Staphylococcus aureus

J Bacteriol, 1998 Nov, 180(21), 5780 - 3
trans-complementation of a Staphylococcus aureus agr mutant by Staphylococcus lugdunensis agr RNAIII; Benito Y et al.; RNAIII from Staphylococcus lugdunensis (RNAIII-sl) in a Staphylococcus aureus agr mutant partially restored the Agr phenotype . A chimeric construct consisting of the 5' end of RNAIII-sl and the 3' end of RNAIII from S . aureus restored the Agr phenotype to a greater extent, suggesting the presence of independent regulatory domains.

J Surg Res, 1998 Nov, 80(1), 28 - 34
Immobilized IgG and fibrinogen differentially affect the cytoskeletal organization and bactericidal function of adherent neutrophils; De La Cruz C et al.; The infection of a vascular prosthesis is a dreaded clinical outcome . Since fibrinogen (FBGN) and immunoglobulin (IgG) coat the implanted biomaterial surface, it is with these immobilized proteins that the neutrophil (PMN) interacts . This study tests the hypothesis that PMN are impaired in their ability to kill bacteria when bound to immobilized IgG or FBGN . Isolated human PMN were bound to FBGN or IgG and then left untreated or exposed to phorbol myristate acetate (PMA; 10(-7) M) . PMN adhered loosely, but did not spread, onto FBGN . In contrast, PMN spread fully onto IgG, exhibiting polarized pseudopodia . PMA treatment induced spreading of the FBGN bound cells . Suspended and adherent PMN were incubated 1 h with 14C-labeled Staphylococcus aureus; then, phagocytosis was assessed by radioactive uptake or bacterial kill was determined by plating recovered bacteria and colony counting . Data were analyzed by unpaired t test . We observed that both the phagocytic and the killing ability of FBGN-bound PMN were similar to that of suspended PMN . Conversely, IgG-bound PMN displayed a 62 +/- 6% (P < 0.01) decrease in phagocytosis and 33 +/- 7% (P < 0.05) reduction in kill vs suspended cells . PMA induced a 74 +/- 6% (P < 0.01) reduction in phagocytosis and 68 +/- 5% (P < 0.01) reduction in kill of bacteria for PMN bound to FBGN with no further effect on IgG-bound PMN . Using fluorescent vital dyes and confocal microscopy we determined that 33% fewer PMN were engaged in phagocytosis when bound to IgG vs FBGN . We conclude that Fc receptor ligation by immobilized IgG or PMA treatment of the FBGN-adherent PMN triggers cell spreading and reduced bactericidal activity . These results indicate that excessive cytoskeletal organization may impair the ability of PMN to kill bacteria and result in vascular graft infections .

Proc Natl Acad Sci U S A, 1998 Oct 27, 95(22), 13125 - 9
Interleukin 12 deficiency associated with recurrent infections; Haraguchi S et al.; A 3-yr-old female patient exhibited interleukin 12 (IL-12) deficiency that was associated with recurrent episodes of pneumococcal pneumonia with sepsis and other infections in the absence of fevers . The patient's peripheral blood mononuclear cells (PBMCs) exhibited normal proliferative responses to antigens . Immune responses, including in vivo production of antibodies to diphtheria, tetanus, or pneumococcal antigens, were normal . Ig levels and B cell and T cell phenotypes were also normal . In contrast, IL-12 p70 heterodimer production was undetectable by using supernatants of the patient's stimulated PBMCs when compared with control cells treated similarly . Although present, interferon gamma (IFN-gamma) was reduced . The addition of recombinant IFN-gamma to control cells enhanced the production of IL-12 by up to sixfold . By contrast, IL-12 was undetectable in supernatants of the patient's cells in the presence of recombinant IFN-gamma . IL-12 p40 subunit mRNA by using the patient's PBMCs after stimulation with Staphylococcus aureus Cowan strain 1 or lipopolysaccharide was also undetectable by reverse transcription-PCR when compared with control cells . Production of IL-2, IL-6, tumor necrosis factor alpha, or IFN-gamma of the patient's PBMCs after appropriate stimulation was observed . This patient has either a defect in Staphylococcus aureus Cowan strain 1-lipopolysaccharide- or staphylococcal enterotoxin A-induced signaling pathways for the activation of IL-12 p40 gene expression, or an abnormality in the IL-12 p40 gene itself.

Zentralbl Hyg Umweltmed, 1998 Sep, 201(3), 285 - 96
{Frequency and antibiotic susceptibility of oxacillin resistant Staphylococcus aureus in a teaching hospital}; Ritter E et al.; From October 1993 till October 1994, 115 oxacillin resistant Staphylococus aureus strains were isolated in the laboratory of a teaching hospital . This was 2.4% of all of the Staphylococcus aureus strains . The bacteria were isolated from 30 patients, 7 medical personnel and in the environment of the infected patients . Most of the isolates were cultured from blood cultures, wound swabs and drains . If the referring hospitals has been informed about the MRSA status of the patients, several transmissions could have been prevented . In 10 infected patients, the MRSA strains were isolated from the nose, throat and hands . The isolates were also found on the hands of several personnel and in the patients environment, suggesting that the strains had been widely spread . The MRSA strains predominated in the medical and surgical intensive care units and in 2 general surgical wards . They were only found sporadically in other departments (Ophthalmology, Gynaecology, Paediatrics and Urology) . MRSA-strains were more resistant to imipenem, ofloxacin, gentamicin, trimethoprim-sulfamethoxazole, tetracycline, erythromycin and clindamycin as oxacillin-sensitive Straphylococcus aureus strains . Genotyping (Restriction-Fragment-Length-Polymorphism) revealed six different strain patterns . The same RFLP types were mainly found on different wards . We conclude that various clones of MRSA may have emerged independently within one hospital and that their spread between wards was remarkably limited . Subsequent intensive hygiene measures have been successful in reducing the number of new isolates.

J Clin Invest, 1998 Oct 15, 102(8), 1583 - 90
Antibacterial activity of human neutrophil defensins in experimental infections in mice is accompanied by increased leukocyte accumulation; Welling MM et al.; Neutrophil defensins (or human neutrophil peptides-HNP) are major constituents of the azurophilic granules of human neutrophils and have been shown to display broad-spectrum antimicrobial activity . Other activities of these defensins, which are released from stimulated neutrophils, include cytotoxic, stimulatory, and chemotactic activities toward a variety of target cells . We studied the potential use of HNP-1 for antibacterial therapy of experimental bacterial infections in mice . In experimental peritoneal Klebsiella pneumoniae infections in mice, HNP-1 injection was shown to markedly reduce bacterial numbers in the infected peritoneal cavity 24 h after infection . This antibacterial effect was found to be associated with an increased influx of macrophages, granulocytes, and lymphocytes into the peritoneal cavity . These leukocytes appeared to be a requirement for the antibacterial effect, since in leukocytopenic mice administration of HNP-1 did not display antibacterial activity . HNP-1 treatment also reduced bacterial numbers in experimental K . pneumoniae or Staphylococcus aureus thigh muscle infections . In this model, radiolabeled HNP-1 was found to accumulate at the site of infection, whereas most of the injected HNP-1 was rapidly removed from the circulation via renal excretion . These results demonstrate that neutrophil defensins display marked in vivo antibacterial activity in experimental infections in mice and that this activity appears to be mediated, at least in part, by local leukocyte accumulation.

J Clin Invest, 1998 Oct 15, 102(8), 1473 - 80
Interactions between stromal cell--derived keratinocyte growth factor and epithelial transforming growth factor in immune-mediated crypt cell hyperplasia; Bajaj-Elliott M et al.; Immune reactions in the gut are associated with increased epithelial cell proliferation . Here we have studied the role of keratinocyte growth factor (KGF; FGF7) and transforming growth factor-alpha (TGF-alpha) in the epithelial cell hyperplasia seen in explants of fetal human small intestine after activation of lamina propria T cells with the superantigen Staphylococcus aureus enterotoxin B (SEB) . After the addition of SEB to the explants there is a 10-fold increase in KGF mRNA by 72 h of culture . KGF transcripts were abundant in the lamina propria using in situ hybridization and the culture supernatants contained elevated amounts of KGF protein . SEB had no direct effect on KGF mRNA and protein production by cultured lamina propria mesenchymal cells, but both were upregulated by TNF-alpha . Accompanying the increase in KGF there was also an increase in TGF-alpha precursor proteins in the culture supernatants and the phosphorylated form of the EGFR receptor was also detected in the tissue . Increased TGF-alpha precursor proteins were also detected in the supernatants of control explants stimulated with KGF alone . The direct addition of KGF and TGF-alpha enhanced epithelial cell proliferation and antibodies against KGF and TGF-alpha partially inhibited SEB-induced crypt hyperplasia . These results suggest molecular cross-talk between the KGF/KGFR and the TGF-alpha/EGFR in immune-mediated crypt cell hyperplasia.

J Biol Chem, 1998 Oct 30, 273(44), 29143 - 9
Anchor structure of staphylococcal surface proteins . III . Role of the FemA, FemB, and FemX factors in anchoring surface proteins to the bacterial cell wall; Ton-That H et al.; Surface proteins of Staphylococcus aureus are covalently linked to the bacterial cell wall by a mechanism requiring a COOH-terminal sorting signal with a conserved LPXTG motif . Cleavage between the threonine and the glycine of the LPXTG motif liberates the carboxyl of threonine to form an amide bond with the pentaglycyl cross-bridge in the staphylococcal peptidoglycan . Here, we asked whether altered peptidoglycan cross-bridges interfere with the sorting reaction and investigated surface protein anchoring in staphylococcal fem mutants . S . aureus strains carrying mutations in the femA, femB, femAB, or the femAX genes synthesize altered cross-bridges, and each of these strains displayed decreased sorting activity . Characterization of cell wall anchor structures purified from the fem mutants revealed that surface proteins were linked to cross-bridges containing one, three, or five glycyl residues, but not to the epsilon-amino of lysyl in muropeptides without glycine . When tested in a femAB strain synthesizing cross-bridges with mono-, tri-, and pentaglycyl as well as tetraglycyl-monoseryl, surface proteins were found anchored mostly to the five-residue cross-bridges (pentaglycyl or tetraglycyl-monoseryl) . Thus, although wild-type peptidoglycan appears to be the preferred substrate for the sorting reaction, altered cell wall cross-bridges can be linked to the COOH-terminal end of surface proteins.

J Biol Chem, 1998 Oct 30, 273(44), 29135 - 42
Anchor structure of staphylococcal surface proteins . II . Cooh-terminal structure of muramidase and amidase-solubilized surface protein; Navarre WW et al.; Surface proteins of the Gram-positive organism Staphylococcus aureus are anchored to the bacterial cell wall by a transpeptidation mechanism during which the polypeptide is cleaved between the threonine (T) and the glycine (G) of the LPXTG motif . The carboxyl of threonine is subsequently amide linked to the amino of the pentaglycyl cross-bridge within the staphylococcal peptidoglycan . Previous work examined the anchor structure of surface proteins solubilized from the peptidoglycan by treatment with lysostaphin or phi11 hydrolase and identified COOH-terminally linked triglycyl or L-Ala-D-iGln-L-Lys(Gly5)-D-Ala and MurNAc-{L-Ala-D-iGln-L-Lys(Gly5)-D-Ala}(beta1-4)-GlcNAc, respectively . Here, we report the anchor structure of surface proteins solubilized with N-acetylmuramidase and N-acetylmuramyl-L-alanine amidase . N-Acetylmuramidase-released surface protein was linked to MurNAc-{L-Ala-D-iGln-L-Lys(Gly5)-D-Ala}(beta1-4)-GlcNAc, whereas N-acetylmuramyl-L-alanine amidase treatment of the cell wall solubilized surface proteins linked to L-Ala-D-iGln-L-Lys(Gly5)-D-Ala . Most, but not all, anchor structures were cross-linked to other cell wall subunits, in which the D-alanyl at position four was amide linked to the pentaglycyl of a neighboring wall peptide.

J Antimicrob Chemother, 1998 Sep, 42(3), 315 - 20
Increase in glutamine-non-amidated muropeptides in the peptidoglycan of vancomycin-resistant Staphylococcus aureus strain Mu50; Hanaki H et al.; The peptidoglycan compositions of vancomycin-resistant Staphylococcus aureus (VRSA) strain Mu50 (MIC 8 mg/L) and hetero-VRSA strain Mu3 (MIC 3 mg/L) were compared in order to understand the mechanism of vancomycin resistance . As compared with Mu3, the cell wall of Mu50 had increased amounts of glutamine-non-amidated muropeptides and decreased cross-linking of peptidoglycan with a greatly decreased dimer/monomer ratio of muropeptides . In agreement with this observation, the peptidoglycan of Mu50 bound 1.4 times more vancomycin than that of Mu3 . The increase in non-amidated muropeptides and the reduced cross-linking of the cell-wall peptidoglycan may contribute to the vancomycin resistance by increasing the consumption of vancomycin by the pre-existing cell wall of Mu50 and reducing the amount of vancomycin reaching the cytoplasmic membrane where the vital targets of the antibiotic are situated.

N Z Med J, 1998 Sep 11, 111(1073), 345 - 7
Spinal epidural abscess; Wong D et al.; AIMS: To review the clinical presentation and outcome of patients with spinal epidural abscess . METHODS: Following an index case, additional cases were identified during 1991-6 . RESULTS: There were a total of seven patients with spinal epidural abscess and an average age of 52 years (range 24-75 years) . The abscess locations were cervical (3), thoracic (3) or thoracolumbar (1), and extended on average 4.3 vertebral bodies (range 2-9) . Staphylococcus aureus was the aetiologic agent in all of the six microbiologically confirmed cases . Three abscesses arose from adjacent vertebral osteomyelitis, one followed epidural anaesthesia and two arose by haematogenous spread . New spinal or radicular pain were the most frequent early symptoms, later, nerve root weakness or a sensory level . An ESR > 30 mm/hour was consistently present but fever and leukocytosis were absent in some patients . MRI (five cases) and myelography (one case) were diagnostic . Five patients underwent laminectomy and abscess drainage; in three, limb weakness improved markedly post operatively . Three of the four patients with paralysis died, two despite laminectomy . CONCLUSIONS: New spinal pain, radicular symptoms or signs, and a raised ESR were the most consistent early abnormalities in patients with a spinal epidural abscess . Diagnosis at an early clinical stage was associated with a better outcome.

Microbios, 1998, 94(378), 95 - 102
Attenuated mutants of Staphylococcus aureus with two temperature-sensitive lesions: isolation and characterization; Sordelli DO et al.; The feasibility of constructing attenuated mutants of Staphylococcus aureus with two temperature-sensitive (ts) lesions for ultimate development of a live-attenuated strain was investigated . Temperature-sensitive S . aureus strain G/1/2, which grows well at 31 degrees C but does not replicate at 37 degrees C, was subjected to chemical mutagenesis . After two enrichment cycles, fifteen mutants able to grow at 25 degrees C but unable to grow at 31 degrees C, were identified . Growth curves with temperature shifts from 25 to 31 degrees C, and from 31 to 37 degrees C confirmed that these were mutants with two lesions (dts), each with a different cut-off temperature . The reversion frequency of mutant G/1/2 at 37 degrees C was 2 x 10(-6) whereas those of several dts mutants were much lower (dts7: 7 x 10(-9) and dts12: 1 x 10(-9)) . There was no increase in ts mutation reversion rate in response to prolonged incubation at 37 degrees C . The data support the further development of these mutants for use as a stable attenuated vaccine.

Infect Immun, 1998 Nov, 66(11), 5183 - 9
Staphylococcus aureus serotype 5 capsular polysaccharide is antiphagocytic and enhances bacterial virulence in a murine bacteremia model; Thakker M et al.; Controversy persists over the role that the capsular polysaccharide plays in the pathogenesis of Staphylococcus aureus infections . To address this issue, we compared the mouse virulence of S . aureus Reynolds and capsule-defective mutant strains cultivated under conditions of high or low capsule expression . Strain Reynolds cells cultivated on Columbia salt agar plates expressed approximately 100-fold more type 5 capsular polysaccharide than did cells cultivated in Columbia salt broth . The relative virulence of strain Reynolds and its capsule-defective mutants after growth on either solid or liquid medium was examined in mice challenged intraperitoneally or intravenously . The results indicated that agar-grown Reynolds cells were cleared from the bloodstream of mice less readily than broth-grown Reynolds cells . When the parental and mutant strains were cultivated on solid medium, strain Reynolds sustained a higher level of bacteremia than did the capsular mutants . We performed in vitro opsonophagocytic killing assays to determine whether staphylococcal virulence for mice correlated with resistance to phagocytosis . S . aureus Reynolds cultivated on solid medium was susceptible to phagocytic killing only in the presence of specific capsular antibodies and complement . Strain Reynolds grown in broth showed opsonic requirements for phagocytic killing that were similar to those of the capsular mutants (grown in broth or on agar); i.e., the bacteria were opsonized for phagocytosis by nonimmune serum with complement activity . These studies indicate that optimal expression of capsule enhances bacterial virulence in the mouse model of bacteremia, probably by rendering the organisms resistant to opsonophagocytic killing by leukocytes.

J Nat Toxins, 1998 Oct, 7(3), 193 - 213
Induction of type 2 cytokines by a staphylococcal enterotoxin superantigen; Ferens WA et al.; Persistent intramammary infections of dairy cows with Staphylococcus aureus may involve immunosuppression mediated by bacterial toxins such as enterotoxins and other super-antigens (SAgs) . Previously we found that stimulation of bovine PBMC with staphylococcal enterotoxin C (SEC) induced a unique phenotype of activated CD8+ T cells expressing a newly identified activation molecule, ACT3 . In the present study we found that SEC induced the expression of interleukin (IL)-4 and IL-10 mRNAs, two cytokines associated with type 2 responses . Elevated levels of IL-4 and IL-10, observed between day 0 and day 4 of culture, were associated with temporary inhibition of proliferative responses of T cells, evidenced by a decrease in numbers of CD4+ T cells and a small increase in numbers of CD8+ T cells . Vigorous proliferation of T cells occurred between days 4 and 7 of culture and with a bias towards CD8+ T cells . Acquisition of the ACT3+ phenotype by CD8+ T cells was preceded by induction of IL-4 mRNA . Thus, in the bovine system, SAgs may hinder protective responses by inducing type 2 cytokines, which interfere with immune clearance of many microbial pathogens . The results of the study are consistent with the hypothesis that SAgs are involved in immunosuppression, and suggest possible immunomodulatory mechanisms.

Eur Arch Otorhinolaryngol, 1998, 255(7), 347 - 51
A molecular epidemiologic study of methicillin-resistant Staphylococcus aureus infection in patients undergoing middle ear surgery; Suh HK et al.; The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections after middle ear surgery has recently increased at our hospital . Most of these infections were thought to be hospital-acquired when medical personnel in contact with an MRSA-infected patient may have inadvertently transmitted the pathogen to other patients . To prevent further transmission it is essential that such sources of MRSA infection and transmission routes be selected out and eradicated . Therefore, it is necessary to determine whether the strains of MRSA isolated from infected patients are identical to those obtained from medical personnel in order to prove a reciprocal transmission of organisms between medical personnel and patients . Surveillance bacterial cultures from the anterior nares and hands of medical personnel working in the Department of Otolaryngology, Korea University Guro Hospital, were performed at two different time points: 6 December 1994 and 17 June 1996 . Ribotyping with Southern blot technique was used to compare 12 MRSA strains from medical carriers with 60 strains identified from the otorrhea of MRSA-infected patients undergoing middle ear surgery . As results, six different MRSA strains were identified (types I, II, III, IV, V and VI) from ribotyping with EcoR1 . One distinct subtype, type I strain, was the most frequently identified strain in both medical carriers and patients . Results also showed that 6 MRSA isolates from 10 medical carriers and 20 from 30 patients contained type I ribotype at first culture . Two medical carriers' isolates and 13 isolates from 30 patients shared the same type I strain at the second surveillance culture . In all, 41 out of 72 MRSA strains (56.9%) shared an identical ribotype pattern . Postoperative MRSA infection rates after treatment of medical carriers and the application of rigorous preventive procedures decreased from 11.9 to 5.7% after first culture and 9.0 to 7.7% following second cultures . These findings confirm that MRSA transmission can occur between medical personnel and patients and that effective preventive measures can reduce the postoperative infection rate.

Ostomy Wound Manage, 1998 Aug, 44(8), 32 - 40; discussion 34-8; quiz 41-2
Bacteria for the nineties; Devlin HR; Staphylococcus aureus and Enterococci have gained prominence as the causes of wound infections during this decade . Methicillin-resistant Staphylococcus aureus (MRSA) became commonplace in the United States during the 1980s . In Canada, infections with MRSA have been increasing in frequency since 1995 . MRSA develops resistance by producing an altered penicillin-binding protein, PBP 2a, coded for by the mecA gene . Vancomycin is the usual drug of choice . Recently, strains with intermediate resistance to vancomycin (VISA) have been isolated from patients in Japan and the United States . Interim guidelines for their control have been developed by the Centers for Disease Control . Enterococci have developed a resistance to a variety of antimicrobials during the past three decades, including beta-lactams and aminoglycosides . Recently, strains resistant to vancomycin (VRE) have been found in the United States and Canada . They are particularly difficult to treat, although some success has been achieved with experimental drugs . These microorganisms have the ability to escape control by antimicrobials almost as soon as they are developed . Thus, we must practice good infection control and reserve antimicrobials only for clear cases of infection if we are to prevent or delay the emergence of resistance.

Microbiology, 1998 Sep, 144 ( Pt 9), 2469 - 79
The role of environmental factors in the regulation of virulence-determinant expression in Staphylococcus aureus 8325-4; Chan PF et al.; Staphylococcus aureus is a major human pathogen, which produces a variety of virulence determinants . To study environmental regulation of virulence-determinant production, several transcriptional reporter gene fusions were constructed . Chromosomal fusions were made with the staphylococcal accessory regulator (sarA), alpha-haemolysin (hla), surface protein A (spa) and toxic-shock syndrome toxin-1 (tst) genes . The effect of many different environmental conditions on the expression of the fusions was examined . Expression of hla, tst and spa was strongly repressed in the presence of sodium chloride (1 M) or sucrose (20 mM), but sarA was relatively unaffected . The global regulator of expression of virulence-determinant genes, agr (accessory gene regulator) was not involved in the salt or sucrose repression . Novobiocin, a DNA gyrase inhibitor, did not significantly increase the expression of tst in wild-type or agr backgrounds and failed to relieve the salt suppression . Expression of tst was strongly stimulated in several low-metal environments, independently of agr, whilst spa levels were significantly reduced by EGTA . The complex, interactive role of environmental factors in the control of expression of the virulence determinants is discussed.

Chirurg, 1998 Aug, 69(8), 872 - 6
{The infected arterial stent}; Muller G et al.; Vascular infections after percutaneous endovascular procedures are rare . We report a case of bacterial arteritis following PTA and stent implantation into an iliac artery . It was complicated by septic embolization, ipsilateral empyema of the knee joint and formation of an infected false aneurysm . Contamination of the stent with Staphylococcus aureus is likely to be the cause . The treatment included resection of the infected arterial segment, removal of the stent, and autologous reconstruction.

Chirurg, 1998 Aug, 69(8), 801 - 5
{Methicillin-resistant Staphylococcus aureus (MRSA)--clinical implications}; Peltroche-Llacsahuanga H et al.; The isolation rate of MRSA from Staphylococcus aureus infections rose to 8.7% in German hospitals between 1990 and 1995 . Patients undergoing surgical treatment or physiotherapy showed a threefold increase in the risk of being colonized or infected with MRSA . Surgical wound infection is the most frequent among MRSA-induced infections (28%) . The main transmission path of MRSA inside a hospital is bacterial spread from one patient to another through contact with the hands of nursing staff . Therefore, the crucial strategy in avoiding the spread of bacteria is strict hygiene management through hand disinfection . The most widespread therapeutic regimen for simultaneous eradication of nasal colonization and treatment of infection on other body sites is mupirocin nasal ointment combined with parenteral vancomycin application . The non-indicated use of vancomycin, e.g., for perioperative prophylaxis or prevention of catheter-induced infections, should be avoided, especially after the appearance of vancomycin-intermediately sensitive S . aureus (VISA) strains that have been reported recently from Japan and the USA.

J Orthop Trauma, 1998 Sep-Oct, 12(7), 479 - 84
High pressure pulsatile lavage of contaminated human tibiae: an in vitro study; Bhandari M et al.; OBJECTIVE: This study was designed to examine the effect of high pressure pulsatile lavage (HPPL) on bone destruction and propagation of bacteria in experimentally contaminated human tibiae . METHODS: Using an in vitro model, nine human tibiae from above-knee amputations were tested . A mid-diaphyseal tibial shaft fracture was created, and each end of the fracture was contaminated with bacteria (six tibiae with Staphylococcus aureus, three tibiae with Escherichia coli) . The proximal end was designated as the control and the distal end was the test site . The test site was debrided by HPPL (seventy pounds/square inch, 1,200 milliliters/minute, 1,050 cycles/minute) with three liters of normal saline, whereas the control site did not receive any form of irrigation . Serial sections at increasing distance from the fracture site were cultured and the numbers of bacterial colony-forming units (CFUs) were determined at each level . The degree of macroscopic architectural change in each serial section was graded on an ordinal scale . RESULTS: Analysis of culture data revealed a reproducible pattern of bacterial propagation into the intramedullary canal . Peak bacterial seeding occurred at two to three centimeters from the fracture site (p = 0.023, Wilcoxon signed rank test) . The degree of bone destruction varied proportionally with the depth into the canal and was found to be predictive of the extent of bacterial propagation determined by culture data . CONCLUSION: In an in vitro model of a contaminated fracture, HPPL resulted in bacterial seeding into the intramedullary canal and significant damage to the architecture of the bone . These observations might have clinical significance.

FEBS Lett, 1998 Oct 2, 436(2), 202 - 8
Characterization of a novel structural member, LukE-LukD, of the bi-component staphylococcal leucotoxins family; Gravet A et al.; A new member of the staphylococcal bi-component leucotoxins family, LukE (32 kDa) and LukD (34.3 kDa) has been characterized from Staphylococcus aureus strain Newman . LukE was 58-68% identical with the class S proteins, whereas LukD was 71-77% identical with the class F proteins of the family . A partial immunoreactivity with the various affinity-purified antibodies specific for the other proteins was observed . Immunoprecipitation assay and gene probing confirmed a 30% frequency among human clinical isolates, differing from the distribution of the other known leucotoxins (P<0.005) . LukE+LukD was as effective as the Panton-Valentine leucocidin for inducing dermonecrosis when injected in the rabbit skin, but not hemolytic and poorly leucotoxic compared to other leucotoxins expressed by Staphylococcus aureus.

Adv Exp Med Biol, 1998, 443, 321 - 30
Effect of lactoferrin on the phagocytic activity of polymorphonuclear leucocytes isolated from blood of patients with autoimmune diseases and Staphylococcus aureus allergy; Manev V et al.; Phagocytic number (PN) and phagocytic index (PI) of neutrophils isolated from blood of patients with autoimmune diseases, allergy to Staphylococcus aureus and from blood of healthy individuals were examined . Our results concerning the influence of lactoferrin (Lf); (6.7 mg/l) on the PI of PMN showed that: 1) Lf enhances reliable PI of PMN at the 30-th minute starting the phagocytic reaction in patients with autoimmune disease in an active stage, in blood donors treated as healthy with the presence of autoantibodies, in patients with autoimmune diseases and proved autoantibodies against tissue, cell antigens and collagen, 2) Lf influences non-significantly PI of PMN in patients with autoimmune collagen diseases in remission, 3) Lf increases PI of PMN with 19% only in 58% from the assessed patients with Staphylococcus aureus, and 4) Lf decreases non-significantly PI of PMN in the healthy controls . Our studies on the effect of Lf on the phagocytic activity of PMN suggest that Lf has stronger effect on the PN compared to the PI: 1) Lf enhances with 86% the PN in patients with Staphylococcus aureus, 2) Lf increases PN of PMN in all of the assessed patients with autoimmune collagen diseases in active stage (mean with 72%), and 3) Lf increases PN of PMN in 4 from the 5 investigated healthy controls (mean with 22%) . Our results show a "corrective" effect of Lf on the phagocytic functions in the investigated groups of patients . The possible mechanisms, by which Lf increases PN and PI of neutrophils, is discussed: 1) they may concern the antioxidative properties of Lf to block the iron ions in their catalytic inactive form or to take part as ferric-Lf in an oxidative-reduction processes on the plasma membrane and controlling transmembrane transport systems, 2) Lf decreases the negative surface charge and thus enhances the adherent ability of the PMN . Probably to this stimulated adherent ability dues the increased ingestion of bacteria in the presence of Lf, and 3) The "changed" membrane of PMN may have higher number receptors for Lf to bind more molecules of exogenous Lf . The increase of Lf binding which enhances the adherence and aggregation of neutrophils, facilitates the phagocytosis.

Rev Prat, 1998 Mar 1, 48(5), 523 - 7
{Surgery of infectious endocarditis}; Gandjbakhch I et al.; Thirty to fifty percent of patients with infective endocarditis are operated on during the active phase of the disease; this percentage is higher in case of some valvular localizations (aortic), in case of early prosthetic valve endocarditis, in case of some microorganisms (Staphylococcus aureus, gram-negative, fungus, intracellular microorganism) . Operative death (at 30 days) is below 10% in native valve endocarditis, close to 50% in early prosthetic valve endocarditis, and below 20% in late prosthetic valve endocarditis . When active infective disease has been healed by medical treatment alone, half the patients need surgery in the first 2 years of follow-up; the indications for surgery are the functional status, the degree of valvular leaks and other lesions, the degree of ventricular dilatation.

Yeast, 1998 Sep 15, 14(12), 1139 - 46
New constructs and strategies for efficient PCR-based gene manipulations in yeast; Puig O et al.; Gene disruption and tagging can be achieved by homologous recombination in the yeast genome . Several PCR-based methods have been described towards this end . However these strategies are often limited in their applications and/or their efficiencies and may be technically demanding . Here we describe two plasmids for C-terminal tagging of proteins with the IgG binding domain of the Staphylococcus aureus protein A . We also present simple and reliable strategies based on PCR to promote efficient integration of exogenous DNA into the yeast genome . These simple methods are not limited to specific strains or markers and can be used for any application requiring homologous recombination such as gene disruption and epitope tagging . These strategies can be used for consecutive introduction of various constructs into a single yeast strain.

Mol Biotechnol, 1998 Aug, 10(1), 9 - 16
A study of the interactions between an IgG-binding domain based on the B domain of staphylococcal protein A and rabbit IgG; Brown NL et al.; The nonantigenic interaction between a recombinant immunoglobulin G (IgG)-binding protein based on the B domain of Protein A from Staphylococcus aureus (termed SpA1) and the Fc fragment of rabbit IgG has been investigated . The contribution to binding of four putative hydrogen bond contacts between SpA1 and IgG-Fc were examined by the individual substitution of the residues in SpA1 involved in these interactions by others unable to form hydrogen bonds . It was found that the most important of the hydrogen bonds involved Tyr 18 which, when replaced by Phe, resulted in a twofold decrease in IgG-binding affinity . The residues of SpA1 proposed to make close, mainly hydrophobic, contacts with Fc were replaced by residues with potential electrostatic charge to establish the importance of the hydrophobic interaction in the complex . The IgG-binding affinities of the mutant proteins were compared to the wild-type protein by a competitive enzyme-linked immunosorbent assay . The replacement of individual hydrophobic residues by His generated a number of novel IgG-binding proteins with reduced binding affinity at pH 5.0 but which maintained strong binding affinities at pH 8.0 . The elution profile of human IgG1-Fc (Fc fragment of human IgG1) from a column made from an immobilized two-domain mutant protein shows that the complex dissociates at a higher pH relative to that of the non-mutated protein thus offering favorable elution characteristics.

Infect Dis Clin North Am, 1998 Sep, 12(3), 613 - 30, viii
Resistance issues and treatment implications: pneumococcus, Staphylococcus aureus, and gram-negative rods; Low DE; During the last decade there has been an unexpectedly rapid evolution of antimicrobial resistance in the respiratory pathogens for community- and hospital-acquired pneumonia . In order to choose the most optimal therapy for their patients, it is essential that physicians be aware of the prevalence and mechanisms of resistance and their implications on the effectiveness of the various antimicrobials.

Can J Cardiol, 1998 Sep, 14(9), 1148 - 50
Staphylococcus aureus pericarditis with tamponade complicating coronary angioplasty and stenting; Amin H et al.; Infectious complications of coronary angioplasty and stenting are uncommon . A 70-year-old man is presented who underwent percutaneous transluminal coronary angioplasty (PTCA) and stenting of an occluded left anterior descending artery . This was complicated by Staphylococcus aureus pericarditis with tamponade . He was successfully treated with a closed drainage and antibiotics . This is the first reported case in the literature that documents purulent pericarditis and tamponade following percutaneous revascularization.

Infect Control Hosp Epidemiol, 1998 Sep, 19(9), 643 - 6
Central venous catheters as a source of hemodialysis-related bacteremia; Taylor GD et al.; OBJECTIVE: To describe investigations into an increase in hemodialysis-related bacteremia that occurred in our hospital in the first 6 months of 1996 . SETTING: Hemodialysis unit in a tertiary-care medical center . METHODS: Prospective surveillance for hemodialysis bacteremia has been performed for several years . Cases that occurred in 1995 were compared to cases in the first 6 months of 1996 . Unit data on dialysis runs and method of dialysis access were used to calculate rates . Nested polymerase chain reaction (PCR) was used to type 18 Staphylococcus aureus isolates from 1996 . A case-control study comparing 80 randomly selected hemodialysis patients from 1995 and 1996 was performed to examine infection risk factors . RESULTS: The hemodialysis bacteremia rate was 1.2 per 1,000 runs in 1995 and 2.8 per 1,000 in the first 6 months of 1996 (P=.0009) . The 25 cases in 1995 and 32 in the first half of 1996 were similar in age, gender, means of vascular access, and microbial etiology . Central venous catheter (CVC) access accounted for >90% of cases in both time periods . S aureus was the most common microbial etiology (53% of the 1996 cases) . PCR typing of S aureus isolates from 1996 demonstrated five different strains, the most common having six isolates . The use of CVCs as a means of vascular access abruptly increased in the unit in January 1996, from <30% of dialysis runs in 1995 to >40% in 1996 (P<.001), associated with structural changes in healthcare delivery in the region resulting in delays in performing surgical procedures, such as creation of vascular grafts and fistulae . CONCLUSION: A marked increase in hemodialysis bacteremia occurred in 1996, associated with increased reliance on CVCs for vascular access in hemodialysis patients during a period of healthcare restructuring.

J Hosp Infect, 1998 Sep, 40 Suppl B, S39 - 44
New strategies for the use of mupirocin for the prevention of serious infection; Mehtar S; Nasal mupirocin has an important role to play in the prevention of Staphylococcus aureus infection by eliminating nasal carriage of this organism . Indeed, in many countries nasal mupirocin is one of the mainstays for controlling outbreaks of methicillin-resistant S . aureus . Eradication of nasal S . aureus with mupirocin has been shown to be effective in preventing postoperative infections in patients undergoing cardiothoracic surgery and in preventing exit-site infections in patients undergoing haemodialysis . It has been proposed that the use of mupirocin should be extended to other situations, such as the prevention of postoperative infections in patients undergoing implant surgery and the prevention of bacteraemias in high-risk patients . Clinical trials are needed to establish the efficacy of mupirocin in these situations . Both low-level and high-level resistance have been reported during treatment with nasal mupirocin . Low-level resistance does not represent a significant clinical problem but high-level resistance resulting from indiscriminate use may give grounds for concern . Further review of these issues is required . As with any antibiotic, mupirocin should be used judiciously, as part of an integrated programme of infection control.

J Hosp Infect, 1998 Sep, 40 Suppl B, S31 - 7
Eradication of nasal carriage of Staphylococcus aureus--is it cost-effective?
Davey P.
In cardiothoracic surgery, the costs of surgical-site infection (SSI) arise from additional postoperative procedures (approximately US $5000 per patient) and prolonged hospital stay (approximately $11,500 per patient) . Application of nasal mupirocin reduced SSIs by 63% compared with historical controls . This would have resulted in savings provided that the attributable cost of an SSI was more than $245 . Mupirocin was estimated to reduce the risk of bacteraemia in haemodialysis patients by 84% compared with historical controls . A model using data on Medicare payments for haemodialysis admissions was used to estimate the impact on hospital costs . The conclusion was that mupirocin would have been cost-saving but the model did not provide sufficient detail about hospital costing to allow assessment of its relevance in other settings . In a prospective, randomized, placebo-controlled trial in continuous ambulatory peritoneal dialysis (CAPD) patients, mupirocin reduced the risk of staphylococcal exit-site infection (ESI) from 0.42 to 0.14 per patient-year . However, as in a previous comparison with historical controls, there was an increase in the rates of ESIs caused by Gram-negative bacteria in patients who received mupirocin, bringing the rate of total ESIs up to that observed in the placebo group . There was some evidence that infections caused by Gram-negative bacteria had less severe consequences than staphylococcal infections . It is concluded that application of nasal mupirocin to nasal carriers of Staphylococcus aureus may be cost-saving in patients undergoing cardiac surgery or haemodialysis but, if the analysis is restricted to the cost of management of ESIs, it may not be cost-saving in CAPD . However, reducing the risk of staphylococcal ESI may reduce the risk of catheter loss and subsequent transfer to haemodialysis and this merits further study.

J Hosp Infect, 1998 Sep, 40 Suppl B, S25 - 9
Reduction of surgical site infections in major surgery by elimination of nasal carriage of Staphylococcus aureus; Kluytmans J; Staphylococcus aureus has long been recognized as an important pathogen in human disease . Staphylococcal infections occur regularly in hospital patients and, despite antibiotic therapy, have severe consequences . An increasing number of such infections are caused by methicillin-resistant S . aureus (MRSA) strains, many of which have become multi-resistant to treatment . In an unblinded intervention trial, with historical controls, perioperative nasal carriage of S . aureus was eliminated using mupirocin nasal ointment . A significant reduction in surgical site infection was observed post-intervention in the treated group of patients . No resistant to mupirocin was observed . The results of this study warrant a prospective randomized, placebo-controlled study to confirm the efficacy of mupirocin.

J Hosp Infect, 1998 Sep, 40 Suppl B, S13 - 23
Reduction of Staphylococcus aureus nasal carriage and infection in dialysis patients; Herwaldt LA; Numerous studies conducted in different countries and in different populations of patients on dialysis have consistently documented that a large proportion of such patients carry Staphylococcus aureus in their nares and that the risk of them becoming infected with their own strains is quite high . Furthermore, S . aureus infections can cause considerable morbidity and mortality in these patients . Thus, decolonization of the nares may prevent S . aureus infections and the attendant complications . The published data that support the use of rifampicin, intranasal mupirocin and povidone-iodine to prevent S . aureus infections in patients on dialysis are reviewed in detail.

J Hosp Infect, 1998 Sep, 40 Suppl B, S3 - 11
The nose: an underestimated source of Staphylococcus aureus causing wound infection; Casewell MW; For the last fifty years, the nose has been intermittently recognized and targeted as a source of Staphylococcus aureus causing surgical site infection . In London in 1959, Williams and co-workers established for the first time that nasal carriers had increased rates of surgical sepsis compared with non-carriers . For half of these patients, the source was the patient's own nose . Post-admission acquisition of tetracycline-resistant strains was associated with even higher rates of infection . The increasing appearance of epidemic methicillin-resistant S . aureus (MRSA) in the 1980s rekindled interest in these (largely overlooked) studies, when the elimination of nasal carriage by topical mupirocin proved pivotal for the control of MRSA in Northern Europe and elsewhere . In the late 1980s and 1990s, Boelaert, Holton and others, appreciating the work performed forty years previously, used nasal mupirocin for the successful prevention of sepsis with S . aureus in patients on haemodialysis and continuous ambulatory peritoneal dialysis without incurring problems with mupirocin resistance . In 1995, Kluytmans and colleagues demonstrated that nasal carriage of S . aureus is a significant risk factor for wound infection after cardiac surgery . Towards the year 2000, the use of prophylactic nasal mupirocin for the prevention of serious sepsis in major clean surgery is emerging as a plausible and exciting new strategy.

J Hosp Infect, 1998 Sep, 40(1), 61 - 5
Investigation of gaseous ozone for MRSA decontamination of hospital side-rooms; Berrington AW et al.; A domestic, gaseous ozone generator was investigated for use in the decontamination of hospital side-rooms that have housed patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) . Three models of bacterial contamination were used . These were exposed to ozone generation in a standard hospital side-room for 4 and 7 h . A methicillin-sensitive and a methicillin-resistant strain of S . aureus were compared . Ozone concentrations of 0.14 ppm were reached, levels which are sufficient to cause mild pulmonary toxicity . Bacterial counts were reduced in the vicinity of the gas generator in most instances, but the effect elsewhere in the room was, at best, limited . MRSA appeared more resistant to the effects of ozone than methicillin-sensitive S . aureus . We conclude that the device tested would be inadequate for the decontamination of such hospital side-rooms.

Ann Acad Med Singapore, 1998 May, 27(3), 358 - 62
Use of central venous lines in paediatrics--a local experience; Chua MC et al.; Central venous catheters are widely used in the care of critically ill patients . This paper reviews our experience with central lines in paediatric patients requiring intensive care, between the period August 1994 and August 1995 . A total of 57 insertions were performed in 40 patients, all less than 12 years of age . We found that the most common indication for catheter use was nutritional support (40%) . The overall complication rate was 58% . Catheter-related infection was the most serious problem, occurring in 32% of all insertions . Coagulase-negative Staphylococcus aureus was the organism most frequently isolated . Maintenance problems affected 17 of our catheters in which 9 were blocked . Both infected and blocked catheters were promptly removed . We had 3 cases of perforation and 2 cases of thrombosis . There were no deaths directly attributed to catheter use . Recommendations made include: 1) staff education and new guidelines for catheter care, 2) use of bacteria filters, 3) careful prospective monitoring of catheter infection rate, 4) heparinisation when infusion rate less than 2 ml/h, 5) eliminate use of stiff polyethylene catheters and 6) routine confirmatory X-ray or waveform monitoring before catheter use, if possible . We concluded that central venous catheterisations greatly facilitated the management of our patients . However, one must bear in mind that the use of such catheters is associated with problems which must be recognised early and promptly treated and, if possible, prevented with safe practice.

Wound Repair Regen, 1998 Mar-Apr, 6(2), 149 - 56
Nonviable Staphylococcus aureus and its peptidoglycan stimulate macrophage recruitment, angiogenesis, fibroplasia, and collagen accumulation in wounded rats; Kilcullen JK et al.; We have previously shown that local application at the time of operation of Staphylococcus aureus, nonviable S . aureus, its cell wall, or S . aureus peptidoglycan accelerates wound healing . We hypothesized that this effect is due to both direct and indirect mechanisms, among which is an increase in the inflammatory response to wounding, resulting in an increase in macrophages, angiogenesis, and fibroblasts . Twenty-seven Sprague-Dawley male rats were anesthetized, and two 7-cm paravertebral skin incisions were made . Four polyvinyl alcohol sponges, two on each side, containing either 100 microliter of isotonic saline or 0.5 mg of nonviable S . aureus or S . aureus peptidoglycan in 100-microliter saline were implanted subcutaneously . Nonviable S . aureus or S . aureus peptidoglycan (860 microgram/cm incision) in 200-microliter saline were inoculated into the incisions at closure . The rats ate a commercial rat chow and drank tap water ad libitum throughout . After days 3 and 7 postwounding, rats were euthanized, and tissues were examined for immunohistochemical features of reparative tissue using ED-1, Factor VIII, and vimentin antibodies, markers for monocyte/macrophages, endothelial cells, and mesenchymal cells (including fibroblasts), respectively . Incisions treated with nonviable S . aureus or S . aureus peptidoglycan showed more macrophages along and deep in the wound tract 7 days postoperatively . Nonviable S . aureus or S . aureus peptidoglycan-treated sponges were surrounded and penetrated by much larger capsules of reparative tissue than saline-treated sponges at both 3 and 7 days . Neutrophil influx was much greater in nonviable S . aureus or S . aureus peptidoglycan-treated sponges, especially in central regions, and there were many more ED-1-stained macrophages in distinct geographic locations, specifically, the more peripheral-cortical areas . Some clustering of macrophages occurred around areas of invasion by reparative tissue into the surrounding subcutaneous fat and within the interstices of the sponges at the interface between reparative tissue and acute inflammatory cells . In contrast, saline-treated sponge reparative tissue had significantly fewer macrophages, much thinner and flimsy reparative tissue, with proportionately fewer macrophages clustering centrally . There were many more mesenchymal cells (notably fibroblasts) and new blood vessels and much more reparative collagen in the nonviable S . aureus or S . aureus peptidoglycan-treated sponges . We conclude that local application of nonviable S . aureus or S . aureus peptidoglycan at wounding induces an increased number and alteration in location of macrophages, increased influx (or proliferation) of mesenchymal cells (notably fibroblasts), and increased angiogenesis and reparative collagen accumulation, as well as increasing the overall acute inflammatory response to wounding.

Rev Bras Enferm, 1997 Apr-Jun, 50(2), 291 - 6
{Nursing research on the use of venous catheters for hospitalized patients}; Utyama IK et al.; This report shows that intravenous catheterisation has been required for 59.4% of the patients in this sample . The main reason identified for catheterisation was the difficulty in accessing peripheral veins . The wound dressing was applied for 100% of the patients and the procedure itself was carried out each 48 hours in 89.8% of them . The intravenous catheter stood for 10 days in 52% of the cases and it was removed in 34.8% for intravenous drugs interruption and the other reasons were related as to technical problems . The most present microorganism was Staphylococcus aureus in 20.3% of the catheter cultures.

Rev Med Interne, 1998 Mar, 19(3), 185 - 91
{Rare hyperimmunoglobulinemia E syndromes}; Katchourine I et al.; Total immunoglobulin E levels are very frequently measured, particularly for allergy . Their high levels are ordinarily found in atopy and parasitosis . This article subject is to determine rare diseases where high levels of total immunoglobulin E are found except in classic diseases . These rare hyper-immunoglobulin E syndromes are more often associated with immunologic deficiency more or less intense that lead to viral, fungal and bacterial infections . Buckley syndrome: deep infections due to Staphylococcus aureus, chronic dermatitis . Netherton disease: cutaneous and hair disease, allergic manifestations . Wiskott-Aldrich syndrome: thrombocytopeny and -pathy, dermatitis . Di-George disease: hypoparathyroidism, infections . Selective deficit of immunoglobulin A: recurrent infections . It is difficult to differentiate between atopic dermatitis and Buckley syndrome and Netherton disease because of eczematiform chronic dermatitis and high-levels of total immunoglobulin E found in all these diseases.

Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1995 Feb, 28(1), 47 - 58
{Coagulase type and antimicrobial susceptibility of Staphylococcus aureus isolated from various areas in Taiwan}; Hsieh SE et al.; A total of 129 strains of Staphylococcus aureus, isolated from clinical specimens in Taiwan between February 1992 and December 1993, were subjected to coagulase typing and susceptibility testing to 21 kinds of antimicrobial agents using Pasco MIC Gram-positive panels . In the determination of minimum inhibition concentration (MIC), there were 94 strains (72.9%) resistant to penicillin and ampicillin, 54 strains (41.9%) resistant to tetracycline and erythromycin, and 21 strains (16.3%) resistant to oxacillin (oxacillin-resistant S . aureus; ORSA), but none of them was resistant to vancomycin or nitrofurantoin . As the susceptibility of the isolates from four different geographic districts was compared, no statistical difference was found except that the resistance rate to penicillin and ampicillin was higher in southern Taiwan, and resistance rate to rifampin and gentamicin was higher in central Taiwan . The ORSA strains were all resistant to penicillin, ampicillin, tetracycline; 95.2% of the strains were resistant to gentamicin, tobramycin and erythromycin . The resistance rates to drugs tested for ORSA strains were statistically higher than those for OSSA strains except vancomycin, nitrofurantoin, trimethoprim/sulfamethoxazole and ampicillin/sulbactam . In the coagulase typing of 127 strains, Type IV, III and VII were most frequently encountered . Among the coagulase types, Type IV was mostly encountered in the North, the South and the East of Taiwan; Type III was mostly encountered in central Taiwan . Among the ORSA strains, coagulase Type III was most predominant (85%) . In conclusion, analysis of an antibiogram is easy to perform and the results can provide clinicians not only with correct guides for patient treatment but also with a useful tool for epidemiological studies . However, if antibiogram and coagulase typing are carried out simultaneously, results will be more reliable in epidemiological studies, including nosocomial infection survey.

Tidsskr Nor Laegeforen . 1998 Sep 10;118(21):3282.
{Tropical pyomyositis}; Iversen PO et al.; Tropical pyomyositis is rarely observed among permanent residents of temperate or cold climates and is, to our knowledge, not described among Norwegians . It is a clinical entity comprising general symptoms of infection and abscesses in skeletal muscles . We present one case of tropical pyomyositis acquired in the Dominican Republic . The patient, a female, had an insidious progression of the disease with fever, chills, and general malaise . On admission she had also developed multiple abscesses affecting muscles of the extremities . She required surgical drainage in addition to antibiotics . Cultures from purulent material revealed Staphylococcus aureus.

Clin Infect Dis, 1998 Sep, 27(3), 478 - 86
Outcome of Staphylococcus aureus bacteremia according to compliance with recommendations of infectious diseases specialists: experience with 244 patients; Fowler VG Jr et al.; To determine whether recommendations of infectious diseases specialists affect outcome for patients, we evaluated 244 hospitalized patients with Staphylococcus aureus bacteremia . We offered our management recommendations to each patient's physicians and then assessed the clinical outcome for both patients for whom our consultative advice was followed and those for whom our advice was not heeded . All patients were followed up for 12 weeks after their first positive blood culture . Our management advice was followed for 112 patients (45.9%) and partially or completely ignored for 132 patients (54.1%) . Patients for whom our recommendations were followed were more likely to be cured of their S . aureus infection and less likely to relapse (P < .01), despite having significantly more metastatic infections (P < .01) at the outset of therapy, than were those for whom our recommendations were not followed . Failure to follow recommendations to remove an infected intravascular device was the most important risk for treatment failure . After controlling for other factors, logistic regression analysis revealed that patients whose intravascular device was not removed were 6.5 times more likely to relapse or die of their infection than were those whose device was removed . Our findings suggest that patient-specific management advice by infectious diseases consultants can improve the clinical outcome for patients with S . aureus bacteremia.

FEMS Microbiol Lett, 1998 Sep 15, 166(2), 225 - 30
A human transferrin-binding protein of Staphylococcus aureus is immunogenic in vivo and has an epitope in common with human transferrin receptor; Lim Y et al.; To understand human immune responses against the human transferrin-binding protein of Staphylococcus aureus (SA-tbp), we examined cell wall proteins from S . aureus ATCC 6538 using human convalescent sera, and a monoclonal antibody specific for human transferrin receptor (McAb-HTR) . The SA-tbp, detected by immunoblot assay, was iron-repressible, reacted with the convalescent sera, and cross-reacted with McAb-HTR . Immunoelectron microscopy probed with McAb-HTR showed a reaction zone around the test strain from the deferrated BHI . After being preincubated with an S . aureus-bacteremic serum, the electroblot of the SA-tbp still reacted with McAb-HTR, but not with human transferrin-horseradish peroxidase conjugate . We conclude, there are at least two kinds of epitopes in the SA-tbp; one able to bind to human transferrin is immunogenic in humans, but the other sharing epitopes common with human transferrin receptor is not immunogenic in humans.

Pathology, 1998 Aug, 30(3), 299 - 303
Heterogeneous expression of fusidic acid resistance in Staphylococcus aureus with plasmid or chromosomally encoded fusidic acid resistance genes; O'Brien FG et al.; Fusidic acid resistance expression in a methicillin susceptible Staphylococcus aureus strain (WBG1576), which carries fusidic acid resistance on plasmid pUB101, and a prevalent Western Australian methicillin-fusidic acid resistant strain (WBG8287) were compared . WBG8287 carries fusidic acid resistance on the chromosome and its plasmid content has no effect on the levels of this resistance . WBG1576 and WBG8287 exhibited similar heterogeneous populations in respect to fusidic acid resistance levels in population analyses . A high-level fusidic acid resistant mutant of WBG1576 (BE8) had alterations in Smal chromosomal profiles, but not in plasmid size or resistance expression . Mutations causing increased fusidic acid resistance in WBG1576 are chromosomally located . A high-level fusidic acid resistant mutant of WBG8287 (BE3) had no alterations in Smal chromosomal profiles, or plasmid content and resistances . Comparison of resistance levels to kanamycin and spectinomycin, between high-level resistant colonies of WBG8287 and WBG8287, indicate that mutations in the chromosomal gene fusA, which encodes elongation factor-G, are probably the cause of the increased resistance levels observed in these mutant strains.

Clin Infect Dis, 1998 Sep, 27(3), 543 - 50
Selective screening of carriers for control of methicillin-resistant Staphylococcus aureus (MRSA) in high-risk hospital areas with a high level of endemic MRSA; Girou E et al.; Screening for methicillin-resistant Staphylococcus aureus (MRSA) carriage in patients at risk was evaluated as part of a control program in a 26-bed medical intensive care unit (ICU) of a university hospital with a high level of endemic MRSA . Control measures included isolation and barrier precautions, skin decolonization with chlorhexidine of patients from whom MRSA was recovered, and mupirocin treatment of nasal carriers of MRSA . Of 3,686 patients admitted during a 4-year period, 44% were screened, which occurred during admission for 38%; MRSA was recovered from 293 patients (8%) . There were 150 imported cases and 143 ICU-acquired cases, of which 51% and 45%, respectively, were first identified through screening . Nasal swab cultures identified 84% of MRSA carriers . The incidence of all ICU-acquired cases and of acquired colonization or infection decreased from 5.8% and 5.6% to 2.6% and 1.4% (P = .002 and P < .001), respectively, whereas that of imported cases remained unchanged (range, 3.8% to 4.3%; P = .8) . Selective screening for nasal carriage during admission to high-risk areas may contribute to identification of a substantial proportion of cases of MRSA and to early implementation of effective control measures.

Clin Infect Dis, 1998 Sep, 27(3), 458 - 62
Is bacterial tracheitis changing? A 14-month experience in a pediatric intensive care unit; Bernstein T et al.; Bacterial tracheitis is characterized by acute upper-airway obstruction and purulent secretions within the trachea . Historically, affected children were young, stridorous, and toxic-appearing and required tracheal intubation, and morbidity and mortality were significant . Staphylococcus aureus was the most common organism involved . During the 14 months of this retrospective study, 46 children were admitted to the pediatric intensive care unit because of this diagnosis, and their medical records were reviewed . Compared with those in previous reports, children in this study were older (mean +/- standard error of the mean {SEM}, 69.3 +/- 6.8 months) and less toxic . Only 26 (57%) of 46 patients required tracheal intubation . Intubated patients were significantly younger than nonintubated patients (mean +/- SEM, 46.9 +/- 6.5 vs . 98.9 +/- 9.9 months) . Moraxella catarrhalis was identified in 12 (27%) of 45 bacterial respiratory cultures, while influenza A virus was recovered from 18 (72%) of 25 viral respiratory cultures . There were no major complications . This series represents the largest reported cohort of patients with this condition and suggests an epidemiological change toward a less morbid condition.

Pathol Biol (Paris), 1998 Apr, 46(4), 227 - 34
{Methicillin-resistant Staphylococcus aureus: evolution and epidemiology, clinical impact, and prevention}; Brun-Buisson C; Methicillin-resistant Staphylococcus aureus (MRSA) strains have become endemic in hospitals in many countries . In most cases, epidemic clones emerge occasionally on the endemic background . Early institution of simple measures aimed at preventing hand-borne cross-contamination has resulted in low rates of MRSAs in a few countries of northern Europe . Although environmental contamination plays a role in some cases, colonized or infected patients are the main reservoir . Three significant problems have been identified in countries with high levels of endemicity, namely identification of the reservoir in the hospital, including detection of healthy carriers who are readmitted; notification of departments that receive healthy carriers transferred from another department in the same hospital or from another hospital; and the increasing and hard-to-control reservoir of resistant bacteria in extended-care facilities . These three problems are related to the current level of endemicity and to the risk of dissemination of resistant strains during hospital-to-hospital patient transfers . The technical responses to these problems vary with the environment and available means . They include detection of carriers in high-risk units, use of standardized reporting forms for patient transfers, and recording of the presence of MRSA in computerized medical records . Decontamination of carriers can help to prevent cross-contamination in some situations . It is of the utmost importance that all the facets of MRSA endemicity be taken into account at the level of the hospital as a whole and that all decision makers and health care providers make a commitment to reducing MRSA endemicity.

Pathol Biol (Paris), 1998 Apr, 46(4), 213 - 6
{Antibiotic resistance in the European countries}; Carlet J; The overall level of resistance to antimicrobials is high in Europe, most notably in intensive care units . Variations exist across countries, with the levels being highest in southern Europe . Staphylococcus aureus remains the most hazardous pathogen . Glycopeptide-resistant enterococci are relatively infrequent in Europe for the time being . Differences in measures used to control antimicrobial use and to prevent cross-contamination probably explain country-to-country differences in resistance levels . Substantial efforts are needed in both these areas in many countries, including France.

Pathol Biol (Paris), 1998 Jun, 46(6), 435 - 41
{Pore-forming leukotoxins from Staphylococcus aureus: variability of the target cells and 2 pharmacological processes}; Prevost G et al.; The staphylococcal bi-component leukotoxins constitute a family included in the super-family of the beta-sheet-structured pore-forming toxins . They may be produced by Staphylococcus aureus and by Staphylococcus intermedius and their target cells vary according to the molecules . The mode of action proceeds by the sequential binding of the class S proteins, then by that of the class F proteins at the surface of the membranes . Then, the activation of cellular calcium-channels precedes the pore formation which seems to be sensitive to several monovalent cations . The cell response is inflammatory and includes the neosynthesis as well as the secretion of leukotriene B4, interleukin -8, histamine . The injection of leukotoxins to rabbits generates cell chemotaxis , vasodilatation, and tissue necrosis . The association of the production of leukotoxins with clinical syndromes concerns several aspects of the pathology of S . aureus, and confers to these leukotoxins an important role of virulence factors.

J Allergy Clin Immunol, 1998 Sep, 102(3), 428 - 35
Reduced prevalence of allergic disease in patients with multiple sclerosis is associated with enhanced IL-12 production; Tang L et al.; BACKGROUND: We previously showed that the prevalence of allergic disease is decreased in patients with multiple sclerosis (MS); however, the mechanisms that explain this finding have not previously been defined . OBJECTIVES: We have demonstrated that protection of patients with MS from allergic disease may be caused by the production in monocytes from these patients of elevated quantities of IL-12 compared with that observed in monocytes from individuals with allergies . METHODS: Purified monocytes from peripheral blood of subjects with or without allergies and from individuals with MS were directly stimulated with Staphylococcus aureus Cowan strain I in the absence of T cells . IL-12 was quantitated by a sensitive reverse transcription, competitive PCR . RESULTS: IL-12 production was 5-fold greater in monocytes from patients with MS (n = 11) than that from individuals with allergies (n = 10) (for subjects with MS, 1.90+/-0.18 vs 1.24+/-0.19 log10 fmol/microL for individuals with allergies) (P = .02) . Although the production of IL-12 in monocytes from patients with MS was slightly higher than that from subjects without allergies, this difference was not statistically significant . CONCLUSIONS: IL-12 production in individuals with MS is much greater than in individuals with allergies . Because IL-12 induces TH1 cytokine synthesis and reduces the production of TH2 cytokines, which amplify and prolong allergic inflammation, these studies suggest that enhanced IL-12 production may protect individuals with MS from the development of allergy but may predispose such individuals toward autoimmune inflammation in the central nervous system.

Ann Chir Plast Esthet, 1997 Feb, 42(1), 70 - 4
{Covering of a thoraco-lumbar defect by omentoplasty}; Le Fourn B et al.; With a case of thoraco-lumbar defect, the authors discuss about different procedures to cover it . In this place, the better procedure is certainly the latissimus dorsi flap, in all combinations . The indication for omentoplasty at this spinal site should not be performed by first intention but by exclusion of other procedures, as in the case considered by the authors . It was a 37-year-old man, paraplegic from the age of 16, with a deep chronic spinal wound, secondary to sepsis of a posterior segmental fixations . A staphylococcus aureus infection which developed as a surgical complication was initially treated with antibiotics and surgical cleaning procedures without removing instrumentation . However, the infection remained active and the material was finally removed . Spinal immobilisation was strengthened by external fixation . The area was cleared of all suspect material, including bone graft, leaving a wide back-wound open to the spine . Spontaneous healing was first attempted, but the size and the chronicity of the wound led us to use pedicled greater omentum to close the defect . The omentum was pedicled on the right gastroepiploic vessels and transferred to the back wound through the posterior abdominal wall muscles, next to the right kidney . This procedure allows rapid healing . In association with suitable antibiotics, it has prevented any recurrent infection after 18 months of follow-up . It was no feasible to cover the wound with a latissimus dorsi flap, considering the importance of this muscle in the movements of a paraplegic and considering the initial impossibility of removing the external fixation.

Br J Dermatol, 1998 Aug, 139(2), 319 - 24
Chronic staphylococcal scalded skin syndrome; Shelley ED et al.; Staphylococcal scalded skin syndrome (SSSS), not previously recorded as a chronic disease, persisted for 2 years in a 50-year-old woman with epilepsy and cerebellar ataxia . Lesions initially suggestive of erythema multiforme and toxic epidermal necrolysis evolved over 2 years into those typical for SSSS, with extensive erosions and subcorneal blisters, showing an epidermal split at the granular cell layer . Exfoliatin A-producing phage I-III Staphylococcus aureus, previously linked only to acute mild adult cases of SSSS, was cultured from purulent discharge in the patient's eyes, ears and open skin lesions . The roles of epilepsy and antiepileptic medications are discussed as possible predisposing factors.

J Antibiot (Tokyo), 1998 Aug, 51(8), 750 - 6
Antibiotic activities and affinities for bacterial cell wall analogue of N-demethylvancomycin and its derivatives; Yan H et al.; N-Demethylvancomycin, which has been clinically used in China, is one member of vancomycin group (glycopeptide) antibiotics . It differs from vancomycin only in that methyl group on the amino group of the N-terminal residue of vancomycin has been replaced by H . By reductive alkylation of N-demethylvancomycin, we synthesized N-alkyl and N,N'-dialkyl N-demethylvancomycins, which closely correlated with vancomycin in structure . The association constants of the complexes of N-demethylvancomycin and its analogues with di-N-Ac-L-Lys-D-Ala-D-Ala and the antibiotic activity against Staphylococcus aureus of the glycopeptides were determined . Results showed that N-demethylvancomycin has higher affinity for bacterial cell wall analogue di-N-Ac-L-Lys-D-Ala-D-Ala and more potent antibiotic activity against Staphylococcus aureus than vancomycin . Both N-alkylation and N,N'-dialkylation of N-demethylvancomycin reduced the affinity and antibiotic activity . The longer the alkyl groups, the less potent antibiotic activities and lower affinities have the glycopeptides . The antibiotic activities against Staphylococcus aureus of N-demethylvancomycin and its analogues roughly parallel their affinities for di-N-Ac-L-Lys-D-Ala-D-Ala.

Res Microbiol, 1998 Jul-Aug, 149(7), 497 - 507
Genetic diversification of methicillin-resistant Staphylococcus aureus as a function of prolonged geographic dissemination and as measured by binary typing and other genotyping methods; van Leeuwen W et al.; The aim of the present study was to determine the extent of genome evolution among methicillin-resistant Staghylococcus aureus (MRSA) strains . Three different collections of strains were analysed, comprising locally, nationally and internationally disseminated genotypes . Various genotyping assays displaying different levels of resolution were used . Geographically and temporally diverse MRSA strains comprised the international group . MRSA strains recovered during an outbreak in a New York City hospital and Portuguese MRSA isolates, all resembling the so-called Iberian clone, were included in the local and national collections, respectively . Genotypes were determined by genome scanning typing techniques and procedures which analyse specific DNA elements only . The outbreak strains showed subclonal variation, whereas the Portuguese isolates displayed an increased number of genotypes . Among the epidemiologically unrelated MRSA strains, the different genotyping techniques revealed a wide heterogeneity of types . Different typing techniques appeared to show different levels of resolution, which could be correlated with the extent of geographic spread; the more pronounced the spread, the higher the degree of genome evolution . Binary typing and randomly amplified polymorphic DNA analysis are the typing methods of choice for determining (non)identity among strains that have a recent common ancestor and have undergone yet limited dissemination.

Ann Acad Med Stetin, 1998, Suppl 41, 1 - 72
{Aortoiliac graft infection as a diagnostic and treatment problem}; Gutowski P; Aortoiliac graft infection occurs in 2-6% of patients with such prosthesis . This condition is seldom properly diagnosed by conventional radiographic methods, leading to high morbidity and mortality . Clinically, the diagnosis of aortic graft infection is difficult because patients may have a variety of nondescript clinical complaints . The diagnosis of graft infection when associated with minimal or absent clinical signs of low-grade infection is uncertain, but is critically important to avoid frequently catastrophic complications such as sepsis, gastrointestinal hemorrhage, and suture line disruption . Aim of the study: identification of bacterial flora present in aortoiliac graft infection; the presentation of my own experience in the detection of aortoiliac graft infection with special description of isotopic study with WBC labeled 99mTc HM-PAO and estimation of the usefulness of this test in comparison with computed tomography, ultrasonography, fistulography and angiography; evaluation of the usefulness of various treatment methods; establishing principles (algorithm) of diagnostic and therapeutic procedures in the case of the suspicion of aortoiliac graft infection . As many as 1190 patients with implanted aortoiliac graft in 1986-1996 at the General and Vascular Surgery Clinic in Szczecin were studied (Tab . 2) . Thirty-one patients in the study had deep aortoiliac graft infection (Tab . 3), while 9 patients had, in addition, prosthetic-enteric fistulae and 1 had arterio-enteric secondary fistulae . The group of 31 patients with deep graft infection, that is 2.6% of all patients (1190), had aortoiliac graft implanted at the mentioned time period (Tab . 4, 5) . Test results for detection of graft infection have been analysed (Tab . 17) . The results of isotopic investigation (Tab . 16), computed tomography (Tab . 11), ultrasonography (Tab . 13), fistulography (Tab . 14) and angiography (Tab . 15) were compared with intraoperative state or in a case of exclusion of infection, with results of follow up . Results of various paths of treatment were estimated (Tab . 18) . Based on performed cultures most common bacterial flora from infected grafts, was identified (Tab . 9, 10) . The sensitivity of the isotopic study with labeled white blood cells in detection of graft infection was 88%, specificity was 97%, accuracy 93%, positive predictive value 96% . Other useful diagnostic procedures in detection of aortic graft infection are: computed tomography with an accuracy of 75%, endoscopic investigation useful in detection of arterio-enteric fistulae with an accuracy of 50% and ultrasonography with an accuracy of 35.5% (Tab . 17) . The choice of the best treatment is still controversial . In my material total excision of infected graft and extraanatomic revascularization were burdened with 50% mortality rate . Among patients treated less radically the mortality rate was considerably lower . In a group of patients with the excision of the infected graft only, the mortality rate was 9% but the amputation rate was 36.4% and in a group of patients with excision of infected graft and reconstruction in situ, the mortality rate was 25% (Tab . 18) . Taking into consideration our results, less aggressive methods of aortic graft infection treatment such as the excision of the infected part of the prosthesis with or without in situ revascularization if only possible should be recommended . Most common in bacterial cultures from infected aortoiliac grafts with prosthetic-enteric fistulae were Escherichia coli found (Tab . 10) . In infections without fistula various types of Staphylococcus aureus were identified (Tab . 9) . CONCLUSIONS: 1 . In cases of aortoiliac graft infection the most common cultured bacteria are found to be Staphylococcus aureus . If there is additional prosthetic-enteric fistula Escherichia coli is the most common cultured bacteria . 2 . In a case there was suspicion of aortoiliac graft infection, proper diagnostic procedures are most important for effective ma

J Pharmacol Exp Ther, 1998 Oct, 287(1), 128 - 36
Epithelial ion transport and barrier abnormalities evoked by superantigen-activated immune cells are inhibited by interleukin-10 but not interleukin-4; Lu J et al.; Many studies have indicated an association between bacteria and the severity of enteric secretory or inflammatory disorders . We previously showed that monolayers of human T84 epithelial cells display altered ion transport and permeability after coculture with Staphylococcus aureus enterotoxin B (SEB, a model superantigen)-activated immune cells, where interferon-gamma and tumor necrosis factor-alpha were key mediators in the pathophysiology . Here we examined whether the regulatory Th2-type cytokines, interleukin (IL)-10 and IL-4, could prevent these epithelial irregularities . T84 monolayers were cocultured with human peripheral blood mononuclear cells (PBMC) or T cell-enriched, monocyte-depleted PBMC (T + B cells) +/- SEB for 20 hr in the presence or absence of IL-10 or IL-4 . Subsequently, T84 monolayers were mounted in Ussing chambers and ion transport (short-circuit current (Isc) and DeltaIsc evoked by forskolin) and permeability (ion resistance and probe fluxes) were assessed . IL-10 dose-dependently inhibited the increased T84 permeability and the reduced responsiveness to forskolin that were evoked by coculture with SEB-activated PBMC or T + B cells . Similar changes in T84 function occurred in response to conditioned medium from SEB-activated immune cells; however, addition of IL-10 to the conditioned medium did not prevent the changes in epithelial function . In contrast, when PBMC were stimulated with SEB in the presence of IL-10, the subsequent conditioned medium was less effective in evoking altered epithelial function . These data suggest that the affect of IL-10 was due to effects on the immune cells and not directly on the epithelium . In contrast to IL-10, IL-4 did not ameliorate any of the immune-mediated changes in T84 function . We conclude that IL-10 can reduce the epithelial functional changes caused by SEB-activated immune cells and this data adds further support for IL-10 immunotherapy in the treatment of intestinal secretory or inflammatory disorders.

Acta Crystallogr D Biol Crystallogr, 1998 Mar 1, 54 ( Pt 2), 276 - 8
Crystallization of the alpha-hemolysin heptamer solubilized in decyldimethyl- and decyldiethylphosphine oxide; Song L et al.; Crystals of the alpha-hemolysin heptamer, a transmembrane pore-forming toxin from Staphylococcus aureus, have been grown using the nonionic detergents n-decyldimethyl- and n-decyldiethylphosphine oxide, phosphorus homologs of the ionic amine oxide detergents . Five crystal forms were obtained, one of which diffracted X-rays to 3 A resolution . This crystal form displayed elements of pseudo mm symmetry in screened precession photographs yet it was triclinic with unit-cell dimensions a = 173, b = 173, c = 102 A, alpha = 92.6, beta = 94.8, gamma = 90.2 degrees.

J Bone Joint Surg Am, 1998 Sep, 80(9), 1336 - 40
Anti-infective efficacy of antiseptic-coated intramedullary nails; Darouiche RO et al.; The coating of medical devices with antimicrobial agents has recently emerged as a potentially effective method for the prevention of device-related infections . We examined the anti-infective efficacy of intramedullary nails coated with an antiseptic combination of chlorhexidine and chloroxylenol in a rabbit model of device-related infection after fixation of an open tibial fracture . The rabbits were randomized to receive 2.8-by-100-millimeter stainless-steel tibial intramedullary nails that either were uncoated or were coated with antiseptic . After administration of anesthesia and preoperative antibiotic prophylaxis, a tibial fracture was created and then reduced with insertion of the intramedullary nail . A bacterial inoculum of 10(6) colony-forming units of Staphylococcus aureus was injected into the intramedullary canal, and the wound was sutured . Radiographs of the tibiae were made postoperatively, and the rabbits were monitored daily . They were killed at six weeks, or earlier if there was dehiscence of the wound, the fracture became grossly unstable, or the rabbit failed to thrive . The use of the antiseptic-coated nails was associated with a significantly lower rate of device-related osteomyelitis (two of twenty-two; 9 per cent) than the use of the uncoated nails (thirteen of twenty-one; 62 per cent) (p = 0.0003) . The radiographic and histopathological findings were generally similar in the two groups of rabbits . Antiseptic agents were not detected in serum . The results suggest that antiseptic-coated fracture-fixation devices provide significant local protection against Staphylococcus aureus, which is the most common cause of infections related to orthopaedic devices.

Infect Control Hosp Epidemiol, 1998 Aug, 19(8), 552 - 9
Methicillin-resistant Staphylococcus aureus and its relationship to antimicrobial use: possible implications for control; Monnet DL; The control of methicillin-resistant Staphylococcus aureus (MRSA) is still an unresolved issue in numerous healthcare institutions worldwide . Guidelines for the control of MRSA in hospitals focus on measures to control cross-transmission and prevent colonization, but rarely specifically mention the control of antimicrobial use . We reviewed the different types of evidence for a causal relationship between MRSA and antimicrobial use by classifying them in four categories: consistent associations, dose-effect relationships, concomitant variations, and arguments to support a plausible biological model to explain this relationship . Although the relative participation of cross-transmission and antimicrobial selection pressure in the level of MRSA observed in a healthcare setting remains to be determined, we found lines of evidence to support the existence of a relationship between MRSA and antimicrobial use in each of the four categories . This review points out the relative lack of studies specifically designed to investigate this aspect of MRSA epidemiology and the need to implement such studies quickly . In the meantime, the results presented here should encourage the implementation of antimicrobial-use improvement programs in hospitals in addition to existing infection control measures, which are still a priority in countries with high MRSA prevalence.

Gene, 1998 Sep 28, 219(1-2), 9 - 17
Sequence of the putative alanine racemase operon in Staphylococcus aureus: insertional interruption of this operon reduces D-alanine substitution of lipoteichoic acid and autolysis; Kullik I et al.; A gene cluster comprising the alanine racemase gene alr was identified 5' to the sigB operon in Staphylococcus aureus . It is flanked upstream by four ORFs of which one shows similarity to the dpj gene of Escherichia coli, and downstream by two ORFs of which the last shows similarity to the E . coli pemK gene . Preliminary data suggest that the seven ORFs orf1-orf2-orf3-dpj-alr-orf6-pemK may form an operon . Disruption of the proposed operon by insertional mutagenesis leads to a drastic loss in the d-alanine (d-Ala) substitution of lipoteichoic acid and to delayed autolysis, without affecting the d-Ala substitution of the wall teichoic acid.

Antimicrob Agents Chemother, 1998 Oct, 42(10), 2739 - 44
In vitro studies of pharmacodynamic properties of vancomycin against Staphylococcus aureus and Staphylococcus epidermidis; Lowdin E et al.; The bactericidal activities of vancomycin against two reference strains and two clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis were studied with five different concentrations ranging from 2x to 64x the MIC . The decrease in the numbers of CFU at 24 h was at least 3 log10 CFU/ml for all strains . No concentration-dependent killing was observed . The postantibiotic effect (PAE) was determined by obtaining viable counts for two of the reference strains, and the viable counts varied markedly: 1.2 h for S . aureus and 6.0 h for S . epidermidis . The determinations of the PAE, the postantibiotic sub-MIC effect (PA SME), and the sub-MIC effect (SME) for all strains were done with BioScreen C, a computerized incubator for bacteria . The PA SMEs were longer than the SMEs for all strains tested . A newly developed in vitro kinetic model was used to expose the bacteria to continuously decreasing concentrations of vancomycin . A filter prevented the loss of bacteria during the experiments . One reference strain each of S . aureus and S . epidermidis and two clinical isolates of S . aureus were exposed to an initial concentration of 10x the MIC of vancomycin with two different half-lives (t1/2s): 1 or 5 h . The post-MIC effect (PME) was calculated as the difference in time for the bacteria to grow 1 log10 CFU/ml from the numbers of CFU obtained at the time when the MIC was reached and the corresponding time for an unexposed control culture . The difference in PME between the strains was not as pronounced as that for the PAE . Furthermore, the PME was shorter when a t1/2 of 5 h (approximate terminal t1/2 in humans) was used . The PMEs at t1/2s of 1 and 5 h were 6.5 and 3.6 h, respectively, for S . aureus . The corresponding figures for S . epidermidis were 10.3 and less than 6 h . The shorter PMEs achieved with a t1/2 of 5 h and the lack of concentration-dependent killing indicate that the time above the MIC is the parameter most important for the efficacy of vancomycin.

Antimicrob Agents Chemother, 1998 Oct, 42(10), 2678 - 81
Inhibitory activities of gatifloxacin (AM-1155), a newly developed fluoroquinolone, against bacterial and mammalian type II topoisomerases; Takei M et al.; We determined the inhibitory activities of gatifloxacin against Staphylococcus aureus topoisomerase IV, Escherichia coli DNA gyrase, and HeLa cell topoisomerase II and compared them with those of several quinolones . The inhibitory activities of quinolones against these type II topoisomerases significantly correlated with their antibacterial activities or cytotoxicities (correlation coefficient {r} = 0.926 for S . aureus, r = 0.972 for E . coli, and r = 0.648 for HeLa cells) . Gatifloxacin possessed potent inhibitory activities against bacterial type II topoisomerases (50% inhibitory concentration {IC50} = 13.8 microg/ml for S . aureus topoisomerase IV; IC50 = 0.109 microg/ml for E . coli DNA gyrase) but the lowest activity against HeLa cell topoisomerase II (IC50 = 265 microg/ml) among the quinolones tested . There was also a significant correlation between the inhibitory activities of quinolones against S . aureus topoisomerase IV and those against E . coli DNA gyrase (r = 0.969) . However, the inhibitory activity against HeLa cell topoisomerase II did not correlate with that against either bacterial enzyme . The IC50 of gatifloxacin for HeLa cell topoisomerase II was 19 and was more than 2,400 times higher than that for S . aureus topoisomerase IV and that for E . coli DNA gyrase . These ratios were higher than those for other quinolones, indicating that gatifloxacin possesses a higher selectivity for bacterial type II topoisomerases.

Antimicrob Agents Chemother, 1998 Oct, 42(10), 2590 - 4
Characterization of mutations in the rpoB gene that confer rifampin resistance in Staphylococcus aureus; Aubry-Damon H et al.; Mutations in the rifampin resistance-determining (Rif) regions of the rpoB gene of Staphylococcus aureus mutants obtained during therapy or in vitro were analyzed by gene amplification and sequencing . Each of the resistant clinical isolates, including five nonrelated clones and two strains isolated from the same patient, and of the 10 in vitro mutants had a single base pair change that resulted in an amino acid substitution in the beta subunit of RNA polymerase . Eight mutational changes at seven positions were found in cluster I of the central Rif region . Certain substitutions (His481/Tyr and Asp471/Tyr {S . aureus coordinates}) were present in several mutants . Substitutions Gln468/Arg, His481/Tyr, and Arg484/His, which conferred high-level rifampin resistance, were identical or in the same codon as those described in other bacterial genera, whereas Asp550/Gly has not been reported previously . Substitutions at codon 477 conferred high- or low-level resistance, depending on the nature of the new amino acid . The levels of resistance of in vivo and one-step in vitro mutants carrying identical mutations were similar, suggesting that no other resistance mechanism was present in the clinical isolates . On the basis of these data and the population distribution of more than 4,000 clinical S . aureus isolates, we propose </=0.5 and >/=8 microg/ml as new breakpoints for the clinical categorization of this species relative to rifampin.

J Biochem (Tokyo), 1998 Oct, 124(4), 778 - 83
Pyrrolidone carboxyl peptidase from the hyperthermophilic Archaeon Pyrococcus furiosus: cloning and overexpression in Escherichia coli of the gene, and its application to protein sequence analysis; Tsunasawa S et al.; A gene for a pyrrolidone carboxyl peptidase (Pcp: EC 3.4.19.3, pyroglutamyl peptidase), which removes amino-terminal pyroglutamyl residues from peptides and proteins, has been cloned from the hyperthermophilic Archaeon Pyrococcus furiosus using its cosmid protein library, sequenced, and expressed in Escherichia coli . The DNA sequence encodes a protein containing 208 amino acid residues with methionine at the N-terminus . Analysis of the recombinant protein expressed in E . coli, including amino acid sequence analysis from the N-terminus by automated Edman degradation and ionspray mass spectrometric analysis of the peptides generated by enzymatic digestions with lysylendopeptidase and Staphylococcus aureus V8 protease, showed its primary structure to be completely identical with that deduced from its cDNA sequence . Comparison of the amino acid sequence of P . furiosus Pcp (P.f.Pcp) with those of bacterial Pcps revealed that a high degree of sequence identity (more than 40%) and conservation of the amino acid residues comprising the catalytic triad, Cys142, His166, and Glu79 . On the other hand, a unique short stretch sequence (positions around 175-185) that is absent in bacterial Pcps was found in P.f.Pcp . A similar stretch has also been reported recently in the amino acid sequence of Pcp from the hyperthermophilic Archaeon Thermococcus litoralis {Littlechild et al., in abstracts of the "International Congress on Exthermophiles '98" p . 58 (1998)} . To elucidate their contribution to the hyperthermostability of these enzymes, further structural studies are required.

Int J Immunopharmacol, 1998 Jul, 20(7), 345 - 57
IL-6 functions in cynomolgus monkeys blocked by a humanized antibody to human IL-6 receptor; Imazeki I et al.; A humanized antibody to the human interleukin-6 receptor (IL-6R), hPM-1, blocked the interleukin-6 (IL-6) functions in normal cynomolgus monkey lymphocytes in vitro . The binding activity of hPM-1 to non-human primate IL-6R was examined in peripheral blood lymphocytes by flow cytometry . PM-1 recognized the IL-6R on T lymphocytes of cynomolgus and rhesus monkeys, but did not on those of marmosets . The homology between human IL-6R and its cynomolgus monkey counterpart was 97.3% in the extracellular domain of the amino acid sequence, as determined by DNA sequencing of the PCR product from peripheral blood mononuclear cells . PM-1 inhibited two functional parameters in vitro in cynomolgus monkeys: (1), T-cell proliferation stimulated by phytohemaglutinin and human IL-6; (2), Immunoglobulin G-production evoked by Staphylococcus aureus Cowan-1- and human IL-6-stimulated B lymphocytes . These data show that hPM-1 binds to and functionally blocks the cynomolgus monkey IL-6 receptors.

Jpn J Antibiot, 1998 Jun, 51(6), 432 - 6
{Transferability of tazobactam/piperacillin (TAZ/PIPC) to cerebrospinal fluid of rabbit with meningitis caused by Staphylococcus aureus}; Haruta T et al.; The transferability of tazobactam/piperacillin (TAZ/PIPC) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus . 125 or 250 mg/kg of TAZ/PIPC was intravenously administered to rabbits with experimental meningitis then concentrations of TAZ and PIPC in CSF and serum were measured . In the group to which 125 mg/kg of TAZ/PIPC was administered, mean concentration of TAZ in CSF was 7.3 and 2.4 micrograms/ml at 30 and 60 min after administration, respectively, and concerning PIPC, it was 10.1 and 3.5 micrograms/ml, respectively . CSF/serum ratio of TAZ was 29.4% and 31.4%, respectively, and that of PIPC was 24.3 and 35.6%, respectively . In the group to which 250 mg/kg of TAZ/PIPC was administered, mean concentration of TAZ in CSF was 16.5 and 12.6% micrograms/ml, respectively, and concerning PIPC, it was 25.6 and 18.2 micrograms/ml, respectively . CSF/serum ratio of TAZ was 22.1 and 56.1%, respectively, and that of PIPC was 12.2 and 51.9%, respectively . Addition of TAZ did not make significant change of transferability of PIPC to CSF . Considering the antibacterial effect of TAZ/PIPC against main causative organism of meningitis, this agent was thought to be effective for the treatment of purulent meningitis.

Jpn J Antibiot, 1998 Jul, 51(7), 494 - 500
{Resistance to macrolide antibiotics found in methicillin-resistant Japanese clinical isolates of Staphylococcus aureus in 1996}; Nakamura A et al.; Minimum inhibitory concentrations (MICs) of erythromycin, clarithromycin, roxithromycin, oleandomycin, triacetyloleandomycin, azithromycin, josamycin and midecamycin were investigated using 200 strains of methicillin-resistant Staphylococcus aureus (MRSA) clinically isolated in Japan during 1996 . The results show that the MRSAs could be classified into five groups according to MIC patterns to various macrolides and that more than 88% of the strains used were highly-resistant to all macrolides tested . It was found that 9.0% of the strains examined showed a unique MIC pattern different to that of macrolide-lincosamide-streptogramin B antibiotic resistance type . This group was found to be highly resistant to 14-membered but susceptible to 16-membered macrolides . The resistance induction by erythromycin or oleandomycin was observed to increase for clarithromycin and roxithromycin resistances in a part of strains used . On the other hand, for azithromycin, such induction was not observed.

Ned Tijdschr Geneeskd, 1998 Jun 20, 142(25), 1425 - 9
{Pain in the hip area accompanied by a fever}; Veldman BA et al.; In 3 patients, 2 women aged 16 and 64 years and 1 man aged 64 years, with pain in the left hip region and fever, the diagnosis psoas abscess was made . After antibiotic treatment and drainage they recovered well . The primary from of psoas abscess is presumably caused by haematogenous spread of bacteria, mostly Staphylococcus aureus . The secondary form is caused by spread of infection from surrounding tissue, mostly gastrointestinal micro-organisms with Crohn's disease and diverticulitis . Painful passive extension and endorotation as well as a painful flexion stress-test of the hip joint can indicate a psoas abscess . Echography and blood cultures should be performed if a psoas abscess is suspected . If echography is inconclusive, CT-scan can establish the diagnosis . The psoas abscess should be treated by percutaneous or surgical drainage combined with antibiotic therapy . The underlying cause of a secondary psoas abscess should be treated separately.

Ann Fr Anesth Reanim, 1997, 16(8), 964 - 6
{Peridural abscess complicating spinal anesthesia in a diabetic patient}; Popesco D et al.; Infectious complications of spinal or epidural anaesthesia are rare, particularly after spinal anaesthesia . Most of them consist of a meningitis . We report a case of epidural abscess due to Staphylococcus aureus following spinal anaesthesia in a 62-year-old diabetic patient, diagnosed 45 days after the puncture with bacterial samples and magnetic resonance imaging . The pejorative neurological outcome required a laminectomy in spite of an efficient anti-staphylococcal treatment.

Lett Appl Microbiol, 1998 Aug, 27(2), 98 - 100
Anti-MRSA activity of sophoraflavanone G and synergism with other antibacterial agents; Sakagami Y et al.; Anti-MRSA activity of sophoraflavanone G (SFG) and synergism between SFG and antibacterial agents against MRSA (methicillin-resistant Staphylococcus aureus) were evaluated by means of Minimal Inhibitory Concentrations (MIC) . The MICs of SFG against 27 strains of MRSA ranged from 3.13 to 6.25 micrograms ml-1 . Synergism between SFG and vancomycin hydrochloride (VCM) or fosfomycin (FOM) was observed (the fraction inhibitory concentration (FIC) indices were 0.16 and 0.48), while partial synergism was admitted between SFG and other antibacterial agents such as methicillin (DMPPC), cefzonam (CZON), gentamicin (GM), minocycline (MINO) and levofloxacin (LVFX) (the FIC indices were 0.71, 0.73, 0.69, 0.65 and 0.58, respectively) . These findings suggest that SFG in combination with VCM or FOM may be useful in controlling MRSA infections.

J Appl Microbiol, 1998 Sep, 85(3), 537 - 44
Growth and enterotoxin production of Staphylococcus aureus during the manufacture and ripening of Camembert-type cheeses from raw goats' milk; Meyrand A et al.; Tests were carried out to determine the effect of manufacturing procedures for a Camembert-type cheese from raw goats' milk on the growth and survival of Staphylococcus aureus organisms added to milk at the start of the process, and to study the possible presence of staphylococcal enterotoxin A in these cheeses . The initial staphylococcal counts were, respectively, 2, 3, 4, 5 and 6 log cfu ml-1 . Cheese was prepared following the industrial specifications and ripened for 41 d . Detection of enterotoxins was done by the Vidas SET test and by an indirect double-sandwich ELISA technique using antienterotoxin monoclonal antibodies . Generally, numbers of microbes increased at a similar rate during manufacture in all cheeses until salting . During the ripening period, the aerobic plate count population and Staph . aureus levels remained stable and high . There was an approximately 1 log reduction of Staph . aureus in cheeses made with an initial inoculum of Staph . aureus greater than 10(3) cfu ml-1 at the end of the ripening period (41 d) compared with the count at 22 h . The level of staphylococcal enterotoxin A recovered varied from 1 to 3.2 ng g-1 of cheese made with an initial population of 10(3)-10(6) cfu ml-1 . No trace of enterotoxin A was detected in cheeses made with the lowest Staph . aureus inoculum used in this study.

Arch Biochem Biophys, 1998 Oct 1, 358(1), 68 - 73
Neuronal nitric oxide synthase-membrane phospholipid interactions; Watanabe Y et al.; Most of the neuronal nitric oxide synthase (nNOS) is present in the particulate fraction of tissue extracts . Here, we show that the calmodulin (CaM)-binding domain of nNOS interacts with anionic phospholipid vesicles but not with neutral ones . Identification of residues in the CaM-binding domain of nNOS as the key domain for the interaction is also documented . Recombinant wild-type nNOS was found to associate with phosphatidylserine (PS) or phosphatidic acid (PA) but not with phosphatidylethanolamine (PE) or phosphatidylcholine (PC), indicating that nNOS-phospholipid binding requires an electrostatic interaction . A synthetic peptide corresponding to residues 732-754 blocked the interaction of nNOS with PS . Furthermore, a purified fusion protein containing residues 724-755 interacted with PS in a competitive fashion with CaM . Inactive nNOS lacking CaM-binding ability, generated by mutation of (Lys732LysLeu) to (Asp732AspGlu) (Watanabe, Y., Hu, Y., and Hidaka, H., FEBS Lett . 403, 75-78, 1997) did not interact with PS . Preincubation of nNOS with PS protected subsequent limited proteolysis of the synthase by Staphylococcus aureus V8 protease, probably as a result of conformational changes in the protein . Wild-type nNOS was found almost entirely in the membrane fraction of Sf9 cells, whereas inactive nNOS was also found in cytosolic fraction in Sf9 cells expressing the mutant enzyme . These results demonstrate that the mutated hydrophobic/basic amino acid cluster in nNOS sequence, Lys732LysLeu, is essential for nNOS-PS and nNOS-CaM interactions .

Arch Mal Coeur Vaiss, 1998 Jun, 91(6), 753 - 7
{Infections secondary to implantation of cardiac pacemakers}; Da Costa A et al.; Infectious complications of pacemaker implantation are not common but may be particularly severe . Localised wound infections at the site of implantation have been reported in 0.5% of cases in the most recent series with an average of about 2% . The incidence of septicaemia and infectious endocarditis is lower, about 0.5% of cases . The operator's experience, the duration of the procedure and repeat procedures are considered to be predisposing factors . The main cause of these infections is though to be local contamination during the implantation . The commonest causal organism is the staphylococcus (75 to 92%), the staphylococcus aureus being the cause of acute infections whereas the staphylococcus epidermis is associated with cases of secondary infection . The usual clinical presentation is infection at the site of the pacemaker but other forms such as abscess, endocarditis, rejection of the implanted material, septic emboli and septic phlebitis have been described . The diagnosis is confirmed by local and systemic biological investigations and by echocardiography (especially transoesophageal echocardiography) in cases of right heart endocarditis . There are two axes of treatment: bactericidal double antibiotherapy and surgical ablation of the infected material either percutaneously or by cardiotomy . Though controversial, and unsupported by scientific evidence, the role of systematic, preoperative, prophylactic antibiotic therapy in the prevention of these complications seems to be increasing.

Arch Mal Coeur Vaiss, 1998 Jul, 91(7), 893 - 7
{Communication between the left ventricle and the right atrium in infectious endocarditis . Diagnosis using Doppler-echocardiography}; Grand A et al.; The diagnosis of a communication between the left ventricle and right atrium was made by transthoracic and transoesophageal echocardiography in a 67 year old man with a recurrence of a methicillin-resistant staphylococcus aureus infectious endocarditis complicating aortic valve replacement with a bioprosthesis seven weeks previously . This diagnosis was confirmed at surgery; the left ventricular-right atrial communication was closed by suturing its edges and a new aortic valve prosthesis was implanted . Unfortunately, the patient died 4 months later of myocardial dysfunction although the infectious endocarditis seemed to have been sterilised by antibiotic therapy . Doppler echocardiography, especially using the transoesophageal approach is the best diagnostic method for rare complications of infectious endocarditis, usually of the aortic valve, the prognosis of which is improved by early surgery and appropriate antibiotic therapy for the causal organisms.

Br J Dermatol, 1998 Jun, 138(6), 1036 - 8
Phagocytosis and oxidative burst by neutrophils in patients with recurrent furunculosis; Demircay Z et al.; Neutrophil phagocytosis of fluorescently labelled Staphylococcus aureus and oxidative burst by the neutrophils were assessed by flow cytometry in 22 patients with recurrent furunculosis and in 17 controls . Phagocytosis and oxidative burst were not found to be significantly different between the patients and controls . Low serum iron concentrations were demonstrated in six patients (27%) . In these patients with hypoferraemia, oxidative burst was significantly lower than in the patients without hypoferraemia and in the controls . These data suggest that hypoferraemia may be an important predisposing factor in a subgroup of patients with recurrent furunculosis in impairing oxidative killing by neutrophils.

Br J Dermatol, 1998 Jun, 138(6), 1022 - 9
Flucloxacillin in the treatment of atopic dermatitis; Ewing CI et al.; Although colonization of atopic dermatitis by Staphylococcus aureus is universal and bacterial infection is common, it is not known whether antibiotic therapy is helpful in eczematous children who do not have any signs suggestive of bacterial infection . Fifty children aged 1-16 years with atopic dermatitis took part in a randomized double-blind placebo-controlled study of 4 weeks treatment with oral flucloxacillin, with an 8-week follow-up period . The change in the mean of the log10 of the counts/cm2 of S . aureus after 4 weeks of treatment was significantly different for patients receiving treatment, compared with the change for those receiving the placebo (P = 0.008) . However, the difference in the change at 14 days after stopping treatment was not significant (P = 0.32) . Methicillin-resistant strains of S . aureus were cultured from five children during or after treatment . Flucloxacillin did not improve the symptoms or clinical appearance of atopic dermatitis and only temporarily changed skin colonization by S . aureus.

Anasthesiol Intensivmed Notfallmed Schmerzther, 1998 Aug, 33(8), 497 - 500
{Methicillin-reistant Staphylococcus aureus: risk factors for infection-colonization and clonal heterogeneity in intensive care units}; Wichelhaus TA et al.; PURPOSE: The aim of this study was to determine the risk factors associated with colonisation/infection by methicillin-resistant Staphylococcus aureus (MRSA) and to demonstrate the chain of infections by genotyping of all MRSA isolates . METHODS: A total of 6143 microbiological samples from 1753 patients was obtained at a surgical ICU of Frankfurt University hospital during 1995 . RESULTS: MRSA was detected in 1.6% of patients and three members of staff (3.3%) . Typing of these 31 MRSA-strains (first isolates) by macrorestriction analysis of chromosomal DNA revealed nine different genotypes . More than 60% of all isolates belonged to one type that was confirmed to be closely related to the "South Germany" epidemic strain . A strong correlation between severity of underlying disease and length of hospitalisation on the one hand and detection of MRSA on the other could be demonstrated . Detection of MRSA was significantly more common in patients with adult respiratory distress syndrome (ARDS), sepsis, kidney failure, prolong respiratory treatment and in patients with prolonged phases of haemodynamic instability . It appeared that the mortality rate of MRSA-infected patients was higher (28.6%) than the mortality rate of all patients (6.5%) . CONCLUSION: Following of a strict hygiene regime is important to prevent clonal spread of MRSA and especially to protect immunocompromised patients from complicating infections.

Caries Res, 1998, 32(6), 441 - 6
Efficacy of sterilisation methods and their effect on enamel demineralisation; Amaechi BT et al.; The aim of this project was to determine the effectiveness of sterilisation methods for dental enamel for use in intra-oral cariogenicity tests, and their possible effect on the degree of demineralisation of enamel . Bovine incisors were cut vertically into five portions and each assigned to one of five groups . Group 1 was used as a control while the other four groups were subjected, respectively, to gamma irradiation ( congruent with 25kGy), steam autoclaving (121 degrees C for 15 min), sodium hypochlorite (12% w/v for 24h) and povidone-iodine (7.5% w/v for 24h) . Total viable counts of microorganisms remaining following sterilisation of the specimens were performed following incubation of the specimens for 24h at 37 degrees C . Caries-like lesions were produced in each specimen using an acidic buffer solution (pH4.5) . Sections were cut from each specimen, ground to 80-microgram thickness, and microradiographed . Mineral loss and lesion depth were quantified using transverse microradiography . Statistical analysis was by ANOVA . Dunnett's and Tukey's tests . Microbial growth (Staphylococcus aureus and bacilli) was observed only in control specimens in both brain heart infusion broth and on blood agar plates . The sterilisation methods affected the enamel surface as follows: gamma irradiation (cream discolouration), NaOCl (bleaching), and povidone-iodine (white spot-like lesion) . Compared with the control, there was no significant difference in mineral loss and lesion depth with any of the groups, but the numerical values of mineral loss and lesion depth in groups can be ranked as follows: gamma irradiation <povidone-iodine <control <autoclave <NaOCl . In conclusion, the four sterilisation methods were all effective to sterilise enamel, but gamma irradiation proved the most acceptable method for enamel to be used in cariogenicity tests having the least adverse effect.

Infect Immun, 1998 Oct, 66(10), 4588 - 92
Antigenic determinants of Staphylococcus aureus type 5 and type 8 capsular polysaccharide vaccines; Fattom AI et al.; Bacterial capsular polysaccharides (CP) are carbohydrate polymers comprised of repeating saccharide units . Several of these CP have side chains attached to their backbone structures . The side chains may include O-acetyl, phosphate, sialic acid, and other moieties . Those moieties represent the immunodominant epitopes and the most functional ones . The clinically significant Staphylococcus aureus type 5 CP (CP 5) and type 8 CP (CP 8) are comprised of a trisaccharide repeat unit with one O-acetyl group attached to each repeat unit . The immunogenicity of these CP and the functionality of antibodies to the backbone and the O-acetyl moieties were investigated . Immunization with the native CP conjugates (CP with 75% O-acetylation) elicited a high proportion of antibodies directed against the O-acetyl moiety . Nonetheless, all of the vaccinees produced antibodies to the backbone moieties as well . Conjugate vaccines made of de-O-acetylated CP elicited backbone antibodies only . Antibodies to both backbone and O-acetyl groups were found to be opsonic against S . aureus strains which varied in their O-acetyl content . Absorption studies with O-acetylated and de-O-acetylated CP showed that (i) native CP conjugates generated antibodies to both backbone and O-acetyl groups and (ii) O-acetylated isolates were opsonized by both populations of antibodies while the non-O-acetylated strains were predominantly opsonized by the backbone antibodies . These results suggest that S . aureus CP conjugate vaccines elicit multiple populations of antibodies with diverse specificities . Moreover, the antibodies of different specificities (backbone or O-acetyl) are all functional and efficient against the variations in bacterial CP that may occur among clinically significant S . aureus pathogenic isolates.

Zhonghua Yi Xue Za Zhi (Taipei), 1998 Aug, 61(8), 488 - 91
Pyomyositis in childhood: a case report; Liew KL et al.; Pyomyositis is a primary infection of skeletal muscle . We report the case of a previously healthy six-year-old who suffered from pyomyositis in the right lower back . He presented with lower back pain and low-grade fever for one week . After a series of laboratory and imaging studies, the diagnosis of right multifidus muscle pyomyositis with abscess formation was made . The patient recovered rapidly after incision and drainage therapy, accompanied by antibiotic treatment . Methicillin-resistant Staphylococcus aureus was cultured from the abscess discharge . It was strongly suspected that herbal medicines and common cold medication the patient had been prescribed before admission to our hospital produced a masking effect that delayed the diagnosis.

J Immunol, 1998 Sep 15, 161(6), 3161 - 8
High resolution mapping of the B cell epitopes of staphylokinase in humans using negative selection of a phage-displayed antigen library; Jenne S et al.; Staphylokinase (Sak), a 16-kDa protein secreted by Staphylococcus aureus, induces fibrin-specific thrombolysis in patients with thrombotic disorders . However, Sak also elicits high titers of neutralizing Abs that persist for several months and preclude its repeated use in humans . To identify the antigenic determinants of Sak recognized by humans, a phage-displayed library of Sak variants was selected for mutants that escape binding to an affinity matrix derivatized with patient-specific polyclonal anti-Sak Abs . Fifty-six escape Sak variants were identified after three selection cycles using human polyclonal anti-Sak IgGs obtained from four different patients . DNA sequencing revealed 213 amino acid substitutions, of which 73% were found at 25 positions clustered in eight discontinuous Sak antigenic segments . Although each antigenic segment was recognized to a variable extent by each patient antiserum, the main epitopes of Sak in all patients were roughly targeted to two large discontinuous areas covering 35% of the solvent-accessible surface of Sak . The antigenic area I comprises three segments centered on residues 66, 73, and 135, while the antigenic area II consists of four segments centered on positions 20, 95, 102, and 121 . These results suggest that a secondary immune response against Sak can occur in patients, and confirm an initial site-directed mutagenesis study wherein amino acid Lys74 was shown to play a prominent antigenic role . Comprehensive mapping of the most relevant sites of Sak that are antigenic for humans will guide efforts to modulate the immunogenicity of this therapeutically important molecule.

FEMS Microbiol Lett, 1998 Sep 1, 166(1), 103 - 7
Conditions that induce Staphylococcus aureus heat shock proteins also inhibit autolysis; Qoronfleh MW et al.; When Staphylococcus aureus strain 8325 was grown at 30 degrees C and heat shocked at 40 degrees C the rate of cell autolysis in buffer with or without Triton X-100 was reduced . Treatment of growing cells with other agents (CdCl2, ethanol, NaCl) known to induce heat shock proteins also resulted in cells that showed a decreased rate of autolysis . Heat shocked cells showed lower rates of freeze-thaw autolysin activity on purified cell walls, and isolated crude cell walls from heat shocked cells had lower rates of autolytic activity compared to controls . No differences in the peptidoglycan hydrolase activity profiles of control and heat shocked cells were detected by renaturing sodium dodecyl sulfate polyacrylamide gel electrophoresis . It is proposed that autolysins are damaged by heat shock and their targeting to the cell wall is impaired, possibly by complexing with heat shock proteins, which may also inhibit autolysin activity . Heat shock also inhibited the autolytic activity of methicillin-resistant and related-susceptible strains, and the possible relationship of this to the expression of methicillin resistance is discussed.

Pharmazie, 1998 Aug, 53(8), 578 - 81
Corollosporine, a new phthalide derivative from the marine fungus Corollospora maritima Werderm . 1069; Liberra K et al.; Extracts of the culture medium from the marine fungus Corollospora maritima exhibited concentration dependent antibacterial activity against Staphylococcus aureus and other microorganisms . Bioactivity-guided fractionation and purification afforded the new isobenzofuranone or phthalid type compound corollosporine.

Ann Dermatol Venereol, 1997, 124(10), 684 - 6
{Staphylococcus aureus septicemia producing Panton-Valentine leukocidin . 3 cases}; Couppie P et al.; BACKGROUND: A strong association has been observed between furuncles and Panton-Valentine leukocidin-producing Staphylococcus aureus . CASE REPORTS: Within one year, we cared for three men at the Cayenne hospital who had Staphylococcus aureus septicemia with severe pleuropulmonary involvement originating from furuncular lesions . The Staphylococcus aureus strains isolated from the skin lesions and from blood cultures produced Panton-Valentine leukocidin . CONCLUSION: These cases demonstrate the gravity of S . aureus septicemia in young patients with furunculosis . These cases are the first reported with severe S . aureus infections associated with Panton-Valentine leukocidin producing strains.

J Invest Dermatol, 1998 Sep, 111(3), 452 - 6
Role of Staphylococcus aureus surface-associated proteins in the attachment to cultured HaCaT keratinocytes in a new adhesion assay; Mempel M et al.; Colonization of human skin with Staphylococcus aureus is a common feature in a variety of dermatologic diseases . In order to reproducibly investigate the adherence of Staphylococcus aureus to human epidermal cells, an in vitro assay was established using the biotin/streptavidine labeling system and the HaCaT cell line . This assay was used to define the role of several Staphylococcus aureus surface proteins with regard to their function in the staphylococcal adhesion process . Our studies included the standard laboratory strain Newman as well as its genetically constructed mutants DU5873, DU5852, DU5854, and DU5886 generated by allele replacement or transposon mutagenesis, which are deficient in the elaboration of staphylococcal protein A (spa), clumping factor (clfA), coagulase (coa), and the fibronectin-binding proteins A and B (fnbA/B), respectively . In comparison with strain Newman all mutants showed remarkably reduced adherence to the HaCaT keratinocyte cell line in our assay, yielding only between 43% and 60% of the adherence capacity of strain Newman after 60 min . Bacterial adherence could be re-established by introducing the cloned wild-type genes for the surface proteins on shuttle plasmids into the chromosomally defective mutants, thus suggesting a pathogenetic role of these proteins in the attachment of Staphylococcus aureus to human keratinocytes . Bacterial adherence was additionally enhanced by alkaline pH-values that are characteristic for skin conditions with epidermal barrier dysfunction . The use of Staphylococcus aureus mutant strains, deficient in the elaboration of defined proteins, allows specific investigation of colonization and virulence factors of this dermatologic relevant microorganism.

Am J Kidney Dis, 1998 Sep, 32(3), 401 - 9
Cefazolin in chronic hemodialysis patients: a safe, effective alternative to vancomycin; Fogel MA et al.; Vancomycin use is common in hemodialysis patients, due in part to the ease of dosing, but can lead to the development of resistant organisms, including vancomycin-resistant enterococcus . Alternate antibiotics may be equally effective and allow similar dosing in the chronic hemodialysis population . A retrospective review of culture results from a 217-patient, non-hospital-based outpatient hemodialysis center was performed over a 7-month period . Wound and blood culture sensitivity to cefazolin, vancomycin, cefazolin plus gentamicin, and vancomycin plus gentamicin was analyzed . Cefazolin was equivalent to vancomycin for empiric treatment of clinically significant infections in a population with a low rate of methicillin-resistant Staphylococcus aureus infection . Cefazolin plus gentamicin was superior to vancomycin alone . The vancomycin plus gentamicin combination did provide minimally broader coverage than the cefazolin plus gentamicin combination . A prospective pharmacokinetic analysis of postdialysis cefazolin dosing was performed in anuric chronic hemodialysis patients dialyzed with polysulfone dialyzers . Peak, predialysis, and postdialysis cefazolin levels were obtained . Nondialysis clearance of cefazolin was sufficiently low (k(e), 0.027; t(1/2), 26.4 hours) and dialysis clearance sufficiently high (k(e), 0.254; t(1/2), 3.19 hours) to provide for safe and effective peak and trough cefazolin levels with postdialysis dosing in anuric hemodialysis patients . In conclusion, cefazolin alone or with gentamicin in an appropriate empiric antibiotic choice in chronic hemodialysis patients dialyzed in a nonhospital setting with low methicillin-resistant S . aureus infection rates . For infections with documented sensitivity to cefazolin, a 1 g intravenous dose postdialysis (750 mg in patients weighing <50 kg) is safe and effective.

Ann Dermatol Venereol, 1997, 124(9), 612 - 4
{Methi-resistant Staphylococcus aureus myositis}; Milochau P et al.; INTRODUCTION: Pyomyositis are relatively rare in our countries . CASE REPORT: A 73-year-old-man presented with leg pains and septicemia . Diagnosis of pyomyositis was made and a large incision was performed after which the patient had a progressive improvement . DISCUSSION: Diagnosis of pyomyositis may be difficult in early stages . Diagnosis is greatly facilitated by magnetic resonance imaging . Responsibility of Staphylococcus aureus in cases of pyomyositis due to methi-resistant Staphylococcus aureus may be evocated even if patients was not hospitalized.

Brain Res, 1998 Sep 28, 806(2), 152 - 64
Correlation between potentiation of AP1 DNA binding and expression of c-Fos in association with phosphorylation of CREB at serine133 in thalamus of gerbils with ischemia; Kuramoto N et al.; Protein biosynthesis is mainly under the control at the level of gene transcription in eukaryotes . Transcription factors are nuclear proteins with abilities to modulate the activity of RNA polymerase II which is responsible for the formation of messenger RNA from double stranded DNA in the cell nuclei . Binding of a radiolabeled oligonucleotide probe for the transcription factor activator protein-1 (AP1) was transiently potentiated 1 to 6 h after the recirculation of blood supply in the thalamus and striatum, but not in the entorhinal cortex, olfactory bulb, frontal cortex, cerebellar cortex and medulla-pons, in gerbils with transient global forebrain ischemia for 5 min, in addition to the hippocampal subregions . The ischemic insult not only increased the immunoreactivity with an antibody against cyclic AMP response element binding protein (CREB) phosphorylated at serine133, but also induced the expression of both c-Jun and c-Fos family proteins 3 h after the recirculation in the thalamus . Limited proteolysis by Staphylococcus aureus (S . aureus) V8 protease revealed the expression of different partner proteins of AP1 in response to ischemic signals in the thalamus . Moreover, ischemia for 2 min led to more prolonged elevation of AP1 binding in the thalamus at least up to 12 h after the reperfusion than that seen with ischemia for 5 min . These results suggest that potentiation of AP1 DNA binding may at least in part involve mechanisms associated with the expression of c-Fos protein through phosphorylation of CREB at serine133 in the thalamus of gerbils with ischemia .

Eur J Biochem, 1998 Aug 1, 255(3), 647 - 53
Purification and characterization of the respiratory arsenate reductase of Chrysiogenes arsenatis; Krafft T et al.; Chrysiogenes arsenatis is the only bacterium known that respires anaerobically using arsenate as the terminal electron acceptor and the respiratory substrate acetate as the electron donor . During growth, the arsenate is reduced to arsenite; the reduction is catalyzed by an arsenate reductase . This study describes the purification and characterization of a respiratory arsenate reductase (Arr) . The enzyme consists of two subunits with molecular masses of 87 kDa (ArrA) and 29 kDa (ArrB), and is a heterodimer alpha1beta1 with a native molecular mass of 123 kDa . The arsenate reductase contains molybdenum, iron, acid-labile sulfur and zinc as cofactor constituents . The Km of the enzyme for arsenate is 0.3 mM and the Vmax is 7013 micromol arsenate reduced x min(-1) x mg protein(-1) . Nitrate, sulfate, selenate and fumarate cannot serve as alternative electron acceptors for the arsenate reductase . Synthesis of the protein is regulated, as arsenate must be present during growth for the enzyme to be fully induced . The N-terminus of ArrA is similar to a number of procaryotic molybdenum-containing polypeptides (e.g . the formate dehydrogenases H and N of Escherichia coli) . The N-terminus of ArrB is similar to iron-sulfur proteins . The respiratory arsenate reductase of C . arsenatis is different from the non-respiratory arsenate reductases of E . coli and Staphylococcus aureus.

J Antimicrob Chemother, 1998 Aug, 42(2), 233 - 9
Efficacy and safety of teicoplanin plus rifampicin in the treatment of bacteraemic infections caused by Staphylococcus aureus; Yzerman EP et al.; An open study was carried out on 16 patients with hospital-acquired, bacteraemic Staphylococcus aureus infections to evaluate the safety and efficacy of teicoplanin plus rifampicin . Patients received teicoplanin 400 mg bd for the first 24 h followed by 400 mg od thereafter, and rifampicin 600 mg bd . Both agents were given intravenously . Serum samples were collected to determine trough and peak antibiotic concentrations . The MIC of teicoplanin and rifampicin and the MBC of teicoplanin were determined for all S . aureus isolates . Time-kill curves were performed for the drugs individually and in combination . Clinical efficacy was assessed by the APACHE II scoring system . Bacteriological success was evaluated by elimination, persistence or recurrence of S . aureus . Safety was carefully monitored by regular biochemical and haematological testing and recording of adverse events . Fifteen patients were evaluable, of whom 13 (86.7%) were clinically cured with elimination of S . aureus . One patient died, but death was not attributed to the study drugs . Treatment failed in another patient who relapsed with a high fever . S . aureus was recovered from blood cultures from this patient, and resistance to rifampicin had developed . Time-kill curves all showed adequate killing of S . aureus at the drug concentrations measured in vivo . Neither synergy nor antagonism between teicoplanin and rifampicin was demonstrated . The combination of teicoplanin and rifampicin is an effective and well-tolerated treatment for bacteraemic S . aureus infections, but in deep-seated foci of infection resistance to rifampicin may develop.

J Antimicrob Chemother, 1998 Aug, 42(2), 221 - 6
The effect of dicloxacillin and fusidic acid on the extracellular and intracellular killing of Staphylococcus aureus; Nielsen SL et al.; The effect of dicloxacillin and fusidic acid used alone and in combination on the extracellular and intracellular killing of four isolates of Staphylococcus aureus in the presence of serum was studied . At the extracellular level, dicloxacillin (8 mg/L) had a bactericidal effect on all four isolates, whereas fusidic acid (64 mg/L) had a bacteriostatic effect on two isolates and no effect on the two other isolates . Fusidic acid significantly inhibited the extracellular bactericidal effect of dicloxacillin on two isolates . Intracellular killing was measured in human neutrophil granulocytes . Dicloxacillin (8 mg/L) significantly increased the intracellular killing of all four isolates, while fusidic acid (64 mg/L) significantly increased the intracellular killing of three isolates, but the killing was significantly lower than that of dicloxacillin . When the antibiotics were combined the intracellular killing of three of the isolates was significantly lower than that of dicloxacillin alone . The viability of the granulocytes and their ability to produce superoxide anion were not affected by the antibiotics . In conclusion, we found that the increased intracellular killing of S . aureus by dicloxacillin was inhibited by fusidic acid.

J Antimicrob Chemother, 1998 Aug, 42(2), 211 - 6
The effect of a component of tea (Camellia sinensis) on methicillin resistance, PBP2' synthesis, and beta-lactamase production in Staphylococcus aureus; Yam TS et al.; Extracts of tea (Camellia sinensis) can reverse methicillin resistance in methicillin-resistant Staphylococcus aureus (MRSA) and also, to some extent, penicillin resistance in beta-lactamase-producing S . aureus . These phenomena are explained by prevention of PBP2' synthesis and inhibition of secretion of beta-lactamase, respectively . Synergy between beta-lactams and tea extracts were demonstrated by disc diffusion, chequerboard titration and growth curves . Partition chromatography of an extract of green tea on Sephadex LH-20 yielded several fractions, one of which contained a virtually pure compound that showed the above-mentioned activities, at concentrations above about 2 mg/L . The observed activities are novel and distinct from the previously reported direct antibacterial activity of tea extracts . Prevention of PBP2' synthesis offers an interesting possible new approach for the treatment of infections caused by MRSA.

J Antimicrob Chemother, 1998 Aug, 42(2), 199 - 209
Activated cell-wall synthesis is associated with vancomycin resistance in methicillin-resistant Staphylococcus aureus clinical strains Mu3 and Mu50; Hanaki H et al.; We have previously reported methicillin-resistant Staphylococcus aureus clinical strains, Mu50 and Mu3, representing two categories of vancomycin resistance: Mu50 representing vancomycin-resistant S . aureus (VRSA) with MICs > or = 8 mg/L, and Mu3 representing hetero-VRSA with MICs < or = 4 mg/L using standard MIC determination methods . The mechanisms of vancomycin resistance in these strains were investigated . These strains did not carry the enterococcal vancomycin-resistance genes, vanA, vanB, or vanC1-3, as tested by PCR using specific primers . However, both strains produced three to five times the amount of penicillin-binding proteins (PBPs) 2 and 2' when compared with vancomycin-susceptible S . aureus control strains with or without methicillin resistance; the amounts of PBP2 produced in Mu3 and Mu50 were comparable to those in the vancomycin-resistant S . aureus mutant strains selected in vitro . Incorporation of 14C-labelled Nacetyl-glucosamine into the cell was three to 20 times increased in Mu50 and Mu3, and release of the radioactive cell wall material was increased in Mu3 (and also in Mu50, though to a lesser extent), compared with control strains . The amounts of intracellular murein monomer precursor in these strains were three to eight times greater than those found in control strains . Transmission electron microscopy showed a doubling in the cell wall thickness in Mu50 compared with the control strains . Mu3 did not show obvious cell wall thickening . These data indicate that activated synthesis and an increased rate of cell wall turnover are common features of Mu3 and Mu50 and may be the prerequisite for the expression of vancomycin resistance in S . aureus.

J Antimicrob Chemother, 1998 Aug, 42(2), 189 - 97
Glycopeptide tolerance in Staphylococcus aureus; May J et al.; Treatment failures with vancomycin prompted us to investigate the phenomenon of tolerance to glycopeptides in recent clinical isolates of Staphylococcus aureus . We used both MBC/MIC determinations and time-kill measurements to study tolerance to vancomycin and teicoplanin in 35 blood or heart valve isolates of S . aureus from patients with endocarditis or bacteraemia . There was generally good agreement between vancomycin tolerance indicated by an MBC:MIC ratio of > or =32 and by < or =90% kill after 6 h incubation in the presence of 20 mg/L vancomycin . However, two isolates were tolerant according to their MBC:MIC ratios but non-tolerant as judged by time-kill measurements . Seven of 15 methicillin-resistant S . aureus (MRSA) isolates but only two of 20 methicillin-susceptible ones were tolerant as judged by time-kill experiments (chi2 = 4.27 with Yates' correction, P = 0.04) . Seven of the 16 isolates from patients with endocarditis were tolerant, compared with only two of the 19 isolates from patients with other conditions (chi2 = 3.43 with Yates' correction, P = 0.06) . Within the endocarditis and non-endocarditis subgroups, tolerance was associated more frequently with methicillin resistance than with susceptibility, but the numbers were too small for the differences to be statistically significant . Most of the vancomycin-tolerant isolates were also tolerant to teicoplanin . We conclude that glycopeptide tolerance is a real phenomenon in S . aureus, particularly amongst MRSA isolates, and can be reliably determined by our method of time-kill analysis . Tolerance may compromise glycopeptide therapy of serious S . aureus infection and should be taken into account when deciding treatment.

J Leukoc Biol, 1998 Sep, 64(3), 322 - 30
Effect of trifluoromethyl ketone-based elastase inhibitors on neutrophil function in vitro; Huang YI et al.; Neutrophils release elastase, which is known secondarily to cause tissue damage . However, it is rapidly inactivated by the endogenous alpha1-proteinase inhibitor (alpha1Pi) . Nevertheless, under pathological conditions, alpha1i is inactivated by oxidants released from neutrophils, resulting in an excess of elastase at the site of inflammation . This elastase/alpha1Pi imbalance has been implicated as a pathogenic factor in cystic fibrosis, acute respiratory distress syndrome, and emphysema . Elastase inhibitors, which do not interfere with the microbicidal activity of neutrophils and are resistant to neutrophil-released oxidants, would undoubtedly represent an important advance in the management of neutrophil-mediated tissue injury . We report that a new family of elastase inhibitors ICI200355 and ZD0892 was found to be resistant toward superoxide, hypochlorous acid, hydrogen peroxide, hydroxyl radical, and peroxynitrite mediated degradation as well as having no effect on the formation of these oxidants by activated neutrophils . More importantly, we found that these inhibitors did not interfere with the ability of human neutrophils to phagocytose and to kill Staphylococcus aureus . In conclusion, a new potent class of elastase inhibitors, while blocking the effects of neutrophil elastase, was found not to impede various physiological functions of human neutrophils, in particular the ability of these phagocytic cells to phagocytose and kill bacteria.

Ann Thorac Cardiovasc Surg, 1998 Aug, 4(4), 226 - 9
A case successfully treated by conservative management for mediastinitis and infected composite graft due to methicillin-resistant coagulase negative staphylococcus; Sakurai H et al.; A 72 year-old man underwent a Bentall procedure for aortic regurgitation secondary to annulo-aortic ectasia and ascending aortic aneurysm . On the 11th postoperative day, the C-reactive protein (CRP) level and white blood cell (WBC) count rose . Echocardiography and a computed tomographic scan showed the appearance of pericardial effusion . A diagnosis of mediastinitis and composite graft infection was made, and mediastinal drainage and irrigation were performed . Methicillin-resistant coagulase negative staphylococcus (MRCNS) was identified as the causative organism . Vancomycin, arbekacin and minocycline were used intravenously . Additionally, a continuous mediastinal irrigation was performed through the chest tubes . CRP level and WBC count were gradually reduced to normal range . He has now been free from signs of infection for more than 3 years . Because MRCNS is considered less virulent than methicillin-resistant Staphylococcus aureus, mediastinitis and composite graft infection due to MRCNS might be treatable by such conservative therapy even in patients with prosthetic implants . Since MRCNS often becomes ubiquitous, preventing infections by strict attention to asepsis is important.

J Clin Microbiol, 1998 Oct, 36(10), 3057 - 9
Staphylococcal scalded-skin syndrome complicating wound infection in a preterm infant with postoperative chylothorax; Peters B et al.; The course of infection in a 3-week-old premature newborn suffering from extensive dermatitis with flaccid blisters is described . Staphylococcus aureus was recovered from a local wound infection around a chest tube inserted to drain a postoperative chylothorax . The strain isolated tested positive for the eta gene for exfoliative toxin A, the causative agent of staphylococcal scalded-skin syndrome (SSSS) . In this case, prematurity and loss of chylus with consecutive lymphopenia may have contributed to development of SSSS.

Clin Exp Immunol, 1998 Sep, 113(3), 415 - 22
FcgammaRIa-gamma-chain complexes trigger antibody-dependent cell-mediated cytotoxicity (ADCC) in CD5+ B cell/macrophage IIA1.6 cells; Van Vugt MJ et al.; Most receptors for immunoglobulins exist as multi-subunit complexes, with unique ligand binding alpha-chains, combined with accessory signalling (gamma-, beta-, or zeta-) chains . The myeloid class I receptor for IgG (FcgammaRIa) has been shown to be dependent on the FcR gamma-chain for surface expression in vivo . In this study we assess the capacity of FcgammaRIa-gamma-chain complexes expressed in IIA1.6 cells to trigger phagocytosis and ADCC . An intact immunoreceptor tyrosine-based activation motif (ITAM) signalling motif proved essential for triggering of biological function via the FcgammaRIa receptor complex . Both the FcR gamma-chain and the FcgammaRIIa-ITAM proved active in directing phagocytosis of Staphylococcus aureus and ADCC of erythrocytes, triggered by the FcgammaRIa complex . The capacity of FcgammaRIa to trigger phagocytic and cytolytic activity by IIA1.6 cells, both considered 'professional phagocyte' functions, motivated us to re-evaluate the cell lineage and developmental stage of IIA1.6 cells . Although originally described as mouse B lymphocytes, the IIA1.6 cells proved positive for non-specific esterase activity and expressed the CD5 antigen . These combined characteristics place the IIA1.6 cells within a unique CD5+ B cell/macrophage lineage, optimally suited for cell biological analyses of phagocyte receptors.

J Vasc Surg, 1998 Sep, 28(3), 547 - 50
Mycotic renal artery degeneration and systemic sepsis caused by infected renal artery stent; DeMaioribus CA et al.; A case of Staphylococcus aureus renal artery stent infection was studied . Fourteen days after the procedure, the patient had a fever, hypotension, and an elevated white blood cell (WBC) count . Blood cultures were positive for S . aureus on admission and during the patient's hospitalization, despite intravenous vancomycin therapy . Evaluation included serial CT scans, revealing increasing persistent inflammation with development of multiple renal intraparenchymal abscesses, and arteriography, showing marked degeneration of the renal artery . Therapy required resection of the renal artery/stent and nephrectomy . This case confirms the severe nature of S . aureus stent infection; we recommend prophylactic antibiotics before these procedures, as well as expeditious evaluation and consideration for aggressive surgical therapy if this complication is suspected.

Proc Natl Acad Sci U S A, 1998 Sep 15, 95(19), 11095 - 100
Increase in the 64-kDa subunit of the polyadenylation/cleavage stimulatory factor during the G0 to S phase transition; Martincic K et al.; The amount of the 64-kDa subunit of polyadenylation/cleavage stimulatory factor (CstF-64) increases 5-fold during the G0 to S phase transition and concomitant proliferation induced by serum in 3T6 fibroblasts . Higher levels of CstF-64 result in an increase in CstF trimer . The rise in CstF-64 occurs at a time when the amount of poly(A)-containing RNA rose at least 5-8 fold in the cytoplasm . Primary human splenic B cells, resting in G0, show a similar 5-fold increase in CstF-64 when cultured under conditions inducing proliferation (CD40 ligand exposure) . Therefore, the increase in CstF-64 is associated with the G0 to S phase transition . As B cell development progresses, RNA processing changes occur at the Ig heavy chain locus resulting in a switch from the membrane- to the upstream secretory-specific poly(A) site . Treating resting B cells with agents triggering this switch in Ig mRNA production along with proliferation (CD40 ligand plus lymphokines or Staphylococcus aureus protein A) induces no further increase in CstF-64 above that seen for proliferation alone . The rise in CstF-64 is therefore insufficient to induce secretion . After stimulation of a continuously growing B cell line with lymphokines, a switch to Ig micrometer secretory mRNA and protein occurs but without a change in the CstF-64 level . Therefore, an increase in CstF-64 levels is not necessary to mediate the differentiation-induced switch to secreted forms of Ig-micrometer heavy chain . Because augmentation of CstF-64 levels is neither necessary nor sufficient for Ig secretory mRNA production, we conclude that other lymphokine-induced factors play a role.

Am J Vet Res, 1998 Sep, 59(9), 1122 - 4
Role of horn flies (Haematobia irritans) in Staphylococcus aureus-induced mastitis in dairy heifers; Owens WE et al.; OBJECTIVE: To determine whether Staphylococcus aureus can colonize in horn flies and whether colonization is sufficiently persistent for transmission of the organism to cows by flies . ANIMALS: 2 Jersey heifers exposed to infected horn flies . PROCEDURE: Staphylococcus aureus was allowed to colonize in horn flies, and duration of colonization was determined . Flies with colonized S aureus were allowed to feed on teats of uninfected heifers to determine whether intramammary infection could be transmitted from fly to heifer . Scab material from naturally infected heifers was submitted for bacteriologic culture to determine whether S aureus was present and whether scabs could serve as a possible source of S aureus for flies . RESULTS: Staphylococcus aureus colonized in horn flies and remained for up to 96 hours after exposure . Exposure of teats of uninfected heifers to horn flies colonized with S aureus resulted in intramammary infection in 3 of 4 exposed teats . Culture of scab material from teats of naturally infected heifers revealed high concentration of S aureus (> 107 colony-forming units/mg), and flies without previously colonized S aureus were allowed to feed on scabs; S aureus colonized in them just as readily as it did in flies that had fed on experimentally infected blood . CONCLUSIONS: Horn flies are capable of transmitting S aureus-induced intramammary infection to heifers, and scabs on teats are a potential source of S aureus . Fly control on dairy cows in herds with known S aureus problems is recommended as a method to help prevent these infections.

J Med Microbiol, 1998 Sep, 47(9), 829 - 35
Heterogeneous location of the mupA high-level mupirocin resistance gene in Staphylococcus aureus; Woodford N et al.; Epidemiologically unrelated clinical isolates of Staphylococcus aureus with high-level resistance to mupirocin (MIC > or = 512 mg/L) were studied to determine the location of the mupA resistance gene . The gene was carried on plasmids of variable size, some of which were transferable in vitro . DNA hybridisation of genomic DNA from 85 isolates showed that mupA was located on EcoRI fragments of seven different sizes; the most frequently observed fragments were 7 kb (46 isolates) or 4.1 kb (21 isolates) . All isolates retained a 1.6-kb Nco I fragment that hybridised with mupA probes, but showed heterogeneous hybridisation patterns after digestion with Hinc II . These data suggested that mupA may be conserved, but that variation occurs in the flanking DNA proximal to it . Amplification of spacer regions between mupA and closest proximal copy of IS257 yielded products of variable size and was consistent with the presence of IS257 in either orientation . It is proposed that IS257-mediated events are responsible for the heterogeneity observed . The location of mupA varied between epidemiologically unrelated isolates of the same strain, including isolates of EMRSA-16 -- one of the two predominant methicillin-resistant strains in UK hospitals at the present time -- and this correlated with variations in the digestion patterns of the mupirocin resistance plasmids . The variable location of mupA should be evaluated further as a potential epidemiological tool with which to monitor the spread of high-level mupirocin resistance in EMRSA-16 or other strains of S . aureus.

Clin Nucl Med, 1998 Sep, 23(9), 582 - 4
Perivalvular abscess complicating infective endocarditis: complementary role of echocardiography and indium-111-labeled leukocytes; Campeau RJ et al.; A 49-year-old black man with hypertension-induced chronic renal failure requiring hemodialysis and a history of arteriovenous access graft infection was admitted with Staphylococcus aureus sepsis, dyspnea, and peri-incisional erythema over his arteriovenous graft fistula . Results of a transthoracic echo demonstrated aortic sclerosis and concentric left ventricular hypertrophy . Results of a whole-body In-111 white cell (WBC) scan were negative over the arteriovenous graft site; however, an intense abnormal focus of labeled WBCs was evident to the left of the sternum . A subsequent transesophageal echocardiogram showed a mixed cystic-solid calcified mass adjacent the left aortic cusp . Surgery confirmed a perivalvular abscess . As a whole-body imaging modality, the In-111 WBC scintigram indicated the true location of the infectious process responsible for the patient's sepsis . The combination of echocardiography and radiolabeled WBC imaging increases sensitivity for detection of endocarditis/perivalvular abscess . Radiolabeled WBC imaging is more efficacious for monitoring therapy because the echocardiogram often does not change with treatment of endocarditis/perivalvular abscess.

Biochem Biophys Res Commun, 1998 Sep 8, 250(1), 15 - 21
Mechanism of protein A-induced amelioration of toxicity of anti-AIDS drug, zidovudine; Subbulakshmi V et al.; Long-term treatment with 3-azido-3-deoxy thymidine (AZT) is often associated with myelosuppression . In AZT-treated Swiss mice, similar toxicological manifestations in terms of reduction of red blood and white blood cell counts and hemoglobin content had been observed as in AZT-treated AIDS patients . Pretreatment of animals with Protein A (PA) of Staphylococcus aureus Cowan I (1 microgram/ml), twice a week for two weeks, alleviated such hematopoietic toxicity due to AZT . AZT-induced reduction in colony-forming unit-erythroid (CFU-E) and colony-forming unit-granulocyte monocyte (CFU-GM) were also reversed by the combined treatment of AZT and PA . PA treatment showed an increased level of erythropoietin in the blood plasma, and cellularity of spleen, thymus, and bonemarrow was also increased in the group receiving combined treatment (PA+AZT), higher than that in the AZT group . AZT or its metabolites inhibited the activities of liver microsomal monooxygenases, which, however, could be regenerated in an accelerated manner by pretreatment of mice with PA . Moreover, the PA-treated group showed an accelerated clearance of AZT and/or its metabolites . These results suggest that such an immunopharmacologic approach might substantially reduce the toxic effects of drugs, such as AZT .

Int J Syst Bacteriol, 1998 Jul, 48 Pt 3, 1049 - 55
Identification of Staphylococcus species by 16S-23S rDNA intergenic spacer PCR analysis; Mendoza M et al.; To investigate whether 16S-23S rDNA (rDNA) spacer region length polymorphisms are suitable for the identification of Staphylococcus strains, the 16S-23S rDNA intergenic spacer region lengths of 221 strains belonging to 31 species were studied by using a PCR-based method . Each species presented a specific 16S-23S pattern made of 1-8 fragments ranging from 104-771 bp, with the exception of the species Staphylococcus warnei, Staphylococcus caprae and Staphylococcus piscifermentans, which presented larger or smaller fragments . Very few species showed more than one pattern, Staphylococcus saprophyticus subsp . saprophyticus and Staphylococcus aureus being the most heterogeneous species (five different patterns for eight strains) . Five clinical strains that could not be identified at the species level by phenotypical tests were finally identified using this method . Discrimination between some species that showed close patterns (Staphylococcus aureus/Staphylococcus chromogenes/Staphylococcus equorum, Staphylococcus aureus/staphylococcus intermedius, Staphylococcus delphini/Staphylococcus felis, Staphylococcus gallinarum, Staphylococcus delphini/Staphylococcus felis, Staphylococcus vitulus/Staphylococcus auricularis) was further achieved after Dral digestion of the PCR products . Although it does not allow discrimination of subspecies, the use of 16S-23S spacer region length data determined by PCR-mediated amplification is suitable for the identification of the 31 Staphylococcus species tested in this study . The method is rapid, easy and may be a useful tool for the identification of Staphylococcus species in the clinical microbiology laboratory.

Int J Syst Bacteriol, 1998 Jul, 48 Pt 3, 651 - 8
Staphylococcus condimenti sp . nov., from soy sauce mash, and Staphylococcus carnosus (Schleifer and Fischer 1982) subsp . utilis subsp . nov; Probst AJ et al.; Based on the sequence data of 23S rRNA of Staphylococcus carnosus, Staphylococcus piscifermentans, Staphylococcus aureus and Staphylococcus epidermidis, species-specific probes were constructed . Their application revealed a heterogeneity within 18 strains previously identified as S . carnosus . Strains of this group were selected, and their 23S rRNA sequence was determined . It was revealed that the strains of S . carnosus can be placed in at least three sub-groups . This grouping was supported by physiological data and DNA-DNA similarity studies . Based on these results, were propose the new species Staphylococcus condimenti sp . nov . The type strain is S . condimenti F-2T (=DSM 11674T) . The phylogenetic position of the new species within the radiation of other staphylococcal strains is reflected by a 16S nRNA-based tree . Furthermore, it is proposed to designate the new subspecies of Staphylococcus carnosus Schleifer and Fischer 1982, Staphylococcus carnosus subsp . utilis subsp . nov . The type strain of S . carnosus subsp . utilis is SK 11T (= DSM 11676T).

J Bacteriol, 1998 Sep, 180(18), 4814 - 20
Deletion of the alternative sigma factor sigmaB in Staphylococcus aureus reveals its function as a global regulator of virulence genes; Kullik I et al.; A deletion of the sigB operon was constructed in three genetically distinct Staphylococcus aureus strains, and the phenotypes of the resulting mutants were analyzed . Compared to the corresponding wild-type strains, the DeltasigB mutants showed reduced pigmentation, accelerated sedimentation, and increased sensitivity to hydrogen peroxide during the stationary growth phase . A cytoplasmic protein missing in the DeltasigB mutants was identified as alkaline shock protein 23, and an extracellular protein excreted at higher levels in one of the DeltasigB mutants was identified as staphylococcal thermonuclease . Interestingly, most sigB deletion phenotypes were only seen in S . aureus COL and Newman and not in 8325, which was found to contain an 11-bp deletion in the regulator gene rsbU . Taken together, our results show that sigmaB is a global regulator which modulates the expression of several virulence factors in S . aureus and that laboratory strain 8325 is a sigmaB-defective mutant.

J Med Chem, 1998 Sep 10, 41(19), 3727 - 35
Piperazinyl oxazolidinone antibacterial agents containing a pyridine, diazene, or triazene heteroaromatic ring; Tucker JA et al.; Oxazolidinones are a novel class of synthetic antibacterial agents active against gram-positive organisms including methicillin-resistant Staphylococcus aureus as well as selected anaerobic organisms . Important representatives of this class include the morpholine derivative linezolid 2, which is currently in phase III clinical trials, and the piperazine derivative eperezolid 3 . As part of an investigation of the structure-activity relationships of structurally related oxazolidinones, we have prepared and evaluated the antibacterial properties of a series of piperazinyl oxazolidinones in which the distal nitrogen of the piperazinyl ring is substituted with a six-membered heteroaromatic ring . Compounds having MIC values </= 2 microg/mL vs selected gram-positive pathogens were discovered among each of the pyridine, pyridazine, and pyrimidine structural classes . Among these the cyanopyridine 17, the pyridazines 25 and 26, and the pyrimidine 31 exhibited in vivo potency vs S . aureus comparable to that of linezolid.

Dermatology, 1998, 197(2), 174 - 7
Abscess-forming neutrophilic dermatosis: report of three cases associated with hemopathies; Horiguchi Y et al.; BACKGROUND: The development of different types of neutrophilic dermatosis is reported to occur in the course of malignant hemopathies . These concern mainly Sweet's syndrome, pyoderma gangrenosum, erythema elevatum et diutinum and neutrophilic eccrine hidradenitis . OBSERVATIONS: We have recently encountered the cases of 3 patients who presented all with multiple acneiform papules and dome-shaped aseptic abscesses leaving scars . Pus was sterile in all except case 3 in which slight Staphylococcus aureus growth was shown . However, in this patient, only steroids were effective demonstrating that this bacterium was not responsible for the disease . Histopathology disclosed a dense dermal polymorphonuclear neutrophil infiltrate and some mononuclear cells . Two of these patients had myelodysplastic syndromes while one had IgA myeloma . CONCLUSION: Abscess-forming neutrophilic dermatosis seems to be another type of neutrophilic dermatosis associated with hematological malignancies.

Chemotherapy, 1998 Sep-Oct, 44(5), 318 - 23
Comparative in vitro activity of vancomycin and other antimicrobial agents against methicillin-resistant staphylococcus aureus and enterococcus faecium in the Tohoku district of Japan; Lutfor AB et al.; Susceptibility patterns of methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium obtained from various hospitals of the Tohoku district were documented . MICs of 6 antimicrobial agents against a total of 480 strains (380 strains were MRSA and 100 were E . faecium) were estimated . All MRSAs were susceptible to vancomycin, teicoplanin and quinupristin/dalfopristin, but all of them were resistant to ampicillin and benzylpenicillin . None of the E . faecium strains were found to be resistant to vancomycin, teicoplanin and quinupristin/dalfopristin . Excluding these, almost all strains of E . faecium were resistant to the remaining drugs . These data suggest that despite the emergence of vancomycin resistance to E . faecium in Europe and in the United States, vancomycin, teicoplanin and quinupristin/dalfopristin will nevertheless provide effective bactericidal activity in the Tohoku area of Japan.

Pharmacology, 1998 Oct, 57(4), 215 - 21
Peripheral benzodiazepine receptor expression on leukocytes and neutrophil function during anticonvulsant monotherapy; Caldiroli E et al.; Epileptic patients on long-term therapy with a single anticonvulsant showed enhanced expression of peripheral benzodiazepine receptors (pBZrs) on neutrophils, monocytes and lymphocytes . N-Formyl-methionyl-leucyl-phenylalanine-induced chemotaxis was significantly impaired in neutrophils from patients on carbamazepine (p < 0.01 vs . controls) . Neutrophils from patients on phenytoin had enhanced phorbol myristate acetate-stimulated O-2 production (p < 0 . 01 vs . controls) and neutrophils from patients on valproic acid had impaired phagocytosis frequency and Staphylococcus aureus lethality index (p < 0.01 vs . controls) . Overexpression of pBZrs on leukocytes may reflect the clinical response to anticonvulsants and may play a role in the immunological effects of some of these drugs.

Neuroradiology, 1998 Jul, 40(7), 455 - 8
Spinal cord abscess in a heroin addict: case report; Sverzut JM et al.; Spinal cord abscesses are extremely rare, even in intravenous drug abusers . They usually have a poor prognosis unless diagnosed and treated promptly . MRI is the best imaging modality for diagnosis and follow-up . We report a 42-year-old man, an active intravenous drug user, HIV negative, who developed subacute tetraplegia from an intramedullary abscess caused by Staphylococcus aureus . Immediate decompressive surgery and antibiotic treatment led to progressive recovery.

Bioorg Med Chem, 1998 Jul, 6(7), 1009 - 17
Novel cephalosporin derivatives possessing a bicyclic heterocycle at the 3-position . Part I: Synthesis and biological activities of 3-(benzothiazol-2-yl)thiocephalosporin derivatives, CP0467 and related compounds; Tsushima M et al.; A series of cephalosporin derivatives with various bicyclic heterocycles at the C-3 position was synthesized and evaluated for antibacterial activity . Among them CP0467 (3a) showed excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) (MIC90 = 6.25 microg/mL), and extremely high affinity for the penicillin binding protein 2' of MRSA (I50 = 0.49 microg/mL) . Furthermore, 3a showed a long-acting pharmacokinetic profile in mice (AUC(infinity) = 482.3 microg/h/mL and T(1/2) = 1.9 h).

Biochem J, 1998 Sep 15, 334 ( Pt 3), 511 - 7
Channelling of intermediates in the biosynthesis of phosphatidylcholine and phosphatidylethanolamine in mammalian cells; Bladergroen BA et al.; Previous studies with electropermeabilized cells have suggested the occurrence of metabolic compartmentation and Ca2+-dependent channeling of intermediates of phosphatidylcholine (PC) biosynthesis in C6 rat glioma cells . With a more accessible permeabilization technique, we investigated whether this is a more general phenomenon also occurring in other cell types and whether channeling is involved in phosphatidylethanolamine (PE) synthesis as well . C6 rat glioma cells, C3H10T12 fibroblasts and rat hepatocytes were permeabilized with Staphylococcus aureus alpha-toxin, and the incorporation of the radiolabelled precursors choline, phosphocholine (P-choline), ethanolamine and phosphoethanolamine (P-EA) into PC and PE were measured both at high and low Ca2+ concentrations . In glioma cells, permeabilization at high Ca2+ concentration did not affect {14C}choline or {14C}P-choline incorporation into PC . However, reduction of free Ca2+ in the medium from 1.8 mM to <1 nM resulted in a dramatic increase in {14C}P-choline incorporation into permeabilized cells, whereas {14C}choline incorporation remained unaffected . Also, in fibroblasts, reduction of extracellular Ca2+ increased {14C}P-choline and {14C}P-EA incorporation into PC and PE respectively . In hepatocytes, a combination of alpha-toxin and low Ca2+ concentration severely impaired {14C}choline incorporation into PC . Therefore, alpha-toxin-permeabilized hepatocytes are not a good model in which to study channeling of intermediates in PC biosynthesis . In conclusion, our results indicate that channeling is involved in PC synthesis in glioma cells and fibroblasts . PE synthesis in fibroblasts is also at least partly dependent on channeling.

AIDS, 1998 Aug 20, 12(12), 1437 - 49
Impairment of B-lymphocyte differentiation induced by dual triggering of the B-cell antigen receptor and CD40 in advanced HIV-1-disease; Conge AM et al.; OBJECTIVE: This study was performed to investigate the hyporeactivity of purified B lymphocytes from HIV-1-infected patients . DESIGN: Given the importance of the B-cell Ag receptor (BCR) and CD40 in B-lymphocyte activation, we assessed the capacity of purified peripheral blood B lymphocytes from HIV-1-infected patients to differentiate into Ig-secreting cells in a T-cell- and accessory-cell-independent system of BCR and CD40 costimulation . METHODS: B lymphocytes from 21 HIV-1-infected patients were purified by immunomagnetic cell separation and costimulated with immobilized anti-CD40 monoclonal antibodies and Staphylococcus aureus Cowan I particles in the presence of interleukin (IL)-2 and IL-10 . Homotypic aggregate formation, apoptosis, cell cycle entrance, proliferation and Ig secretion of B cells were analysed . RESULTS: Costimulation by the BCR and CD40 induced proliferation and differentiation of B lymphocytes into Ig-secreting cells in 13 patients (group I) but not in eight patients (group II) . For three patients in group II, the dual triggering induced apoptosis of B cells . The unexpected inability of these cells to differentiate was associated with a high CD38 expression and a weak spontaneous production of Ig or anti-HIV-1 antibodies in patients with a high viral load and a low CD4+ lymphocyte count . Despite this anomaly, the B cells from group II were able to progress through the cell cycle after stimulation with a combination of phorbol ester and ionomycin in complete medium, suggesting an impairment in BCR and CD40 early signal transduction . CONCLUSION: Intrinsic in vitro hyporeactivity of B lymphocytes to dual triggering of BCR and CD40 was observed in advanced HIV-1 disease and appeared to be related to in vivo hyperactivation of B cells.

Appl Environ Microbiol, 1998 Sep, 64(9), 3147 - 52
Cloning and expression of the Listeria monocytogenes scott A ptsH and ptsI genes, coding for HPr and enzyme I, respectively, of the phosphotransferase system; Christensen DP et al.; The phosphoenolpyruvate (PEP)-dependent phosphotransferase system (PTS) utilizes high-energy phosphate present in PEP to drive the uptake of several different carbohydrates in bacteria . In order to examine the role of the PTS in the physiology of Listeria monocytogenes, we identified the ptsH and ptsI genes encoding the HPr and enzyme I proteins, respectively, of the PTS . Nucleotide sequence analysis indicated that the predicted proteins are nearly 70% similar to HPr and enzyme I proteins from other organisms . Purified L . monocytogenes HPr overexpressed in Escherichia coli was also capable of complementing an HPr defect in heterologous extracts of Staphylococcus aureus ptsH mutants . Additional studies of the transcriptional organization and control indicated that the ptsH and ptsI genes are organized into a transcription unit that is under the control of a consensus-like promoter and that expression of these genes is mediated by glucose availability and pH or by by-products of glucose metabolism.

Burns, 1998 Aug, 24(5), 393 - 7
Methicillin-resistant Staphylococcus aureus in burns patients--why all the fuss?
Reardon CM, Brown TP, Stephenson AJ, Freedlander E.
Procedures designed to limit spread of methicillin-resistant Staphylococcus aureus (MRSA) in burns units demand time and resources . To assess the significance of MRSA in burns patients we performed a retrospective review of MRSA colonization in in-patients over a 41-month period at the North Trent Sub-regional Burns Unit . Patients were compared with MRSA free controls, matched for age and percentage body surface area (BSA) burn and admitted during the same time period . Length of stay, number of operations and deaths were outcome indicators . All patients managed non-operatively were excluded, leaving 40 MRSA patients and 46 controls . There was no statistical difference between the two groups with regard to number of operations (p= 0.07), duration of admission (p = 0.12) or mortality (p = 0.09) . Of the control group, 83% had wound swabs positive for methicillin-sensitive Staphylococcus aureus (MSSA) . there was no statistical difference in any outcome variables between this sub-group of controls and MRSA patients . Colonization with S . aureus (both MRSA and MSSA) was associated with larger burns (p<0.05), twice as many operative procedures (p<0.05) and prolonged admissions (p<0.01) . Mortality was unaltered by staphylococcal colonization (p = 0.8) . Although our study lacks power, we would suggest that methicillin resistance per se is not associated with increased morbidity or mortality in burns patients.

J Immunol, 1998 Sep 1, 161(5), 2586 - 93
Histamine potently suppresses human IL-12 and stimulates IL-10 production via H2 receptors; Elenkov IJ et al.; IL-12 and IL-10, respectively, stimulate Th1 and Th2 immune responses . The development of some allergic reactions, infections, and tumors are associated with excessive histamine production and a shift toward Th2 responses . Here we address the possibility that this association is causally linked, at least in part, to modulation of IL-12 and IL-10 production by histamine . We report that histamine dose-dependently inhibited the secretion of human IL-12 (p70) and increased the production of IL-10 in LPS-stimulated whole blood cultures . These effects of histamine were antagonized by cimetidine, an H2 receptor antagonist, but not by selective H1 and H3 receptor blockers, and were mimicked by an H2 receptor agonist . The effects of histamine on IL-12 and IL-10 secretion were independent of endogenous secretion of IL-10 or exogenous addition of IL-12, while Ro 20-1724, a phosphodiesterase inhibitor, potentiated the effects of histamine on IL-12 and IL-10 production, implicating cAMP in its actions . Similar modulatory effects of histamine on IL-12 and IL-10 production, which were reversed by the H2 antagonist cimetidine, were observed in PBMC and isolated monocytes stimulated by Staphylococcus aureus Cowan strain 1 and LPS, respectively . Thus, histamine, via stimulation of H2 receptors on peripheral monocytes and subsequent elevation of cAMP, suppresses IL-12 and stimulates IL-10 secretion, changes that may result in a shift of Th1/Th2 balance toward Th2-dominance . This may represent a novel mechanism by which excessive secretion of histamine potentiates Th2-mediated allergic reactions and contributes to the development of certain infections and tumors normally eliminated by Th1-dependent immune mechanisms.

Vet Rec, 1998 Aug 1, 143(5), 131 - 5
Study of leg weakness in two commercial broiler flocks; McNamee PT et al.; The major causes of leg weakness/lameness were investigated in two male commercial broiler flocks . The numbers of dead and lame birds culled from the flocks each day were recorded by the flock managers . Forty-four lame birds and 22 sound birds were examined postmortem during a period of six weeks and the proximal and distal end of each femur, tibiotarsus and tarsometatarsus were examined histologically . Attempts were made to isolate bacteria and viruses from the proximal end of each femur . Blood samples were examined for antibodies to chicken anaemia virus (CAV), infectious bursal disease virus (IBDV) and Mycoplasma species . Bacterial chondronecrosis with osteomyelitis was identified in the proximal end of the femur of eight of the 44 lame birds, and in the proximal end of the tibiotarsus of a further bird (20.4 per cent) . Gram-positive bacteria were present in all the lesions . Staphylococcus aureus was recovered from 62.5 per cent of the lesions confirmed by histology . Bacterial chondronecrosis associated with S aureus has thus been identified as an important cause of leg weakness in these commercial broilers . Lesions suggestive of the condition were visible macroscopically in only 11.1 per cent of the cases subsequently diagnosed by histology and bone histology is therefore required before a diagnosis can be excluded . Angular limb deformities (13.6 per cent) and spondylolisthesis (11.4 per cent) were the most common macroscopic lesions identified as causes of lameness . The overall incidence of tibial dyschondroplasia was similar in both the lame and sound broilers, but severe lesions were found only in lame birds (4.5 per cent).

Bull Hosp Jt Dis, 1998, 57(2), 69 - 73
Blood transfusion and postoperative wound infection in intracapsular femoral neck fractures; Levi N et al.; The relationship between blood transfusion and postoperative wound infection was studied in 695 operations for cervical hip fractures . A total of 156 (22%) patients were transfused with a total of 392 units of blood . A total of 31 (4.5%) patients developed a postoperative superficial or deep wound infection . Cultures identified Staphylococcus aureus as the cause in 71% and E . coli in 9.7% of the infections . A total of 11 out of 156 (7.05%) transfused patients developed a wound infection . In contrast only 20 out of 539 (3.71%) non-transfused patients developed a wound infection (p < 0.05).

J R Soc Health, 1998 Feb, 118(1), 18 - 22
Antiseptics: a forgotten weapon in the control of antibiotic resistant bacteria in hospital and community settings?
Payne DN, Gibson SA, Lewis R.
The aim of this study was to ascertain the activity of a selection of widely-used antiseptic/disinfectant agents against antibiotic resistant bacteria and strains isolated from patients infected with clinically significant species . Four antiseptic agents (Dettol, Dettol Hospital Concentrate, Savlon and Betadine) were tested against Staphylococcus aureus, Methicillin Resistant S . aureus (MRSA), Enterococcus hirae, Vancomicin Resistant Enterococcus sp (VRE), Escherichia coli and E . coli 0157 . The antiseptics were applied at recommended use dilutions and at a half and a quarter of those concentrations in a standard suspension test (EST) . Organic material was added to mimic the presence of blood, protein and other such contaminants to be found in the clinical situation . All antiseptics tested were effective against both the antibiotic sensitive and antibiotic resistant strains of S . aureus and E . hirae as well as normal and clinical strains of E . coli at recommended concentrations . All but Betadine were also effective against the antibiotic resistant bacteria at a half and a quarter of normal concentration . The iodine containing antiseptic, however, failed the test against MRSA at a half normal concentration and showed virtually no activity against MRSA at a quarter normal concentration.

Curr Eye Res, 1998 Aug, 17(8), 808 - 12
Effectiveness of ciprofloxacin-polystyrene sulfonate (PSS), ciprofloxacin and ofloxacin in a Staphylococcus keratitis model; Moreau JM et al.; PURPOSE: Staphylococcus aureus causes severe corneal infections that often result in corneal scarring and blindness . Presently, therapy often involves the use of a fluoroquinolone antibiotic . This study, employing an experimental rabbit model of Staphylococcus keratitis, compared the effectiveness of two commonly prescribed formulations of fluoroquinolones to an experimental formulation, ciprofloxacin with polystyrene sulfonate (ciprofloxacin-PSS) . The ciprofloxacin-PSS formulation uses an ion exchange resin to aid in the delivery of drug to the cornea . METHODS: Early (4-9 h postinfection, PI) and late (10-15 h PI) therapies were studied, employing 5 groups: ciprofloxacin-PSS, ciprofloxacin, ofloxacin, PSS vehicle . and untreated . Dosing regimens were: every 30 min, 60 min, or a single drop applied at 9 h PI . Eyes were observed by slit lamp examination (SLE) and bacterial colony forming units (CFU) per cornea were determined . RESULTS: Early phase therapy with ciprofloxacin-PSS, ciprofloxacin, or ofloxacin administered every 30 or 60 min were equally effective (P > or = 0.2880), decreasing CFU per cornea by >5 log . Ciprofloxacin was significantly more active than ciprofloxacin-PSS or ofloxacin (P < or = 0.0410) when applied as a single drop . Late therapy with ciprofloxacin-PSS, ciprofloxacin, or ofloxacin administered every 30 or 60 min resulted in >3 log decrease in CFU per cornea relative to controls (P < or = 0.0001) . CONCLUSIONS: Topical treatment of experimental Staphylococcus keratitis with ciprofloxacin-PSS, ciprofloxacin, or ofloxacin was effective . The effectiveness of ciprofloxacin-PSS suggests that improved drug delivery systems employing an ion exchange resin could be useful in an ocular fluoroquinolone formulation.

Curr Eye Res, 1998 Aug, 17(8), 783 - 7
Purification of an antimicrobial peptide from rabbit aqueous humour; Diamond JP et al.; PURPOSE: To identify an antimicrobial factor previously demonstrated in rabbit aqueous humour . METHODS: Rabbit aqueous humour was fractionated by a multi-stage process involving anion-exchange and size-exclusion liquid chromatography . The antimicrobial effect of aqueous humour fractions upon Staphylococcus aureus were evaluated in an in vitro model . The components of aqueous humour fractions mediating an antimicrobial effect were investigated by SDS-PAGE . RESULTS: A single peptide of molecular weight approximately 8 kDa was identified which mediated an antimicrobial effect upon Staphylococcus aureus . Attempts to identify the peptide have been unsuccessful . CONCLUSIONS: Rabbit aqueous humour contains an unidentified peptide that mediates an antimicrobial effect upon Staphylococcus aureus . If such a peptide is present in human aqueous humour it may contribute to the apparent resistance to bacterial infection manifest in the anterior chamber.

Mol Microbiol, 1998 Aug, 29(3), 871 - 81
Cloning of aas, a gene encoding a Staphylococcus saprophyticus surface protein with adhesive and autolytic properties; Hell W et al.; A gene encoding a novel cell wall-associated protein of Staphylococcus saprophyticus that binds fibronectin and to sheep erythrocytes has been cloned and sequenced . The 4392 bp open reading frame codes for an amino acid sequence that is quite similar to the Atl, an autolysin, of Staphylococcus aureus and to the AtlE of S . epidermidis . The two regions of most pronounced homology code for an N-acetyl-muramyl-L-alanine amidase and for an endo-beta-N-acetyl-D-glucosaminidase . The cloned protein lysed cells of S . saprophyticus and Micrococcus luteus exogenously . Subcloning localized the enzymatic activities to the regions of high homology and demonstrated that the interposed sequence is responsible for the adhesive activities . Two allelic replacement mutants were constructed that lacked autolytic activity and adhesive properties . The N-terminal portion of the protein contains seven highly conserved, contiguous repeats with no similarity to published sequences . It lacks the motifs typical of Gram-positive surface proteins and shows a different overall organization . This autolysin/adhesin of S . saprophyticus (Aas) appears to represent a new class of staphylococcal adhesins.

Mech Ageing Dev, 1998 Jul 15, 103(3), 235 - 54
Age-related loss of immunoregulatory function in peripheral blood CD8 T cells; Crisi GM et al.; CD8+ T cells from young individuals become inhibitory for the (Staphylococcus aureus + interleukin 2)-induced differentiation of autologous B cells into immunoglobulin secreting cells (ISC) after exposure to pokeweed mitogen (PWM), dimaprit or intracellular cAMP raising agents, such as forskolin or dibutyryl-cAMP . In the present study this immunoregulatory activity was found to be lacking in CD8+ T cells from peripheral blood lymphocytes (PBL) of aged (> 67 years old) subjects . Splenic CD8+ T cells from most individuals examined, including some aged subjects, exhibited this activity . While an age-related decrease in the CD8+ T cell subset, primarily in the virgin CD8+ T cells in PBL, was detected, this decrease was not sufficient to explain a total absence of activity . There was no age-related decrease in cAMP upregulation by forskolin or dimaprit in peripheral blood T cells . However, whereas PWM induced a highly significant increase in mRNA for transforming growth factor-beta (TGF-beta) in T cells from young individuals, no such increase could be detected in T cells from aged subjects . It is suggested that the decrease in immunoregulatory activity in PBL from the elderly may at least in part be due to a decrease in TGF-beta production.

J Pediatr Surg, 1998 Aug, 33(8), 1279 - 82
Superficial suppurative thrombophlebitis in children, caused by anaerobic bacteria; Brook I; OBJECTIVE: The purpose of this study was to present the microbiology and clinical features of six children with superficial suppurative thrombophlebitis (SST) caused by anaerobic bacteria . METHODS: A retrospective review of microbiological and clinical data was undertaken . RESULTS: Anaerobic bacteria alone were recovered in four instances, and they were mixed with facultative bacteria in two . There were 12 bacterial isolates (10 anaerobic and 2 facultatives) . The bacteria were Peptostreptococcus species (four isolates), Prevotella species (three), and one isolate each of Fusobacterium nucleatum, Propionibacterium acnes, Staphylococcus aureus, and Staphylococcus epidermidis . SST at an intravenous infusion site developed in all but one patient . One patient sustained trauma to the leg, and cellulitis developed . Anaerobes of oral origin (Prevotella and Fusobacterium species) were recovered in scalp vein SST, and of gastrointestinal origin (Bacteroides fragilis) in a lower extremity SST . CONCLUSION: This study highlights the potential importance of anaerobic bacteria in children with SST.

Microbios, 1998, 93(376), 179 - 85
Nickel sequestering by polyphosphate bodies in Staphylococcus aureus; Gonzalez H et al.; Metal incorporation and possible cellular compartmentalization of nickel by Staphylococcus aureus was investigated . Cells grown on nutrient agar were removed, washed and exposed to 10, 20, 50 or 100 ppm of nickel in distilled water . The cells were air-dried on Formvar coated grids and then examined in a transmission electron microscope operating in the scanning transmission mode . The spot setting was used in conjunction with an energy dispersive X-ray spectrometer to determine the location and relative amount of the nickel in different parts of the cells . The study showed that polyphosphate bodies bind large amounts of the metal . The peak height for nickel increased in the higher exposure amounts of nickel . No nickel was detected in the cell wall or cytoplasmic areas . The results are discussed in relation to nickel transport in cells and staphylococcal infections in humans.

Am J Infect Control, 1998 Aug, 26(4), 388 - 92
Impact of a dedicated intravenous therapy team on nosocomial bloodstream infection rates; Meier PA et al.; BACKGROUND: Meticulous care of intravenous catheters could be expected to minimize associated nosocomial bloodstream infections, but care is often suboptimal . METHODS: To examine the ostensible benefits of a professional, dedicated intravenous therapy team, we compared the secular trends in nosocomial bloodstream infections before and after such a team was established . RESULTS: After the introduction of the team at the Veterans Administration Medical Center, the rate of primary nosocomial bloodstream infection decreased by 35% (1.1 to 0.7 infections/1000 patients-days, P < .01), including a 51% decrease in bloodstream infections caused by Staphylococcus aureus (P < .01) . The excess cost of the team was $252,000 per year . The excess costs per life saved and infection prevented were projected to be $53,000 and $14,000, respectively . CONCLUSIONS: The introduction of a dedicated intravenous therapy team was associated with a significant reduction in nosocomial bloodstream infections . Further work is needed to maximize the cost-benefit ratio of this intervention.

J Bacteriol, 1998 Sep, 180(17), 4350 - 9
Complete nucleotide sequence of pSK41: evolution of staphylococcal conjugative multiresistance plasmids; Berg T et al.; The 46.4-kb nucleotide sequence of pSK41, a prototypical multiresistance plasmid from Staphylococcus aureus, has been determined, representing the first completely sequenced conjugative plasmid from a gram-positive organism . Analysis of the sequence has enabled the identification of the probable replication, maintenance, and transfer functions of the plasmid and has provided insights into the evolution of a clinically significant group of plasmids . The basis of deletions commonly associated with pSK41 family plasmids has been investigated, as has the observed insertion site specificity of Tn552-like beta-lactamase transposons within them . Several of the resistance determinants carried by pSK41-like plasmids were found to be located on up to four smaller cointegrated plasmids . pSK41 and related plasmids appear to represent a consolidation of antimicrobial resistance functions, collected by a preexisting conjugative plasmid via transposon insertion and IS257-mediated cointegrative capture of other plasmids.

Gastroenterology, 1998 Sep, 115(3), 573 - 83
Suppression of T cell-mediated injury in human gut by interleukin 10: role of matrix metalloproteinases; Pender SL et al.; BACKGROUND & AIMS: Activation of lamina propria T cells with pokeweed mitogen in human fetal gut explant cultures results in severe mucosal injury . In the same system, Staphylococcus aureus enterotoxin B produces villus atrophy and crypt cell hyperplasia . The aim of this study was to examine the ability of interleukin (IL)-10 to modify these changes . METHODS: Mucosal pathology and lamina propria glycosaminoglycans were assessed histologically, and CD3(+), CD25(+) and alpha-actin smooth muscle-positive cells were determined by immunohistochemistry . Reverse plaque assays and quantitative reverse-transcriptase polymerase chain reaction were used to analyze the cytokine response . Matrix metalloproteinase production was analyzed by Western blotting, in situ hybridization, and zymography . RESULTS: Both experimental enteropathies produced mucosal damage, although injury was greater after pokeweed mitogen activation than S . aureus enterotoxin B . In both cases, the increase in cytokine-secreting cells and transcripts observed after T-cell activation was inhibited by IL-10 . IL-10 also inhibited the increase in collagenase and stromelysin-1 in the explant culture supernatants and the loss of glycosaminoglycans . IL-10 decreased metalloproteinase production in control explants and increased matrix . In mesenchymal cells, IL-10 had a minor effect on metalloproteinase production . CONCLUSIONS: IL-10 down-regulates mucosal T-cell activation, metalloproteinase production, and loss of extracellular matrix and prevents mucosal damage in the gut.

Mol Microbiol, 1998 Jul, 29(2), 527 - 43
The gene for toxic shock toxin is carried by a family of mobile pathogenicity islands in Staphylococcus aureus; Lindsay JA et al.; Tst, the gene for toxic shock syndrome toxin-1 (TSST-1), is part of a 15.2 kb genetic element in Staphylococcus aureus that is absent in TSST-1-negative strains . The prototype, in RN4282, is flanked by a 17 nucleotide direct repeat and contains genes for a second possible superantigen toxin, a Dichelobacter nodosus VapE homologue and a putative integrase . It is readily transferred to a recA recipient, and it always inserts into a unique chromosomal copy of the 17 nucleotide sequence in the same orientation . It is excised and circularized by staphylococcal phages phi13 and 80alpha and replicates during the growth of the latter, which transduces it at very high frequency . Because of its site and orientation specificity and because it lacks other identifiable phage-like genes, we consider it to be a pathogenicity island (PI) rather than a transposon or a defective phage . The tst element in RN4282, near tyrB, is designated SaPI1 . That in RN3984 in the trp region is only partially homologous to SaPI1 and is excised by phage 80 but not by 80alpha . It is designated SaPI2 . These PIs are the first in any gram-positive species and the first for which mobility has been demonstrated . Their mobility may be responsible for the spread of TSST-1 production among S . aureus strains.

Chem Phys Lipids, 1998 Jun, 93(1-2), 15 - 25
Staphylococcal lipases: molecular characterisation, secretion, and processing; Gotz F et al.; Up to date five different staphylococcal lipase genes, two of Staphylococcus aureus (sal-1 and sal-2), two of Staphylococcus epidermidis (sel-1 and sel-2) and one of Staphylococcus hyicus (sh1) have been cloned and sequenced . All corresponding proteins are organised as pre-pro-enzymes: the pre-region represents the signal peptide, the pro-region has a length between 207 and 267 amino acids, and the mature part comprises 380 to 400 amino acids . We found that the lipases are secreted in the pro-lipase form . The processing of the pro-form to the mature enzyme occurs extracellular by a specific protease . Interestingly the pro-lipase reveals not much less activity compared to the mature lipase . There are evidences that the pro-region acts as an intramolecular chaperone which facilitates translocation not only of the native lipase but also of a number of completely unrelated proteins fused to the pro-peptide . It was also observed that the pro-region protects the proteins from proteolytic degradation . While the Staphylococcus aureus and Staphylococcus epidermidis lipases have only lipase (esterase) activity, the related Staphylococcus hyicus enzyme (SHL) is distinguished by both lipase and phospho-lipase activity . The biochemical and catalytic properties of these lipases are described in the accompanying article (Simons, J.W., Gotz, F., Egmont, M.R . and Verheij, H.M., 1998 . Staphylococcal lipases: Biochemical properties . Accompanying article).

Mol Biotechnol, 1998 Jun, 9(3), 187 - 93
Filamentous bacteriophage display of a bifunctional protein A::scFv fusion; Li Y et al.; Filamentous bacteriophage display is a powerful and widely used technology for the selection of affinity ligands . However, the commonly used phagemid systems result in the production of a population of phage of which those displaying the ligand of interest represent only a small proportion . Through simple dilution and nonspecific binding effects, the presence of large numbers of ligand-free phage reduces the likelihood that weak binders will be successfully selected from a ligand library . To provide a means of avoiding such problems, we have introduced an affinity handle into the phage that permits the purification of ligand-displaying phage . The IgG binding domains of Staphylococcus aureus protein A (SpA) were fused to a ligand (single chain Fv{scFv}) which is displayed as a fusion with the phage surface protein delta pIII . Phage-displaying SpA were separated by affinity chromatography using immobilized human IgG from non-displaying phage and the purified phage were shown to possess functional scFv . Comparisons of fusion proteins in which either the scFv or the affinity handle occupied the amino terminus of the fusion protein showed that, whereas SpA function was unaffected by position, scFv function was compromised when the scFv did not occupy the amino terminus.

J Magn Reson, 1998 Aug, 133(2), 364 - 7
An alpha/beta-HSQC-alpha/beta experiment for spin-state selective editing of IS cross peaks
Andersson P, Annila A, Otting G.
A generalized version of the TROSY experiment allows the spin-state selective editing of the four multiplet components of 15N-1H cross peaks of amide groups in proteins into four different subspectra, with no penalty in sensitivity . An improvement by <SGMLEXP TYPE="INLINE">2 in sensitivity results, if only two of the four multiplet components are selected . Use of the experiment for the measurement of 1JHN coupling constants is discussed . A water flip-back version of the experiment is demonstrated with a 45 kDa fragment of 15N/2H labeled Staphylococcus aureus gyrase B .

Clin Cancer Res, 1998 Aug, 4(8), 1943 - 8
Advanced colorectal cancer is associated with impaired interleukin 12 and enhanced interleukin 10 production; O'Hara RJ et al.; Interleukin 12 (IL-12) is a heterodimeric cytokine that has been demonstrated to have a major role in stimulating a cell-mediated antitumor response . IL-10, a product of T helper 2 lymphocytes, is its most potent inhibitor . The aim of this study was to investigate whether patients with colorectal cancer had an imbalance in production of IL-12 and IL-10 preoperatively, and whether this was associated with advanced disease at surgery . Blood was obtained before surgery from 60 patients with colorectal cancer and from 30 controls . Peripheral blood mononuclear cells were incubated with Staphylococcus aureus Cowan's strain 1 in vitro for 24 h to assess IL-12 expression after stimulation, and serum was used for IL-10 measurement . IL-12 and IL-10 levels were assessed by ELISA . A single pathologist staged the tumors according to the tumor-node-metastasis (TNM) and Dukes' classifications . Patients with colorectal cancer had significantly lower levels of IL-12 (P <0.001) and higher levels of IL-10(P = 0.004) compared to controls . In addition, lower levels of IL-12 were detected in those patients who were node positive (P<0.05), had Dukes' C lesions (P < or = 0.001), and T3 or T4 lesions (P<0.033) when compared to controls . Patients with Dukes' B and C lesions (P<0.01) and T3 and T4 lesions (P<0.05) also had higher levels of IL-10 compared to controls . This study is the first to demonstrate that patients with colorectal cancer have decreased IL-12 production and increased serum IL-10 . This suggests an impaired T helper 1 cell-mediated antitumor response and provides some justification for exogenous IL-12 therapy or anti-IL-10 therapy in these patients.

J Postgrad Med, 1996 Jan-Mar, 42(1), 1 - 3
A pilot programme of MRSA surveillance in India . (MRSA Surveillance Study Group); Mehta A et al.; This surveillance study was conducted simultaneously at three centres across India . A total of 13,610 test samples from various sites were obtained . Microbiological methods employed were similar at the three centres . Identification of S aureus was based on the recognition of the production of coagulase with positive isolates being recorded as S aureus . Both tube coagulase tests and slide coagulase test were performed . Antimicrobial susceptibility testing of the isolated strains of staphylococcus aureus and staphylococcus epidermidis to various antimicrobial discs were carried out according to standardized disk diffusion method recommended by NCCLS . Of the total 739 cultures of S aureus, 235 (32%) were found to be multiply resistant with the individual figures for resistance being 27% (Bombay), 42.5% (Delhi) and 47% (Bangalore) . MRSA is emerging to be a significant problem pathogen in the surgical setting with vancomycin probably the only reliable choice for these infections.

J Trauma, 1998 Aug, 45(2), 383 - 7
Trimethoprim-sulfamethoxazole for the prevention of methicillin-resistant Staphylococcus aureus pneumonia in severely burned patients; Kimura A et al.; BACKGROUND: Patients with severe burns are at increased risk of developing methicillin-resistant Staphylococcus aureus (MRSA) ventilator-associated pneumonia . This study was designed to determine whether MRSA pneumonia can be prevented by prophylactic administration of trimethoprim-sulfamethoxazole (TMP-SMX) . METHODS: We conducted a prospective, randomized, placebo-controlled study in patients with severe burns (> or = 20%), who required ventilator support . Prophylaxis was done with oral TMP-SMX (80 mg/400 mg) three times daily for 10 days from 4 to 6 days after burn injury . The incidence of MRSA pneumonia and the side effects were evaluated during the administration period . RESULTS: Twenty-one patients were assigned to receive TMP-SMX, and 19 patients to receive placebo . The incidence of MRSA pneumonia was 4.8% in the TMP-SMX group and 36.8% in the placebo group, showing a significant difference (p = 0.017) . No major side effects of therapy were seen in the TMP-SMX group . CONCLUSION: Prophylactic treatment with TMP-SMX can prevent MRSA pneumonia in severely burned patients.

Thorac Cardiovasc Surg, 1998 Jun, 46(3), 162 - 4
Prevention of pulmonary embolization during excision of an infected venous thrombus; Sakakibara Y et al.; We describe the case of a 64-year-old woman with an iatrogenic pseudoaneurysm, arteriovenous fistula, and thrombotic occlusion of the right femoral vein with Staphylococcus aureus infection resistant to methicillin as complications of femoral catheterization for hemodialysis access . A temporary caval filter was introduced just prior to operation and kept in place for 4 days . An infected thrombus was captured and removed with a filter-catheter device . The placement of a temporary caval filter should be considered for prevention of pulmonary embolism in patients with infected venous thrombosis which requires surgical thrombectomy.

J Food Prot, 1998 Aug, 61(8), 994 - 9
Microbiological quality of filled pasta in relation to the nature of heat treatment; Chaves Lopez C et al.; The microbial population present in 49 samples of Italian industrially processed filled pasta was characterized and its changes during refrigerated storage were evaluated . The most frequently isolated species belonged to the genus Bacillus . No pathogenic organisms were isolated from the processed industrial pasta . As a consequence of the diversity of composition and thermal treatment a wide variability was observed (from less than 3 days to more than 1 month) in the shelf life at 4 degrees C of the industrial "fresh filled pasta." However, the results obtained suggested that the shelf life of the processed products depend not only on the number of surviving cells but also on the textural or microstructural changes induced by the heat treatment . Challenge tests using Staphylococcus aureus showed that even pasteurization values (P 70(10), expressed as an equivalent process time, in minutes, necessary to obtain at 70 degrees C the same lethal effect as during the actual process) not exceeding 2 were able to remarkably reduce the cell load of this organism . Subsequent growth of the surviving S . aureus cells occurred only at temperatures > 7 degrees C, particularly when the water activity (aw) values were higher than 0.97.

Anticancer Res, 1998 Jul-Aug, 18(4C), 3049 - 52
Nitric oxide production and MDR expression by human brain endothelial cells; Mandi Y et al.; The endothelium both initiates and responds to a cascade of events triggered by cytokines . Enhanced formation of NO, especially by inducible nitric oxide- synthase (i NOS), is largely stimulated by tumor necrosis factor (TNF) . Nitrogen oxides are reactive intermediate molecules functioning in neural transmission, and vasodilatation . The aim of our study was to investigate the effect of TNF and Staphylococcus aureus, a TNF inducing agent on the NO production of brain endothelial cells in vitro . The effect of the same agent was investigated on the MDR expression of endothelial cells . Both TNF and Staphylococcus aureus resulted in enhanced NO production . Western blot analysis showed enhanced expression of iNOS, which could be inhibited by pentoxifylline, an inhibitor of TNF synthesis . Flow cytometric analysis revealed that the brain capillary endothelial cells exerted P-glycoprotein expression, which was not influenced by TNF . However, the mdr function itself in these cells was decreased by TNF . Cultured endothelial cells are excellent tools for the investigation of the possible connection between the NO production and MDR function, and for the estimation the effect of different agents influencing these activities, which might be important in blood-brain barrier function.

J Immunol, 1998 Aug 15, 161(4), 2011 - 8
IFN-alpha priming of human monocytes differentially regulates gram-positive and gram-negative bacteria-induced IL-10 release and selectively enhances IL-12p70, CD80, and MHC class I expression; Hermann P et al.; Administration of IFN-gamma and IFN-alpha may protect or induce autoimmune diseases . Although the in vitro regulation of monokine secretion by IFN-gamma have been extensively studied, the regulatory function of IFN-alpha has not yet been elucidated . We compared IFN-alpha and IFN-gamma, added alone or simultaneously before bacterial stimulation, for the control of monokine release and the expression of costimulatory molecules by human monocytes . Our data show that: 1) IFN-alpha primes monocytes for increased production of IL-10 in response to Staphylococcus aureus Cowan I strain (SAC) but not to LPS, leading to a lack of IFN-alpha priming for TNF-alpha secretion; 2) pretreatment of monocytes with IFN-alpha inhibits LPS- or SAC-induced IL-12p40 production but unexpectedly enhances the release of the biologically active form of IL-12 (IL-12p70); 3) IFN-alpha and IFN-gamma exert an antagonistic effect on LPS- and SAC-induced IL-10 as well as IL-12p40 release, whereas they further enhance IL-12p70 production when added simultaneously; 4) in contrast to IFN-alpha, IFN-gamma primes monocytes to enhance LPS- or SAC-induced TNF-alpha and IL-12 production, but surprisingly, it increases IL-10 production by monocytes following LPS but not SAC stimulation; and finally, 5) IFN-alpha pretreatment selectively up-regulates CD80 and MHC class I expression on monocytes . It is proposed that the outcome of the immune response at the site of inflammation may depend on both the type of bacterial injury (gram-positive or -negative) and of locally produced IFNs, and that the differential and opposite effects of type I and type II IFNs on monocytes may account for the beneficial or detrimental effects of IFN-alpha therapy.

J Dairy Sci, 1998 Jul, 81(7), 1904 - 9
A comparison of two methods of evaluation of teat skin pathology; Burmeister JE et al.; A split-plot design with repeated measures was used to test the relationship between visual teat skin condition score, the degree of transepidermal water loss from the skin, and the colonization by Staphylococcus aureus on experimentally chapped and inoculated teats of 20 lactating Holstein cows . Visual teat skin chapping score and the number of S . aureus colonies obtained from a teat skin swab were correlated (r = 0.53) . Transepidermal water loss and S . aureus count were not correlated (r = 0.02) . Results indicated that visual teat skin evaluation is superior to measurements of transepidermal water loss in the prediction of the susceptibility of teat skin to colonization by S . aureus.

Clin Infect Dis, 1998 Aug, 27 Suppl 1, S68 - 74
Staphylococcal small colony variants have novel mechanisms for antibiotic resistance; Proctor RA et al.; Over the past 4 years, a variant subpopulation of Staphylococcus aureus has been characterized that is defective in electron transport . These organisms grow slowly and are typical of the previously described small colony variants (SCVs) . Indeed, many earlier papers included data that are consistent with defective respiratory activity in SCVs . We present a hypothesis that serves as biochemical basis for the development of SCVs . These variants are particularly interesting because they have been associated with very persistent infections, and they are more resistant to many antibiotics than normal S . aureus . Because of their slow growth, atypical colonial morphology, and unusual biochemical profile, they are easily missed or misidentified in the clinical laboratory . This is of some significance, as this subpopulation is more resistant to antibiotics than the parent population from which they arose . When an infection is particularly resistant to therapy, persists for a long period, or fails to respond to apparently adequate antimicrobial therapy, clinicians and clinical laboratory personnel should consider special efforts to search for SCVs.

J Clin Invest, 1998 Aug 15, 102(4), 853 - 60
Absence of IgD-CD27(+) memory B cell population in X-linked hyper-IgM syndrome; Agematsu K et al.; The present study analyzed peripheral blood B cell populations separated by IgD and CD27 expression in six males with X-linked hyper-IgM syndrome (XHIM) . Costimulation of mononuclear cells from most of the patients induced no to low levels of class switching from IgM to IgG and IgA with Staphylococcus aureus Cowan strain (SAC) plus IL-2 or anti-CD40 mAb (anti-CD40) plus IL-10 . Measurable levels of IgE were secreted in some of the patients after stimulation with anti-CD40 plus IL-4 . Costimulation with SAC plus IL-2 plus anti-CD40 plus IL-10 yielded secretion of significant levels of IgG in addition to IgM, but not IgA . The most striking finding was that peripheral blood B cells from all of the six patients were composed of only IgD+ CD27(-) and IgD+ CD27(+) B cells; IgD- CD27(+) memory B cells were greatly decreased . IgD+ CD27(+) B cells from an XHIM patient produced IgM predominantly . Our data indicate that the low response of IgG production in XHIM patients is due to reduced numbers of IgD- CD27(+) memory B cells . However, the IgG production can be induced by stimulation of immunoglobulin receptors and CD40 in cooperation with such cytokines as IL-2 and IL-10 in vitro.

FEBS Lett, 1998 Jul 31, 432(1-2), 40 - 4
Activation of NF-kappaB in human neutrophils during phagocytosis of bacteria independently of oxidant generation; Vollebregt M et al.; We have exposed human neutrophils to opsonized Staphylococcus aureus and used an electrophoretic mobility shift assay to show activation of the transcription factor NF-kappaB above basal levels . Activation was evident within 10 min and was increased with higher bacteria:neutrophil ratios . The neutrophil NADPH oxidase inhibitor diphenylene iodonium, catalase, and other oxidant scavengers did not inhibit NF-kappaB activation, and no activation was seen with added hydrogen peroxide . Oxidants produced during phagocytosis, therefore, are not involved in the activation mechanism.

Clin Infect Dis, 1998 Aug, 27(2), 245 - 9; quiz 250-1
Vancomycin-resistant Staphylococcus aureus: infection control considerations; Wenzel RP et al.; The lessons of the antibiotic era are crystal clear: in the footrace between humans and microbes, the organisms' genetic repertoire and efficient response to environmental changes will win the day . New antibiotics are essential, but their shelf life will be enhanced only if used wisely and sparingly . The antibiotic era is continually threatened by inappropriate decisions regarding use, inappropriate choices, and unnecessary durations of treatment . In concert with improved prescribing habits, efforts to identify and isolate resistant organisms introduced from outside institutions are essential . Last, continual energy is needed to influence the behavior of health care professionals and to maintain optimal infection control policies and procedures . We remain optimistic about the ability of infectious diseases physicians to respond appropriately to continued microbial challenges with research, education, and wise practice.

Transfusion, 1998 Aug, 38(8), 713 - 21
Neutrophil transfusions: kinetics and functions of neutrophils mobilized with granulocyte-colony-stimulating factor and dexamethasone; Dale DC et al.; BACKGROUND: The collection of adequate numbers of neutrophils (polymorphonuclear leukocytes, PMNs) from normal donors has long hampered the development of neutrophil transfusion therapy . The stimulation of donors with granulocyte-colony-stimulating factor (G-CSF) plus dexamethasone is a promising way of improving PMN collections . STUDY DESIGN AND METHODS: Sixteen normal subjects received G-CSF (600 micrograms subcutaneously) and dexamethasone (8 mg by mouth) 12 hours before leukapheresis . Measurements included PMN morphology, immunophenotype analysis, chemiluminescence, bactericidal activity, in vivo kinetics, and adverse effects . RESULTS: A mean of 77.4 +/- 6.4 x 10(9) PMNs was collected with each leukapheresis; 14 percent were bands . PMNs had increased surface expression of CD11b, CD18, CD14, CD32, and CD64 . Bactericidal capacity against Staphylococcus aureus was normal . Inducible respiratory burst was maintained, although the responses to some agonists were diminished . Returned leukapheresis cells labeled with 3H-diisopropylfluorophosphate had a modestly decreased percentage of recovery and circulated with a prolonged half-life . Migration of these cells to skin chambers was approximately equal to that of the subjects' own blood PMNs . Adverse effects included transient bone pain, headache, hunger, and insomnia . CONCLUSIONS: Precollection treatment of leukapheresis donors with G-CSF plus dexamethasone is an effective way to enhance the collection of PMNs with normal or near-normal functional properties for PMN transfusion therapy.

J Food Prot, 1998 May, 61(5), 629 - 32
Prevalence and characteristics of Staphylococcus aureus strains isolated from bulk and composite milk and cattle handlers; Adesiyun AA et al.; The prevalence and characteristics of Staphylococcus aureus strains isolated from bulk and composite milk and from cattle handlers on dairy farms in Trinidad were determined . S . aureus strains were isolated from all 175 bulk milk samples tested (100%) while 280 of 287 composite milk samples (97.6%) yielded S . aureus . The mean counts of S . aureus in bulk milk ranged from 5.9 x 10(3) to 1.2 x 10(5) CFU/ml compared with mean S . aureus counts in composite milk which ranged from 2.4 x 10(3) to 3.0 x 10(4) CFU/ml . Of the 105 strains of S . aureus from bulk milk tested, 45 (42.9%) were enterotoxigenic elaborating staphylococcal enterotoxin A (SEA), SEB, SEC, SED, or a combination compared to 69 of 146 strains (47.3%) recovered from composite milk which were enterotoxigenic, but the difference was not statistically significant (P > = 0.05; chi 2) . Twenty-two of 42 bulk milk samples containing enterotoxigenic S . aureus (52.4%) had counts of the organism which exceeded 10(4) CFU/ml . For S . aureus strains isolated from cattle handlers, 66 of 146 (45.2%) were enterotoxigenic . Prevalence of resistance to nine antimicrobial agents tested was 18.7% and 12.9% among bulk milk and composite milk isolates, respectively, compared to 49.3% and 69.5% . among isolates from human anterior nares and hand swabs, respectively . Resistance to ampicillin and penicillin was highest among both milk (12.2%) and human (53.6%) isolates of S . aureus, and the difference was statistically significant (P < or = 0.001; chi 2) . It was concluded that bulk milk containing relatively high counts of enterotoxigenic S . aureus may constitute a health hazard to consumers.

J Food Prot, 1998 May, 61(5), 626 - 8
Microbial evaluation of Alaska salmon caviar; Himelbloom BH et al.; Microbial quality of pink salmon caviar (ikura) processed at one plant in Alaska during a 30-day season was examined . Ikura (aw = 0.98; pH 6.1) averaged 49% water, 32% protein, 11% fat, 7% ash, and 3% salt . Aerobic plate counts (APCs) ranged from < 10(2)/g to 4.5 x 10(7)/g with increasing APC toward season's end . Coliform counts ranged from < 3/g to 2.4 x 10(3)/g . Escherichia coli, Staphylococcus aureus, yeasts, and molds were not detected . High-APC (10(7)/g) thawed caviar exhibited predominantly lactic acid bacteria; low-APC (10(3)/g) thawed caviar exhibited predominantly gram-negative bacteria . Freezing had little effect on the microbial counts, and shelf life of thawed caviar was 3 to 5 days at 2 degrees C.

J Food Prot, 1998 Apr, 61(4), 432 - 6
The combined effect of high hydrostatic pressure and mild heat on inactivation of pathogens in milk and poultry; Patterson MF et al.; The combined effects of high hydrostatic pressure and heat on the inactivation of Escherichia coli O157:H7 NCTC 12079 and Staphylococcus aureus NCTC 10652 in poultry meat and ultra-high-temperature-treated (UHT) milk were investigated . The to have a significant effect on the survival of the pathogens during treatment . For E . coli O157:H7, a 15-min treatment of 400 MPa at 50 degrees C resulted in approximately a 6.0-log10 reduction in CFU/g in poultry meat and a 5.0-log10 reduction in UHT milk; however, a < 1-log10 reduction was achieved with either treatment alone . In contrast, for S . aureus, a 15-min treatment of 500 MPa at 50 degrees C was required to achieve a 5.0-log10 reduction in poultry meat and a 6.0-log10 reduction in UHT milk . As before, a < 1-log10 reduction in numbers was achieved with either treatment alone . The pressure-temperature inactivation curves of each organism, in each substrate, were fitted using the Gompertz equation . Polynomial expression derived from the Gompertz variables were used to devise simple models which predicted the inactivation of each pathogen at various pressure-temperature combinations . Thus, a number of different pressure-temperature conditions could be chosen to achieve a desired inactivation level . The use of such models will provide flexibility in selecting optimum pressure conditions without compromising microbiological safety.

Immunology, 1998 May, 94(1), 1 - 4
V beta 11+ T-lymphocyte expansion by toxic shock syndrome toxin-1 differs in mice bearing H-2q versus H-2b haplotypes; Zhao YX et al.; We have recently demonstrated that toxic shock syndrome toxin-1 (TSST-1) expanded V beta 11+ T lymphocytes contribute to Staphylococcus aureus arthritis and sepsis-induced mortality . Interestingly, V beta 11+ T-cell mediated joint pathology varies in different mouse strains . In this study, we characterized the in vitro pattern of V beta 11+ T-cell expansion by TSST-1 in mice with various genetic backgrounds . Mice expressing major histocompatibility complex (MHC) class II I-E molecules did not expand V beta 11+ T cells upon stimulation with TSST-1 . Using B10 congeneic I-E negative mouse strains, we found that the TSST-1-expanded V beta 11+ T cells in B10Q (H-2q) and B10M (H-2f) mice but not in B10B (H-2b) mice . Antigen-presenting cells (APC) from B10Q mice, L cells and lymphoma cell line transfected with a q gene did not restore the deficient V beta 11+ T-cell expansion by TSST-1 in purified T cells from B10B mice . In contrast, I-Ab APC were able to stimulate V beta 11+ T cells from H-2q mice . Furthermore, V beta 11+ T cells in H-2b mice did expand when exposed to staphylococcal enterotoxin A (SEA) . These findings suggest that the T-cell repertoire, skewed by clonal deletion and inactivation of self-reactive T cells, accounts for the different magnitude of V beta 11+ T-cell expansion among the different mouse strains.

Int J Food Microbiol, 1998 Jun 16, 41(3), 205 - 12
Detection and analysis of Staphylococcal enterotoxin A in food by Western immunoblotting; Rasooly A et al.; Western blotting has the potential to overcome some of the major problems associated with enzyme-linked immunosorbent assay (ELISA) detection of toxins in food, such as cross-reactivity with unrelated antigens and insensitivity with heat-treated foods, because the Western procedure solubilizes denatured protein and allows characterization of the antigen that reacts with the antibody . A simple Western immunoblotting protocol was developed to identify and measure the level of Staphylococcus aureus enterotoxin A (SEA) in food . Test samples are merely homogenized with no additional solubilization or pretreatment steps . The immunoblots detect SEA at levels as low as 100 pg/ml . Using the simplified sample preparation, both native and heat-denatured SEA were identified in a variety of foods including mushrooms, milk, potato salad and meat products . Our data suggest that SEA is being secreted at mid-log growth in BHI media as well as in mushrooms . These results suggest that Western blotting is a useful tool for determining the presence of SEA in foods because it allows characterization of the antigen reacting with the antibody and can be used for heat-treated foods, thus overcoming some of the limitations of the ELISA test.

J Clin Microbiol, 1998 Sep, 36(9), 2590 - 6
Intercontinental spread of a multidrug-resistant methicillin-resistant Staphylococcus aureus clone; Aires de Sousa M et al.; Two hundred ten methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered between 1990 and 1997 from three Portuguese hospitals located in Lisbon and Oporto were analyzed by molecular fingerprinting techniques . The hybridization of ClaI restriction digests with the mecA- and Tn554-specific DNA probes combined with pulsed-field gel electrophoresis documented the abrupt appearance and extensive intrahospital spread of the Brazilian epidemic MRSA clone in the 1995 samples of each one of the three hospitals analyzed-suggesting the intercontinental transfer of this strain from Brazil to Portugal . The appearance of this clone may challenge the dominance of another highly epidemic imported clone-the Iberian MRSA, currently the most widely spread MRSA clone in Portuguese hospitals.

J Clin Microbiol, 1998 Sep, 36(9), 2548 - 53
Rapid and specific detection of toxigenic Staphylococcus aureus: use of two multiplex PCR enzyme immunoassays for amplification and hybridization of staphylococcal enterotoxin genes, exfoliative toxin genes, and toxic shock syndrome toxin 1 gene; Becker K et al.; Two multiplex PCR enzyme immunoassays (PCR-EIAs) were developed for Staphylococcus aureus exotoxin gene screening as an alternative to the conventional biological assays, which depend on detectable amounts of toxins produced . One set of oligonucleotide primers and probes was designed to search for enterotoxin A to E genes (entA, entB, entC, entD, and entE), and the other one was designed to detect the staphylococcal exfoliative toxin genes (eta and etb) and the toxic shock syndrome toxin 1 gene (tst) . Oligonucleotide primers were used as published previously, modified or newly developed to meet the requirements of both good size-distinguishable amplification bands of multiplex PCR and the temperature limit of the uracil DNA glycosylase system for carryover protection . Amplification products were visualized by agarose gel electrophoresis, and specificity was controlled with the aid of a DNA EIA system using oligonucleotide probes derived from the sequences of the S . aureus toxin genes . PCR procedures were performed by using template nucleic acids extracted from a panel of S . aureus reference strains and from a collection of 50 clinical strains . The PCR results were compared with those of immunological toxin production assays . This multiplex PCR-EIA system offers an alternative method for the rapid, sensitive, specific, and simultaneous detection of the clinically important exotoxin potency of isolated S . aureus strains for diagnostic purposes as well as research studies.

Trop Med Int Health, 1998 Jul, 3(7), 576 - 83
Molecular, antibiogram and serological typing of Staphylococcus aureus isolates recovered from Al-Makased Hospital in East Jerusalem; Essawi T et al.; Staphylococcus aureus is a major cause of nosocomial infections and a risk in patients who have either undergone surgery or are on haemodialysis . The S . aureus infections in patients admitted to the clinical departments of Al-Makased Charitable Hospital in Jerusalem during a period of one year were investigated . Isolates included were from blood, surgical wounds, or other nonsuperficial sites . Of 63 isolates available for analysis, 46 (73.0%) expressed type 8 capsular polysaccharide; 13 (20.7%), type 5 capsular polysaccharide; only 4 isolates (6.3%) did not express type 5 or type 8 antibodies . The strains fitted in 7 different antibiogram types, with the type showing resistance only to penicillin and ampicillin prevalent in 34 out of 63 isolates (54.0%) . Of the 12 methicillin-resistant S . aureus (MRSA) isolates (19.1%), 8(66.7%) possessed the type 8 capsule and 4(33.7%) the type 5 capsule . Pulsed-field gel electrophoresis of all isolates with the restriction-endonuclease enzymes Sma I revealed 34 patterns demonstrating that no single methicillin-sensitive S . aureus strain was endemic in the hospital . However, all MRSA isolates with a type 8 capsule showed identical PFGE patterns using the 2 restriction-endonuclease enzymes Sma I and SST II . Moreover, type 5 isolates showed identical patterns (one isolate differed from the rest with one band only) . These data suggest and confirm the clonality of type 5 and type 8 MRSA isolates . Analysing the results of the capsular and antibiogram typing schemes in conjunction proved useful and suggested that such an analysis can be employed as a helpful epidemiological tool in hospitals with limited resources.

Cardiovasc Surg, 1998 Jun, 6(3), 268 - 73
An increased concentration of rifampicin bonded to gelatin-sealed Dacron reduces the incidence of subsequent graft infections following a staphylococcal challenge; Vicaretti M et al.; The purpose of this study was to determine if 10 mg/ml rifampicin bonded to gelatin-sealed Dacron (Gelsoft) reduced staphylococcal infection . Grafts soaked in rifampicin were interposed in the left carotid artery of 20 merino sheep and then inoculated with 10(8) colony-forming units of MRSA (10 sheep) or a slime producing Staphylococcus epidermidis (10 sheep) . Grafts were harvested at 3 weeks, and perigraft abscess, anastomotic disruption and graft occlusion recorded . Swabs were taken to assess bacterial growth of the perigraft tissues, and external and internal graft surface . Grafts segments were incubated in broth medium . Results were compared with previously published results that used graft that were not soaked in rifampicin (control) and grafts soaked in 1.2 mg/ml rifampicin . A total of 4/50 cultures were positive and significantly reduced for S . epidermidis compared with the control group of 30/50 (P < 0.05) and the 1.2 mg/ml group of 13/45 (P < 0.05) . For the methicillin resistant staphylococcus aureus (MRSA) group, 6/40 cultures were positive, which was significantly reduced compared with the control group (38/40, P < 0.05) and the 1.2-mg/ml group (19/32, P < 0.05) . In conclusion an increased concentration of rifampicin significantly reduced the incidence of prosthetic vascular graft infection following a challenge of MRSA or S . epidermidis.

Biochem Biophys Res Commun, 1998 Jul 30, 248(3), 690 - 5
Identification of functional domains in Efb, a fibrinogen binding protein of Staphylococcus aureus; Wade D et al.; Staphylococcus aureus produces and secretes a protein, Efb, that binds to fibrinogen, seems to be required for virulence, and may benefit the microorganism by delaying wound healing . Interactions of Efb with fibrinogen are influenced by divalent metal cations, including Ca2+ . Increasing concentrations of Ca2+ increased the binding of fibrinogen to immobilized Efb, whereas binding of Efb to immobilized fibrinogen was decreased with increasing Ca2+ concentration . Studies with synthetic peptides showed that peptides from the carboxyl terminal half of Efb bound to soluble fibrinogen and enhanced the binding of fibrinogen to Efb . A peptide corresponding to a repeated sequence in the amino terminal half of the protein also bound fibrinogen and inhibited binding of fibrinogen to Efb . These results may provide clues to the biological function of Efb and aid in the rational design of agents to block the Efb fibrinogen interaction.

Biol Pharm Bull, 1998 Jul, 21(7), 678 - 81
Screening of an inhibitor of the tetracycline efflux pump in a tetracycline-resistant clinical-isolate of Staphylococcus aureus 743; Hirata T et al.; Clinically-isolated methicillin-resistant Staphylococcus aureus (MRSA) strain 743 exhibited resistance to tetracycline as judged from the active efflux of the drug . The efflux of tetracycline was inhibited by an uncoupler, carbonyl cyanide m-chlorophenylhydrazone (CCCP), and minocycline . Inhibitors of the efflux pump were examined in this strain to determine the cellular accumulation of tetracycline . Out of seven compounds examined, three caused a significant increase in the cellular concentration of tetracycline by inhibiting the efflux pump . Two of them seem to be energy inhibitors . Ro 07-3149 inhibited the efflux pump without affecting the energy state, and exhibited very low antibacterial activity but showed weak synergy with tetracycline.

Infect Dis Obstet Gynecol, 1998, 6(2), 61 - 5
Studies on the pathogenicity of anaerobes, especially Prevotella bivia, in a rat pyometra model; Mikamo H et al.; OBJECTIVE: Prevotella bivia is one of the anaerobic bacteria that resides in the flora of the female genital tract . We studied the pathogenicity of P . bivia in a rat pyometra model . METHODS: The experimental animal (rat) model of pyometra was developed to investigate the pathogenicity of P . bivia in a rat pyometra model . RESULTS: In the groups inoculated with aerobes alone, the infection rate was 10% (1/10) in the Staphylococcus aureus- or Staphylococcus agalactiae-inoculated group and 20% (2/10) in the Escherichia coli-inoculated group . Infection was not established in the groups inoculated with anaerobes alone . High infection rates were observed in all the mixed-infection groups . In the S . agalactiae- and Bacteroides fragilis-, S . agalactiae- and P . bivia-, F . coli- and B . fragilis-, and E . coli- and P . bivia-inoculated groups, an infection rate of 100% (10/10) was demonstrated . The efficacy of antibiotics such as flomoxef (FMOX) could be determined using a rat pyometra model . In relation to the alteration of vaginal microbial flora during the menstrual cycle, estrogen increased the growth of P . bivia . CONCLUSION: Mixture of aerobic bacteria and P . bivia increased the pathogenicity of P . bivia . Estrogen would be useful for raising up the inflammatory change of the uterus in experimental models of genital tract infection due to P . bivia.

Clin Cardiol, 1998 Aug, 21(8), 572 - 8
Relative value of clinical and transesophageal echocardiographic variables for risk stratification in patients with infective endocarditis; Lancellotti P et al.; BACKGROUND: Infective endocarditis remains a life-threatening disease, and its optimal management is of paramount importance . Transesophageal echocardiography (TEE) is useful for the diagnosis of endocarditis-induced lesions, but the prognostic significance of the method remains controversial . HYPOTHESIS: The purpose of this study was to relate clinical and TEE characteristics to the occurrence of mortality and/or systemic embolization in a consecutive series of 45 patients with a diagnosis of infective endocarditis . METHODS: All patients underwent at least one monoplane TEE . Clinical data, episodes of embolization, and echocardiographic characteristics were prospectively recorded . Stepwise logistic discriminant analysis was performed to identify the independent variables that best predicted three binary outcomes: systemic embolization, death, and systemic embolization and/or death . RESULTS: Twelve of the 45 patients (27%) died from the endocarditis . Significant univariate predictors of death were the presence of paravalvular abscess (p = 0.025), number of vegetations (p = 0.021), Staphylococcus aureus isolated in blood cultures (p = 0.002), medical treatment alone (p < 0.002), and systemic embolism (p < 0.001) . In multivariate analysis, systemic embolism (chi 2 = 29.3; p < 0.01), echocardiographic evidence of paravalvular abscess (chi 2 = 5.6; p = 0.018), Staphylococcus aureus endocarditis (chi 2 = 5.5; p = 0.016), and medical treatment alone (chi 2 = 5.11; p = 0.024) emerged as optimal predictors of death . Systemic embolization occurred in 12 patients . Independent variables predicting systemic embolization were a total length of vegetations > 14 mm (p = 0.01), greater age (p = 0.02), and medical treatment alone (p = 0.03) . When two or more vegetations were observed, the total length is the sum of the individual sizes . Independent risk factors for the development of systemic emboli and/or death as a combined end point were total length of vegetations on TEE (chi 2 = 6.4; p = 0.003) and medical treatment alone (chi 2 = 4.1; p = 0.047) . CONCLUSIONS: High-risk patients may be identified by the combination of clinical variables and TEE characteristics.

Arch Pathol Lab Med, 1998 Aug, 122(8), 715 - 20
A method to differentiate between thyroglobulin derived from normal thyroid tissue and from thyroid carcinoma based on analysis of reactivity to lectins; Maruyama M et al.; OBJECTIVE: The composition of sugar chains on thyroglobulin (Tg) produced in thyroid carcinoma cells (C-Tg) is different from Tg produced in normal thyroid tissues (N-Tg) . In this study, we designed a new method for detecting Tg derived from thyroid carcinoma based on the differences between C-Tg and N-Tg in the reactivity with lectins . MATERIALS AND METHODS: Thyroglobulin preparations obtained from various thyroid tissues were incubated with lectins, and the amount of lectin-unbound Tg (ub-Tg) in the supernatant relative to Tg untreated with lectin was determined by enzyme-linked immunosorbent assay and expressed as ub-Tg(%) . In addition, to study further the differences in glycosylation between C-Tg and N-Tg, concanavalin A binding to Tg digested with Staphylococcus aureus V8 protease was analyzed on nitrocellulose membrane after Western blotting . RESULTS: The ub-Tg(%) in C-Tg from papillary carcinoma was significantly higher than in Tg from Graves' disease, benign goiter, and normal thyroid tissue for both concanavalin A and ricinus communis agglutinin-120 . Concanavalin A did not appear to bind to Tg from papillary carcinoma after V8 treatment by Western blot analysis . The ub-Tg(%) in Tg from follicular adenoma was significantly higher than C-Tg from follicular carcinoma, whereas there were no differences in ub-Tg(%) between follicular carcinoma and normal thyroid tissue in concanavalin A treatment . CONCLUSIONS: These results suggest our new methods can distinguish both between C-Tg from papillary carcinoma and N-Tg, and between follicular carcinoma and follicular adenoma in thyroid tissue specimens . Thus, this type of analysis may be applicable to differentiate C-Tg from N-Tg in thyroid aspirates for the adjunctive cytodiagnosis of thyroid carcinoma.

J Antimicrob Chemother, 1998 Jul, 42(1), 83 - 6
Altered membrane permeability as the basis of bactericidal action of methdilazine; Chattopadhyay D et al.; The growth inhibition of Escherichia coli and Staphylococcus aureus was accompanied by significant release of K+ and UV-absorbing small molecules upon exposure to methdilazine, an extensively used phenothiazine antihistamine . A severe decrease in {U-14C} glucose uptake and a rapid efflux of hexose from sugar-preloaded bacteria were also observed but without visible cellular lysis . Considerable damage to membrane permeability by methdilazine was proposed to explain the rapid loss in cfu/mL of the bacteria.

J Antimicrob Chemother, 1998 Jul, 42(1), 67 - 73
The independent evolution of resistance to ciprofloxacin, rifampicin, and fusidic acid in methicillin-resistant Staphylococcus aureus in Australian teaching hospitals (1990-1995) . Australian Group for Antimicrobial Resistance (AGAR); Gottlieb T et al.; Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in teaching hospitals in eastern Australian states, with prevalence rates averaging 25-30% of all S . aureus . Between 1990 and 1995, 1467 non-duplicate MRSA isolates from clinically infected sites were tested in Sydney, Melbourne, and Brisbane as part of a national survey of staphylococcal susceptibility . We reviewed the differing evolution of resistance to ciprofloxacin, rifampicin, and fusidic acid . Despite similarities in community and hospital antibiotic use and MRSA prevalence rates, trends in resistance to the oral antibiotics in these cities have progressed independently of each other . In the 1995 survey in individual hospitals in Melbourne, 16-24% of strains were ciprofloxacin-resistant, compared with 80-100% in Sydney and 30-44% in Brisbane . There was great diversity of phage type patterns for ciprofloxacin-resistant strains, suggesting heterogeneous development of resistance . Rifampicin resistance was more closely associated with distinct dominant epidemic phage types, common to institutions in the same city, but without spread to the other cites . Between 1990 and 1995, these comprised 30-60% of all MRSA in Brisbane, compared with 5-10% in Melbourne and < 25% in Sydney . Fusidic acid resistance was uncommon and sporadic (< 5%), and was distributed equally between methicillin-resistant and methicillin-susceptible strains . Resistance to the oral agents in MRSA is due to a complex mix of antibiotic selection pressures and cross-infection with local and epidemic strains in closely related institutions . Each of these mechanisms can predominate, dependent on local factors and the antibiotics used.

J Hosp Infect, 1998 Jul, 39(3), 221 - 5
Infections caused by multiple strains of methicillin-resistant Staphylococcus aureus--a pressing epidemiological issue; Wang J et al.; The genotype of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from several foci in the same patient was studied to identify the rate of infections caused by multiple MRSA strains during hospitalization . Twenty-one patients with MRSA bacteraemia and other specimens diagnosed between 1990-1994 were studied . Clinical data were retrospectively collected from the medical records . Genotyping of 113 MRSA isolates was performed by pulsed-field gel electrophoresis (PFGE), using the Gene Navigator System . More than one type of MRSA was detected from different foci in eight of 21 (38%) patients, and three types were identified in a single patient . Our results indicate that epidemiological investigations must be conducted carefully, especially in immunocompromised hosts with MRSA bacteraemia, as the probability of infection with multiple strains among these patients is relatively high.

J Hosp Infect, 1998 Jul, 39(3), 213 - 9
The effect of increased bed numbers on MRSA transmission in acute medical wards; Kibbler CC et al.; An 18-month prospective survey was performed to examine the effect of adding a fifth bed to four-bedded bays in three acute medical wards on colonization by methicillin-resistant Staphylococcus aureus (MRSA) . Screening procedures were in accordance with the UK national guidelines . All patients newly colonized with MRSA were visited, and their bed location determined . Data from the five-bedded bays were compared with those from four-bedded bays in similar wards . Potential routes of transmission were investigated by observational surveys . The relative risk of colonization in five-bedded medium dependency bays was 3.15 compared with that of similar four-bedded bays (P < 0.005), and in five-bedded low dependency bays was 3.16 (P < 0.005) . Increasing the number of beds in a fixed area heightens the risk of cross-infection with MRSA.

J Infect Dis, 1998 Aug, 178(2), 577 - 80
Methicillin-resistant Staphylococcus aureus in two child care centers; Adcock PM et al.; Methicillin-resistant Staphylococcus aureus (MRSA) has not been studied in child care centers . The prevalence of MRSA colonization was determined at two centers with an index patient . Two (3%) of 61 children at center X had MRSA; strains from both children and the index illness were pulsed-field gel electrophoresis type B . Nine (24%) of 40 children at center Y had MRSA; strains from 5 children and the index illness were type B, and strains from 4 children were type A . Ten of 11 colonized children were in classes with 2- and 3-year-old children . Colonization with MRSA was not associated with health care contact by subjects or by members of their households . MRSA in child day care centers indicates accelerated spread of MRSA in the community.

J Dermatol Sci, 1998 Jul, 17(3), 214 - 22
Roxithromycin down-modulates antigen-presenting and interleukin-1 beta-producing abilities of murine Langerhans cells; Ohshima A et al.; The immunomodulatory effect of the macrolide antibiotic, roxithromycin (RXM) on Langerhans cells (LC) was studied in mice . RXM inhibited the ability of LC to present superantigen and hapten to T cells at 100 microM . The superantigen-presenting activity of LC was more profoundly abrogated by RXM than the hapten-presenting activity . This functional reduction was partly attributed to an RXM-induced decrease in promotion of the expression of major histocompatibility complex class II molecules on LC . On the other hand, RXM down-modulated the production of interleukin-1 beta by LC at a lower concentration of 10 microM than concentrations that inhibited antigen presentation . These results imply that RXM exerts therapeutic effectiveness via not only bacteriocidal action but also inhibitory effect on the LC ability in T-cell-mediated cutaneous diseases that can be exacerbated by skin-colonized Staphylococcus aureus.

Cytometry, 1998 Jun 15, 34(3), 152 - 8
Multiparameter flow cytometric analysis of polymorphonuclear leucocytes in whole blood from patients with adult rapidly progressive periodontitis reveals low expression of the adhesion molecule L-selectin (Cd62L); Macey MG et al.; Numerous studies of polymorphonuclear leucocyte (PMN) function in patients with adult periodontitis, including rapidly progressive periodontitis, have yielded conflicting findings, perhaps because most of the assays were performed on PMNs that had been separated from whole blood by a variety of procedures . To avoid the problems associated with in vitro analysis of isolated cells, PMN function and antigen expression in live whole unmanipulated blood of eight patients with rapidly progressive periodontitis were compared with those of age-, race-, and sex-matched controls . Using multiparameter flow cytometry, a) L-selectin (CD62L) expression, b) cell size, and c) respiratory burst activity were measured in PMNs in whole blood immediately ex vivo and during incubation with Porphyromonas gingivalis and Staphylococcus aureus . By comparison with PMNs from the control group, PMNs from the patient group expressed significantly lower levels of CD62L and had an increased size before stimulation . PMNs from both groups produced respiratory bursts similar to those of the two bacteria, but in both groups the responses to S . aureus were significantly greater than those to P . gingivalis . The significantly reduced expression of the adhesion molecule CD62L on PMNs in the patient group may lead to reduced tethering of neutrophils at sites of inflammation and may partly explain the susceptibility of these individuals to recurrent and severe periodontal infections.

J Bacteriol, 1998 Aug, 180(16), 4024 - 9
Molecular characterization of a chromosomal determinant conferring resistance to zinc and cobalt ions in Staphylococcus aureus; Xiong A et al.; A DNA fragment conferring resistance to zinc and cobalt ions was isolated from a genomic DNA library of Staphylococcus aureus RN450 . The DNA sequence analysis revealed two consecutive open reading frames, designated zntR and zntA . The predicted ZntR and ZntA showed significant homology to members of ArsR and cation diffusion families, respectively . A mutant strain containing the null allele of zntA was more sensitive to zinc and cobalt ions than was the parent strain . The metal-sensitive phenotype of the mutant was complemented by a 2.9-kb DNA fragment containing zntR and zntA . An S . aureus strain harboring multiple copies of zntR and zntA showed an increased resistance to zinc . The resistance to zinc in the wild-type strain was inducible . Transcriptional analysis indicated that zntR and zntA genes were cotranscribed . The zinc uptake studies suggested that the zntA product was involved in the export of zinc ions out of cells.

Eur J Surg, 1998 Jun, 164(6), 411 - 8
Methicillin-resistant Staphylococcus aureus: acquisition and risk of death in patients in the intensive care unit; Ibelings MM et al.; OBJECTIVE: To evaluate the risk of patients in intensive care units (ICU) of becoming infected with methicillin-resistant Staphylococcus aureus (MRSA) and to assess the mortality during a six week follow-up period, compared with patients who developed methicillin-sensitive S . aureus (MSSA) infection . DESIGN: Point prevalence survey . SETTING: 1417 ICU in 17 Western European countries . SUBJECTS: 10038 patients in ICU who were part in the EPIC (European Prevalence of Infection in Intensive Care) Study . MAIN OUTCOME MEASURES: Prevalence of MRSA and MSSA ICU-acquired infections, risk factors, and mortality . RESULTS: On the study day 21% of patients had ICU-acquired infections . The most commonly reported pathogen was Staphylococcus aureus (30%) . Overall, 60% of strains of S . aureus were resistant to methicillin (with a wide intercountry variation) . The most commonly reported MRSA infections were pneumonia and lower respiratory tract infections . The most important risk factor for MRSA was the length of stay in the ICU . MRSA infection reduced the chance of survival, particularly when it was found in lower respiratory tract infections: the risk of mortality was three times higher in patients with MRSA than in those with MSSA . CONCLUSION: Patients in ICU are at high risk of becoming infected with MRSA . The longer they stay, the higher the risk . Patients with MRSA infections are less likely to survive than those with MSSA.

Microbiology, 1998 Jul, 144 ( Pt 7), 1755 - 63
Starvation recovery of Staphylococcus aureus 8325-4; Clements MO et al.; Nutrient limitation of Staphylococcus aureus induces a starvation-survival state which enables it to survive until sufficient nutrients become available to support growth . The response of starved S . aureus cells to nutritional upshift was analysed to characterize the recovery mechanism which results in the resumption of rapid growth . S . aureus 8325-4 starved for 7 d in a chemically defined medium limited for glucose was able to resume growth upon the addition of complex medium (brain heart infusion broth) or a mixture of amino acids and glucose . The addition of either glucose or amino acids alone did not lead to recovery of cells . Prior to the first cell division event, a lag period of about 120-150 min was observed, the duration of which was independent of the length of starvation survival . During this lag period, RNA synthesis increased immediately upon the addition of nutrients whilst protein synthesis was delayed by approximately 5 min . Cells rapidly enlarged within 30 min of recovery, and initiation of chromosome replication could be detected after 90 min . Changes in the profile of proteins expressed during the recovery period revealed that several starvation-specific proteins were down-regulated within 30 min, whilst other proteins were common to both starvation and recovery . Two proteins were identified which were only transiently expressed during the first 60 min of recovery . Protein synthesis could be detected during recovery even if the cells had been treated with the RNA synthesis inhibitor rifampicin for 30 min prior to the addition of recovery nutrients, demonstrating that several proteins are translated from long-lived mRNA transcripts present in starved cells.

N Z Med J, 1998 Jul 10, 111(1069), 251 - 3
Staphylococcal neonatal necrotising fasciitis: survival without radical debridement; Chen JW et al.; Necrotising fasciitis is a serious infection associated with high morbidity and mortality . The conventional treatment is radical resection of the involved area with antibiotic as well as intensive supportive therapy . We describe a case of extensive truncal necrotising fasciitis in a neonate, secondary to Staphylococcus aureus infection successfully treated with intensive antibiotic therapy and multi-organ support, followed by fasciotomies, drainage and betadine irrigation . The successful outcome without radical resection could be due to the viability of superficial skin, S aureus as the causative organism and the excellent blood supply of cutaneous neonatal tissue.

Nippon Ishinkin Gakkai Zasshi, 1998, 39(3), 147 - 50
{Structure of the bacterial cell wall}; Umeda A et al.; The fine structure of the cell walls of Gram-positive and -negative bacteria were determined by electron microscopy with the new technique of freeze substitution method, and analysed the cell wall structure of Staphylococcus aureus in detail . The surface of Staphylococcal cell wall was covered with a fuzzy coat consisting of fine fibers or electron-dence mass . This coat was completely removed after extraction of teichoic acid from the cell wall with trichloroacetic acid treatment, but was not affected by sodium dodecyl sulfate or trypsin treatment . It was suggested that many amount of teichoic acid was located on the surface of the cell wall and less inside the cell wall . The capsule of strain Smith diffuse was assumed to play the role as the barrier protected from the penetration of antibody against teichoic acid.

Biochemistry, 1998 Jul 28, 37(30), 10635 - 42
Nuclear magnetic resonance solution structure of the plasminogen-activator protein staphylokinase; Ohlenschlager O et al.; Staphylokinase, a 15.5 kDa protein from Staphylococcus aureus, is a plasminogen activator which is currently undergoing clinical trials for the therapy of myocardial infarction and peripheral thrombosis . The three-dimensional (3D) NMR solution structure has been determined by multidimensional heteronuclear NMR spectroscopy on uniformly 15N- and 15N,13C-labeled samples of staphylokinase . Structural constraints were obtained from 82 3JHNH alpha as well as 22 3JNH beta scalar coupling constants and 2345 NOE cross-peaks, derived from 15N-edited and 13C-edited 3D NOE spectra . NOE cross-peak assignments were confirmed by analysis of inverted question mark15N,13C inverted question mark-edited and inverted question mark13C,13C inverted question mark-edited 4D NOE spectra . The structure is presented as a family of 20 conformers which show an average rmsd of 1.02 +/- 0.15 A from the mean structure for the backbone atoms . The tertiary structure of staphylokinase shows a well-defined global structure consisting of a central 13-residue alpha-helix flanked by a two-stranded beta-sheet, both of which are located above a five-stranded beta-sheet . Two of the connecting loops exhibit a higher conformational heterogeneity . Overall, staphylokinase shows a strong asymmetry of hydrophilic and hydrophobic surfaces . The N-terminal sequence, including Lys10 which is the site of the initial proteolytic cleavage during activation of plasminogen, folds back onto the protein core, thereby shielding amino acids with functional importance in the plasminogen activation process . From a comparison of the structure with mutational studies, a binding region for plasminogen is proposed.

Eur J Biochem, 1998 Jul 1, 255(1), 107 - 15
Disulphide bonds assignment in the inter-alpha-inhibitor heavy chains--structural and functional implications; Flahaut C et al.; Human inter-alpha-inhibitor (IalphaI) is a plasma serine-proteinase inhibitor . It consists of three polypeptide chains covalently linked by a glycosaminoglycan: a light one named bikunin, carrying the antiproteinase activity and two heavy chains H1 and H2 . The amino acid sequences of these heavy chains are highly similar; however when IalphaI is digested by neutrophil proteinases, their proteolytic susceptibility strongly differs {Balduyck, M., Piva, F., Mizon, C., Maes, P., Malki, N., Gressier, B., Michalski, C . & Mizon, J . (1993) Human leucocyte elastase (HLE) preferentially cleaves the heavy chain H2 of inter-alpha-trypsin inhibitor (ITI), Biol . Chem . Hoppe-Seyler 374, 895-901} . We mapped the disulphide topology of the IalphaI heavy chains in order to investigate whether or not disulphide bonds might be responsible for their differential susceptibility to proteolysis . Using amino acid sequencing and mass spectrometry analysis, we demonstrate that the H1 heavy chain contains one free thiol group and two disulphide bridges of which one links two largely spaced cysteine residues (Cys239 and Cys511) . Thus H1 is clearly different from H2 which contains two disulphide bonds between closely located cysteine residues . However, using immunoprint analysis, we show that, when IalphaI is subjected to a limited digestion by Staphylococcus aureus V-8 proteinase, the two polypeptide chains are similarly susceptible to proteolysis . This enzyme preferentially cleaves the IalphaI heavy chains from their N-terminal extremity . These results are consistent with the circular dichroism (CD) analysis, suggesting that the conformation of the polypeptide backbone of H1 is not very different from that of H2, with calculated alpha-helicities of 24% and 28%, respectively . The CD measurements reveal that the aromatic amino acids of H1 and H2 are in a different asymmetrical environment . Inside the IalphaI molecule, the heavy chains are linked to the glycosaminoglycan chain via their C-terminal aspartic acid residue . Thus we suggest that the affinity of cationic neutrophil proteinases for the anionic glycosaminoglycan is responsible for the cleavage of the heavy chains (mainly H2) near their C-terminal end and the high susceptibility of IalphaI to these proteinases.

Neuroscience, 1998 Sep, 86(1), 79 - 97
Possible involvement of activator protein-1 DNA binding in mechanisms underlying ischemic tolerance in the CA1 subfield of gerbil hippocampus; Yoneda Y et al.; Transcription factors are nuclear proteins with an ability to recognize particular nucleotide sequences on double stranded genomic DNAs and thereby modulate the activity of RNA polymerase II which is responsible for the formation of messenger RNAs in cell nuclei . Gel retardation electrophoresis revealed that transient forebrain ischemia for 5 min led to drastic potentiation of binding of a radiolabelled double-stranded oligonucleotide probe for the transcription factor activator protein-1, in the thalamus as well as the CA1 and CA3 subfields and the dentate gyrus of the hippocampus of the gerbils previously given ischemia for 2 min two days before, which is known to induce tolerance to subsequent severe ischemia in the CA1 subfield . By contrast, ischemia for 5 min resulted in prolonged potentiation of activator protein-1 binding in the vulnerable CA1 subfield of the gerbils with prior ischemia for 5 min 14 days before, which is shown to induce delayed death of the pyramidal neurons exclusively in this subfield . Similar prolongation was seen with activator protein-1 binding in the vulnerable thalamus but not in the resistant CA3 subfield and dentate gyrus of the gerbils with such repeated ischemia for 5 min . Limited proteolysis by Staphylococcus aureus V8 protease as well as supershift assays using antibodies against c-Fos and c-Jun proteins demonstrated the possible difference in constructive partner proteins of activator protein-1 among nuclear extracts of the CA1 subfield obtained from gerbils with single, tolerated and repeated ischemia . These results suggest that de novo protein synthesis may underlie molecular mechanisms associated with acquisition of the ischemic tolerance through modulation at the level of gene transcription by activator protein-1 composed of different constructive partner proteins in the CA1 subfield . Possible participation of glial cells in the modulation is also suggested in particular situations.

Epidemiol Infect, 1998 Jun, 120(3), 271 - 9
Analysis of methicillin-resistant Staphylococcus aureus by IS1181 profiling; Symms C et al.; Variation in the genomic location and copy number of the insertion element IS1181 in methicillin-resistant Staphylococcus aureus (MRSA) was investigated . Sixty-three isolates representing the Jevons type strain (NCTC 10442), phage-propagating strains, and epidemic strains were examined . A PCR amplicon of the insertion element was used to probe genomic restriction endonuclease digests . HindIII genomic digests gave 25 distinct IS1181 patterns, while EcoRI digests gave 20 patterns . EMRSA-01, -02, -04, -06, -07, -09, -10, -11, -13 and -14 contained the element but could not be subtyped by profiling it . EMRSA-16 did not contain IS1181, consistent with a unique evolutionary origin for this major UK epidemic strain . Marked heterogeneity was observed among isolates of EMRSA-03 . Each EMRSA-03 strain examined gave a unique pattern, thereby allowing subtyping of an important epidemic phage type for the purposes of hospital cross-infection control.

Res Vet Sci, 1998 May-Jun, 64(3), 267 - 70
Characterisation of duck thrombocytes; Bertram EM et al.; Duck thrombocytes were initially identified in peripheral blood mononuclear cells (PBMCs) purified from whole blood on Ficoll-Paque density gradients by examining stained smears of these cells . These thrombocytes could be readily purified from lymphocytes on the FACStar cell sorter by their increased side-scatter . They were similar to chicken thrombocytes in both appearance and function; they had a diameter of 4.5-6 microm and contained large vacuoles and were able to phagocytose carbon and Staphylococcus aureus . A monoclonal antibody (mAb) BA3 was generated which binds specifically to duck thrombocytes and has facilitated the characterisation of these cells which comprise up to 50-60 per cent of cells in Ficoll-Paque purified duck PBMCs.

Acta Anaesthesiol Scand, 1998 Jul, 42(6), 614 - 20
Epidural abscess complicating epidural anesthesia and analgesia . An analysis of the literature; Kindler CH et al.; BACKGROUND: Epidural abscess is a serious complication of epidural block . Because of its low incidence, the risk factors and the symptoms and cause of epidural abscess related to epidural anesthesia and analgesia are not well known by anesthesiologists . METHODS: A computer-assisted search of the literature on epidural catheter-related abscess was performed to describe the clinical course and bacteriology of this complication, to determine possible risk factors, and to assess the index of suspicion among physicians . RESULTS: Forty-two patients with a catheter-related epidural abscess were identified . Only in 15 patients was the correct diagnosis considered initially . The time from insertion of the epidural catheter to symptoms varied between 1 and 60 d . Initial symptoms included back pain, fever, and leukocytosis . The time from symptoms to treatment was a few hours to 108 d . Interval from first symptoms to treatment was significantly longer in patients with persistent neurologic deficits compared with patients who completely recovered . Staphylococcus aureus was the most common etiologic agent . Outcome was reported in 39 patients, but only 19 made a full recovery . CONCLUSION: The index of suspicion among anesthesiologists, other physicians and nurses taking care of patients with epidural catheters must be increased for this complication; this should shorten the interval from symptoms to treatment and lower the incidence of neurological sequelae.

FEBS Lett, 1998 Jul 3, 430(3), 283 - 7
Purification, crystallization and preliminary X-ray diffraction studies of the bacteriophage phi29 connector particle; Guasch A et al.; The connector or portal particle from double-stranded DNA bacteriophage phi29 has been crystallized . This structure, which connects the head of the virus with the tail and plays a central role in prohead assembly and DNA packaging and translocation, is formed by 12 subunits of the p10 protein and has a molecular weight of 430 kDa . The connector structure was proteolysed with endoproteinase Glu-C from Staphylococcus aureus V8, which removes 13 and 18 amino acids from the amino- and carboxy-terminal regions of the p10 protein, respectively . Two crystal forms were grown from drops containing an alcohol solution and paraffin oil . Crystals of form I are monoclinic, space group C2 with cell dimensions a = 416.86 A, b = 227.62 A, c = 236.68 A and beta = 96.3 degrees and contain four connector particles per asymmetric unit . Crystals of form II are tetragonal, space group P4(2)2(1)2 with cell dimensions a = b = 170.2 A, c = 156.9 A and contain half a particle per asymmetric unit . X-ray diffraction data from both native crystal forms have been collected to 6.0 and 3.2 A respectively, using synchrotron radiation . Crystals of form II are likely to have the same packing arrangement as the two-dimensional crystals analyzed previously by electron microscopy.

Int J Gynaecol Obstet, 1998 Jun, 61(3), 245 - 51
Systemic antibiotic prophylaxis in elective cesarean delivery; Rizk DE et al.; OBJECTIVE: To test the value of using prophylactic antibiotics at elective cesarean delivery . METHOD: One-hundred and twenty women delivered by elective cesarean in the absence of labor and before the rupture of membranes were randomized to receive either 1.5 g of cefuroxime intravenously at cord clamping (n = 59) or no prophylaxis (control group, n = 61) . RESULTS: Twelve women developed febrile morbidity (six study, six control, P = 0.09) . Of these, five had endometritis (two study, three control, P = 0.09) and two had wound infection (one study, one control, P = 0.09) . Ten more women had microbiological evidence of endometritis and wound infection (six study, four control, P = 0.08) . There was no significant difference in the hospital stay (6.5 days study, 6.8 days control, P = 0.06) . Staphylococcus aureus was the commonest pathogen accounting for 14 infection episodes . Amniotic fluid culture could not predict the development of infection . CONCLUSION: Administration of prophylactic antibiotics at elective cesarean deliveries was not associated with decreased postoperative morbidity.

Burns, 1998 Jun, 24(4), 369 - 73
Acute bacterial endocarditis following burns: case report and review; Cartotto RC et al.; Acute bacterial endocarditis (ABE) is a rare but deadly complication following major thermal injury . Typically the presentation is silent, with persistent fever and positive blood cultures being the only consistent findings . Fibrin-platelet vegetations on the valvular endocardium are thought to be seeded during bacteremic episodes . Manipulation of the burn wound is probably the most likely source of bacteremia, with Staphylococcus aureus and Gram-negative bacilli being the most commonly implicated bacteria . In addition to causing local damage to a valve or the myocardium, infected vegetations may dislodge septic emboli systemically . Diagnosis is most easily obtained by echocardiography . Treatment usually involves prolonged administration of intravenous antibiotics . In rare circumstances, valvular resection and replacement may be indicated.

Antimicrob Agents Chemother, 1998 Aug, 42(8), 2122 - 4
Topoisomerase mutations in trovafloxacin-resistant Staphylococcus aureus; Fitzgibbon JE et al.; A total of 201 Staphylococcus aureus isolates were surveyed for susceptibility to ciprofloxacin and trovafloxacin . Of 66 methicillin-resistant isolates, 89% were ciprofloxacin resistant and 6% were also trovafloxacin resistant . Trovafloxacin-resistant strains had unusual patterns of quinoline resistance mutations in DNA topoisomerase genes, including two mutations in the A subunit (encoded by grlA) of topoisomerase IV.

Antimicrob Agents Chemother, 1998 Aug, 42(8), 2109 - 12
Effects of mutations in GrlA of topoisomerase IV from Staphylococcus aureus on quinolone and coumarin activity; Fournier B et al.; The grlA genes of Staphylococcus aureus ISP794 (wild type), MT5224c4 (grlA {Phe-80}), MT5224c2 (grlA {Pro-116}), and MT111 (grlA {Glu-116}) were cloned in pSK950, a shuttle vector, and introduced into S . aureus strains derived from strain RN4220 . The mutations at position 116 of GrlA (Ala-->Pro or Glu) caused an increase in the level of fluoroquinolone resistance and a decrease in the level of coumarin susceptibility, whereas the mutation at position 80 (Ser-->Phe) caused only an increase in the level of fluoroquinolone resistance . In multicopy alleles, both types of mutations were codominant for fluoroquinolone resistance, and mutations at position 116 were also codominant for coumarin resistance.

Antimicrob Agents Chemother, 1998 Aug, 42(8), 1917 - 22
Antibacterial activity of gatifloxacin (AM-1155, CG5501, BMS-206584), a newly developed fluoroquinolone, against sequentially acquired quinolone-resistant mutants and the norA transformant of Staphylococcus aureus; Fukuda H et al.; Alternate mutations in the grlA and gyrA genes were observed through the first- to fourth-step mutants which were obtained from four Staphylococcus aureus strains by sequential selection with several fluoroquinolones . The increases in the MICs of gatifloxacin accompanying those mutational steps suggest that primary targets of gatifloxacin in the wild type and the first-, second-, and third-step mutants are wild-type topoisomerase IV (topo IV), wild-type DNA gyrase, singly mutated topo IV, and singly mutated DNA gyrase, respectively . Gatifloxacin had activity equal to that of tosufloxacin and activity more potent than those of norfloxacin, ofloxacin, ciprofloxacin, and sparfloxacin against the second-step mutants (grlA gyrA; gatifloxacin MIC range, 1.56 to 3.13 microg/ml) and had the most potent activity against the third-step mutants (grlA gyrA grlA; gatifloxacin MIC range, 1.56 to 6.25 microg/ml), suggesting that gatifloxacin possesses the most potent inhibitory activity against singly mutated topo IV and singly mutated DNA gyrase among the quinolones tested . Moreover, gatifloxacin selected resistant mutants from wild-type and the second-step mutants at a low frequency . Gatifloxacin possessed potent activity (MIC, 0.39 microg/ml) against the NorA-overproducing strain S . aureus NY12, the norA transformant, which was slightly lower than that against the parent strain SA113 . The increases in the MICs of the quinolones tested against NY12 were negatively correlated with the hydrophobicity of the quinolones (correlation coefficient, -0.93; P < 0.01) . Therefore, this slight decrease in the activity of gatifloxacin is attributable to its high hydrophobicity . Those properties of gatifloxacin likely explain its good activity against quinolone-resistant clinical isolates of S . aureus harboring the grlA, gyrA, and/or norA mutations.

J Oral Rehabil, 1998 Jun, 25(6), 403 - 8
Bacterial leakage into and from prefabricated screw-retained implant-borne crowns in vitro; Guindy JS et al.; A mean gap of less than 4 microm following laboratory procedures and continuous loading was demonstrated in prefabricated crowns of the Ha-Ti implant system in earlier studies . The clinical relevance of such high precision in maintaining inflammation free marginal mucosa is yet to be determined . In this present investigation, the complete assembly of Ha-Ti implants including prefabricated screw-retained crowns was tested for bacterial leakage under controlled conditions in vitro . The gaps were shown not to be a barrier for Staphylococcus aureus which were used as test bacteria . Bacterial leakage through these gaps from the environment to the interior of the assembly and vice versa was observed within 24-120 h . The main path of bacterial penetration was possibly found to be through the transversal screw hole and not through the marginal gap of the prefabricated crowns.

Adv Ren Replace Ther, 1998 Jul, 5(3), 157 - 67
Sclerosing peritonitis in continuous ambulatory peritoneal dialysis patients: one center's experience and review of the literature; Afthentopoulos IE et al.; Sclerosing peritonitis (SP) is a severe life-threatening condition for patients undergoing continuous ambulatory peritoneal dialysis (CAPD) . This report reviews our experience and that reported in the literature concerning the prevalence of SP in CAPD patients, predisposing factors, and in particular, the role of peritonitis, its clinical presentation, diagnosis, treatment, and prevention . A total of 1,288 end-stage renal disease (ESRD) patients entered our peritoneal dialysis (PD) program between September 1977 and September 1997, seven of whom (0.54%) developed SP . The annual incidence of SP was 0.37 per 1,000 patient years, male-to-female ratio was 2.5 (M/F:5/2), mean age was 39+/-16 (median, 37; range, 23 to 61) years, and the median duration on CAPD was 62 (range, 12 to 144) months . Five patients were on CAPD for > or =4 years and two for less than 4 years before they were diagnosed with SP . All SP patients presented with clinical symptoms suggestive of intestinal obstruction, and five patients had decreased solute or fluid removal and had to increase the daily dialysate volume (3/7) or the tonicity of the fluid (4.25%) (3/7) or to combine a regular hemodialysis (HD) session with CAPD (2/7) . There was a mean weight loss of 5+/-6 (median, 2; range, 0 to 18) kg . All patients had an episode of peritonitis at a mean time of 2+/-1 (median, 1; range, 1 to 3) months before the diagnosis of SP . The peritonitis was due to Staphylococcus aureus in four and Staphylococcus epidermidis, fungi, and Escherichia coli in one each . The definitive diagnosis of SP was established by laparotomy in four patients or postmortem examination in one patient, while in the remaining two there was no surgical confirmation; however, we believe the diagnosis was extremely likely because of the presence of clinical and radiologic criteria for SP . After the diagnosis of SP, all patients had their catheters removed, CAPD was discontinued permanently, and they were transferred to HD . Although there are isolated case reports of successful outcomes after surgical intervention, especially in patients in whom a peritoneal "cocoon" is related to severe peritonitis, usually the prognosis following surgery is poor . Treatment with immunosuppressive agents has been reported to be beneficial in the treatment of SP, although this has not been confirmed by all investigators . Among our SP patients, five (72%) died of sepsis (3/5) in a mean period of 10+/-5 (median, 9; range, 6 to 17) months after the diagnosis of SP and two are still alive on HD . SP is a rare but serious complication of CAPD . Severe peritonitis, especially in patients on dialysis for more than 4 years, may lead to SP As the prevalence of SP increases in patients on long-term CAPD, early detection is important because of the high morbidity and mortality associated with this condition.

Rev Cubana Med Trop, 1997, 49(2), 125 - 9
{Identification of mosquitoes' human food source by using the co-agglutination technique}; Castex M et al.; The utilization of a coagglutination technique for the identification of a human source for feeding mosquitoes is described . The dilution of ingested blood samples in filter paper was performed in 2 mL of a sodium chloride solution at 0.85% . It was used a suspension of sensibilized Staphylococcus aureus with rabbit's serum, human plasmatic anti-proteins, and human anti-IgG rabbit's serum discriminated well between human and non human blood . No agglutination was observed with the negative control . This technique proved to be sensitive to identify 100% of the human blood samples taken to the paper 24 hours after the mosquitoes completed their feeding at a temperature of 26 to 28 degrees C . Among mosquitoes fed and collected in the fields the test had a satisfactory result . Therefore, it may be used in routine work in the fields . The results showed the sensitivity and specificity of this method for identifying human blood ingested by mosquitoes.

Am J Med, 1998 May 29, 104(5A), 24S - 33S
Clinical implications of nosocomial gram-positive bacteremia and superimposed antimicrobial resistance; Linden PK; The coexistence of a pathogen population with an ever-increasing resistance to many antibiotics and a patient population characterized by increasingly complex clinical problems has contributed to an increase in the bloodstream infections associated with gram-positive bacteria . This serious therapeutic challenge has already been associated with an increase in infection-related morbidity and mortality, a prolongation of hospital stays, and an escalation of healthcare costs . Vancomycin resistance, long prevalent among the enterococci, has emerged in strains of Staphylococcus aureus . Several cases of infection caused by S . aureus strains with intermediate-level resistance to vancomycin (MIC=8 microg/mL) have recently been reported . As glycopeptide resistance accelerates among the gram-positive bacteria, so does the potential for adverse clinical consequences associated with bloodstream infections caused by these pathogens . The patients least able to tolerate the effects of uncontrolled bloodstream infections are also those at the highest risk for the development of infections caused by glycopeptide-resistant pathogens . In this at-risk population, a poor outcome may be anticipated if effective antibiotic therapy is unavailable . Appropriate rationing of vancomycin and other antimicrobial agents that increase the selection of antibiotic-resistant strains of gram-positive bacteria and the rapid development of novel antimicrobial agents with reliable gram-positive activity must be immediate priorities if the threat posed by glycopeptide-resistant gram-positive pathogens is to be countered.

Am J Med, 1998 May 29, 104(5A), 17S - 23S
Hospital-acquired pneumonia: methicillin resistance and intensive care unit admission; Fagon JY et al.; Although epidemiologic investigations of hospital-acquired pneumonia have certain intrinsic limitations because of the heterogeneity of the study populations, the difficulties in making a clinical diagnosis of nosocomial pneumonia, and the need for better microbiologic assays, recent studies have provided new and important data concerning the role of Staphylococcus aureus in this disease . This pathogen has now been identified as the most frequent cause of nosocomial pneumonia in hospitals in both Europe and the United States among patients in general hospital units as well as in the intensive care unit (ICU) . Patients who have been treated with mechanical ventilation are at especially high risk for S . aureus pneumonia . The incidence of nosocomial pneumonia related to methicillin-resistant S . aureus (MRSA) has increased in recent years in many countries, especially among patients in the ICU . Because hospitalized patients with suspected nosocomial pneumonia often have many risk factors for MRSA infection, it seems advisable to include coverage of MRSA in the initial therapeutic regimen for these patients until MRSA infection is excluded.

Am J Med, 1998 May 29, 104(5A), 11S - 16S
Postoperative infections in the age of drug-resistant gram-positive bacteria; Nichols RL; Postoperative infection is a significant cause of surgical morbidity and mortality . The risk of infection after surgery depends on a number of factors, including the type and length of the surgical procedure; the age, underlying conditions, and previous history of the patient; the skill of the surgeon; the diligence with which infection control procedures are applied; and the type and timing of preoperative antibiotic prophylaxis . Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, now implicated in many postoperative infections, have been joined most recently by strains of S . aureus that show intermediate levels of resistance to vancomycin . Postoperative infections caused by drug-resistant pathogens are more difficult to treat and are associated with a higher morbidity and mortality . New antibiotics that are effective against drug-resistant pathogens are urgently needed, as is renewed dedication to the prevention of postoperative infection and to the use of the principles of infection control.

Am J Med, 1998 May 29, 104(5A), 7S - 10S
The emergence of Staphylococcus aureus with reduced susceptibility to vancomycin in Japan; Hiramatsu K; Within the past year, infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains with reduced susceptibility to vancomycin (MIC=8 microg/mL) have been reported in both Japan and the United States . The emergence of these strains poses a potentially serious threat to public health . After 2 such strains (Mu3 and Mu50) were identified at Juntendo Hospital in 1996, a screening program to identify MRSA strains with reduced susceptibility to vancomycin was initiated . Of 970 MRSA strains tested at 195 nonuniversity hospitals throughout Japan, 13 (1.3%) were found to have subpopulations with reduced vancomycin susceptibility (heterogeneous vancomycin resistance) . Among 129 MRSA strains identified at 7 university hospitals, 12 (9.3%) demonstrated heterogeneity for vancomycin resistance; 1 of these strains had a vancomycin MIC of 7 microg/mL . Although resistance in these strains is not the result of the transfer of enterococcal vancomycin resistance genes (vanA or vanB), the clonal dissemination of MRSA strains with vancomycin-resistant subpopulations is obviously undesirable . Intensified testing of MRSA strains for resistance to vancomycin and appropriate measures for the prevention of the spread of such strains are recommended.

Am J Trop Med Hyg, 1998 Jul, 59(1), 42 - 4
Pyomyositis associated with Bacteroides fragilis in a patient with multiple myeloma; Matsuno O et al.; Pyomyositis is an infection of the skeletal muscle that is usually caused by Staphylococcus aureus . We report a 68-year-old Japanese woman who developed pyomyositis caused by Bacteroides fragilis following treatment for multiple myeloma . There are only two cases of pyomyositis associated with multiple myeloma in the literature . After receiving melphalan and prednisolone for five days, she developed multiple abscesses in the muscles of the right arm and thigh . Purulent exudate was aspirated from the abscess, and B . fragilis was identified . This is the first case of B . fragilis pyomyositis . Magnetic resonance imaging aided the diagnosis . Treatment consisted of surgical incision and drainage, with antibiotic administration . The immunosuppression caused by the myeloma and/or the chemotherapy presented a risk factor for the unusual infection observed in this patient.

Eye, 1998, 12 ( Pt 2), 252 - 5
Intravitreal penetration of teicoplanin; Briggs MC et al.; Teicoplanin is a glycopeptide antibiotic, similar to vancomycin, but safer and better tolerated . The purpose of this study was to evaluate the penetration of teicoplanin into the vitreous when administered topically and intravenously . Twenty-five patients undergoing routine vitrectomy were recruited . Twenty were given intravenous teicoplanin: five 1 h pre-operatively, five 12 h pre-operatively, five 24 h pre-operatively and five 24 h as well as 48 h pre-operatively . Five received teicoplanin drops half-hourly for the 6 h immediately preceding vitrectomy . Undiluted vitreous specimens were obtained at the beginning of each vitrectomy procedure . Teicoplanin levels were measured using a biological assay with Staphylococcus aureus as the indicator organism . Teicoplanin activity was detected in 8 of the 20 specimens from those patients receiving the intravenous antibiotic . Teicoplanin did not penetrate readily into the vitreous cavities in these eyes despite the blood-ocular barrier being compromised in some patients, although there was evidence of accumulation with time . No activity was detected in the vitreous of those patients who received topical teicoplanin.

J Orthop Sci, 1998, 3(3), 163 - 8
Vancomycin-impregnated polymethylmethacrylate beads for methicillin-resistant Staphylococcus aureus (MRSA) infection: report of two cases; Ozaki T et al.; Two patients with methicillin-resistant Staphylococcus aureus (MRSA) infection were treated with vancomycin (VCM)-impregnated polymethylmethacrylate (PMMA) beads . One patient, who had a history of polycystic kidney and diabetes mellitus, who was receiving hemodialysis due because of non-functional kidney, underwent resection of an intermediate grade chondrosarcoma in the pelvis . MRSA infection developed and curettage of the lesion was performed, but MRSA infection recurred . During the second revision surgery, VCM-impregnated PMMA beads were implanted . MRSA infection has not recurred for 16 months since the implantation of the VCM beads . The second patient had a history of total hip arthroplasty (THA) performed because of coxarthrosis . After the initial surgery, MRSA infection developed, recurring after the second revision surgery for THA . After curettage following removal of the prosthesis, VCM beads were implanted with a spacer composed of VCM-PMMA and a Luque rod . Infection did not recur and THA revision was performed 3 months after the VCM beads implantation . Fifteen months after the last revision surgery, infection has not recurred.

Arch Microbiol, 1998 Sep, 170(3), 171 - 8
Teichoic acid content in different lineages of Staphylococcus aureus NCTC8325; Jenni R et al.; A series of mec transformants of Staphylococcus aureus strain NCTC8325 were analysed for alterations in wall teichoic acid and lipoteichoic acid . Although the methicillin resistance determinant alters the autolytic behaviour of S . aureus, it had no effects on the cellular content, chain length, and alanine substitution of the lipoteichoic acid, or on the wall teichoic acid content and composition . However, independently of the presence or absence of the methicillin resistance determinant, level of methicillin resistance, or autolytic behaviour, a correlation was found between a 25% reduced cell wall phosphate content and either loss of prophages phi11 and 13 or a 30-kb deletion in the chomosmal SmaI-F fragment adjacent to the prophage φ11 attachment site.

J Bacteriol, 1998 Aug, 180(15), 3828 - 36
Transcriptional analysis of different promoters in the sar locus in Staphylococcus aureus; Manna AC et al.; The expression of extracellular virulence determinants in Staphylococcus aureus is controlled by a 510-nucleotide RNA molecule (RNAIII) which is a part of the agr system . The agr operon, which encodes a multicomponent signal transduction system, is partially under the influence of an unlinked regulatory locus called sar . The sar locus is composed of three overlapping transcripts, designated sarA (0.56 kb), sarC (0.8 kb), and sarB (1.2 kb), originating from the P1, P3, and P2 promoters, respectively . In this study, we analyzed the differential expression of these promoters by using transcriptional fusion with the xylE reporter gene to study the activation of the sar locus . The data confirm the existence of three independent promoters with different promoter activities . Maximal promoter activity was observed with the combined fusion of P2-P3-P1 promoters . Expression studies with a sigB mutant revealed that the P3 promoter is SigB dependent . Analysis of these transcriptional fusions in a sarA mutant and in complemented strains with each of the sar transcriptional units revealed that the sar locus is autoregulatory, with SarA acting as a positive regulator . From various transcriptional fusion studies of the upstream region of the P1 promoter, we have localized a 34-bp sequence which seems to play a role in down-modulating P1 transcription . Using heparin-Sepharose and DNA-specific columns, we partially purified a 12-kDa protein, possibly a repressor, which binds to the promoter regions upstream of P2 and P1 and which also binds to the 34-bp sequence . These data indicated that the regulation of the sar locus is complex and may involve the sar gene product(s) and other regulatory protein(s).

Blood Purif, 1998, 16(3), 171 - 8
Effect of prolonged subcutaneous implantation of peritoneal catheter on peritonitis rate during CAPD: a prospective randomized study; Park MS et al.; We conducted a prospective randomized controlled study to confirm our earlier observation that prolonged subcutaneous implantation of peritoneal catheter reduced peritonitis rate when compared to retrospective data from patients with catheters placed by conventional access technique . A total of 60 patients were randomized into two groups: 30 patients had catheters left implanted subcutaneously for 6 weeks (I) and the other 30 patients had catheters inserted by conventional technique and had 6 weeks of break-in period (C) . Subgroups of 15 patients each with new and conventional techniques used Y-connector (IY, CY) and remaining patients used standard spikes (IS, CS) . Mean age was 47.7 years (range 16-71); 61.0% were male and 44.1% diabetics . Peritonitis, exit site infection, simultaneous peritonitis and exit site infection, and complication related to Staphylococcus or Pseudomonas infections were observed for up to 2 years in each patient after initiation of bag exchange or until termination of CAPD by transfer to hemodialysis or by death . Total duration of observation was 493.2 patient-months for new access technique and 409.6 patient-months for conventional technique . Patients in IY group had the lowest incidence of peritonitis (1/14.9 patient-months) and exit site infection (1/16.8 patient-months) among four subgroups . Peritonitis rate in IY was significantly lower compared to CY or CS . The total peritonitis-free period in those patients who did not experience peritonitis during the observation period was also significantly longer in IY (120 patient-months) than in CY (26 patient-months), IS (10.6 patient-months), or CS (10.4 patient-months) . Simultaneous peritonitis and exit site infection was observed in none of IY group but 3 episodes in CY, 4 episodes in IS, and 3 episodes in CS . The rates of complications related to Staphylococcus aureus and Pseudomonas infections were also significantly lower in IY than in CY, IS, or CS . Technique survival did not differ between the two groups . The present results confirm our previous observation that the new access technique reduces the incidence of peritonitis probably by reducing infection via periluminal route . The Y-connector system further reduces peritonitis rate by reducing infection via intraluminal route.

Ann Pharmacother, 1998 Jul-Aug, 32(7-8), 758 - 60
Vancomycin intermediate-resistant Staphylococcus aureus; Turco TF et al.; OBJECTIVE: To describe further details about the third reported case of vancomycin intermediate-resistant Staphylococcus aureus (VISA) . CASE SUMMARY: A patient with a history of recurrent methicillin-resistant S . aureus (MRSA) bacteremia was treated with several courses of vancomycin for 18 of 23 possible weeks on an inpatient/outpatient basis . After 6 months of repeated courses, an isolate of MRSA showed a minimum inhibitory concentration of 8 micrograms/mL, indicating intermediate resistance to vancomycin . The patient continued to receive a vancomycin/aminoglycoside/rifampin regimen and, when he was hospitalized several weeks later, no further MRSA or VISA was detected . DISCUSSION: Prolonged, intermittent vancomycin use (18 of 23 possible weeks) for MRSA bacteremia on an inpatient/outpatient basis most likely contributed to the development of VISA . Infection control measures prevented the spread of VISA among patients and healthcare workers . CONCLUSIONS: Infection control measures and evaluation of antimicrobial prescribing need to be strongly enforced to further prevent the spread and development of resistant organisms.

Int J Dermatol, 1998 Jul, 37(7), 520 - 3
Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis in northeastern Malaysia; Kamaliah MD et al.; BACKGROUND: Previous studies have reported that drugs and infections are common causes of erythema multiforme (EM) and Stevens-Johnson syndrome (SJS) . Toxic epidermal necrolysis (TEN) is mainly related to drugs . No study has been conducted in Kelantan, the northeastern state of Malaysia, to assess these cutaneous reactions . METHODS: A retrospective study of all hospitalized cases of EM, SJS, and TEN was conducted covering an 8-year period from 1987 to 1994 . RESULTS: There were four cases (13.8%) of EM, 22 cases (75.9%) of SJS, and three cases (10.3%) of TEN . Drugs as a definitive cause was observed in one case (25%) of EM, 12 cases (54.5%) of SJS, and two cases (66.7%) of TEN . Drugs as a probable cause was observed in seven cases (31.8%) of SJS and one case (33.3%) of TEN . The male to female ratio was equal in EM and SJS . Antiepileptics were the commonest culprits, followed by antibiotics . One patient died of SJS and one patient died of TEN, giving mortality rates of 4.5% and 33.5% respectively . Fever was noted in 18 patients (62.1%) . Leukocytosis was noted in 10 patients (34.5%), and nine patients (31.0%) had elevated liver transaminase enzymes . No significant correlation was noted between these biochemical changes and cutaneous eruption . Secondary infections were observed in 11 patients (37.9%): Staphylococcus aureus was the commonest isolated organism . CONCLUSIONS: This study shows that drugs remain the commonest culprit in SJS and TEN . Despite adequate treatment, the mortality rate remains high, especially in TEN . These findings are similar to those of other reported studies.

Hiroshima J Med Sci, 1998 Jun, 47(2), 73 - 83
The mechanism of sensitizing effect of a triazine dye, cibacron blue F3GA, on methicillin-resistant Staphylococcus aureus to oxacillin; Shirai C et al.; We recently found that a triazinyl dye, cibacron blue F3GA (CB), has a sensitizing effect on the in-vitro susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) to oxacillin (C . Shirai, M . Sugai, H . Komatsuzawa, K . Ohta, M . Yamakido, H . Suginaka, Antimicrob . Agents Chemother . 42: 1278-1280, 1998) . Among nine triazinyl dyes tested, CB the strongest sensitizing effect . Population analysis demonstrated that CB reduced the resistance level of MRSA . In the presence of oxacillin at subinhibitory concentrations, CB inhibited the growth of MRSA, but its effect on the cells appeared to be bacteriostatic . Under experimental conditions, CB did not affect the amount of PBP2', binding of {14C}benzylpenicillin to PBP2', or peptidoglycan susceptibilities to bacteriolytic enzymes . Autolytic enzyme-deficient MRSA mutants were equally as sensitive as the parent strain to the effect of CB on the susceptibility to oxacillin . CB affected the resistance level of MRSA irrespective of the status of the mecI/mecR1 element and/or penicillinase plasmids . The sensitivities of several bacteriolytic enzymes to heat-inactivated MRSA cells were not affected when the cells grown in the presence of CB . CB did not stimulate the release of lipoteichoic acid from the cells . These results suggest that the sensitization effect of CB cannot be simply explained by its effect on mecA related products, autolysins, femAB products or the release of lipoteichoic acid.

J Vet Pharmacol Ther, 1998 Jun, 21(3), 209 - 13
Pharmacokinetics and penetration of danofloxacin from the blood into the milk of cows; Shem-Tov M et al.; The single-dose disposition kinetics of danofloxacin were determined in clinically normal lactating cows after intravenous (i.v.) and intramuscular (i.m.) administration of the drug at 1.25 mg/kg . The drug concentrations in blood serum and milk were determined by microbiological assay methods and the data were subjected to kinetic analysis . The mean i.v . and i.m . elimination half-lives (t1/2el) in serum were 54.9 and 135.7 min, respectively . The steady-state volume of distribution (Vss) was 2.04 L/kg . The drug was quickly absorbed after i.m . injection but a 'flip flop' effect was clearly evident and bioavailability was > 100% . Penetration of danofloxacin from blood into milk was rapid and extensive with drug concentrations in milk exceeding those in serum beginning 90-120 min after i.v . and i.m . administration and onwards . Milk danofloxacin concentrations equal to or higher than the minimal inhibitory concentrations (MIC) for pathogenic Gram-negative bacteria and Mycoplasma species were maintained over approximately 24 h . Concentrations greater than the MIC for Staphylococcus aureus were maintained in the milk for 12 h.

Infect Immun, 1998 Aug, 66(8), 4004 - 7
Synthesis of microcapsule by Staphylococcus aureus is not responsive to environmental phosphate concentrations; Fox KF et al.; The polysaccharide microcapsule of Staphylococcus aureus has been reported to be differentially expressed depending on growth conditions, with phosphate concentration being the critical environmental component . This study evaluated the effect of growth of a serotype 8 strain of S . aureus in phosphate-replete and phosphate-limiting media on microcapsule production . The presence of the cell wall polymers microcapsule and teichoic acid was measured by both gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry . Production of microcapsule was unaffected by changes in the environmental phosphate concentration . There was, additionally, no evidence for a shift from teichoic acid to teichuronic acid synthesis.

Am J Emerg Med, 1998 Jul, 16(4), 379 - 81
Comparison of normal saline with tap water for wound irrigation; Moscati R et al.; This study compared irrigation with tap water versus saline for removing bacteria from simple skin lacerations . The study was conducted in an animal model with a randomized, nonblinded crossover design using 10 500-g laboratory rats . Two full-thickness skin lacerations were made on each animal and inoculated with standardized concentrations of Staphylococcus aureus broth . Tissue specimens were removed before and after irrigation with 250 cc of either normal saline from a sterile syringe or water from a faucet . Bacterial counts were determined for each specimen and compared before and after irrigation . There was a mean reduction in bacterial counts of 81.6% with saline and 65.3% with tap water (P = .34) . One tap water specimen had markedly aberrant bacterial counts compared with others . Excluding this specimen, the mean reduction for tap water was 80.2% . In this model, reduction in bacterial contamination of simple lacerations was not different comparing tap water with normal saline as an irrigant.

Immunol Lett, 1998 May, 62(1), 25 - 31
Captopril and lisinopril suppress production of interleukin-12 by human peripheral blood mononuclear cells; Constantinescu CS et al.; Angiotensin converting enzyme (ACE) inhibitors have immunomodulatory functions and can suppress a number of proinflammatory, monocyte/macrophage-derived cytokines . Interleukin-12 is a cytokine produced primarily by monocytes and macrophages, which plays an essential role in cell mediated immunity and stimulates the development of T helper type 1 immune responses . In this study, we investigated the ability of ACE inhibitors, captopril and lisinopril, to suppress IL-12 production by human peripheral blood mononuclear cells (PBMC) . We show that both ACE inhibitors significantly inhibit production of IL-12 by PBMC stimulated with bacterial lipopolysaccharide (LPS) or Staphylococcus aureus Cowan (SAC) . Although both ACE inhibitors also suppressed IFN-gamma production by human anti-CD3/anti-CD28-stimulated T-cells, the addition of exogenous IFN-gamma to the PBMC stimulation medium does not abrogate the ability of ACE inhibitors to suppress IL-12 production . Inhibition of IL-12 was not associated with inhibition of IL-1beta, but correlated with the suppression of ACE . Therefore, suppression of IL-12 may contribute to the immunomodulatory effect of ACE inhibitors and may be responsible for the beneficial effect of captopril and other ACE inhibitors in inflammatory or autoimmune conditions in which IL-12 is involved.

AIDS Res Hum Retroviruses, 1998 Jul 1, 14(10), 845 - 9
HIV type 1 Tat protein inhibits interleukin 12 production by human peripheral blood mononuclear cells; Ito M et al.; HIV-1 Tat protein, which trans-activates HIV-1 expression, exerts many effects on host immune function . Meanwhile, PBMCs and pulmonary macrophages from HIV-1-infected patients produce only a small amount of IL-12, which plays an essential role in the development of helper T type 1 (Th1) cells, and in the generation of cytotoxic T lymphocytes . We examined the possibility that Tat suppresses IL-12 production by PBMCs from healthy donors . Tat significantly inhibited IL-12 production by human PBMCs stimulated with Staphylococcus aureus Cowan 1 strain (SAC) at concentrations between 5 and 40 ng/ml . Immunoabsorption by using polyclonal antibody to Tat abolished the suppression of the IL-12 production by Tat . Tat at the same concentrations did not affect IL-10, IL-6, or TNF-alpha production . Other HIV-1 proteins (Nef and gp120) did not influence IL-12 production . Tat also suppressed the expression of mRNA encoding the p40 chain of IL-12, whereas it did not affect the expression of mRNA encoding IL-10 and beta-actin . IL-12 production by monocytes, separated from PBMCs by the adhesion method, was also inhibited by Tat . These results suggest that Tat protein is one of the main causes of decreased IL-12 production by PBMCs (mostly by monocytes) from HIV-1-infected individuals.

Microbios, 1997, 92(372-373), 147 - 55
Phage-mediated transfer of tetracycline resistance in Staphylococcus aureus isolated from cattle in Brazil; Pereira MS et al.; Tetracycline-resistant strains of Staphylococcus aureus isolated from cattle in Brazil, were used as prospective donors for the transfer of resistance to laboratory strains, using mixed-culture and filter-mating protocols . Three lysogenic donors transferred tetracycline resistance in both mixed culture and during filter mating . In contrast, when a non-lysogenic strain was used as prospective donor, transfer was not detected using either mating protocol . In order to evaluate the involvement of phage, successful transfer experiments were repeated with the addition of sodium citrate, which sequestered calcium ions . Mixed-culture and filter-mating protocols did not result in the transfer of resistance . These results support the notion that transfer of the resistance determinant under both sets of conditions described here involve the same bacteriophage-mediated mechanism . Although transfer of tetracycline resistance was detected, without any attempt to create specialized transduction agents or to extract phages, the co-transfer of additional resistance markers indicated that it could not be conventional transduction.

Spinal Cord, 1998 Jul, 36(7), 507 - 13
Infectious disease of the spine: outcome of rehabilitation; Yen HL et al.; Infectious disease of the spine is infrequently seen in the rehabilitation setting . We examined retrospectively 26 patients with spinal infections admitted to the rehabilitation centre over a 6-year period to determine the demographic characteristics, clinical features and outcome after rehabilitation . Their ages ranged from 24 to 83 years (mean = 56.4); 65.4% were males . The infection was due to pyogenic bacteria in 14 patients (53.8%) and Mycobacterium tuberculosis in 12 (46.2%) . Staphylococcus aureus was the causative agent in 69% of those with pyogenic infections . A history of diabetes mellitus was present in 35.7% of the pyogenic group but in only 8.3% of the tuberculous group . Localised back pain, fever and neurological deficits were the typical clinical manifestations . The most common site of infection was the thoracic region . Surgery was performed on 24 patients and all received prolonged courses of antibiotics . All but three patients completed the rehabilitation programme . The motor score for the lower limbs and the modified Barthel scores for activities of daily living (ADL) and mobility improved significantly (P < 0.05) for both pyogenic and tuberculous groups . The amounts of improvement achieved were not significantly different between the pyogenic and tuberculous groups except for ADL . Age, gender and the presence of diabetes mellitus did not appear to significantly affect the neurological or functional outcome in our study population . The majority of patients (87.5%) were discharged to their own homes.

J Chemother, 1998 Jun, 10(3), 203 - 7
Parameterization of inoculum effect via mathematical modeling: aminoglycosides against Staphylococcus aureus and Escherichia coli; Li RC et al.; Inoculum effect describes the inoculum size dependent changes in minimum inhibitory concentrations (MIC) exhibited by antibiotic-bacterium combinations demonstrating such effect . Traditionally, inoculum effect has been loosely defined based on the extent of increase in the MIC with respect to the increase in inoculum size . In most studies, assessment of MIC data has relied on the arbitrary selection of a point of reference for both baseline MIC and inoculum size . More importantly, this conventional method of assessment does not permit information conveyed in a complete MIC versus inoculum size profile to be fully explored . To undertake these issues, a mathematical model was developed for the description of the entire inoculum effect profile . With the employment of three key parameter estimates, i.e., the baseline MIC, the threshold inoculum size at which the increase in MIC commences, and the rate of increase in MIC with respect to inoculum size, both the shape and location of the profile could be adequately defined . To verify the application of this model, a series of four aminoglycosides were tested against standard strains of E . coli and S . aureus . Results showed a good degree of organism specificity and antibiotic-class dependency of the inoculum effect profiles . Analysis of the parameter estimates obtained provided further support for these observations . In conclusion, the mathematical model developed in the present study adequately described the inoculum effect exhibited by the various aminoglycoside-bacterium combinations tested . The parameter estimates generated by the modeling approach allowed comparison and quantitative analysis of the inoculum effect profiles with minimal difficulties.

Infect Control Hosp Epidemiol, 1998 Jun, 19(6), 395 - 400
Epidemiology of methicillin-resistant Staphylococcus aureus in three Canadian tertiary-care centers; Suh K et al.; OBJECTIVE: To describe the epidemiology and spread of methicillin-resistant Staphylococcus aureus (MRSA) in three tertiary-care centers in Ottawa, Ontario, Canada, where MRSA is encountered infrequently . DESIGN: Retrospective review over a 6-year period, from January 1, 1990, through December 31, 1995 . SETTING: Three tertiary-care teaching hospitals in Ottawa . PARTICIPANTS: Patients and healthcare workers (HCWs) with MRSA isolated from any body site . METHODS: Patients and HCWs were identified retrospectively through hospital microbiology and infection control records . Patient charts were reviewed for clinical and epidemiological data, including age, gender, previous hospital admissions (where noted), and current and recent antibiotic use . MRSA isolates that were available were typed using pulsed-field gel electrophoresis (PFGE) . Methicillin resistance was confirmed by standard methods and by polymerase chain reaction using mecA-specific primers . RESULTS: MRSA was identified in 53 patients and 2 HCWs . Three patients were excluded from further analysis because medical records were incomplete . Epidemiological data were collected on the remaining 52 individuals . Thirty-nine isolates from 31 patients and 2 HCWs were available for PFGE typing . Five epidemiologically linked nosocomial clusters involving 10 patients and 2 HCWs were identified and were confirmed by PFGE . MRSA isolates from a sixth cluster were not available for PFGE . In each cluster, nosocomial spread was minimized by standard infection control practices, including strict isolation of patients and screening of contacts . There was no evidence of secondary spread of MRSA involving the remaining 36 patients . Recent antibiotic use, surgery, admission to an intensive-care unit, and previous hospitalization were common among patients . There was no evidence of spread of MRSA among the three hospitals, and no endemic strains were apparent in any of these centers . CONCLUSIONS: MRSA remains an infrequent isolate in our centers, with no apparent interhospital spread . In institutions with little or no endemic MRSA, rigorous application of standard infection control practices is effective in limiting nosocomial transmission of this organism.

J Pathol, 1998 Apr, 184(4), 436 - 45
Glomerular injury induced by cationic 70-kD staphylococcal protein; specific immune response is not involved in early phase in rats; Fujigaki Y et al.; A highly cationic staphylococal protein (designated p70, MW 70 kD, pI > 10) belongs to the groups of bacterial proteins that can bind immunoglobulin without specific antigen-antibody recognition; heparin inhibition tests indicated a charge interaction . This study evaluated the nephritogenicity of p70, which has affinity for the glomerular basement membrane (GBM), and the influence of various mediator systems on the induction of glomerulonephritis by p70 . The left kidneys of intact rats, rats given cobra venom factor (complement-depleted), or rats given anti-adhesion molecules (ICAM-1 and LFA-1a) were perfused with p70 . Proteinuria started within 24 h and persisted at day 5 . Intraglomerular infiltration of cells was seen as early as 15 min, peaking at day 1 . Deposits of rat IgG and C3 were seen in a subendothelial location 15 min after p70 perfusion in the left kidney and were found in a predominantly subepithelial location from 1 day onwards . Complement depletion and blockade of adhesion molecules suppressed proteinuria from day 2 onwards; these manipulations also prevented the recruitment of infiltrating cells and partially hindered the transfer of IgG across the GBM and the accumulation of IgG in the subepithelial region . In the non-perfused right kidneys, deposits of IgG and C3 were comparable to those in the left kidneys, suggesting that p70-IgG complexes formed in the circulation may also contribute to the deposits in the GBM . Heparin inhibition tests indicated an electrostatic interaction between p70 and immunoglobulin . Complement and inflammatory mediator systems (granulocytes, monocytes/macrophages, and/or lymphocytes) were required to provoke glomerular injury . p70 might play a role in acute glomerulonephritis following Staphylococcus aureus infection.

Eur J Surg, 1998 May, 164(5), 339 - 43
Surgical trauma does not decrease resistance to infection; De Wilde JP et al.; OBJECTIVE: To investigate the effect on survival of two operations done at various intervals before the induction of monobacterial or multibacterial peritonitis in rats . DESIGN: Laboratory study . SETTING: Teaching hospital, Belgium . MATERIAL: Inbred male white wistar R/A rats . INTERVENTIONS: Posterolateral laparotomy, hindleg amputation, or control (anaesthetic only) (n=90 animals in each group), followed by induction of Escherichia coli or Staphylococcus aureus peritonitis at 1, 7 or 14 days . Further groups of rats were similarly operated on (50 in each group), but peritonitis was induced by caecal ligation and puncture . MAIN OUTCOME MEASURE: Survival 7 days after induction of peritonitis . RESULTS: Of the rats in which E . coli was used to induce peritonitis 27/28 (96%), 29/29 (100%), and 21/30 (70%) had survived 7 days after induction of peritonitis in the group that underwent posterolateral laparotomy, compared with 18/30 (60%), 20/28 (71%), and 18/28 (64%) in the control group; p 0.001, 0.002, and 0.78, respectively . The figures for hindleg amputation were 21/27 (78%), 23/27 (85%), and 17/30 (57%) . The corresponding figures for S . aureus peritonitis were for posterolateral laparotomy 28/30 (93%), 20/30 (67%), and 24/29 (83%) compared with controls 21/30 (70%), 9/30 (30%), and 20/29 (69%); p 0.04, 0.009, and 0.75, respectively . The figures for hindleg amputation were 21/30 (70%), 12/30 (40%), and 23/30 (77%) . Similar results were obtained with peritonitis induced by caecal ligation and puncture . CONCLUSIONS: Although surgical trauma may depress various aspects of the immune response in rats, it does not decrease their resistance to intraperitoneal microbial infections . The previous opening of the peritoneal cavity seemed to improve survival in our model.

Br J Dermatol, 1998 May, 138(5), 867 - 71
Bullous pemphigoid associated with acute glomerulonephritis; Barnadas MA et al.; We report an 82-year-old man who presented with bullous pemphigoid and who later developed an acute glomerulonephritis with the histopathological and immunofluorescence pattern of a postinfectious glomerulonephritis . Antibodies directed against 230 and 180 kDa bullous pemphigoid antigens were detected in the patient's serum by means of the immunoprecipitation technique . Staphylococcus aureus and methicillin-resistant S . aureus were isolated from the patient's skin . We consider that in this particular patient the cutaneous infection played a part in the development of the kidney complication.

Gene, 1998 Jul 17, 215(1), 57 - 67
Complete nucleotide sequence and molecular characterization of the temperate staphylococcal bacteriophage phiPVL carrying Panton-Valentine leukocidin genes; Kaneko J et al.; The staphylococcal Panton-Valentine leukocidin (PVL) genes, {lukS-PV-lukF-PV}, exist on the genome of a temperate bacteriophage phiPVL isolated from mitomycin C-induced Staphylococcus aureus V8 (ATCC 49775) (Kaneko, J., Kimura, T., Kawakami, Y., Tomita, T., Kamio, Y., 1997b . Panton-Valentine leukocidin genes in phage-like particle isolated from mitomycin C-treated Staphylococcus aureus V8 (ATCC 49775) . Biosci . Biotechnol . Biochem . 61, 1960-1962) . In this study, the complete nucleotide sequence of the phiPVL genome was analyzed, and the att sites (attL, attR, and attB) required for site-specific integration of phiPVL into the host chromosome were also determined . The linear double-stranded phiPVL genome comprised 41401bp with 3' staggered cohesive ends (cos) of nine bases and contained 63 ORFs, among which the regulatory proteins involved in DNA replication, structural proteins, a holin, a lysin, an integrase, and dUTPase, were tentatively identified by the comparison of the deduced amino acid sequences and by the analysis of the proteins isolated from phiPVL particles . The {lukS-PV-lukF-PV}, attP, and int (integrase gene) of phiPVL were all located very close to one another within a 4.0-kb segment on the genome in the order given, and this segment was located at the center from the left and the right cos sites . In addition, the attP region contained five direct repeat sequences that showed a high degree of homology with the recombinase-binding sites of some other S . aureus bacteriophages . The phiPVL genome was found to integrate into an ORF encoding an unknown protein comprising 725 amino acid residues with two leucine zipper-like motifs.

J Clin Microbiol, 1998 Aug, 36(8), 2366 - 8
Rapid and specific molecular identification of methicillin-resistant Staphylococcus aureus in endotracheal aspirates from mechanically ventilated patients; Vannuffel P et al.; Multiplex amplification of femA and mecA genetic determinants allowed an early and rapid identification of methicillin-resistant Staphylococcus aureus (MRSA) in endotracheal aspirates of mechanically ventilated patients . femA and/or mecA amplification and bacteriological results were concordant in 57 of 60 samples . In all three discrepant cases, complementary bacteriological tests confirmed the presence of MRSA first identified by molecular analysis . These results underline the value and rapidity of this molecular diagnosis for MRSA infection and control surveillance in intensive care units . Rapid MRSA detection is expected to have a significant clinical impact not only on patient outcome but also on the costs for isolation and treatment.

J Clin Microbiol, 1998 Aug, 36(8), 2254 - 7
Evaluation of mannitol salt agar for detection of oxacillin resistance in Staphylococcus aureus by disk diffusion and agar screening; Kampf G et al.; Mannitol salt agar was evaluated for detection of oxacillin resistance in 136 Staphylococcus aureus isolates . All mecA-positive isolates (n = 54) were correctly categorized as oxacillin resistant by the disk diffusion test (1-microgram disk; zone diameter, < 16 mm); the specificity was 97.6% . Agar screening (2 micrograms of oxacillin per ml) revealed a sensitivity of 98.1% and a specificity of 95.1%.

J Hand Surg {Br}, 1998 Jun, 23(3), 422 - 4
Osteomyelitis of the scaphoid with sequestration of the primary ossification centre; Monsell FP et al.; An 8-year-old boy presented with Staphylococcus aureus osteomyelitis affecting the left (non-dominant) scaphoid . Surgical drainage resulted in the expulsion of the primary ossification centre as a sequestrum . Seven years later the wrist function was minimally impaired and X-rays showed complete ossification of the cartilage remnant with a relatively normal scaphoid.

Perit Dial Int, 1998 May-Jun, 18(3), 271 - 3
Natural history of Staphylococcus aureus nasal carriage and its relationship to exit-site infection; Turner K et al.; OBJECTIVE: To study the natural history of nasal carriage of Staphylococcus aureus (SA) and its impact on exit-site infection (ESI) . SETTING: A teaching hospital single-center study . DESIGN: A prospective cohort study in prevalent continuous ambulatory peritoneal dialysis (CAPD) patients . PATIENTS: 153 patients (76 male, 77 female; mean age 46 years) with a mean duration of CAPD of 2.4 years . METHODS: Nasal swabs were taken at approximately 2-month intervals over the mean period of follow-up of 22.6 months and cultured for SA . RESULTS: An average of 69% of patients received systemic antibiotics for therapy of ESI, peritonitis, and other infections during the period of the study, but none received local nasal antibiotics . Four groups of patients were identified according to their nasal carriage history: chronic, intermittent, occasional, and noncarriers . The intermittent and chronic carriers had significantly higher SA ESI than the occasional and noncarrier groups . The intermittent group also had the highest percentage of non-SA ES infections . CONCLUSION: Although this study shows that only half of our CAPD patients with nasal carriage were at risk of developing ESI, we recommend that patients with a positive nasal swab at the start of CAPD therapy should be treated with nasal antibiotics or local antibiotics at the exit site.

Perit Dial Int, 1998 May-Jun, 18(3), 261 - 70
Decrease in Staphylococcus aureus exit-site infections and peritonitis in CAPD patients by local application of mupirocin ointment at the catheter exit site; Thodis E et al.; OBJECTIVE: To evaluate the potential effectiveness of the application of mupirocin ointment at the catheter exit site in preventing exit-site infection and peritonitis caused by Staphylococcus aureus (SA) . DESIGN: This prospective, historically controlled study was done on 181 peritoneal dialysis patients treated between 1 November 1996 and 1 November 1997 . They were instructed to apply mupirocin at the catheter exit site daily or three times per week at the conclusion of their exit-site care (Study 1) . The patients were not screened to determine whether they were SA carriers . The group's historical control was the infection data from the previous year among these patients . A second group of 70 patients, who started using mupirocin within a month after catheter implantation (1996-1997), was compared with a historical group of 118 patients (controls) who were on continuous ambulatory peritoneal dialysis (CAPD) for 1 year after in-patient implantation without mupirocin, (1990-1995) (Study 2) . RESULTS: In the group of 181 patients (Study 1), application of mupirocin at the exit site led to a significant reduction in SA exit-site infections--21 versus 3 episodes (0.11 vs 0.01 episodes/patient/year)--and a significant reduction of SA peritonitis--35 episodes in the year preceding mupirocin versus 11 episodes during the year of mupirocin treatment (0.19 vs 0.06 ep/pt/yr) . The same results were observed in Study 2: the incidence of SA exit-site infection was significantly lower in the mupirocin-treated group--17 episodes among the 118 nontreated patients versus 4 episodes among 70 patients using mupirocin (0.14 ep/pt/yr vs 0.06 ep/pt/yr, respectively) . Similarly there were 20 episodes of SA peritonitis among 118 patients during their first year of CAPD versus 4 episodes in 70 mupirocin-treated patients (0.16 ep/pt/yr vs 0.06 ep/pt/yr, respectively) . No adverse effects were observed among the patients treated with mupirocin . Overall peritonitis rates decreased from 0.87 to 0.48 ep/pt/yr (p < 0.01) in Study 1 and from 0.56 to 0.41 ep/pt/yr (p = NS) in Study 2 . We observed no differences in the incidence of exit-site infection and peritonitis rates among patients applying mupirocin ointment at the exit site daily, compared to three times per week . CONCLUSIONS: Mupirocin application at the exit site significantly lowers the incidence of SA exit-site infections and peritonitis due to SA infections . Since SA infections are accompanied by significant morbidity and occasional mortality, this treatment may improve long-term survival of patients on CAPD.

Zh Mikrobiol Epidemiol Immunobiol, 1998 Mar-Apr, (2), 88 - 91
{Lymphocytes as markers of etiologic and pathogenetic factors of infectious diseases}; Iushkova TA; In the examination of patients with the dermato-respiratory syndrome, peptic ulcer, pyoderma and surgical wounds for their immune status for the expression of receptors of immunocytokins (interferon, interleukin-2), autocoids (histamine, serotonin), neuromediators (acetylcholine, dopamine, epinephrine, norepinephrine) and for the presence of Staphylococcus aureus and Helicobacter pylori antigens have revealed that lymphocytes are the markers of the presence of infection in the body, pathogenetic systemic and intersystemic disturbances, adequately chosen therapy and its effectiveness.

Zh Mikrobiol Epidemiol Immunobiol, 1998 Mar-Apr, (2), 26 - 8
{Feasibility of determining occult blood using rapid serologic methods}; Grigor'eva EV et al.; The possibility of obtaining antibodies to human hemoglobin and erythrocytes and their use for the detection of hidden blood in different biological fluids was studied . The test system, based on the reaction of coagglutination with the use of protein A of Staphylococcus aureus Cowan 1 and magnetic sorbent, is proposed.

In Vitro Cell Dev Biol Anim, 1998 Jun, 34(6), 499 - 507
Macrophage cell lines derived from major histocompatibility complex II-negative mice; Beharka AA et al.; Two bone-marrow-derived macrophage cell lines, C2D and C2Dt, were isolated from major histocompatibility class II negative knock-out mice . The C2D cell line was stabilized by continuous culture in colony-stimulating factor-1 and the C2Dt cell line was transformed with SV40 virus large T antigen . These cells exhibited phenotypic properties of macrophages including morphology and expression of Mac 1 and Mac 2 cell surface molecules . These cells also had comparable growth to the bone-marrow-derived macrophage cell line B6MP102 . These new cell lines were not spontaneously cytotoxic and were only capable of modest killing of F5b tumor cells when stimulated with LPS and interferon-gamma, but not when stimulated with LPS alone or with staphylococcal exotoxin . C2D and C2Dt cells phagocytosed labeled Staphylococcus aureus similarly to B6MP102 cells but less well than C2D peritoneal macrophages . These cell lines secreted interleukin-6, but not tumor necrosis factor or nitric oxide in response to LPS or staphlococcal enterotoxins A or B C2D(t) cells were tumorigenic in C2D and C57BL/6J mice but C2D cells were not . These data suggest that macrophage cell lines can be established from bone marrow cells of major histocompatibility complex II-negative mice.

Antimicrob Agents Chemother, 1998 Jul, 42(7), 1713 - 7
Effect of trovafloxacin on production of cytokines by human monocytes; Khan AA et al.; Antibiotics have previously been shown to have immunomodulatory effects . We examined the effect of the broad-spectrum fluoroquinoline antibiotic trovafloxacin on cytokine synthesis by monocytes obtained from healthy human volunteers and stimulated with either lipopolysaccharide or gram-positive cells (heat-killed Staphylococcus aureus {Pansorbin}) . Trovafloxacin levels achievable in humans suppressed in vitro synthesis of each of the cytokines analyzed, viz., interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, IL-10, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha . This effect was not due to direct effects of the drug on cellular viability; at these concentrations, trovafloxacin did not have demonstrable cytotoxicity for the monocytes, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay . Although similar patterns of suppression of cytokine synthesis were observed in samples obtained from the same volunteers on different days, there were significant day-to-day variations . These results reveal that trovafloxacin possesses significant immunomodulatory activity in vitro and suggest that suppression of acute-phase inflammatory responses may occur in vivo, elicited through trovafloxacin's effect on cytokine synthesis by human monocytes.

Antimicrob Agents Chemother, 1998 Jul, 42(7), 1574 - 7
In vitro activities of co-amoxiclav at concentrations achieved in human serum against the resistant subpopulation of heteroresistant Staphylococcus aureus: a controlled study with vancomycin; Prieto J et al.; The effects of concentrations that simulated those in human serum after a single intravenous dose of amoxicillin (2 g), amoxicillin-clavulanic acid (2,000 and 200 mg, respectively), or vancomycin (500 mg), on the viability and beta-lactamase activity of two isogenic (beta-lactamase and non-beta-lactamase producer) heteroresistant Staphylococcus aureus strains were studied in an in vitro pharmacodynamic model . A reduction of > or = 97% of the initial inoculum was obtained with vancomycin and amoxicillin-clavulanic acid against both strains, with respect to the total bacterial population and the oxacillin-resistant subpopulation . The same pattern was observed with amoxicillin and the beta-lactamase-negative strain . beta-Lactamase activity in the beta-lactamase-positive strain changed over time parallel to viability, decreasing with amoxicillin-clavulanic acid or vancomycin and increasing in the amoxicillin and control groups . Clavulanic acid concentrations achievable in serum that changed over time allowed amoxicillin to act against the beta-lactamase-producing methicillin-resistant S . aureus to a similar extent as vancomycin.

J Biol Chem, 1998 Jul 17, 273(29), 18665 - 73
QacR is a repressor protein that regulates expression of the Staphylococcus aureus multidrug efflux pump QacA; Grkovic S et al.; The Staphylococcus aureus QacA protein is a multidrug transporter that confers resistance to a broad range of antimicrobial agents via proton motive force-dependent efflux of the compounds . Primer extension analysis was performed to map the transcription start points of the qacA and divergently transcribed qacR mRNAs . Each gene utilized a single promoter element, the locations of which were confirmed by site-directed mutagenesis . Fusions of the qacA and qacR promoters to a chloramphenicol acetyl transferase reporter gene were used to demonstrate that QacR is a trans-acting repressor of qacA transcription that does not autoregulate its own expression . An inverted repeat overlapping the qacA transcription start site was shown to be the operator sequence for control of qacA gene expression . Removal of one half of the operator prevented QacR-mediated repression of the qacA promoter . Purified QacR protein bound specifically to this operator sequence in DNase I-footprinting experiments . Importantly, addition of diverse QacA substrates was shown to induce qacA expression in vivo, as well as inhibit binding of QacR to operator DNA in vitro, by using gel-mobility shift assays . QacR therefore appears to interact directly with structurally dissimilar inducing compounds that are substrates of the QacA multidrug efflux pump.

J Biol Chem, 1998 Jul 17, 273(29), 18011 - 4
Characterization of the binding site of the tripeptide intermediate D-Phenylalanyl L-prolyl-L-valine in gramicidin S biosynthesis; Leenders F et al.; The tripeptide intermediate D-Phe-Pro-Val in the biosynthesis of gramicidin S was labeled by incorporation of either L-{14C}phenylalanine or L-{14C}valine in an in vitro biosynthetic assay . The gramicidin S synthetase 2-tripeptide complex was first digested with CNBr and subsequently by Staphylococcus aureus V8 protease . The active site peptide carrying the radioactively labeled tripeptide was isolated in pure form by reversed phase high performance liquid chromatography technology and analyzed by liquid phase sequencing, mass spectrometry, and amino acid analysis . It was demonstrated that D-Phe-Pro-Val is attached to the 4'-phosphopantetheine cofactor at the thiolation center for valine of gramicidin S synthetase 2 . In this way the attachment site of a peptide intermediate in nonribosomal peptide biosynthesis was identified for the first time . Our results are in full agreement with the multiple carrier model of nonribosomal peptide biosynthesis (Stein, T., Vater, J., Kruft, V., Otto, A., Wittmann-Liebold, B., Franke, P., Panico, M., McDowell, R., and Morris, H . R . (1996) J . Biol . Chem . 271, 15426-15435), which predicts that the growing peptide chain in the elongation process should always be bound to the thiotemplate site specific for its C-terminal amino acid component.

Rev Med Chil, 1998 Feb, 126(2), 195 - 8
{Septic phlebitis: origin of severe septic condition}; Espinoza R et al.; We report two patients, an 82 years old female and a 71 years old male, who had a severe sepsis with positive blood cultures for Staphylococcus aureus and a superficial phlebitis as the only probable focus . In both the diagnosis of septic phlebitis was reached and an emergency phlebotomy was performed under local anesthesia . The clinical response was satisfactory and the pathological examination of excised veins showed an acute exudative leukocytic thrombophlebitis.

Am J Vet Res, 1998 Jul, 59(7), 807 - 13
Detection of Staphylococcus aureus in milk by use of polymerase chain reaction analysis; Khan MA et al.; OBJECTIVE: To evaluate polymerase chain reaction (PCR) analysis for detection of Staphylococcus aureus (nuc gene) in fresh and formalin-preserved milk . SAMPLE POPULATION: Samples from 80 lactating sheep and 100 lactating dairy cows . PROCEDURE: 4 lactating sheep were inoculated with S aureus by intramammary infusion . A set of primers specific for the nuc gene of S aureus was used to develop a PCR technique, and modification of the rapid boil method was used to isolate bacterial DNA . Milk was obtained from experimentally infected sheep before and after infusion with S aureus, and from the 100 cows and remaining 76 sheep . Samples were screened by bacteriologic culture and PCR . To validate the PCR assay, S aureus or other pathogens were added to distilled water and "normal" sheep milk samples, with and without formalin . RESULTS: The PCR assay was 100% specific for S aureus when known negative and positive samples were tested . Sensitivity was 100% for samples with added S aureus or other pathogens . Sensitivity was lower for samples obtained from experimentally infected sheep, but increased from 53% to 90% with increased washing of target DNA . CONCLUSIONS: The PCR technique based on the nuc gene is able to detect S aureus in sheep milk yields results faster than does traditional culturing, is highly specific, and is able to detect S aureus in formalin-fixed milk samples . CLINICAL RELEVANCE: The assay is particularly suitable for analysis of samples shipped or stored without refrigeration . Although antibiotics in milk may inhibit growth in culture, they should not affect the results of the PCR assay.

Rev Esp Cardiol, 1998, 51 Suppl 2, 86 - 91
{Indications and surgical techniques in the acute phase of infective endocarditis}; Mate I et al.; Infectious endocarditis is increasingly resistant to antibiotic therapy, due to the increasing number of patient with cardiovascular prostheses or those who are severely immunosuppressed . Frequently, this syndrome and its complications can only be solved with surgery . In this article, which is based on the international literature plus own observations in 77 patients, the indications for surgery and the different technical approaches during the acute phase of infectious endocarditis are reviewed . Surgery to control infectious endocarditis is indicated when there is one of the following situations: a) persistence of infection despite an adequate antibiotic treatment, usually due to a specific pathogen (Staphylococcus aureus, fungus, etc.) or to a low antibiotic penetration into the infected issues (abscess); b) progressive hemodynamic deterioration due to tissular destruction and development of valvular incompetence or fistulous communications or c) development of other complications (repetitive embolism, cardiovascular aneurysms, conduction blocks, etc.) . Hemodynamic deterioration due to heart failure refractory to medical treatment is the most frequent indication for cardiovascular surgery, and this was present in 61% of our patients . The timing for surgery is still controversial, although scheduling it at an early stage is generally preferred . The specific surgical technique is chosen according to the degree of tissular destruction and is aimed to remove the infected tissue and to repair the damaged structures or, if this is not feasible, to implant cardiovascular prosthesis.

Rev Esp Cardiol, 1998, 51 Suppl 2, 71 - 8
{Endocarditis in parenteral drug addicts . Right-sided endocarditis . Influence of HIV infection}; de Alarcon A et al.; Infective endocarditis is a life-threatening infective complication in parenteral drug abusers . The tricuspid valve is the structure most frequently affected and Staphylococcus aureus the predominant microorganism . Fever, multiple pulmonary emboli and sustained bacteremia by S . aureus are signs of clinical alert for right-sided endocarditis in these patients . Echocardiography has developed a significant improvement in diagnosis and the transthoracic mode has a considerable reliability when high suspicion is established . Outcome is usually favourable with mortality less than 10% . Recent studies have made shorter treatments possible in selected patients and oral therapy is also considered . HIV infection, in advanced status, may indicate a worse survival rate.

J Bacteriol, 1998 Jul, 180(14), 3724 - 6
Opposing roles of the Staphylococcus aureus virulence regulators, Agr and Sar, in Triton X-100- and penicillin-induced autolysis; Fujimoto DF et al.; The regulation of murein hydrolases is a critical aspect of peptidoglycan growth and metabolism . In the present study, we demonstrate that mutations within the Staphylococcus aureus virulence factor regulatory genes, agr and sar, affect autolysis, resulting in decreased and increased autolysis rates, respectively . Zymographic analyses of these mutant strains suggest that agr and sar exert their effects on autolysis, in part, by modulating murein hydrolase expression and/or activity.

Virology, 1998 Jul 5, 246(2), 241 - 52
The polyvalent staphylococcal phage phi 812: its host-range mutants and related phages; Pantucek R et al.; Ninety-five percent of 782 culture collection strains, as well as hospital strains of Staphylococcus aureus subsp . aureus of different provenance and 43% of 89 culture collection strains of different coagulase-negative species of the genus Staphylococcus, were found to be sensitive to the polyvalent phage phi 812 or to at least one of its host-range mutants or to the polyvalent phages SK311, phi 131, and U16 . Thus sensitivity to the polyvalent staphylococcal phages seems to be one of the common features of S . aureus subsp . aureus strains . The adsorption kinetics and one-step growth characteristics of the phages phi 812 and SK311 were estimated . Restriction genomic maps of the phages phi 812 (146.5 kb) and SK311 (141.1 kb) were constructed by use of the restriction endonucleases AvaII, PstI, KpnI, SacI, SmaI, and XhoI . The host-range mutations of the phage phi 812 were localized on this map . Comparison of restriction patterns of the phages phi 812 and SK311 with those of the polyvalent phages U16 and phi 131 suggests that all these phages are closely related . Their genomes differ from each other mostly by some deletions, insertions (1-3 kb), or inversions . Evidence was given that the phage phi 812 together with SK311, phi 131, and U16 belongs in the phage species Twort, the description of which is substantially supplemented with the data on the phage phi 812 reported in this paper.

Anal Biochem, 1998 Jul 1, 260(2), 230 - 6
Inactivation of alpha1-proteinase inhibitor as a broad screen for detecting proteolytic activities in unknown samples; Nelson D et al.; The need for a quick, simple screening method for the detection of general proteolytic activity prompted us to determine whether cleavage within the reactive site loop region (RSL) of alpha1-proteinase inhibitor (alpha1-PI), a well-characterized member of the serpin family known to be susceptible to proteolytic inactivation, can be utilized for this purpose . Inactivation of alpha1-PI in the RSL region can be measured by loss of residual inhibitory capacity of alpha1-PI against its target proteinase . While we originally utilized this assay to detect a new proteinase from culture supernatants of Porphyromonas gingivalis, the feasibility of extending this assay to scan for proteolytic activity from other systems was also assessed . As an example, we found that the serine proteinase from Staphylococcus aureus (SSP) had virtually the same catalytic efficiency in inactivating alpha1-PI in our assay as it did in the hydrolysis of the synthetic substrate Z-Phe-Leu-Glu-pNA (kcat/Km value of 2 x 10(4) M-1 s-1 vs 2.6 x 10(4) M-1 s-1, respectively) . Additionally, in both assays activity could be readily detected in less than a 1 h incubation at SSP concentrations in the picomolar range . This assay is unique in that proteinases which hydrolyze peptide bonds within the RSL of alpha1-PI can readily be detected as measured by loss of alpha1-PI inhibitory activity .

Rev Port Cardiol, 1998 May, 17(5), 439 - 44
{Clinical manifestations and therapeutic of isolated infective endocarditis of the tricuspid valve}; Sousa L et al.; We reviewed the records of patients admitted to our centre with the diagnosis of isolated tricuspid valve infective endocarditis and analysed the clinical presentation, etiopathogenic agent, echocardiographic features and therapeutic approach, namely the indication for cardiac surgery . Between 1988 and 1996, 11 cases of confirmed tricuspid valve endocarditis were identified, corresponding to 5% of the cases of endocarditis admitted to our centre in the same period . A predisposing factor was found in ten of the patients, half of them intravenous drug addicts and Staphylococcus aureus was the most frequent agent isolated . Fever and pleuro-pulmonary manifestations were predominant clinical features . Transthoracic echocardiography had a crucial role in the diagnosis and transesophageal echocardiography was important to characterize vegetations . Four patients underwent cardiac surgery, for persistent infection . In two cases, excision of the vegetations and ring annuloplasty was performed . In two patients not addicted to drugs, the tricuspid valve was replaced with a bioprosthesis, since the extension of the damage to the valve did not allow repair . One patient, with early endocarditis of a tricuspid bioprosthesis died before surgery was attempted.

Nurse Pract, 1998 Jun, 23(6), 125 - 8, 131-3
Primary care management of otitis externa; La Rosa S; Otitis externa (OE) is an acute, painful inflammatory condition of the external auditory canal that affects all age groups and accounts for about half of all patients presenting with ear pain . Common causes are gram-negative bacteria, Staphylococcus aureus, fungi, and dermatologic conditions such as eczema, seborrhea, and psoriasis . Risk increases with prolonged exposure to heat and moisture, especially in those who swim frequently or live in a tropical climate . Treatment involves cleaning the canal thoroughly and instilling ototopical broad-spectrum antibiotics . Although OE is relatively benign and easy to treat in the primary care setting, it can have life-threatening complications, especially in diabetic and immunocompromised patients . This article reviews the differential diagnosis, outlines treatment, and discusses preventive measures . A patient-education sheet is provided.

Am J Physiol, 1998 Jul, 275(1 Pt 1), G29 - 38
CD4+ T cells mediate superantigen-induced abnormalities in murine jejunal ion transport; McKay DM et al.; The immunomodulatory properties of bacterial superantigens (SAgs) have been defined, yet comparatively little is known of how SAgs may affect enteric physiology . Staphylococcus aureus enterotoxin B (SEB) was used to examine the ability of SAgs to alter epithelial ion transport . BALB/c mice, severe combined immunodeficient (SCID, lack T cells) mice, or SCID mice reconstituted with lymphocytes or CD4+ T cells received SEB intraperitoneally, and jejunal segments were examined in Ussing chambers; controls received saline only . Baseline short-circuit current (Isc, indicates net ion transport) and Isc responses evoked by electrical nerve stimulation, histamine, carbachol, or forskolin were recorded . Serum levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were measured . SEB-treated BALB/c mice showed elevated serum IL-2 and IFN-gamma levels, and jejunal segments displayed a time- and dose-dependent increase in baseline Isc compared with controls . Conversely, evoked ion secretion was selectively reduced in jejunum from SEB-treated mice . Elevated cytokine levels and changes in jejunal Isc were not observed in SEB-treated SCID mice . In contrast, SCID mice reconstituted with T cells were responsive to SEB challenge as shown by increased cytokine production and altered jejunal Isc responses that were similar to those observed in jejunum from SEB-treated BALB/c mice . We conclude that exposure to a model bacterial SAg causes distinct changes in epithelial physiology and that these events can be mediated by CD4+ T cells.

Pediatr Dermatol, 1998 May-Jun, 15(3), 194 - 8
S . aureus isolation from the lesions, the hands, and the anterior nares of patients with atopic dermatitis; Williams JV et al.; Staphylococcus aureus colonization is common in atopic dermatitis (AD) and can exacerbate the disease . Additionally, some evidence shows that patients with AD may act as reservoirs for S . aureus transmission to others . This study compared S . aureus colonization in AD patients and their caregivers with control patients and their caregivers . Quantitative cultures were obtained from the lesions, clinically normal skin, hands, and anterior nares of 100 patients with AD, 100 controls with other cutaneous disorders, and 200 caregivers . AD patients had a significantly greater carriage of S . aureus from lesional and clinically normal skin as well as the hand . Significant increases in carriage of S . aureus were found in the anterior nares and hands of caregivers of AD patients compared with control caregivers . Topical corticosteroid use did not affect recovery of S . aureus . There was a significant correlation between recovery of S . aureus from lesional skin and recovery from the anterior nares (p = .002) and hands (p < .0001) . These findings suggest that the anterior nares and the hands may be important reservoirs and vectors for transmission of S . aureus to lesional skin and to close contacts of these patients.

J Orthop Sci, 1998, 3(2), 95 - 101
Detection of human serum antibody to encapsulated strains of Staphylococcus aureus by enzyme-linked immunosorbent assay inhibition test; Ueda H et al.; A specific and rapid enzyme-linked immunosorbent assay (ELISA) inhibition test was employed for detection of immunoglobulins to Staphylococcus aureus (S . aureus) capsular polysaccharide in human serum . Cap-sular polysaccharide antigens obtained from Smith diffuse (capsular type 2), Reynolds (capsular type 5), or Becker (capsular type 8) strains of S . aureus were added to microplates coated with these strains . Seventy-four patients with open fractures (31 serum samples from those with staphylococcal infections, 10 serum samples from those with non-staphylococcal infections, and 33 serum samples from the non-infected group) and 28 serum samples from healthy controls were then added . The plates were incubated at 37 degreesC for 2 h and the ELISA was performed . The ELISA inhibition assay showed remarkable inhibition with the capsular type 2, 5, and 8 polysaccharides in the 33 serum samples from the non-infected group and in the 28 serum samples from the healthy controls, but low inhibition was observed with the 31 sera with staphylococcal infections . Positive immunoglobulin (Ig)G and IgM titers showed marked inhibition with this assay, but IgA titer were not seen in any samples . These results indicate that the quantitation of human serum antibody against S . aureus capsular polysaccharide by the ELISA inhibition assay is useful for the demonstration of protective activities against S . aureus.

Microbiol Immunol, 1998, 42(5), 407 - 9
Occurrence of coagulase serotype among Staphylococcus aureus strains isolated from healthy individuals--special reference to correlation with size of protein-A gene--; Seki K et al.; One-hundred-and-nineteen strains of Staphylococcus aureus isolated from healthy individuals for 3 years between 1991 and 1993 were subjected to an investigation on the producibility of proteins including protein A, coagulase, enterotoxins and toxic-shock syndrome toxin-1 . Especially, protein A was the center of our interest . Among these strains, 69, 43, 3 and 1 strains were found to have the protein-A gene containing 5, 4, 3 and 2 IgG-binding domains, respectively . On the other hand, only one strain was devoid of the protein-A gene . There were some differences in the profile of the coagulase serotype between the group with 4 IgG-binding domains and that with 5 IgG-binding domains . Differences in the profile of toxin production were also observed between the two groups.

New Horiz, 1998 May, 6(2 Suppl), S53 - 7
Antibiotic prophylaxis in clean surgery: does it work? Should it be used if it does?
Platt R.
Perioperative antibiotic prophylaxis has been demonstrated to prevent postoperative wound infection after clean surgery in a majority of clinical trials with sufficient power to identify a 50% reduction in risk . The low risk of infection after many clean procedures requires studies of more than 1,000 procedures (sometimes many more) to detect such reductions reliably . This is a serious obstacle to performing conclusive tests of efficacy, and it all but precludes use of conventional clinical trials to identify optimal regimens . Regimens that have been shown to be effective have usually been those with efficacy against Staphylococcus aureus and other pathogens that may be carried in the nares or on the skin . In addition, relatively long half-life in the serum and low cost are important considerations . Cefazolin is a good prophylaxis agent for many clean surgical procedures, although special characteristics of the procedure, increased likelihood of antimicrobial resistance, or antibiotic utilization concerns may make other agents more suitable in specific situations The decision to use perioperative antibiotic prophylaxis for clean surgical procedures depends not only on its efficacy, but also on the cost of preventing infection . Few cost-benefit analyses have been performed, especially for procedures in which prophylaxis has been least used . To perform such analyses, it will be necessary to acquire information that is currently lacking for many procedures . This includes the risk and cost of postoperative infection, adverse reactions to the prophylaxis agent, and increased antimicrobial resistance; in addition, detailed information is needed on infection-associated costs of medical care, lost productivity, and the value that the infected person places on avoiding infection . For many procedures, timely use of an appropriate antibiotic is the single most effective infection prevention method that can be implemented and monitored on a broad scale . These features make it amenable to adoption as a subject of continuous quality improvement activities . To accomplish this, it is necessary to articulate standards of care clearly so that systems to support the intended goal can be developed . Both the standards and the support systems can be tailored to specific surgical situations and to the values of providers and patients.

Chem Biol, 1998 Jun, 5(6), 329 - 37
19F NMR in the measurement of binding affinities of chloroeremomycin to model bacterial cell-wall surfaces that mimic VanA and VanB resistance; Entress RM et al.; BACKGROUND: The emergence of bacteria that are resistant to vancomycin, the drug of choice against methicillin-resistant Staphylococcus aureus, has made the study of the binding characteristics of glycopeptides to biologically relevant depsipeptides important . These depsipeptides, terminating in D-alanyl-D-lactate, mimic the cell-wall precursors of resistant bacteria . RESULTS: The use of 19F-labelled ligands in the study of the therapeutically important vancomycin series of antibiotics is demonstrated . The substantial simplification of spectra that occurs when such labelled ligands are employed is used in the measurement of binding affinities of depsipeptides to chloroeremomycin (CE) . Large enhancements of binding affinities are found at a model bacterial cell-wall surface (constituted from depsipeptides that are anchored into vesicles) relative to those measured in free solution . CONCLUSIONS: Surface-enhanced binding, previously shown for strongly dimerizing glycopeptide antibiotics to normal -D-alanyl-D-alanine-terminating cell-wall precursors, is now demonstrated for CE to the surface of models of VanA- and VanB-resistant bacteria . The effect of depsipeptide chain length is shown to be critically important in producing and maximizing this enhancement.

Medicine (Baltimore), 1998 May, 77(3), 177 - 87
Septic arthritis of the glenohumeral joint . A report of 11 cases and review of the literature; Lossos IS et al.; Eleven cases (6 adults and 5 pediatrics) of shoulder septic arthritis are described, and the English literature from 1960 to 1997 reviewed, for a total of 168 cases . Shoulder septic arthritis is an uncommon and difficult diagnosis requiring a high index of suspicion and early evaluation of the affected shoulder by the clinician . The disease usually involves very young infants or elderly patients (65-75 years old) . Associated medical conditions were identified in 60% of the patients and include systemic disorders such as liver diseases, alcoholism, and malignancies in 46%; preceding chronic arthritic disorders in 24%; and associated infectious focus in 13% of the patients . Associated infections were more prevalent in the pediatric population . Intravenous drug abuse appears not to constitute a major risk factor; it was identified in less than 5% of patients . All patients presented with acute shoulder ache or with exacerbation of existing chronic pain in joints previously damaged . Elevated body temperature (over 38 degrees C) appeared in 67% of the adult patients and in over 90% of the pediatric patients . Shoulder arthritis was frequently accompanied by an accelerated erythrocyte sedimentation rate that may rise above 100 mm/hr . Increased white blood cell count was found in approximately 40% of patients . The initial X-rays were frequently normal, while ultrasonography supported the diagnosis in some cases by demonstrating accumulation of fluid inside the joint space . Aspiration of synovial fluid from the affected glenohumeral joint was necessary to evaluate the offending pathogen . False-negative Gram stain appeared in approximately 90% of the patients, whereas synovial fluid cultures demonstrated the pathogen in 88% of patients . Blood cultures were positive in 50% of adult patients and 90% of pediatric patients . The most common isolated pathogen was Staphylococcus aureus, which accounted for 41% of infections . Gram-negative bacilli, which accounted for about 20% of infections, are more prevalent in the pediatric population, especially the neonates . Pyogenic shoulder arthritis should first be treated with intravenous antibiotics, effective at least against staphylococcal infections, until the organisms and sensitivities are identified . Duration of antibiotic therapy should be 3-6 weeks . Unfortunately, our experience in addition to the literature summary does not allow statistical analysis and firm conclusions concerning the best therapeutic approach . However, it appears that in the adult population an operative draining procedure is preferred, whereas in the pediatric population, a closed needle aspiration, if needed at all, is the optimal treatment . With prompt antibiotic therapy and drainage of the shoulder, the patient can be expected to improve clinically, with no serious long-term debilitating effects from the disease.

J Infect Dis, 1998 Jul, 178(1), 164 - 71
Molecular epidemiology of methicillin-resistant Staphylococcus aureus in 12 New York hospitals . MRSA Collaborative Study Group; Roberts RB et al.; Consecutive single-patient methicillin-resistant Staphylococcus aureus (MRSA) isolates (270) from 12 hospitals (8217 beds) in metropolitan New York City were collected during May 1996 . In 11 of 12 hospitals, MRSA was most frequent in the general medical services . DNA typing ("fingerprinting") revealed that mecA:Tn554:PFGE (pulsed-field gel electrophoresis) type I:A:A accounted for 113 (42%) of 270 isolates, was detected in all hospitals, and was the predominant clone in 9 . Thirteen of 15 I:E:F isolates were from 1 hospital, and the remaining 2 were from another hospital of the same health system . Type V:NH:E was isolated from 22 (79%) of the 28 patients with AIDS, including 8 of 9 patients from an additional hospital . Subtype V:NH:E2 was recovered from 11 patients, 9 of whom had AIDS, including all 5 AIDS patients from one floor of a nursing home affiliated with a third hospital . By using both mecA:Tn554 probes and PFGE, MRSA clusters and outbreaks may be detected and provide a rationale for appropriate infection control intervention.

J Hosp Infect, 1998 Jun, 39(2), 127 - 33
Ventilation grilles as a potential source of methicillin-resistant Staphylococcus aureus causing an outbreak in an orthopaedic ward at a district general hospital; Kumari DN et al.; The spread of methicillin-resistant Staphylococcus aureus (MRSA) in a hospital is thought to be mainly by direct contact . Environmental sources such as exhaust ducting systems have been increasingly recognized as a source for MRSA outbreaks in intensive therapy units . We describe an outbreak of MRSA related to ventilation grilles in an orthopaedic ward . Six patients and one nurse were involved in an outbreak with EMRSA-15 during March 1996 . The index case was transferred from a large university hospital in Leeds . One of the patients had shared the same bay with the index case . The rest of the patients were in another bay of the same ward and had no direct contact with the index patient . An environmental source was suspected and the ventilation grilles in boys 1 and 2 were found to be harbouring EMRSA-15 . The ventilation system at that time was working on an intermittent cycle from 4 p.m.-8 a.m . Daily shut-down of the system temporarily created a negative pressure, sucking air in from the ward environment into the ventilation system and probably contaminating the outlet grilles . It is likely that contaminated air was blown back into the ward when the ventilation system was started . The system was thoroughly cleaned, appropriate infection control measures were instituted and the ventilation system was put back on a continuous running cycle and the outbreak terminated . Six months after the outbreak no isolates of EMRSA-15 had been made on the ward.

J Hosp Infect, 1998 Jun, 39(2), 85 - 93
Trying to control MRSA causes more problems than it solves; Barrett SP et al.; Despite occasional reports of local success, the steadily increasing prevalence of strains of Staphylococcus aureus resistant to methicillin (MRSA) shows that attempts to limit their spread do not work . In this commentary we suggest that efforts to control the spread of methicillin-resistance are counterproductive, and that energies should instead be directed towards the control of outbreaks of disease and preventing the emergence of antibiotic resistance.

J Dermatol Sci, 1998 Mar, 16(3), 216 - 25
Effects of various salts and irradiation with UV light on the attachment of Staphylococcus aureus strains; Akiyama H et al.; We investigated the attachment of Staphylococcus aureus isolated from atopic dermatitis lesions to plastic tissue-culture coverslips . We found that attachment was weaker in (rabbit) plasma with 5 or 10% NaCl and in plasma with 5 or 10% sea salts than in the control plasma after incubation for 2 h (P < 0.01) . The attachment was weaker still in plasma with 10% NaCl or 10% sea salts than in the control plasma after incubation for 24 h (P < 0.01) . Plasma coagulation of four S . aureus strains isolated from atopic dermatitis lesions was not detected in plasma with 10% NaCl (pH 5.6) or 10% sea salts (containing 0.372% Mg2+) after incubation for 12, 24, 36 and 60 h . The attachment of S . aureus strain cells to the coverslip in plasma was weaker after irradiation with UVA at 25 or 50 J/cm2 (P < 0.01) and UVB at 0.5 J/cm2 (P < 0.05) both of which are covered by a black cloth, than without irradiation after incubation for 24 h . Plasma coagulation was not detected after irradiation with UVA at 25 or 50 J/cm2 with a black cloth cover (temperature reached 50 degrees C), but was detected after UVA irradiation at the same doses combined with cooling (temperature reached 22 degrees C), after incubation for 24 h . The results suggest that the attachment of S . aureus cells isolated from atopic dermatitis lesions to the coverslip is suppressed in the presence of 10% salts and irradiation with UVA and UVB, and that plasma coagulation of S . aureus cells isolated from atopic dermatitis lesions is suppressed in the presence of 10% salts, irradiation with UVA, and heating.

Microb Drug Resist, 1998 Summer, 4(2), 107 - 12
Spread of the multiresistant Iberian clone of methicillin-resistant Staphylococcus aureus (MRSA) to Italy and Scotland; Mato R et al.; The multidrug-resistant "Iberian" clone of methicillin-resistant Staphylococcus aureus (MRSA) was first identified on the basis of its unique DNA fingerprints as the strain responsible for the massive 1989 outbreak of MRSA disease in the hospital Princeps d'Espanya, Barcelona, Spain . Most Iberian MRSA carry a constitutive beta-lactamase . They are resistant to most beta-lactam antibiotics, macrolides, aminoglycosides, tetracycline, rifampin and ciprofloxacin and are susceptible to fosfomycin, fusidic acid, mupirocin, sulfamethoxazole/trimethoprim and vancomycin . The characteristic DNA fingerprints of the clone include the mecA polymorph I, Tn554 pattern E (or its variants), a chromosomal macrorestriction pattern (pulsed-field gel electrophoretic type) A (or its subtype variants), the lack of the mecI regulatory gene and a homogeneous, high level of expression of methicillin resistance . Molecular surveillance studies have documented the extensive spread of this clone to many Portuguese hospitals during the 1990s . In this article, we describe the spread of the Iberian MRSA to hospitals in Rome, Italy, and Scotland.

Microb Drug Resist, 1998 Summer, 4(2), 85 - 90
Molecular cloning and DNA sequencing of the Staphylococcus aureus UDP-N-acetylmuramyl tripeptide synthetase (murE) gene, essential for the optimal expression of methicillin resistance; Ludovice AM et al.; The Tn551 insertion in mutant RUSA235 of a highly methicillin resistant Staphylococcus aureus strain results in drastic reduction in the level of methicillin resistance and abnormalities, both in the composition of the peptidoglycan and of the cell wall precursor pool . Cloning and sequencing of the inactivated gene indicates that it is the murE gene of Staphylococcus aureus.

Am J Respir Cell Mol Biol, 1998 Jul, 19(1), 83 - 91
Localization of Staphylococcus aureus in infected airways of patients with cystic fibrosis and in a cell culture model of S . aureus adherence; Ulrich M et al.; Staphylococcus aureus causes chronic respiratory tract infections in patients with cystic fibrosis (CF) . Using immunofluorescence and scanning and transmission electron microscopy we located S . aureus in lung specimens of three infected CF patients, in a nasal polyp of one CF patient, and in a suspension cell culture system of primary nasal epithelial cells in vitro . Very little of S . aureus was attached to the lung epithelium, whereas abundant S . aureus was detectable in the mucus of obstructed airways . Similarly, S . aureus adhered to components of secreted mucus on primary nasal epithelial cells of CF patients and healthy control subjects, grown as cell balls in vitro (bacteria/cell +/- SD: CF: 21.9 +/- 1.5; controls: 22 . 0 +/- 5.8) . Mucus depletion of cell balls prior to incubation with S . aureus resulted in a significantly reduced binding (bacteria/cell +/- SD: CF: 4.2 +/- 0.3; P < 0.001; controls: 5.0 +/- 1.3; P < 0 . 007) . Binding of S . aureus to cell balls from CF patients or control subjects did not differ significantly . When cell balls were treated with human neutrophil elastase, hypersecretion caused removal of S . aureus from cell-associated mucus . The results suggest that S . aureus adheres primarily to mucus components of the respiratory epithelium and that significant differences do not exist in binding of S . aureus to CF or non-CF cells.

J Submicrosc Cytol Pathol, 1998 Apr, 30(2), 271 - 7
Further studies on the phagocytic capacity of chicken thrombocytes; DaMatta RA et al.; Thrombocytes, functional analog to mammalian platelets, have been described as the primary circulating phagocyte in chicken blood when challenged with bacteria (Chang and Hamilton, 1979) . In order to determine if the phagocytic capacity could be extended to protozoa, interaction of chicken thrombocytes with tachyzoites of Toxoplasma gondii and bloodstream trypomastigotes of Trypanosoma cruzi was performed . Interaction with Staphylococcus aureus and Escherichia coli was also performed using fluoresceinated and living bacteria, to be examined by fluorescence microscopy (after ethidium bromide staining) and transmission electron microscopy (after ruthenium red fixation) . Using these approaches it was possible to distinguish internalized from attached bacteria . T . cruzi was only found attached to the thrombocyte surface while T . gondii could be observed within the cell . To determine if T . gondii invasion was active or by phagocytosis, interaction was performed under conditions where active penetration and phagocytosis were inhibited by previous fixation of the parasites or treatment of thrombocytes with cytochalasin D, respectively . Interactions with fixed T . gondii showed only attached parasites . Cytochalasin D treated thrombocytes could still be found with internalized T . gondii . By fluorescence and transmission electron microscopy it was possible to observe a small number of bacteria internalized by thrombocytes . These findings show that T . gondii invade thrombocytes through an active penetration process and these blood cells cannot be considered as the primary circulating phagocyte in chicken.

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