S . aureus to mammary epithelial cells and increases the proliferation of S . aureus.

J Biomed Mater Res, 1996 Feb, 30(2), 245 - 50
Contribution of vascular catheter material to the pathogenesis of infection: depletion of complement by silicone elastomer in vitro; Marosok R et al.; We previously have shown that vascular catheters made of silicone elastomer carry a greater risk of subcutaneous infection with Staphylococcus aureus than do polyurethane (PU), polyvinylchloride (PVC), or Teflon catheters . We further have shown that there is greater inflammation surrounding silicone catheters than there is surrounding catheters made of the other materials, suggesting that silicone produces a greater chemotactic gradient than do the other materials . This study used a functional complement opsonization assay and radioimmunoassays to compare the relative abilities of silicone, polyurethane, and polyvinylchloride to activate complement . Serum incubated in silicone catheters for 24 h had less than 30% of the opsonizing ability of fresh serum while > or = 78% of the opsonizing ability remained with serum incubated in PU or PVC catheters . Measurement of C3a des Arg, C4a des Arg, C5a des Arg, and SC5b-9 demonstrated that the loss of opsonizing ability was due to 10-fold greater alternate pathway complement activation by silicone than by PU or PVC . This finding suggests that excessive complement activation by silicone may explain the greater inflammation seen around silicone catheters in vivo and also might play a role in silicone's creating a greater risk of infection.

Protein Eng, 1996 Feb, 9(2), 161 - 71
Molecular modelling of Staphylococcal delta-toxin ion channels by restrained molecular dynamics; Kerr ID et al.; Delta-Toxin is a 26-residue channel-forming peptide from Staphylococcus aureus which forms an amphipathic alpha-helix in a membrane environment . Channel formation in planar bilayers suggests that an average of six delta-toxin helices self-assemble to form transbilayer pores . Molecular models for channels formed by delta-toxin and by a synthetic analogue have been generated using a simulated annealing protocol applied via restrained molecular dynamics . These models are analysed in terms of the predicted geometric and energetic properties of the transbilayer pores . Pore radius calculations of the models demonstrate that rings of channel-lining residues contribute a series of constrictions along the pore . Electrostatic properties of the pores are determined both by pore-lining charged side chains and by the aligned helix dipoles of the parallel helix bundle . Molecular dynamics simulations (100 ps) of delta-toxin models containing intra-pore water were performed . Analysis of the resultant dynamics trajectories further supports the proposal that alternative conformations of pore-constricting side chains may be responsible for the observed conductance heterogeneity of delta-toxin ion channels.

Lett Appl Microbiol, 1996 Feb, 22(2), 165 - 8
Effects of growth conditions on the resistance of some pathogenic and spoilage species to high pressure homogenization; Lanciotti R et al.; The effects of chemico-physical growth conditions such as pH, temperature and water activity (aw) on lethal high homogenization pressure effects on Listeria monocytogenes, Staphylococcus aureus, Escherichia coli and Yarrowia lipolytica were investigated . The results, though based on standard media, emphasize the importance of food system composition and its thermal history on the high pressure tolerance of the microbial population.

Biochem Mol Biol Int, 1996 Feb, 38(1), 81 - 9
The amino acid sequence and structural class of the arachin subunit of molecular weight 29, 100A; Bhushan R et al.; Arachin subunit (mol . wt . 29,100) from peanut of variety G-201 was separated and isolated, its purity and homogeneity were ascertained . The subunit was cleaved with trypsin, chymotrypsin and Staphylococcus aureus V8 protease . The fragments obtained were separated and isolated by PAGE, gel filtration & ion exchange chromatography, these were subjected to amino acid analysis, and Edman degradation . The PTH amino acids obtained were identified by spectroscopy and TLC . The complete amino acid sequence of the subunit (226 residues) was established, and the structural class of arachin was predicted from the amino acid composition.

Ann Med, 1996 Feb, 28(1), 43 - 6
Staphylococcal vaccines: a realistic dream; Fattom AI et al.; Staphylococcus aureus, especially multidrug resistant strains, continues to be a leading cause of serious nosocomial infections . In spite of the debate among investigators in the field, the discovery of serologically distinct capsular polysaccharides on the surface of clinical isolates has renewed the prospects for development of vaccines and passive protective immunity against S . aureus infections . Capsular polysaccharide conjugate vaccines have now been produced and proven to be safe and immunogenic in both healthy and in a significant percentage of immunocompromised patients . Antibodies generated in humans against these vaccines have been shown to mediate type-specific opsonophagocytosis, and to protect animals against lethal challenge with the appropriate S . aureus isolate.

Int J Clin Pharmacol Ther, 1996 Feb, 34(2), 71 - 5
Pharmacokinetics of vancomycin in patients with severely impaired renal function; Gonzalez-Martin G et al.; The pharmacokinetics of 1 g dose of intravenous vancomycin was studied in 8 patients with severe renal failure . Serum vancomycin levels were determined by fluorescence polarization immunoassay . After single dose of vancomycin peak concentrations ranged from 37.8 microg.ml-1 to 109.3 microg.ml-1 (mean 64.9 +/- 21.7 microg.ml-1) . Vancomycin trough concentration 168h after administration of the antibiotic ranged from 2.23 microg.ml-1 to 11.42 microg.ml-1 (mean 6.55 +/- 2.8 microg.ml-1) . The data were analyzed using a PCNONLINE computer program, and in all patients a triexponential model described how concentrations decreased in time . Three-compartment parameters obtained from the 8 patients were t1/2 alpha = 0.312 +/- 0.242 h, t1/2 beta 6.012 +/- 5.36 h, and t1/2 gamma = 131.0 +/- 46.7 h . Vd = 0.158 +/- 0.121 1.kg-1, Vdss = 0.920 +/- 0.248 1.kg-1 and total Cl = 0.10 +/- 0.049 1.h-1 per kg of weight . Between 1.5% and 21.2% of the administered vancomycin dose was eliminated during hemodialysis . The dialysis clearance of vancomycin ranged from 50.6 ml.min-1 to 76.8 ml.min-1 (average: 62.4 +/- 10.4 ml.min-1 . However, after dialysis plasma concentrations returned to pre-dialysis values . In accordance to our kinetic study 1 g of vancomycin given every 7 days is adequate treatment for methicillin-resistant Staphylococcus aureus infections in patients with severe renal failure whose creatinine clearance is lower than 10 ml.min-1.

Kansenshogaku Zasshi, 1996 Feb, 70(2), 151 - 60
{Combination effect of vancomycin and cefpirome against methicillin-resistant Staphylococcus aureus in vitro--antimicrobial activities in postantibiotic phase}; Hasegawa H et al.; The antimicrobial activities of vancomycin (VCM) or cefpirome (CPR) at sub- and above-MICs against clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) during the postantibiotic phase (PAE-phase) induced by CPR or VCM were examined . Antimicrobial activities were determined growth suppression (post antibiotic sub-MIC effect: PA SME) at sub-MICs, and bactericidal activity at sub- and above-MICs . During the PAE-phase induced by VCM, growth suppression and bactericidal activity of CPR were enhanced at sub-MICs, compared with the non PAE-phase . On the other hand, during the PAE-phase induced by CPR, not only were growth suppression and bactericidal activity of VCM enhanced at sub-MICs, but bactericidal activity were enhanced at above-MICs compared with non PAE-phase . These suggest that enhancement of growth suppression and bactericidal activity during PAE-phase was a factor of combination effect of VCM and CPR against MRSA.

Biol Pharm Bull, 1996 Feb, 19(2), 311 - 4
Antibacterial activity of some Garcinia benzophenone derivatives against methicillin-resistant Staphylococcus aureus; Iinuma M et al.; Benzophenone derivatives, garcinol (1) and isogarcinol (2) isolated from the pericarps of Garcinia purpurea (Guttiferae), and xanthochymol (3) and a mixture of isoxanthochymol (4) cycloxanthochymol (5) from the pericarps of G . subelliptica were evaluated for their antibacterial activity against methicillin-resistant Staphylococcus aureus . Among them, 3 showed the lowest minimum inhibitory concentration at 3.1-12.5 micrograms/ml . This concentration is nearly equal to that of the antibiotic, vancomycin.

J Dermatol, 1996 Feb, 23(2), 129 - 32
Bacteroides fragilis pyomyositis in a patient with multiple myeloma; Katagiri K et al.; Pyomyositis is a bacterial infection with abscess formation affecting large skeletal muscles . It is predominantly caused by Staphylococcus aureus . The disease is common in tropical areas, but rare in temperate climates . We report a patient with multiple myeloma who developed a giant elastic tumor on the right thigh and a hen egg-sized tumor on the right upper arm . MR imaging revealed cystic spaces in the femoral quadriceps and brachial biceps muscles . A large amount of pus with foul smell was removed by incision, drainage and aspiration of the two tumors . The lesions were successfully treated with intravenous administration of antibiotics . Repeated bacterial cultures yielded only Bacteroids fragilis . To our knowledge, this is the first report of pyomyositis due to Bacteroides fragilis.

Nippon Rinsho, 1996 Feb, 54(2), 560 - 9
{Advances in genetic diagnostics for respiratory tract infections}; Koga H; The past decade has seen the rapid advancement of molecular biology and its application in the field of infectious diseases . The polymerase chain reaction (PCR) is a technique which brings about the in vitro amplification of DNA, and is clinically useful in the sensitive, specific and rapid diagnosis of various infectious diseases . The fast diagnosis of viral infections using PCR is a prime example, since viral culture may take weeks to grow and since serologic conversion seldom occurs until the convalescent phase of the clinical illness . Similarly, PCR is applicable to the diagnosis of pulmonary infections caused by mycobacteria, Legionella, methicillin-resistant Staphylococcus aureus, anaerobes, Mycoplasma, Chlamydia, Pneumocystis carinii and so on . On the other hand, the drug-resistant phenotype of a microorganism is predictable by the detection of gene alterations related to the drug resistance . For example, the deletion of the catalase-peroxidase gene relating to isoniazid resistance of mycobacteria, and point mutations in the RNA polymerase beta subunit (rpoB) gene relating to rifampicin resistance have been elucidated . As these applied techniques become more widely available and less costly, they should contribute not only to the rapid diagnosis of infectious diseases, but also to the adequate selection of antibiotics and the shortening of hospitalization.

J Clin Microbiol, 1996 Feb, 34(2), 398 - 403
Typing multidrug-resistant Staphylococcus aureus: conflicting epidemiological data produced by genotypic and phenotypic methods clarified by phylogenetic analysis; Jorgensen M et al.; An outbreak of an unusual tetracycline-sensitive, rifampicin- and ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus (MRSA) strain at a large teaching hospital was investigated . Two typing methods, phage typing and restriction fragment length polymorphism (RFLP) by pulsed-field gel electrophoresis (RFLP-PFGE), gave conflicting results which were clarified by phylogenetic analysis . Phage typing identified all the "epidemic-associated" strains as identical, while RFLP-PFGE further divided these strains into four pulsotypes . Phylogenetic analysis showed these four pulsotypes were related genetically and also recognized a second strain of MRSA causing a continuing cross-infection problem . Variation in the RFLP-PFGE pattern was shown to occur following lysogenization of phage-sensitive MRSA . These results indicate that in analyzing outbreaks caused by subgroups of clonal organisms like MRSA, it is necessary to use at least two typing methods and that conflicts between these could be resolved by phylogenetic analysis.

J Am Soc Nephrol, 1996 Feb, 7(2), 247 - 53
Safety and immunogenicity of Staphylococcus aureus type 5 capsular polysaccharide-Pseudomonas aeruginosa recombinant exoprotein A conjugate vaccine in patients on hemodialysis; Welch PG et al.; Seventeen volunteers with ESRD on hemodialysis, negative for infection with HIV or hepatitis B and C and not receiving immunosuppressive therapy, were injected two times 6 wk apart with 25 micrograms of Staphylococcus aureus Type 5 capsular polysaccharide-Pseudomonas aeruginosa exoprotein A (rEPA) conjugate . Controls were healthy adults, 18 to 44 yr old, injected previously with the same vaccine . None of the patients had fever or significant elevations in their SGOT or SGPT attributable to the vaccine . Two vaccinees had transient induration > 1 cm in diameter at the injection site . The preimmunization geometric mean (GM) Type 5 antibody levels of the ESRD patients and controls were similar . Type 5 antibody levels of the three major immunoglobulin (lg) classes rose at 2 and 6 wk after immunization (P < 0.001 for lgG, P < 0.005 for lgM, and P = 0.0001 for lgA) . Reimmunization at 6 wk did not elicit a booster response . At 6 months, the GM lgG level of the patients was approximately 50% of that of the healthy volunteers and 14 of 17 had a more than fourfold higher antibody level than the preimmune value . The GM lgM level, in contrast, declined to the preimmunization value . Vaccine-induced Type 5 antibodies had opsonophagocytic activity . There was a slight increase of lgG antibodies to the heterologous S . aureus Type 8 polysaccharide (P < 0.01) that was sustained at 6 months . The S . aureus Type 5-rEPA vaccine is safe and immunogenic in ESRD patients, and evaluation of its effectiveness against S . aureus bacteremia in this at-risk group is planned.

Eur Respir J, 1996 Feb, 9(2), 386 - 8
Acute respiratory distress syndrome due to methicillin-resistant Staphylococcus aureus sepsis in hyper-IgE syndrome; Sato E et al.; We report the case of a 34 year old woman with acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) due to methicillin-resistant Staphylococcus aureus (MRSA) sepsis with hyperimmunoglobulin E syndrome (HIES) . Although chemotactic activity of neutrophils was impaired in this patient, neutrophils accumulated in the lungs as assessed by bronchoalveolar lavage fluid (BALF) counts . In addition to antibiotics and oxygen therapy, the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) resulted in a remarkable recovery.

Can J Microbiol, 1996 Feb, 42(2), 120 - 3
Phenotypic characterization and virulence of a sae- agr- mutant of Staphylococcus aureus; Giraudo AT et al.; A sae::Tn551 agr::tetM double mutant was constructed and characterized . The production of several exoproteins (e.g., beta-hemolysin, DNase, and proteases) by this mutant was determined and found to be lower than the already diminished production of either isogenic single mutant sae- or agr- . The double mutant also showed, like the agr- mutant, null production of alpha- and delta-hemolysins and diminished levels of lipase . The reduced levels of many exoproteins in the double mutant as compared with their already diminished levels in either single mutant suggest that there is an additive or synergistic interaction between the two mutations involved, sae- and agr- . However, inactivation of both loci, sae and agr, had a different effect on the two exoproteins that are up regulated in the agr- mutant; thus, coagulase dropped to levels close to the null levels of the sae- parental strain, while extracellular protein A displayed the high levels characteristic of the agr- single mutant . The virulence of the sae- agr- double mutant, determined by intraperitoneal injection in mice, was found to be significantly diminished as compared with that of the sae+ agr+ parental strain or the sae- agr+ single mutant.

Jpn J Antibiot, 1996 Feb, 49(2), 194 - 202
{Antibacterial activities of combination uses of isepamicin and beta-lactams in vitro against clinically isolated strains . Part 1 . Activities against Staphylococcus aureus}; Deguchi K et al.; In order to evaluate antibacterial activities of combination uses of isepamicin (ISP) and beta-lactams in vitro, minimum inhibitory concentrations (MICs) these drugs were examined singly and in combination against clinically isolated Staphylococcus aureus . The results are summarized as follows; 1 . MICs of ISP + cefazolin (CEZ), ISP + cefotiam (CTM) and ISP + flomoxef (FMOX) were low and the activities against methicillin (DMPPC)-susceptible S . aureus (MSSA) were dependent on the concentration of ISP . Combined effects were observed when the concentrations of ISP were at sub-MIC levels (1/2 approximately 1/4 concentrations) . 2 . MICs of ISP + CEX, ISP + CTM, ISP + FMOX, ISP + imipenem and ISP + panipenem were low and the activities against DMPPC-resistant S . aureus (MRSA) were dependent on the concentration of ISP, and were similar to those against MSSA . Combined effects were observed when the concentrations of ISP were at sub-MIC levels of ISP . Lower MIC50 or MIC90 was observed at ISP concentrations of 4 approximately 16 micrograms/ml . 3 . The blood Cmax of ISP exceeded 20 micrograms/ml at one-time administration of ISP 400 mg, and these results suggested that antibacterial activities of combination uses of ISP and beta-lactams was clinically effective against MRSA infections.

J Antimicrob Chemother, 1996 Feb, 37(2), 243 - 51
In-vitro susceptibility of isolates of methicillin-resistant Staphylococcus aureus 1988-1993; Scheel O et al.; MICs for 423 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated in Hong Kong during 1988-1993 were performed for 15 antimicrobial agents: erythromycin, chloramphenicol, tetracycline, minocycline, gentamicin, netilmicin, trimethoprim, rifampicin, fusidic acid, ciprofloxacin, vancomycin, teicoplanin, sparfloxacin, clinafloxacin and RP 59500 (quinupristin/dalfopristin) . Susceptibility to antibiotics generally remained stable throughout the study period, with the exception of the quinolones . Resistance to ciprofloxacin (breakpoint 4 mg/L) increased from a low of 9% in 1988 to a high of 82% in 1993 . For sparfloxacin the corresponding figures were 9% and 78%, respectively . Six (1%) clinafloxacin-resistant strains were found . MIC50s and MIC90s of clinafloxacin increased from < or = 0.06 mg/L and 0.25 mg/L in 1988 to 1.0 mg/L and 2.0 mg/L, respectively, in 1993 . All 423 strains were phage typed (typability 70%) and a diversity of phage types which changed during the observation period, with 13 dominating types, was observed . Ciprofloxacin resistance occurred in 12 of the dominating types, in 46 non-typable strains, and also in 23 strains of different, sporadically occurring types, indicating that the emergence of quinolone resistance was not due to dissemination of a single or few MRSA clones . The usefulness of quinolones in the treatment of MRSA infections is likely to be seriously constrained by the emergence of resistance . MICs for RP-59500 were < or = 2 mg/L for all isolates, suggesting that this agent merits further evaluation as an anti-MRSA agent . All MRSA remained susceptible to vancomycin and teicoplanin throughout the study period.

J Paediatr Child Health, 1996 Feb, 32(1), 4 - 6
New perspectives on inflammation in atopic dermatitis; Kemp AS et al.; Recent information implicates the stimulation of T cells by Staphylococcus aureus antigens and exotoxins as a likely factor in provoking the inflammatory response in atopic dermatitis . S . aureus secrets exotoxins called superantigens, which stimulate a large proportion of T cells . In addition, protein A, a component of the cell wall of S . aureus, is a potent B cell mitogen . This understanding provides a rationale for attempting to reduce the staphylococcal skin colonization of patients with severe atopic dermatitis and correlates with the clinical observation in a number of situations of marked improvement in atopic dermatitis following antibiotic treatment.

J Med Microbiol, 1996 Feb, 44(2), 125 - 9
Genetic regulation of fatty acid modifying enzyme from Staphylococcus aureus; Chamberlain NR et al.; Fatty acid modifying enzyme (FAME) is an extracellular enzyme that inactivates staphylocidal lipids by catalysing the esterification of these lipids to cholesterol . In-vitro expression of FAME began at the start of the stationary phase . This expression of FAME was very similar to other staphylococcal extracellular proteins controlled by the global regulators Agr and Sar . A staphylococcus aureus strain ISP546 (Agr-) produced c . 80% less FAME than an isogenic Agr+ strain ISP479C . Similar results were obtained with the isogenic Agr+/Agr- strain pair RN6390 and RN6911 . A S . aureus strain R (Sar-) produced c . 86% less FAME than an isogenic Sar+ strain RN6390 . However, lipase assays on the same culture filtrates from the Sar+/Sar- strains did not demonstrate any affect on lipase production by the sar mutation.

Ann Intern Med, 1996 Feb 1, 124(3), 329 - 34
Vancomycin-resistant Staphylococcus aureus: perspectives on measures needed for control; Edmond MB et al.; Given the dramatic increase in the incidence of vancomycin resistance among the enterococci and experimental evidence for the transfer of vancomycin resistance from enterococci to Staphylococcus aureus, there is concern that strains of S . aureus will emerge that are resistant to vancomycin . The result would be a highly virulent pathogen for which effective antimicrobial therapy would not be available . To prevent the nosocomial transmission of such an organism, stringent infection control policies need to be developed and implemented . We offer proposals that are based on the limited data available on the transmission and control of S . aureus and that may be used as starting points for the development of formal guidelines for the isolation of colonized and infected patients and for microbiology laboratory precautions.

J Bacteriol, 1996 Feb, 178(3), 611 - 8
Identification and molecular characterization of a putative regulatory locus that affects autolysis in Staphylococcus aureus; Brunskill EW et al.; Previously in our laboratory, a PCR-based strategy was used to isolate potential sensor gene fragments from the Staphyloccus aureus genome . One DNA fragment was isolated that shared strong sequence similarity to genes encoding bacterial sensor proteins, indicating that it originated from within a potential staphylococcal sensor protein gene . In this study, the DNA surrounding the PCR product origin was cloned and sequenced . This analysis revealed the presence of two genes, termed lytS and lytR, whose deduced amino acid sequences were similar to those of members of the two-component regulatory system family of proteins . S . aureus cells containing an insertional disruption of lytS exhibited a marked propensity to form aggregates in liquid culture, suggesting that alterations in cell surface components exist in this strain . Transmission electron microscopic examination of these cells revealed that the cell surface was rough and diffuse and that a large proportion of the cell population had lysed . The lytS mutant also exhibited increased autolysis and an altered level of murein hydrolase activity produced compared with the parental strain, NCTC 8325-4 . These data suggest that the lytS and lytR gene products control the rate of autolysis in S . aureus by affecting the intrinsic murein hydrolase activity associated with the cell.

Lancet, 1996 Jan 27, 347(8996), 220 - 3
Chronic granulomatous disease in adults; Liese JG et al.; BACKGROUND: Chronic granulomatous disease (CGD), an inherited disorder of granulocyte function caused by failure of intracellular superoxide production, normally presents in the first years of life with severe recurrent bacterial and fungal infections . METHODS: From the files of two children's hospitals we identified 11 CGD patients who were remarkable for an unusually late diagnosis, at 13-43 years of age . Their clinical and laboratory features were examined . FINDINGS: The first clinical manifestation occurred at a median age of 3.6 years but CGD was not diagnosed until a median age of 22 years . Pneumonias and abscesses caused by Staphylococcus aureus and Aspergillus species were the most frequent infections . Granulomas, often leading to chronic complications, occurred in 7 of the patients . With 1.1 severe infections in 100 patient months, the 11 patients had a lower frequency of severe infections than patients with classic CGD; however, such infections could be equally life-threatening . 8 of the patients had X-linked CGD with small but detectable quantities of cytochrome b558, normally absent in X-linked CGD; and 3 had autosomal-recessive CGD . 9 patients had residual production of reactive oxygen metabolites, a feature that could explain the low incidence of infections . INTERPRETATION: CGD in adults may be more common than previously assumed . In view of the possibility of timely treatment, infection prophylaxis, and genetic counselling for affected families, CGD should be excluded in any patient with unexplained infections or granulomas.

Proc Natl Acad Sci U S A, 1996 Jan 23, 93(2), 734 - 8
Crystallographic analysis of endogenous peptides associated with HLA-DR1 suggests a common, polyproline II-like conformation for bound peptides; Jardetzky TS et al.; The structure of the human major histocompatibility complex (MHC) class II molecule HLA-DR1 derived from the human lymphoblastoid cell line LG-2 has been determined in a complex with the Staphylococcus aureus enterotoxin B superantigen . The HLA-DR1 molecule contains a mixture of endogenous peptides derived from cellular or serum proteins bound in the antigen-binding site, which copurify with the class II molecule . Continuous electron density for 13 amino acid residues is observed in the MHC peptide-binding site, suggesting that this is the core length of peptide that forms common interactions with the MHC molecule . Electron density is also observed for side chains of the endogenous peptides . The electron density corresponding to peptide side chains that interact with the DR1-binding site is more clearly defined than the electron density that extends out of the binding site . The regions of the endogenous peptides that interact with DRI are therefore either more restricted in conformation or sequence than the peptide side chains or amino acids that project out of the peptide-binding site . The hydrogen-bond interactions and conformation of a peptide model built into the electron density are similar to other HLA-DR-peptide structures . The bound peptides assume a regular conformation that is similar to a polyproline type II helix . The side-chain pockets and conserved asparagine residues of the DR1 molecule are well-positioned to interact with peptides in the polyproline type II conformation and may restrict the range of acceptable peptide conformations.

Biochemistry, 1996 Jan 23, 35(3), 999 - 1009
Topological disposition of tyrosine 486 in anion exchanger from human erythrocytes; Kalo MS; The location with respect to the plasma membrane of tyrosine 486 in the native anion exchanger of human erythrocytes has been determined by site-directed immunochemistry . Intact erythrocytes and inside-out vesicles were {125I}radioiodinated by lactoperoxidase in the same vessel . After the erythrocytes and inside-out vesicles had been separated by differential centrifugation, the modified polypeptide of the anion exchanger was isolated from each sample and digested with the proteinase from Staphylococcus aureus strain V8 and trypsin to generate the peptide YIVGR . An immunoadsorbent that was specific for the carboxy-terminal sequence -IVGR was used to purify the peptide YIVGR, which contains tyrosine 486 of the anion exchanger, from the products of the digestion . The {125I}radioiodinated peptides isolated by the immunoadsorbent were submitted to high-pressure liquid chromatography, and their respective mobilities were compared to those of synthetic peptides that had been iodinated at tyrosine . By applying this technique, the peptide containing tyrosine 486 was unambiguously identified, and the incorporation of {125I}iodine into this residue in anion exchanger could be monitored . When inside-out vesicles and intact cells were {125I}radioiodinated in the same suspension, tyrosine 486 was modified to at least a 6-fold greater specific radioactivity in the inside-out vesicles than it was in the intact cells . This amino acid, therefore, was assigned to the cytoplasmic surface of native anion exchanger . It follows that the polypeptide of anion exchanger spans the membrane three times before it reaches the extracellular region surrounding glutamine 550.

J Med Chem, 1996 Jan 19, 39(2), 436 - 45
Studies on 6-aminoquinolones: synthesis and antibacterial evaluation of 6-amino-8-methylquinolones; Cecchetti V et al.; The 6-aminoquinolone had previously been identified as a new class of quinolone antibacterial agents . To continue our structure-activity relationship (SAR) study in this series, novel 6-amino-8-methylquinolone derivatives have now been synthesized and evaluated for in vitro antibacterial activity . We have shown that the coupled presence of a methyl group at the C-8 position with an amino group at C-6 is effective for enhancing antibacterial activity, particularly against Gram-positive bacteria . The SARs associated with the N-1, C-6, and C-7 are discussed . The 1,2,3,4-tetrahydroisoquinolinyl derivative 19v showed the highest antibacterial activity with MIC values on Gram-positive bacteria superior to that of ciprofloxacin, especially against Staphylococcus aureus strains, including those strains which are methicillin-and ciprofloxacin-resistant.

Biochim Biophys Acta, 1996 Jan 19, 1299(2), 223 - 34
Activation of cytosolic phospholipase A2 in permeabilized human neutrophils; Bauldry SA et al.; Neutrophils (PMN) contain two types of phospholipase A2 (PLA2), a 14 kDa 'secretory' Type II PLA2 (sPLA2) and an 85 kDa 'cytosolic' PLA2 (cPLA2), that differ in a number of key characteristics: (1) cPLA2 prefers arachidonate (AA) as a substrate but hydrolyzes all phospholipids; sPLA2 is not AA specific but prefers ethanolamine containing phosphoacylglycerols . (2) cPLA2 is active at nM calcium (Ca2+) concentrations; sPLA2 requires microM Ca2+ levels . (3) cPLA2 activity is regulated by phosphorylation; sPLA2 lacks phosphorylation sites . (4) cPLA2 is insensitive to reduction; sPLA2 is inactivated by agents that reduce disulfide bonds . We utilized PMN permeabilized with Staphylococcus aureus alpha-toxin to determine whether one or both forms of PLA2 were activated in porated cells under conditions designed to differentiate between the two enzymes . PMN were labeled with {3H}AA to measure release from phosphatidylcholine and phosphatidylinositol; gas chromatography-mass spectrometry was utilized to determine total AA release (mainly from phosphatidylethanolamine) and to assess oleate and linoleate mass . A combination of 500 nM Ca2+, a guanine nucleotide, and stimulation with n-formyl-met-leu-phe (FMLP) were necessary to induce maximal AA release in permeabilized PMN measured by either method; AA was preferentially released . {3H}AA and AA mass release occurred in parallel over time . A hydrolyzable form of ATP was necessary for maximum AA release and staurosporin inhibited PLA2 activation . Dithiothreitol treatment had little affect on {3H}AA release and metabolism but inhibited AA mass release . Assay of cell supernatants after cofactor addition did not detect sPLA2 activity and the cytosolic buffer utilized did not support activity of recombinant sPLA2 . These results strongly suggested that cPLA2 was the enzyme activated in the permeabilized cell model and this is the first report which unambiguously demonstrates AA release in response to activation of a specific type of PLA2 in PMN.

Eur J Biochem, 1996 Jan 15, 235(1-2), 431 - 7
O-glycosylated species of natural human tumor-necrosis factor-alpha; Takakura-Yamamoto R et al.; Tumor-necrosis factor-alpha, produced by human B-cell lymphoblastoid cell line BALL-1, was expressed as four protein bands on SDS/PAGE analysis . It may have been glycosylated, based on the fact that the heavier two of the four bands disappeared after neuraminidase treatment . Sugar composition analyses revealed that the tumor necrosis factor-alpha contained galactose, N-acetylgalactosamine and N-acetylneuraminic acid as sugar components . To prepare sugar chains, tumor necrosis factor-alpha was treated with alkaline borodeuteride and the oligosaccharide-alditols liberated were fractionated by gel-filtration chromatography on a Bio-Gel P-4 column, followed by normal-phase HPLC . Three oligosaccharide-alditols were obtained, and the structures of two of them were identified by methylation analysis and exoglycosidase digestion . The structures of these oligosaccharide-alditols were Gal beta 1-3(NeuAc alpha 2-6)GalNAcol and Gal beta 1-3GalNAcol (GalNAcol, N-acetylgalactosaminitol) . The structure of the remaining oligosaccharide-alditol was determined to be NeuAc alpha 2-3Gal1-3GalNAcol by composition and methylation analyses . About 20% of tumor necrosis factor-alpha was found to be 0-glycosylated, based on the results of the sugar composition and structure analyses . An amino acid sequence analysis of the glycosylated peptides was performed after Staphylococcus aureus V8 protease digestion of tumor necrosis factor-alpha had been completed, and it was proved that the 0-glycosylation site of tumor necrosis factor-alpha was Ser 4.

Med J Aust, 1996 Jan 15, 164(2), 68 - 71
Evolution of resistance in Staphylococcus aureus in Australian teaching hospitals . Australian Group on Antimicrobial Resistance (AGAR); Turnidge JD et al.; OBJECTIVE: To assess the changes in antibiotic resistances in Staphylococcus aureus, both methicillin-susceptible and methicillin-resistant strains, in Australia . DESIGN: Retrospective review of data collected annually . SETTING: Twenty metropolitan teaching hospitals in the six States of Australia and the Australian Capital Territory from 1988 to 1994 . OUTCOME MEASURES: Changes in prevalence and resistance rates of methicillin-resistant S . aureus (MRSA) and methicillin-susceptible strains, based on antibiotic susceptibility testing of clinical isolates of S . aureus . RESULTS: Prevalence of MRSA has remained constant on the eastern seaboard of Australia . A distinctive strain of MRSA emerged in Western Australia which had different antimicrobial susceptibilities . Resistances emerged in MRSA strains from eastern Australia, principally to ciprofloxacin and rifampicin, while resistance to fusidic acid remained stable and resistance to chloramphenicol significantly declined . Resistances in methicillin-susceptible strains remained fairly stable, except for a decline in resistance levels for tetracycline . High levels of resistance were seen to penicillin, moderate levels to erythromycin and low levels to trimethoprim and fusidic acid in methicillin-susceptible strains . CONCLUSIONS: The continued high prevalence of and increasing resistance in MRSA in some Australian hospitals have meant that some strains are now untreatable with oral antibiotics.

Proc Natl Acad Sci U S A, 1996 Jan 9, 93(1), 433 - 7
The peptide binding site of the substance P (NK-1) receptor localized by a photoreactive analogue of substance P: presence of a disulfide bond; Boyd ND et al.; Substance P (SP) is a neuropeptide that mediates multiple physiological responses including transmission of painful stimuli and inflammation via an interaction with a receptor of known primary sequence . To identify the regions of the SP receptor, also termed the NK-1 receptor, involved in peptide recognition, we are using analogues of SP containing the photoreactive amino acid p-benzoyl-L-phenylalanine (Bpa) . In the present study, we used radioiodinated Bpa8-SP to covalently label with high efficiency the rat SP receptor expressed in a transfected mammalian cell line . To identify the amino acid residue that serves as the site of covalent attachment, a membrane preparation of labeled receptor was subjected to partial enzymatic cleavage by trypsin . A major digestion product of 22 kDa was identified . Upon reduction with 2-mercaptoethanol the mass of this product decreased to 14 kDa . The 22-kDa tryptic fragment was purified in excellent yield by preparative SDS/PAGE under nonreducing conditions . Subcleavage with Staphylococcus aureus V8 protease and endoproteinase ArgC yielded fragments of 8.2 and 9.0 kDa, respectively . Upon reductive cleavage, the V8 protease fragment decreased to 3.0 kDa while the endoproteinase ArgC fragment decreased to 3.2 kDa . Taking into consideration enzyme specificity, molecular size, determination of the presence or absence of N-glycosylation sites, and recognition by antibodies to specific sequences of the SP receptor, the V8 protease fragment is Thr-173 to Glu-183, while the endoproteinase ArgC fragment is Val-178 to Arg-190 . These two fragments share the common sequence Val-Val-Cys-Met-Ile-Glu (residues 178-183) . The site of covalent attachment of radioiodinated Bpa8-SP is thus restricted to a residue within this overlap sequence . The data presented here also establish that the cysteine residue in this sequence Cys-180, which is positioned in the middle of the second extracellular loop, participates in a disulfide bond that links the first and second extracellular loops of the receptor.

Proc Natl Acad Sci U S A, 1996 Jan 9, 93(1), 362 - 6
Efflux pump of the proton antiporter family confers low-level fluoroquinolone resistance in Mycobacterium smegmatis; Takiff HE et al.; Due to the resurgence of tuberculosis and the emergence of multidrug-resistant strains, fluoroquinolones (FQ) are being used in selected tuberculosis patients, but FQ-resistant strains of Mycobacterium tuberculosis have rapidly begun to appear . The mechanisms involved in FQ resistance need to be elucidated if the effectiveness of this class of antibiotics is to be improved and prolonged . By using the rapid-growing Mycobacterium smegmatis as a model genetic system, a gene was selected that confers low-level FQ resistance when present on a multicopy plasmid . This gene, lfrA, encodes a putative membrane efflux pump of the major facilitator family, which appears to recognize the hydrophilic FQ, ethidium bromide, acridine, and some quaternary ammonium compounds . It is homologous to qacA from Staphylococcus aureus, tcmA, of Streptomyces glaucescens, and actII and mmr, both from Streptomyces coelicoler . Increased expression of lfrA augments the appearance of subsequent mutations to higher-level FQ resistance.

Arch Intern Med, 1996 Jan 8, 156(1), 82 - 4
Contaminated stethoscopes revisited; Smith MA et al.; BACKGROUND: Because of their universal use by medical professionals, stethoscopes can be a source of nosocomial infections . OBJECTIVE: To determine the frequency of contamination of stethoscopes with bacteria and fungi . METHODS: Cultures were obtained from 200 stethoscopes from four area hospitals and outpatient clinics in Houston, Tex . The frequency of stethoscope contamination in different groups of hospital personnel and medical settings was determined . We also measured the frequency of antimicrobial resistance of the staphylococcal strains that were isolated . RESULTS: One hundred fifty-nine (80%) of the 200 stethoscopes surveyed were contaminated with microorganisms . The majority of organisms that were isolated were gram-positive bacteria, primarily Staphylococcus species . Fifty-eight percent of the Staphylococcus species that were isolated, including four (17%) of 24 Staphylococcus aureus isolates, were resistant to methicillin . Physicians' stethoscopes were contaminated more often than those of other medical personnel groups (P = .02) . Stethoscopes used only in designated areas were contaminated less frequently than stethoscopes belonging to individual medical personnel (P = .01) . Although stethoscopes were contaminated in all areas, stethoscopes from the pediatric medical setting were contaminated less frequently than those from other hospital areas (P = .009) . CONCLUSIONS: Stethoscope use may be important in the spread of infectious agents, including antimicrobial-resistant strains, and strategies to reduce the contamination of stethoscopes should be developed . We recommend disinfection of stethoscopes or regular use of disposable stethoscope covers.

Med Dosw Mikrobiol, 1996, 48(3-4), 117 - 21
{Antagonistic properties of bacterial flora in the mouth and throat of children}; Krzeminski Z et al.; The research concerned the antagonistic activity of oral and pharyngeal bacterial flora in 44 children, of both sexes, aged 4-15 . These properties were estimated basing upon in vitro inhibition of the growth of the standard indicator strains Staphylococcus aureus 209P and Escherichia coli K-12 . Bacteria, both aerobic as well as anaerobic, inhibiting the growth of S . aureus 209P were found in every sample . The median percentages of bacteria showing these properties were not significantly different in both environments and they ranged from 25% to 33% . The antagonistic activity of oral and pharyngeal bacterial flora against the indicator strain E . coli K-12 was significantly lower when compared with the activity against the staphylococcal strain.

Microbios, 1996, 88(357), 237 - 51
A high molecular weight protein from Staphylococcus intermedius cross-reacts with Staphylococcus aureus enterotoxin antibodies; Laffan JJ et al.; Enterotoxin production by Staphylococcus species other than Staphylococcus aureus has been reported . Staphylococcus strains (104 in toto) representing twelve species and subspecies were examined for enterotoxins using a commercial staphylococcal enterotoxin ELISA immunoassay (TECRA, International Bioproducts) . Staphylococcus intermedius (24 strains) and S . aureus (7 strains) were positive with this test . Western blots of S . aureus exoproteins demonstrated proteins of approximately 30 kD, consistent with known staphylococcal enterotoxins . The major antigen in all S . intermedius strains, a 75 kD protein, was not analogous to previously described staphylococcal enterotoxins . This protein was unique to S . intermedius . Gel filtration data indicate that the protein is a subunit of a larger protein in vivo . The 75 kD protein cross-reacts with several enterotoxin antibodies . It is unclear whether the protein is a toxin, but its homology with S . aureus enterotoxins may indicate a shared toxic region, or this protein may create false positive results in screening for enterotoxin.

Microb Drug Resist, 1996 Winter, 2(4), 393 - 9
Emergence of a methicillin-resistant Staphylococcus aureus clone related to the Brazilian epidemic clone III::B:A causing invasive disease among AIDS patients in a Brazilian hospital; Teixeira LA et al.; In a previous study we described the extensive geographic spread of a multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA) clone in hospitals located in the southern, southeastern, and northern parts of Brazil . In this study we used a set of molecular markers to demonstrate the emergence of a novel MRSA clone distinct from but closely related to the widely spread Brazilian epidemic clone . The new MRSA clone caused an outbreak among acquired immunodeficiency syndrome patients in a Brazilian hospital specializing in tropical diseases and human immunodeficiency virus- and human T-cell leukemia virus (HLTV)-related infections.

J Med, 1996, 27(5-6), 303 - 17
The pattern of inflammation in rat sepsis due to enterotoxin-producing Staphylococcus aureus: a comparison with ischemia-reperfusion injury; Lin RY et al.; Sepsis and trauma have similarities in their immunopathologic profiles . Both conditions can result in multi-system organ failure which is sometimes associated with cytokine generation and inflammatory cell activation . Furthermore, decreases in peripheral blood monocyte expression of HLA-DR have been noted in both human sepsis and trauma . However, the magnitude, onset, and time course of such stimuli are often difficult to ascertain in human studies . Thus, to study a more detailed in vivo immunologic profile in these conditions, rat models were employed . Our aim was to describe and analyze cytokine and peripheral blood immunophenotype patterns in bacterially induced rat sepsis and to compare this to rat ischemia-reperfusion injury . Sprague-Dawley rats underwent either bacterial injection with enterotoxin producing Staphylococcus aureus or hind limb ischemia/ reperfusion . Two bacterial doses which were either lethal or sublethal at 24-48 hours were utilized . Peripheral blood neutrophils and B-lymphocytes were studied for expression of beta-integrins (CD11b and CD11b/c) and I-A, respectively, using flow cytometry . Corresponding plasma levels of TNF alpha and interferon gamma were measured by ELISA . At 24 hr, a lethal bacterial lethal bacterial dose injection resulted in significantly higher levels of neutrophil CD11b/c expression (p < 0.005) compared with ischemia-reperfusion treatment . B-cell I-A expression was also higher in lethal sepsis . Gamma interferon levels were significantly higher in lethal sepsis compared with ischemia-reperfusion (p = 0.005) . Studies over time showed that CD11b expression and interferon gamma were both more marked at 6 hr than at 24 hr in lethal sepsis . This pattern was not observed in sublethal sepsis or in ischemia-reperfusion . CD11b/c expression on the other hand remained elevated at comparable levels at 6 and 24 hr in lethal sepsis . B-cell I-A expression in ischemia-reperfusion and sublethal sepsis decreased at 24 hr compared with baseline . Lethal sepsis in rats injected with enterotoxin producing staphylococcus results in phasic alterations in neutrophil CD11b and plasma interferon levels prior to death . In analogy to the findings of monocyte decreases in DR expression observed in human trauma and sepsis, rat B-cell I-A expression showed decreases in sublethal sepsis as well as in ischemia-reperfusion injury . However, this was not observed in lethal sepsis . These findings have implications in understanding the immunologic/inflammatory changes observed in human sepsis and trauma.

Autoimmunity, 1996, 24(4), 247 - 55
T helper cell-dependent, microbial superantigen-mediated B cell activation in vivo; Tumang JR et al.; We have utilized a severe combined immune-deficient (SCID) mouse adoptive transfer model to explore the in vivo immunostimulatory effects of bacterial superantigens (SAg) . B cell reconstituted SCID recipients were treated with the Staphylococcus aureus-derived toxic shock syndrome toxin (TSST-1) alone or in conjunction with syngeneic L3T4+ TSST-1-reactive Th cells . Over several months of study, the repetitive administration of TSST-1 resulted in a prompt, transient increase in serum IgG levels . This response required both biologically active TSST-1 and Th cells . These findings demonstrate that certain bacterial SAgs can promote Th cell-dependent B cell activation and differentiation in vivo . These studies strengthen the analogy between SAg-mediated and allospecific Th-B cell interactions responsible for the autoimmune sequelae of graft-versus-host disease.

Acta Microbiol Pol, 1996, 45(3-4), 269 - 78
Phenotyping methods in epidemiological analysis of epidemic Staphylococcus aureus strains; Konopka M et al.; One hundred and fifty hospital Staphylococcus aureus strains isolated on Polish hospitals during an outbreaks were used to evaluate usefulness of S . aureus phenotyping methods . According to the expression of resistance to methicillin (a marker of resistance to all beta-lactam antibiotics) all strains were classified as homogeneously of heterogeneously resistant to methicillin (methicillin resistant S . aureus--MRSA) and as susceptible to this antibiotic (methicillin-susceptible S . aureus--MSSA) . All strains were analysed according to the resistance patterns to fifteen antistaphylococcal drugs, results of crystal violet test, phage patterns and results of biochemical fingerprinting by PhenePlate (PhP) System (BioSys inova) . All MSSA analysed were resistant to penicillin and 22% to tetracycline, and only occasionally resistant to other antimicrobials . They showed sensitive to phages of all international and additional lytic groups . Heterogeneous MRSA were widely susceptible to almost all antimicrobials except tetracycline and were lysed by phages of Ist, IIIrd international groups and additional phages . All these strains produced penicillinases . Homogeneous MRSA were multi-drug resistant and were not typable by phages of Ist and IInd lytic groups and weakly typable by phages of IIIrd and additional groups . PhP Systems divided all used strains into 13 common (with two dominating) and 50 single strain PhP-types . The combination of various phenotyping methods may be useful in epidemiological investigation of hospitals.

Microbios, 1996, 88(354), 55 - 62
Microcalorimetric and electron microscopic investigation on the effects of essential oil from Cymbopogon densiflorus on Staphylococcus aureus; Takaisi-Kikuni NB et al.; Microcalorimetry, optical density measurements and electron microscopy, were used to assess the influence of various amounts of the essential oil of Cymbopogon densiflorus (lemongrass oil) on the metabolic activity, growth and morphology of Staphylococcus aureus . Relatively high concentrations of the oil impaired staphylococcal growth in a bacteriostatic manner (chloramphenicol type), and in low doses metabolism became ineffective due to energy losses in the form of heat . Ultrastructural data revealed morphological changes characteristic for the influence of bactericidal antibiotics inducing bacteriolysis (penicillin type) . The essential oil may have antibacterial activity by influencing bacterial targets involved in cytoplasmic and cell wall metabolism.

Srp Arh Celok Lek, 1996, 124 Suppl 1, 149 - 51
{Our protocol in the treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis}; Kostic S et al.; Peritonitis is a very serious complication in patients treated by CAPD . The frequent and grave episodes are the main cause for CAPD withdrawal . The effective prevention and adequate therapy of peritonitis are very important for a successful CAPD treatment . The aim of this study was to present our results of peritonitis therapy in CAPD patients using the following protocol: Vancomycin 1.0 g.i.p . immediately after the admission to the unit, 250 mg Ceftriaxon (Longaceph) after a bag exchange for seven days, and the 1.0 g Vancomycin . Using this protocol we treated 97 peritonitis episodes; 74 of them (80%) were treated successfully by this antibiotics combination . The clearness of peritoneal fluid was attained 1-3 days within 56.7% of cases, and 4-6 days within the 29.7% peritonitis episodes (86.4%) . A common cause of peritonitis was Staphylococcus epidermidis episodes (28.4%), Staphylococcus aureus (13.5%), and in 39.1% episodes the cultures were sterile . Uneffective antibiotic application according to this protocol was found in cases of pseudomonas and fungal peritonitis . The mentioned antibiotic therapy had no effect in a small number of peritonitides provoked by S . epidermidis (8.7%) and S . aureus (13.0%) This required the application of a third antibiotic . It could be concluded that this antibiotic combination in treatment of peritonitis in patients on CAPD was very effective.

Fiziol Zh, 1996, 42(5-6), 58 - 65
{The isolation of a transfer factor of the delayed-hypersensitivity type to the antigenic substances of Staphylococcus aureus in guinea pigs}; Holieva OH et al.; Immunoactivating effects of guinea pig's staphylococcal Transfer factor (TF) were studied in homologous and heterologous (human leukocytes) systems . In vivo (skin tests) and in vitro (Inhibition of leukocytes migration) tests showed that our TF is able to activate intact as well as sensibilized cells . Antigen-specific properties of TF also were showed.

Biochem Cell Biol, 1996, 74(5), 701 - 13
Modulation of the cleavage of glycosylphosphatidylinositol-anchored proteins by specific bacterial phospholipases; Sharom FJ et al.; Many enzymes are tethered to the extracellular face of the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor . These proteins can be released in soluble form by the action of GPI-specific phospholipase . Little is currently known about the factors modulating this release . We investigated the effects of several experimental variables on the cleavage of the GPI-anchored proteins 5'nucleotidase, acetylcholinesterase, and alkaline phosphatase by phospholipases from Bacillus thuringiensis and Staphylococcus aureus . Phospholipase activity was not inhibited by isotonic salt and was relatively unaffected by buffer type and concentration . In both cases, the optimum pH for cleavage was approximately 6.5 . Over 80% of 5'-nucleotidase activity present in the lymphocyte plasma membrane was cleaved by the B . thuringiensis enzyme, and the initial rate of release was linear with phospholipase concentration . All three GPI-anchored proteins were released from lymphocyte plasma membrane at comparable phospholipase concentrations, suggesting that they have similar anchor structures . The catalytic activity of 5'-nucleotidase appeared to increase following conversion to the soluble form . The relative surface charge of the host plasma membrane modulated catalytic activity towards GPI-anchored proteins, depending on the net charge of the phospholipase . Studies on purified lymphocyte 5'-nucleotidase reconstituted into bilayers of dimyristoylphosphatidylcholine indicated that the efficiency of phospholipase cleavage was 12- to 50-fold lower when compared with the native plasma membrane . The ability of the phospholipase to cleave the GPI anchor was further reduced when the bilayer was in the gel phase.

Antibiot Khimioter, 1996, 41(7-8), 13 - 7
{Actinomycin D resistance of gramicidin-resistant strains of Staphylococcus}; Polin AN et al.; Factors defining actinomycin D resistance in Staphylococcus aureus resistant to gramicidin S were investigated . The results of the thin layer chromatography, high-voltage electrophoresis and bioautography showed that the resistant cells did not inactivate actinomycin D by the hydrolysis of the lactone bond in the antibiotic molecule . The estimation of the cell ability to bind actinomycin D revealed that the antibiotic binding to the resistant cells was lower by 70-75 per cent as compared to the cells of the susceptible strains . Gramicidin S impaired the intactness of the cytoplasmic membranes and increased the absorption of actinomycin D by the susceptible cells and to a much lesser extent by the cells of the resistant strains . Actinomycin D bound by the susceptible cells could not be washed out with a buffer solution . It could be separated from the cells only by extraction with an organic solvent . Comparative electron microscopy of the susceptible and resistant cells demonstrated that the cell walls in the resistant strains were 1.5-2-fold thicker than the cell walls in the susceptible strains . The actinomycin D resistance of the Staphylococcus strains resistant gramicidin S was likely conditioned by the barrier properties of the morphologically changed cell walls.

Acta Clin Belg, 1996, 51(6), 412 - 6
Epidural abscess: case report and review of the literature; Colle I et al.; Spinal epidural abscess is an uncommon site of infection, resulting in back pain, fever, weakness and loss of sensibility . These signs should suggest the diagnosis, and quick confirmation by MRI should be performed . Immediate surgical decompression and antibiotherapy is necessary, because this is the base of a possible successful functional recovery . Empiric therapy consisting of high dose of penicillinase-resistant antibiotics is advised because most often an epidural abscess is caused by Staphylococcus aureus . However, because other bacteria can be involved, an aminoglycoside or a cephalosporin should be added to the empiric treatment, until the results of the cultures are known . When diagnosis and therapy are delayed, permanent paralysis and death are common.

Vestn Khir Im I I Grek, 1996, 155(4), 35 - 7
{The dynamics of the antiseptic resistance of the causative agents of soft-tissue suppurative-inflammatory diseases in children}; Abaev IuK et al.; Opening of purulent foci in children with pyo-inflammatory diseases (PID) of soft tissues often leads to detection of staphylococcus aureus in the monoculture and different associations of this microbe with gram-negative bacteria in amounts exceeding the "critical level" responsible for the development of PID . Repeated examinations revealed a 2 times decreased frequency of detection of staphylococcus monocultures and 1.5 time less diversity of the association of microorganisms . Most efficient antiseptics among the investigated ones in relation to bacteria isolated in the opened purulent foci were found to be iodopyron, pervomur, boric acid, resorcinum, dioxidine.

Sao Paulo Med J, 1996 Jan-Feb, 114(1), 1068 - 72
A genetic study of a Staphylococus aureus plasmid involving cure and transference; Darini AL; High frequency transfer and elimination of drug resistance may indicate an extrachromosomal inheritance of genetic determinants . This study shows the cure and transfer of a small plasmid and tetracycline resistance in Staphylococcus aureus 1030 (55)Tet strains . Several methods are available for plasmid elimination . We used ethidium bromide, an agent that binds to DNA, and thus inhibits DNA polymerase . This caused a high frequency of loss of the small plasmid and resistance to tetracycline . Transfer of tetracycline resistance was done in a mixed culture at a frequency of 10(-6) . This type of study is very important to physicians and epidemiology investigators and provides better knowledge on antibiotic-resistance mechanisms that may occur in vivo in a hospital environment.

Trans Am Ophthalmol Soc, 1996, 94, 241 - 52; discussion 252-7
Intraocular dexamethasone produces a harmful effect on treatment of experimental Staphylococcus aureus endophthalmitis; Meredith TA et al.; BACKGROUND: We created a standardized model of severe Staphylococcus aureus endophthalmitis in the aphakic rabbit eye to test various treatment strategies involving corticosteroid administration in addition to vitrectomy and antibiotic treatment . MATERIALS AND METHODS: In 71 aphakic New Zealand albino rabbit eyes, experimental endophthalmitis was created by injecting 10(5) colony-forming units of Staphylococcal aureus . The animals were divided into 5 groups . One control group was followed up without treatment, while 4 groups were treated with vitrectomy and intraocular cefazolin injection . Two groups were also treated with intramuscular methylprednisolone, 1 group beginning on the day of surgery and 1 group beginning on the following day . In the final group, dexamethasone, 400 micrograms, was injected into the vitreous cavity at the close of surgery . Culture results were compared on the first 2 days after surgery . Inflammatory scores, including development of total corneal opacity, were assessed over a 21-day follow-up period, and histopathologic grading was carried out at the conclusion of the clinical observations . RESULTS: Simultaneous administration of systemic corticosteroids beginning on the day of vitrectomy decreased inflammatory scores 1 week after institution of therapy but did not affect final scores . Delay of initiation of intramuscular corticosteroid until the first postoperative day negated the positive effects . Administration of intraocular corticosteroids was associated with an increase in inflammatory scores throughout the period of observation, an increase in percentage of eyes that developed opaque corneas, an increase in choroidal inflammation graded moderate or severe, and an increase in retinal necrosis compared with vitrectomy and cefazolin injection alone . CONCLUSIONS: This data suggest caution in the use of intraocular corticosteroids in treatment of severe endophthalmitis.

Immunol Lett, 1996 Jan, 49(1-2), 111 - 6
The superantigen exfoliative toxin induces cutaneous lymphocyte-associated antigen expression in peripheral human T lymphocytes; Zollner TM et al.; Several immune-mediated dermatoses including psoriasis and atopic dermatitis can be exacerbated by bacterial infections . Superantigen producing bacteria can be isolated from skin lesions of these dermatoses . Consistent with superantigen effects, skewed T cell receptor variable gene usage has been demonstrated within these lesions . Therefore, the question arises whether superantigen induce a skin-seeking phenotype within peripheral T cells . In this study, we investigated the in vitro influence of the V beta 2-selective superantigen exfoliative toxin from Staphylococcus aureus on the expression of the cutaneous lymphocyte-associated antigen on peripheral T lymphocytes of healthy donors . We demonstrate that exfoliative toxin dramatically upregulates cutaneous lymphocyte-associated antigen expression on T cell receptor V beta 2+ lymphocytes . Up to 69% of V beta 2+ lymphocytes expressed cutaneous lymphocyte-associated antigen after 5 days of in vitro culture . Additionally, exfoliative toxin also increased cutaneous lymphocyte-associated antigen expression in CD3+ T cell receptor V beta 2- lymphocytes indicating a different effect as caused by the superantigen-T cell receptor V beta 2 interaction . Our findings suggest influence of bacterial superantigens on T lymphocyte skin homing in vivo.

J Basic Microbiol, 1996, 36(6), 447 - 52
Cadmium-sensitive targets in the aerobic respiratory metabolism of Staphylococcus aureus; Tynecka Z et al.; Studies on the effect of various Cd2+ concentrations on substrate oxidation by whole cells of cadmium-sensitive Staphylococcus aureus 17810S showed that oxidation of glutamate or pyruvate was highly sensitive to low Cd2+ concentrations (5 microM), whereas L-lactate oxidation was insensitive even to high Cd2+ concentrations (100 microM) . Location of the cadmium-sensitive targets in the enzyme systems involved in oxidation of these substrates was studied in subcellular fractions prepared from cells pretreated with 5 or 100 microM Cd2+ . Activities of the cytoplasmic 2-oxoglutarate dehydrogenase complex (ODHC)') and pyruvate dehydrogenase complex (PDHC) were strongly inhibited with 5 microM Cd2+, while with 100 microM Cd2+ the inhibition was almost complete . In contrast, activities of the cytoplasmic NAD-dependent glutamate dehydrogenase (NAD-GDH), the membrane-bound NADH dehydrogenase (NDH) and HQNO-sensitive NADH oxidase were not sensitive to 100 microM Cd2+ . These data indicate that the accessible, cadmium-sensitive targets are located only in the cytoplasmic ODHC and PDHC . It is postulated that two vicinal dithiols present in ODHC and PDHC may be regarded as the primary cadmium-sensitive targets in the systems oxidizing glutamate or pyruvate . Since activities of the membrane-bound NAD-independent L-lactate dehydrogenase (iLDH) and HQNO-sensitive L-lactate oxidase were not affected by 100 microM Cd2+, this indicates that the L-lactate oxidizing system lacks the accessible, cadmium-sensitive targets . The mechanism of Cd2+ toxicity to energy conservation with glutamate, pyruvate or L-lactate in S . aureus is discussed.

Kurume Med J, 1996, 43(3), 199 - 206
Increased incidence of beta-lactamase-plasmid negative, high level methicillin-resistant Staphylococcus aureus (MRSA); Yokoyama T et al.; Recently isolated strains of methicillin-resistant Staphylococcus aureus (MRSA) have high levels of resistance to the agent and produce beta-lactamase less frequently than methicillin-susceptible strains (MSSA) . This phenomenon has been observed in Japan . The majority of MSSA strains (26 of 30) isolated in 1992 produced beta-lactamase while only 18 of 31 and 25 of 67 MRSA strains, isolated in 1991 and in 1992 respectively, produced the enzyme . We analyzed the beta-lactamase gene (blaZ) in 30 strains each of MRSA and MSSA isolated from our hospital using the polymerase chain reaction . We found that 28 MSSA strains but only 14 MRSA strains possessed the gene . In addition, the present study indicates that many recently isolated MRSA strains, which lacked blaZ gene and were negative for beta-lactamase, consistently produced coagulase of type II (coagulase typing is a marker of epidemiology for Staphylococcus aureus) . These beta-lactamase negative, type II coagulase producing and highly methicillin-resistant MRSA strains are considered to have an increased ability to successfully colonize individuals and an increased epidemic potential, probably because of the saving of the energy otherwise expended in beta-lactamase production and of the loss of beta-lactamase plasmid coding the mecA gene repressor, resulting in constitutive PBP2' production . These factors may contribute to the wide spread of these strains of MRSA in a nosocomial environment.

Microbios, 1996, 85(342), 45 - 65
Antibiotic and biocide resistance in bacteria; Russell AD et al.; Antibiotic-resistant bacteria pose an ever-increasing therapeutic problem . The ways whereby bacteria circumvent drug action are many and varied, ranging from intrinsic impermeability to acquired resistance (involving plasmids, transposons and mutations) . Antibiotics may be unable to reach susceptible target sites, they may be enzymatically inactivated, modified or expelled or mutations may arise such as to render the target sites insusceptible . Mechanisms of bacterial resistance to biocides are less well understood but cellular impermeability is a major factor . Plasmid-mediated efflux of cationic antiseptics in antibiotic-resistant Staphylococcus aureus strains has been demonstrated but its role in the resistance of these organisms to the biocide concentrations used in clinical practice is unclear . An association between resistance to antibiotics and biocides in Gram-negative bacteria has also been observed but it is often difficult at present to reach definite conclusions about genetic linkages between antibiotic resistance and biocide resistance.

Nephrologie, 1996, 17(5), 289 - 95
{B lymphocytes of patients with complete IgA deficiency secrete IgA in response to interleukin 10}; Briere F et al.; We have previously shown that human B lymphocytes cultured in the CD40 system, composed of an anti-CD40 mAb presented by a CD32-transfected fibroblastic cell line, proliferate but do not secrete immunoglobulins (Igs) . However, the addition of particles of Staphylococcus aureus Cowan (SAC) induces B cell to secrete considerable amounts of Igs even in the absence of exogenous cytokines (CD40/SAC system) . Additionally, B lymphocytes cultured in the CD40 system in the presence of human IL-10, produce high level of IgM, IgG and IgA, which are further increased by addition of SAC . Here, we have studied the capacity of peripheral blood lymphocytes from patients with IgA deficiency (IgA-D) to secrete Igs, particularly IgA after CD40 triggering . Peripheral blood mononuclear cells (PBMNC) from IgA-D patients cultured in the CD40/SAC system produced IgM and IgG, but no IgA . The addition of IL-10 to the cultures, enhanced the production of IgM and IgG and most strikingly induced the production of high amounts of IgA . The addition of IL-10 to PBMNC from IgA-D patients activated through CD40 alone resulted in the production of IgA . Thus, IL-10 can remove the block in B cell differentiation and allows B cells from IgA-D patients to differentiate into IgA secreting cells.

Arch Orthop Trauma Surg, 1996, 115(6), 325 - 31
Septic conditions of the shoulder--an up-dating of treatment strategies; Pfeiffenberger J et al.; We report the cases of 28 patients with bacterial infections of the shoulder treated between 1979 and 1991 . There were ten cases of septic arthritis, ten cases of simple osteomyelitis of the proximal humerus, four cases of septic arthritis and concomitant osteomyelitis of the proximal humerus and four cases of periarticular soft-tissue infection . The infections, except for the cases of osteomyelitis, were staged by a "Classification of Exogenic Bacterial Infections" (CEBI) . In septic arthritis and in periarticular soft-tissue infection, the time between the initial symptoms of infection and diagnosis was about 20 days . In the cases with osteomyelitis, there was an average delay of 9 months, which was partly due to the slow evolution of plasmacellular osteomyelitis . Treatment was based on operative debridement and arthrotomy, the insertion of drains, the implantation of gentamicin-polymethylmethacrylate beads and the application of high-dose parenteral antibiotics . In the postoperative period physiotherapy with early active and/or passive range-of-motion exercises favoured the draining of secretions and therefore gave better results than complete immobilisation . Treatment was evaluated using a modification of the shoulder score of Wulker et al . {17} . This study demonstrated that favourable results could only be obtained if the diagnosis was made early . This is particularly true for infections with Staphylococcus aureus (found in 19 patients) . The overall result of the treatment of osteomyelitis and periarticular soft-tissue infection was good or satisfactory, while unsatisfactory results were noted for the patients with septic arthritis, particularly those with both septic arthritis and osteomyelitis.

Dermatology, 1996, 193(2), 83 - 7
Staphylococcus aureus skin colonization in infants with atopic dermatitis; Monti G et al.; BACKGROUND: Coagulase-positive Staphylococcus aureus colonizes eczematous lesions in 78-100% of children and adults with atopic dermatitis (AD), whereas it is found on skin of healthy subjects in only 2-25% of cases . On unaffected skin of subjects with AD the bacterium has been isolated in 51-100% of cases . OBJECTIVE AND METHODS: This paper examines rate and density of S . aureus colonization, using the swab technique and the contact plate method, respectively, on affected and unaffected skin in 72 infants with AD (age 3-24 months) and in a control group, to determine if there are significant differences with respect to what is reported for children and adults with AD . RESULTS AND CONCLUSIONS: The main differences is that on unaffected skin of our infants with AD, bacterium colonization rate is significantly lower than on affected skin.

Int Orthop, 1996, 20(1), 32 - 4
Intervertebral discitis in children: a review of 12 cases; Ventura N et al.; Twelve children with lumbar discitis were reviewed . The average age at diagnosis was 2.5 years . Seven were girls, and the follow-up varied between 2 and 10 years (average 5 years) . The clinical signs were general irritability, abdominal or hip pain and refusal to walk or to sit . The erythrosedimentation rate was elevated in all but two . Radiographic narrowing of the disc space was seen in seven patients . Needle disc aspiration was done in five cases with two being positive for Staphylococcus aureus . Blood culture was positive in one case . Magnetic resonance imaging helped to diagnose the condition in three . Treatment consisted of bed rest and immobilisation of the spine; intravenous antibiotics were given to nine children . The natural course of the disease was benign in all our twelve cases.

Ir J Med Sci, 1996 Jan-Mar, 165(1), 40 - 3
Staphylococcus aureus sensitivity to various antibiotics--a national survey in Ireland 1993; Moorhouse E et al.; The sensitivity of Staphylococcus aureus (S . aureus) to methicillin, penicillin, gentamicin, erythromycin, ciprofloxacin, fusidic acid and mupirocin was tested in 1152 clinical isolates from nine hospital microbiology departments . In all cases standard methods for culture and sensitivity were employed using either the Stokes' or a modified Stokes' method for susceptibility testing . The isolates were recovered from 1150 patients (606 men, 544 women; mean age: 41 years) and only those deemed relevant to the patient's clinical condition were included . Of the total 1152 isolates, 454 were regarded as hospital acquired, 506 were community acquired and the source of the remaining 192 isolates was unknown . The overall percentages of S . aureus sensitive to the tested antibiotics were as follows: methicillin 85%, penicillin 8%, gentamicin 89%, ciprofloxacin 85%, erythromycin 80%, fusidic acid 96%, mupirocin 98% . The sensitivity of the methicillin resistant strains to the other antibiotics tested was generally low except for fusidic acid and mupirocin, both of which retain good activity against methicillin resistant S . aureus (MRSA).

What Is Bioengineering?, What Is Fermentation?, What Is Prokaryote?, What Is Water Purification?, What Is Genetics?, a, Microorganism, r, Microorganisms, e, Bacteria, a, Bacterium, s, Microbiology, s, Streptococci, r, Minimal inhibiting concentration, c, Fermentations, o, S. cerevisiae, s, Acinetobacter, r, Cephalosporin, a, Escherichia coli, i, Candida albicans, r, Klebsiella, i, Growth media, r, Penicillin, n, Antimicrobial, s, Morganella, s, Campylobacter, e, Fermentations, n, Neisseria, a, Cell cultures, o, Escherichia coli, o, Staphylococcus aureus, o, Microbial, e, Culture medium

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005