Bactericidal

J Leukoc Biol, 1997 May, 61(5), 619 - 23
Regulation of ciprofloxacin uptake in human promyelocytic leukemia cells and polymorphonuclear leukocytes; Loo KC et al.; Polymorphonuclear leukocytes (PMNs) actively internalize ciprofloxacin, a capability that can enhance killing of intracellular bacteria and facilitate delivery of the antimicrobial agent to infection sites by migrating PMNs . In this study we investigated mechanisms for up-regulation of this process . Activation with N-formyl-methionyl-leucyl-phenylalanine (fMLP; 100 nM) enhanced PMN ciprofloxacin uptake by 50% (P < 0.05) . Phorbol myristate acetate (PMA; > or = 10 nM) enhanced uptake by at least 36-fold, mainly by stimulating an increase in the Vmax of the ciprofloxacin transporter . This effect of PMA was inhibited by antagonists of protein kinase C (H7 and chelerythrine) and the mitogen-activated protein kinase cascade downstream (PD 098059) . Under resting and PMA-activated conditions, ciprofloxacin uptake by immature human promyelocytic leukemia (HL-60) cells was much lower than in PMNs . However, when HL-60 cells were induced to mature into PMN-like cells, their ciprofloxacin uptake activity increased markedly . These findings implicate a role for protein kinase C in up-regulation of the ciprofloxacin transporter and suggest that myeloid cells acquire an enhanced ability to take up ciprofloxacin as they mature to end-stage PMNs.

J Inorg Biochem, 1997 May 1, 66(2), 77 - 82
Synthesis, crystal structure, and characterization of two metal-quinolone compounds; Turel I et al.; Two novel metal-quinolone compounds have been synthesized and characterized by analytical, spectroscopic, and X-ray diffraction methods . The crystal structure of both, (erxH2) {FeCl4}Cl and (kinoH2){CuCl4} . H2O, is presented and discussed (erxH2 = doubly protonated form of enrofloxacin, kinoH2 = doubly protonated form of the second quinolone) . In both compounds, the hydrogen atom is bonded between the 4-keto oxygen O(1) and carboxylic oxygen O(11), thus preventing the bonding of the metal to this part of the molecule . Antimicrobial activities of metal-quinolone compounds were tested against different microorganisms.

Arch Intern Med, 1997 Apr 28, 157(8), 885 - 92
Fever, C-reactive protein, and other acute-phase reactants during treatment of infective endocarditis; Olaison L et al.; BACKGROUND: Fever and sustained elevations of levels of C-reactive protein, erythrocyte sedimentation rate, and other inflammatory markers are common problems during treatment of infective endocarditis . We studied the value of these measurements during an 8-year period in all episodes of infective endocarditis treated in 1 university-affiliated institution . METHODS: A total of 193 consecutive episodes that fulfilled the criteria for infective endocarditis were prospectively enrolled during 2 periods, 1984 through 1988 and 1993 through 1995 . Fever and results of serial measurements of C-reactive protein, erythrocyte sedimentation rate, white blood cell counts, and platelet counts were related to the clinical course of infective endocarditis . RESULTS: Fever persisted or recurred in 108 episodes (57%) despite appropriate antibiotic treatment . The causes of persistent fever and recurrent fever were different . Persistent fever that lasted 7 days or longer was caused by a complicating cardiac infection in 56% of these episodes . Recurrent fever, noted in 31% of all episodes and the major cause of fever during the third and fourth treatment weeks, was caused most often by hypersensitivity reactions to beta-lactams . Elevations in C-reactive protein levels were significantly prolonged in the episodes with complicated courses compared with the episodes with uncomplicated courses, while mean erythrocyte sedimentation rate remained unchanged during treatment, not differentiating between complicated and uncomplicated episodes . CONCLUSIONS: Fever during treatment must be analyzed in terms of persistence and recurrence to provide a basis for clinical decisions . Serial measurements of C-reactive protein are useful to monitor the response to antimicrobial therapy and to detect complications, while serial determinations of erythrocyte sedimentation rate are of no value.

Transplantation, 1997 Apr 27, 63(8), 1189 - 90
A case of disseminated infection with Nocardia brasiliensis in a lung transplant recipient; Palmer SM Jr et al.; BACKGROUND: Infection with Nocardia species is an increasingly recognized complication of solid organ transplantation . Nocardia asteroides accounts for most transplant-related nocardiosis, while Nocardia brasiliensis rarely causes infection in organ transplant recipients . METHODS: We describe a case of disseminated infection with N brasiliensis in a single-lung transplant recipient who also had concomitant infections with viral and fungal organisms . RESULTS: Although the mortality rate is high in immunocompromised patients with disseminated Nocardia infection, our patient responded favorably to prolonged antimicrobial therapy . CONCLUSIONS: This case illustrates that N brasiliensis, like N asteroides, produces pulmonary disease and dissemination in solid organ transplant recipients, and demonstrates the utility of prolonged treatment with trimethoprim-sulfamethoxazole in Nocardia infections.

J Exp Med, 1997 Apr 7, 185(7), 1231 - 9
Intracellular antimicrobial activity in the absence of interferon-gamma: effect of interleukin-12 in experimental visceral leishmaniasis in interferon-gamma gene-disrupted mice; Taylor AP et al.; Despite permitting uncontrolled intracellular visceral infection for 8 wk, interferon-gamma (IFN-gamma) gene knockout (GKO) mice infected with Leishmania donovani proceeded to reduce liver parasite burdens by 50% by week 12 . This late-developing IFN-gamma-independent antileishmanial mechanism appeared to be dependent largely on endogenous tumor necrosis factor-alpha (TNF-alpha): L . donovani infection induced TNF-alpha mRNA expression in parasitized GKO livers and neutralization of TNF-alpha reversed control at week 12.7 d of treatment of infected GKO mice with interleukin-12 (IL-12) readily induced leishmanicidal activity and also partially restored the near-absent tissue granulomatous response, observations that for the first time expand the antimicrobial repertoire of IL-12 to include IFN-gamma-independent effects . The action of IL-12 against L . donovani was TNF-alpha dependent and required the activity of inducible nitric oxide synthase . These results point to the presence of an IFN-gamma-independent antimicrobial mechanism, mediated by TNF-alpha, which remains quiescent until activated late in the course of experimental visceral leishmaniasis . However, as judged by the effect of exogenous IL-12 this quiescent mechanism can readily be induced to rapidly yield enhanced intracellular antimicrobial activity.

MMWR Recomm Rep, 1997 Apr 4, 46(RR-8), 1 - 24
Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP); Myeloid-related protein (MRP) 8 and MRP14 et al.; Institute of Experimental Dermatology, University of Munster, 48129 Munster, GermanyMyeloid-related protein (MRP) 8 and MRP14, two members of the S100 family expressed in myelomonocytic cells, have been ascribed some extracellular functions, e.g . antimicrobial, cytostatic, and chemotactic activities . Since S100 proteins lack structural requirements for secretion via the classical endoplasmic reticulum/Golgi route, the process of secretion is unclear . We now demonstrate the specific, energy-dependent release of MRP8 and MRP14 by human monocytes after activation of protein kinase C . This secretory process is not blocked by inhibitors of vesicular traffic through the endoplasmic reticulum and Golgi, and comparative studies on tumor necrosis factor-alpha and interleukin-1beta indicate that MRP8 and MRP14 follow neither the classical nor the interleukin-1-like alternative route of secretion . Inhibition by microtubule-depolymerizing agents revealed that MRP8/MRP14 secretion requires an intact tubulin network . Accordingly, upon initiation of MRP8/MRP14 secretion, immunofluorescence microscopy showed a co-localization of both proteins with tubulin filaments . Release of MRP8 and MRP14 is associated with down-regulation of their de novo synthesis, suggesting that extracellular signaling via MRP8/MRP14 is restricted to distinct differentiation stages of monocytes . Our data provide evidence that the S100 proteins MRP8 and MRP14 are secreted after activation of protein kinase C via a novel pathway requiring an intact microtubule network.

Farmaco, 1997 Apr, 52(4), 259 - 61
3,6-Disubstituted 1,2,4-triazolo{3,4-b}{1,3,4}thiadiazoles: synthesis and evaluation for antimicrobial and antiviral activity . III; Invidiata FP et al.; A series of novel 3,6-disubstituted 1,2,4-triazolo{3,4-b}{1,3,4}thiadiazole derivatives was prepared and tested to evaluate their antimycotic, antibacterial and anti-HIV-1 activities . The reaction of thiocarbohydrazide with carboxylic acids at the melting temperature allows an improved preparation of the 5-substituted 4-amino-3-mercapto-1,2,4-triazole heterocycles which in turn allows an easier preparation of the 1,2,4-triazolo{3,4-b} {1,3,4}thiadiazole ring system . All tested compounds didn't show any significant activity.

Farmaco, 1997 Apr, 52(4), 231 - 5
Synthesis, antimicrobial and genotoxic properties of some benzoimidazole derivatives; Benvenuti S et al.; A number of 1H-benzoimidazol-2-ylamine and of 1-methyl-1H-benzoimidazol-2-ylamine derivatives were synthesized and the crystal and molecular structure of N-{4-(2-amino-benzoimidazole-1-sulfonyl)-phenyl} acetamide was determined by X-ray diffraction analysis . The compounds obtained were investigated for antimicrobial and genotoxic activities.

Genitourin Med, 1997 Apr, 73(2), 88 - 94
Health education and promotion for STD prevention: lessons for the next millennium; Darrow WW; OBJECTIVE: To review the evolution of health promotion for STD prevention . MAIN OBSERVATIONS: Information and education programmes were provided at the beginning of the 20th century to warn the public about the dangers of venereal infection and to support the medical model of case identification and case management under the care of qualified physicians . The public health approach offered advice about chemical, chemotherapeutic, and barrier prophylaxis, but avoided the issue of social prophylaxis . With the failure of antimicrobial agents to eradicate syphilis in the 1960s, rapid increases of viral sexually transmitted diseases (STDs) and resistant strains of gonorrhoea in the 1970s, and the discovery of AIDS in the 1980s, alternatives to the traditional public health approach were sought and supported with a modest increase of resources . Three major innovations have been introduced to STD prevention as a result: social marketing, community involvement, and behaviour change programmes based on social and psychological concepts and theoretical models . CONCLUSIONS: Health promotion for STD prevention in the future will be characterised by careful assessments of the social and behavioural determinants of sexual risk taking, development and implementation of targeted interventions designed to reduce risk taking, and evaluation of social and behavioural interventions for improvements in STD prevention.

An Esp Pediatr, 1997 Apr, 46(4), 351 - 6
{Prospective study of 288 cases of acute appendicitis during childhood: characteristics in preschool children}; Alvarez Bernaldo de Quiros M et al.; OBJECTIVE: The purpose of this study was to verify that preschool children with acute appendicitis show some clinical characteristics which, associated with the faster evolution of the infection at this age, result in a higher incidence of perforations, peritonitis and complications . PATIENTS AND METHODS: A group of 288 children between 9 months and 17 years of age with acute appendicitis was studied over a 17-month period, ending July 1993 . They were divided into two age groups: Group I (< 5 years: n = 45) and Group II (5 or more years: n = 243) . Comparisons between clinical, laboratory and radiological findings, appendiceal pathology, microbiology and complications were made . RESULTS: Children fro Group I showed a higher incidence of perforations (29% vs 7.8%), peritonitis (69% vs 36%), appendiceal masses (37% vs 10.2%), positive cultures (66% vs 18%) and complications (24% vs 9.8%) than those from Group II . All differences were found to be significant (p < 0.05) . Children from Group I more frequently showed a set of clinical characteristics forming an atypical picture consisting of: 1) Diffuse abdominal pain (69% vs 30%); 2) Associated infections with non-specific symptoms (33% vs 11.5%); 3) Previous therapy with antimicrobial agents (40% vs 9.8%); 4) X-ray findings compatible with gastroenteritis (27% vs 7.4%); and 5) Inability of the child to specify the intensity and location of pain . CONCLUSIONS: All these factors justified the delay in the diagnosis and its significant relationship with the higher incidence of peritonitis in this age group.

Arzneimittelforschung, 1997 Apr, 47(4A), 475 - 82
Anti-Helicobacter pylori activities of ebrotidine . A review of biochemical and animal experimental studies and data; Slomiany BL et al.; Infection with Helicobacter pylori (H . pylori) is now recognized as a major factor in the pathogenesis of gastric disease, and the successful therapy regimens require a combination of H2 blockers with gastroprotective and antimicrobial agents . Ebrotidine (N-{(E)-{{2-{{{2-{(diaminomethylene) amino}-4-thiazolyl} methyl}thio}ethyl}amino}methylene}-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) is the only drug combining acid-suppressant activity with remarkable gastroprotective and anti-H . pylori properties . The drug not only displays a potent anti-H . pylori activity alone, but also exerts a strong potentiating effect on the efficacy of antimicrobial agents commonly used for H . pylori eradication, and the successful ulcer therapy with ebrotidine induces a significant (4-fold) increase in the H . pylori aggregation titer of gastric mucin . Moreover, the drug exhibits a strong inhibitory effect on H . pylori urease activity, the extent of which exceeds that of ranitidine, omeprazole and lansoprazole . Ebrotidine has also been demonstrated to exert a potent inhibitory action on the enzymatic activities directed towards mucus perimeter of gastric mucosal defense, causing a marked inhibition of H . pylori protease, lipase and phospholipase A2 activities . Another important property of ebrotidine is its ability to efficiently counteract the disruptive effects of H . pylori lipopolysaccharide on the integrity of gastric epithelium . This includes countering the interference by the lipopolysaccharide in mucosal integrin receptor interaction with proteins of extracellular matrix and the reversal of H . pylori disruptive effect on the binding of mucin to its gastric epithelial receptor . Furthermore, most recent data indicate that ebrotidine has the ability to reverse the impairment caused by H . pylori in feedback inhibition of gastrin release by somatostatin . This activity of ebrotidine apparently stems from the drug's ability to counter the untoward effect of H . pylori on the binding of somatostatin to its specific receptor on the gastric mucosal G-cells . The unique combination of acid suppressant, gastroprotective and anti-H . pylori activities makes ebrotidine a drug of choice in the treatment of gastric disease caused by H . pylori.

Arzneimittelforschung, 1997 Apr, 47(4A), 471 - 4
In vitro anti-Helicobacter pylori activity of ebrotidine; Palacin C et al.; The in vitro anti-Helicobacter pylori (H . pylori) activity of ebrotidine (N-{(E)-{{2-{{{2-{(diaminomethylene) amino}-4-thiazolyl}methyl}thio}ethyl}amino}methylene}-4-bromo- benzenesulfonamide, CAS 100981-43-9, FI-3542) versus ranitidine, and their effect on the susceptibility to the antimicrobial agents used in H . pylori eradication were investigated . Assessment was performed by determining the minimum inhibitory concentrations (MIC) against 9 strains of H . pylori, 8 from clinical source and 1 from the American Type Culture Collection (ATCC 43504), in Mueller-Hinton solid media plus 7% blood . The concentration of inocula was 10(7) CFU/ml, incubation was performed at 37 degrees C in microaerophilic atmosphere, and results were read after 5 days of growth . Ebrotidine gave a mean MIC value of 75 micrograms/ml, while that for ranitidine was > 1000 micrograms/ml . Ebrotidine at 100 micrograms/ml enhanced the activity of the antimicrobials studied as follows: erythromycin 3 times, tetracycline 1.1 times, amoxicillin 3 times, metronidazole-sensitive strains 9 times and clarithromycin 5 times . Ranitidine had no effect on the MIC of the antibiotics even at 500 micrograms/ml.

J Antibiot (Tokyo), 1997 Apr, 50(4), 344 - 9
Antimicrobial activities of chemically modified thiazolyl peptide antibiotic MDL 62,879 (GE2270A); Lociuro S et al.; MDL 62,879 (GE2270A) 1 is a new inhibitor of elongation factor-Tu (EF-Tu) and belongs to the class of thiazolyl peptide antibiotics . Controlled acid hydrolysis of 1 followed by treatment with base resulted in the lost of the two terminal amino acids and in the formation of water-soluble MDL 62,935 2 . Although less active in vitro than its parent compound, 2 was able to inhibit by 50% an Escherichia coli cell-free protein synthesis system at roughly the same concentration of 1 . MDL 62,935 2 was subjected to further modification at the beta-phenylserine residue . Derivatives obtained from 2 were less active in both antimicrobial (MIC) and enzymatic (IC50) assays . This suggests that beta-phenylserine plays an important role for the inhibition of EF-Tu by 1 and 2.

J Antibiot (Tokyo), 1997 Apr, 50(4), 334 - 8
Antimicrobial activity of viridiofungins; Onishi JC et al.; A family of aminoacyl alkyl citrate compounds called viridiofungins, are novel squalene synthase inhibitors . The compounds have broad spectrum fungicidal activity but lack antibacterial activity . Although the compounds inhibit squalene synthase, the first committed step in ergosterol biosynthesis, results presented in this paper show that inhibition of fungal growth is not related to inhibition of ergosterol synthesis.

J Antibiot (Tokyo), 1997 Apr, 50(4), 314 - 7
NF00659A1, A2, A3, B1 and B2, novel antitumor antibiotics produced by Aspergillus sp . NF 00659 . I . Taxonomy, fermentation, isolation and biological activities; Suzuki K et al.; Five novel cytotoxic antibiotics, NF00659A1 (1), A2 (2), A3 (3), B1 (4) and B2 (5) were discovered . They were isolated from a culture mycelium of Aspergillus sp . These compounds were proved to have 4,5-seco-tricyclic diterpene alpha-pyrone structure by spectroscopic analyses . They showed potent antitumor activities against human ovarian carcinoma A2780 and human colorectal adenocarcinoma SW480 cells, but did not show any antimicrobial activities at 1,000 micrograms/ml against Gram-positive and Gram-negative bacteria, yeasts and fungi.

Histochem J, 1997 Apr, 29(4), 287 - 91
In situ detection of constitutive superoxide anion production in granules of mast cells; Frederiks WM et al.; 3,3'-Diaminobenzidine, in the presence of manganese and cobalt ions, was applied for the detection of superoxide anions in unfixed cryostat sections of rat oesophagus, trachea, skin and intact mesenterium . In all connective tissues, a blue final reaction product was found in a granular form in mast cells . The amount of final reaction product formed after incubation with diaminobenzidine and cobalt ions was increased by the addition of manganese ions . Electron microscopical analysis revealed that the electron-dense final reaction product was exclusively present in the granules of mast cells and on elastin fibres . It was found that the constitutive spontaneous formation of final reaction product in mast cells was enzymatic and dependent on the presence of oxygen in the medium . Of all the enzyme inhibitors and free radical scavengers tested, only azide strongly reduced the amount of final reaction product . It was concluded that the reaction was partly caused by peroxidase activity, but that superoxide anions are also constitutively and spontaneously produced in mast cell granules . The exact enzymatic source could not be established . Whether this property of mast cell granules plays an antimicrobial role in connective tissues can only be speculated.

Nutrition, 1997 Apr, 13(4 Suppl), 26S - 29S
Prevention of catheter-related infections: the skin; Darouiche RO et al.; Although intravascular devices have become indispensable tools in the care of seriously ill patients, the morbidity and mortality resulting from catheter-related infections and the high cost of managing such complications may offset the benefits derived from these devices . A scientific understanding of the pathogenesis, microbiology, and risk factors involved in catheter-related infection is the cornerstone of any effective preventive approach . Prevention of vascular catheter-related infection mostly centers around inhibiting the adherence to the catheter of microorganisms originating from either the skin or the catheter hub . Two general approaches can be used nonexclusively for successful prevention of vascular catheter-related infection . The first approach does not use antimicrobial agents and includes measures such as placement and maintenance of vascular catheters by a skilled infusion therapy team and use of maximal sterile barriers . The second approach uses antimicrobial agents and involves the application of topical disinfectants such as chlorhexidine, use of silver-impregnated subcutaneous cuffs (for short-term central venous catheters), flushing catheters with a combination of antimicrobial and antithrombotic agents, and coating of catheters with either antiseptic (chlorhexidine and silver sulfadiazine) or antimicrobial agents (minocycline and rifampin).

J Pept Res, 1997 Apr, 49(4), 336 - 40
Location of the three disulfide bonds in an antimicrobial peptide from Amaranthus caudatus using mass spectrometry; el Bouyoussfi M et al.; The disulfide bridge pairing of Ac-AMP2, a 30-residue peptide isolated from the seeds of Amaranthus caudatus, is determined using a fast method involving enzymatic fragmentation followed by identification of the fragments with FAB mass spectrometry . The results confirm the location of the three disulfide bridges as previously established by NMR spectroscopy and molecular modelling.

J Chemother, 1997 Apr, 9(2), 95 - 101
Randomized trial comparing netilmicin plus imipenem-cilastatin versus netilmicin plus ceftazidime as empiric therapy for febrile neutropenic bone marrow transplant recipients; Laszlo D et al.; The aim of this study was to compare the clinical and microbiological efficacy of netilmicin plus imipenem-cilastatin (Net + Imi) vs netilmicin plus ceftazidime (Net + Cef) as empiric antimicrobial therapy in bone marrow transplant (BMT) febrile neutropenic patients (pts) . Sixty-six pts undergoing BMT for hematological malignancies and solid tumors were randomized to receive Net + Imi or Net + Cef as first-line antibiotic therapy . A lasting return of temperature to normal and complete disappearance of either clinical or cultural signs of infection without any modification of therapy was considered as improvement; the persistence of fever after 72 hours, the addition of a third antibiotic or a protocol change was considered as failure . Sixty-nine episodes were randomized during the course of the trial; bacteriological evidence of infection was obtained in 17 (25%) febrile episodes . Overall outcome based on clinical responses was as follows: 80% of pts on Net + Imi responded compared to 73% of those on Net + Cef . For microbiologically documented infections response rates were 70% in Net + Imi group and 43% in the Net + Cef group (p = ns) . Neither septic death nor toxicity were observed . Both empiric regimens were shown to be effective; Net + Imi appeared to be more effective in microbiologically documented infections but there was no statistical significance . In conclusion, both Net + Imi and Net + Cef are active and safe as empirical treatment of febrile episodes in neutropenic BMT pts.

J Ethnopharmacol, 1997 Apr, 56(2), 165 - 9
Antiviral activity of galangin isolated from the aerial parts of Helichrysum aureonitens; Meyer JJ et al.; The in vitro antiviral activity of galangin (3,5,7-trihydroxyflavone), the major antimicrobial compound isolated from the shoots of Helichrysum aureonitens, was investigated against herpes simplex virus type 1 (HSV-1), coxsackie B virus type 1 (Cox B1), adenovirus type 31 (Ad31) and reovirus . At concentrations ranging from 12-47 micrograms/ml galangin showed significant antiviral activity against HSV-1 and CoxB1, limited activity against reovirus, and no antiviral activity against Ad31.

Trop Med Int Health, 1997 Apr, 2(4), 383 - 8
Olive oil aspiration pneumonia (lipoid) in children; Annobil SH et al.; In the Asir region of south-western Saudi Arabia, nasal instillation of olive oil to infants and children in the recumbent position is practised to relieve nasal congestion . Aspiration of olive oil results in lipoid pneumonia resistant to antimicrobial treatment . A series of 5 children, aged 4-72 months, with olive oil-induced lipoid pneumonia is presented . Clinical presentation included persistent coughing, tachypnoea, recurrent febrile illness and chest infections . The pulmonary radiological picture was mainly right middle lobar and perihilar infiltrates . Bronchial lavage and microscopic examination of the aspirate confirmed the presence of fat globules . The pneumonia resolved on treatment with steroids and physiotherapy in the form of clapping and vibrations . For infants and children in this area who present with persistent pulmonary infiltrates which are not responsive to antimicrobials, the differential diagnosis of not only animal fat (ghee, clarified butter) but also of olive oil lipoid pneumonia must be considered.

Mol Microbiol, 1997 Apr, 24(2), 263 - 70
Biochemistry and molecular genetics of cell-wall lipid biosynthesis in mycobacteria; Kolattukudy PE et al.; Tuberculosis and other mycobacterial infections are the most serious infectious diseases in terms of human fatalities . The high content of unique cell-wall lipids helps these organisms to resist antimicrobial drugs and host defences . The biosynthesis of these lipids is discussed briefly . The recent advances in recombinant DNA technology have begun to help to elucidate the nature of some of the enzymes involved in this process and the genes that encode them . Gene disruption and other molecular genetic technologies are beginning to provide new approaches to test for the biological functions of these gene products and may lead to identification of new antimycobacterial drug targets.

J Clin Microbiol, 1997 Apr, 35(4), 847 - 52
Comparison of agar dilution, broth microdilution, disk diffusion, E-test, and BACTEC radiometric methods for antimicrobial susceptibility testing of clinical isolates of the Nocardia asteroides complex; Ambaye A et al.; An evaluation was undertaken to determine the optimal method for the in vitro susceptibility testing of 26 Nocardia asteroides complex isolates to the following antimicrobial agents: amikacin, ampicillin, amoxicillin-clavulanate, ceftriaxone, ciprofloxacin, erythromycin, imipenem, minocycline, and trimethoprim-sulfamethoxazole . Five testing methods were studied including the agar dilution, broth microdilution, and disk diffusion methods, the epsilometer test (E-test), and the BACTEC radiometric method . Results for each antimicrobial agent and each testing method were interpreted as indicating susceptibility, intermediate susceptibility, or resistance according to current guidelines of the National Committee for Clinical Laboratory Standards (NCCLS) for bacteria that grow aerobically and were then compared to a "gold standard" susceptibility test result . The gold standard result for each Nocardia isolate was established by a consensus of the results of the majority of testing methods used in the study . When the results were combined for all antimicrobial agents tested against all Nocardia isolates by all methods, the BACTEC radiometric method produced the highest level of agreement (97.9%) with the consensus results and had the fewest very major (n = 1), major (n = 2), and minor (n = 2) errors . In contrast, the results of the agar dilution method were in least agreement (93.2%) with the consensus results, and this method also produced the most very major (n = 8), major (n = 4), and, along with the disk diffusion method, minor (n = 6) errors . For all test methods, interpretive errors were most frequent when testing ampicillin or amoxicillin-clavulanate . Moreover, for all Nocardia nova isolates tested, ampicillin susceptibility results by any of the testing methods were not in agreement with the results of testing for beta-lactamase by the nitrocefin (Cefinase) disk method . We conclude that among the methods evaluated, the BACTEC radiometric method appeared to be the best for determining the in vitro susceptibilities of members of the N . asteroides complex to a panel of nine antimicrobial agents . However, none of the test methods, including the BACTEC method, accurately predicted the ampicillin resistance of the N . nova isolates tested, all of which produced beta-lactamase . Presuming that this beta-lactamase hydrolyzes ampicillin, this disparity may relate to the NCCLS breakpoints that were used, which may require modification for this antimicrobial agent when tested against N . nova isolates.

Pharm World Sci, 1997 Apr, 19(2), 89 - 92
The anaesthetist as determinant factor of quality of surgical antimicrobial prophylaxis . A survey in a university hospital; Gyssens IC et al.; In actual surgical antimicrobial prophylaxis, the anaesthetist administers the drugs at induction of anaesthesia . In the first phase of our quality-of-use intervention study on antimicrobial drugs in a large university hospital, information on the practice of antimicrobial prophylaxis was needed . The staff of 44 anaesthetists was interviewed by means of a questionnaire . Response rate was 36/44 (82%) . The anaesthetists' method of administering surgical prophylaxis was rather uniform and inexpensive: cephalosporins were almost exclusively administered by bolus method . The main reason was that infusion was more cumbersome (range 77-85%) . Communication between surgeon and anaesthetist was reported to be poor, and in two out of three operating departments, orders of prophylaxis transmitted at or after induction accounted for more than 80% . Seventy-seven percent of the responders asked the surgeon if prophylaxis was necessary if they were in doubt; 20% responded that they checked it systematically . The data collected by the inquiry proved useful in the process of optimizing surgical prophylaxis in our hospital.

Int J Oral Maxillofac Surg, 1997 Apr, 26(2), 131 - 4
Characterization and management of deep neck infections; Sakaguchi M et al.; A retrospective review was conducted of 91 patients with deep neck infections to determine the pattern of clinical disease and formulate a management plan . The spaces involved, as determined by clinical, radiologic, and operative findings, were the peritonsillar space (72 patients), parapharyngeal space (eight patients) submandibular space (seven patients), retropharyngeal space (one patient) superficial space (one patient), anterior visceral space (one patient), and visceral vascular space (one patient) . Of the 19 patients who did not have a peritonsillar space infection the origin of the infection was found in eight; four of these were odontogenic . Thirty-eight patients required surgical drainage of the abscess . Five patients underwent tracheotomy due to increasing dyspnea . One patient with diabetes mellitus and a past history of myocardial infarction died of unknown cause . All other patients had an uneventful recovery without major complications . The combination of early radiologic diagnosis, effective antimicrobial therapy, and intensive surgical management contributed to the good prognosis.

Arzneimittelforschung, 1997 Apr, 47(4), 413 - 5
Aqueous humor penetration of topically applied ciprofloxacin, ofloxacin and tobramycin; Durmaz B et al.; The purpose of this study was to determine the aqueous humor concentrations of topically applied ciprofloxacin (CAS 86393-32-0), ofloxacin (CAS 82419-36-1) and tobramycin (CAS 79645-27-5) . Thirty patients undergoing cataract extraction or trabeculectomy were randomly divided into three groups and each of the group received either 0.3% ciprofloxacin, ofloxacin or tobramycin topical drops preoperatively . Eyedrops were instilled for six times at a frequency of one drop every 15 minutes, beginning 90 minutes before initiation of the surgery . At the time of surgery, 0.1 ml aqueous fluid was aspirated from the anterior chamber . Concentrations of the antimicrobial agents were determined using the microbroth dilution procedure outlined by the National Committee for Clinical Laboratory Standards . Escherichia coli (ATCC 25922) was used as a standard strain for determination of minimal inhibitory concentrations (MICs) . The mean aqueous levels of ciprofloxacin and ofloxacin were found to be 0.092 +/- 0.077 microgram/ml, 0.964 +/- 0.693 microgram/ml, respectively . Tobramycin did not reach the concentration that could be detected by applied method . CONCLUSION: The mean aqueous humor levels of ofloxacin and ciprofloxacin were more than the MICs levels for most of the ocular pathogens which may cause postoperative endophthalmitis.

J Periodontol, 1997 Apr, 68(4), 346 - 52
Clinical and microbiological effects of subgingival antimicrobial irrigation with citric acid as evaluated by an enzyme immunoassay and culture analysis; Renvert S et al.; The purpose of the present study was to compare an enzyme immunoassay with culture samples from untreated and non-surgically treated periodontal pockets and to assess the clinical and microbiological effects of citric acid irrigation as a supplement to scaling and root planing . The enzyme immunoassay used in this study is a chairside diagnostic tool aimed at identifying the presence of P . gingivalis, P . intermedia, and A . actinomycetemcomitans . Six sites with pocket depths > or = 6 mm in each of 16 patients were monitored for 24 weeks using clinical and microbiological parameters . In two out of the six sites, scaling and root planing was supplemented with subgingival citric acid irrigation of the pocket after completion of the mechanical treatment . The sensitivity of the immunoassay in relation to culture was calculated to 85.5% and the specificity to 90.2% . The immunoassay corresponded to a detection level of 10(4) as estimated by culture . Sites treated with a combination of scaling and irrigation with citric acid demonstrated a similar healing pattern as sites treated with scaling and root planing alone . The profile of the marker bacteria was almost parallel for the two groups . The results of this investigation thus indicated that the immunoassay can be used as a screening tool for selected periodontal pathogens and that adjunctive irrigation with citric acid has no measurable clinical or microbiological effects.

Aliment Pharmacol Ther, 1997 Apr, 11 Suppl 1, 55 - 61
Reinfection versus recrudescence in Helicobacter pylori infection; van der Ende A et al.; Antimicrobial treatment of Helicobacter pylori is the proper management strategy in patients with ulcers . A high rate of H . pylori reinfection after successful eradication therapy however, may give rise to ulcer recurrence . The risk of reinfection, depending on the prevalence and the rate of acquisition of H . pylori infection, varies with socioeconomic status, age and geographical location . The rate of reinfection may vary in a similar way . The available data in the literature reveal that reinfection by H . pylori is low or absent in developed countries and may be lower than the initial rate of acquisition . In addition, reported cases of H . pylori reinfection are often cases of recrudescent H . pylori infection . Acquisition rate in developing countries is high, so the reinfection rate is expected to be higher than in developed countries . However, studies discriminating reinfection from recrudescence are lacking and therefore more data from developing regions are needed to settle if 'cured once, cured forever' holds true.

J Antimicrob Chemother, 1997 Apr, 39(4), 543 - 7
Over-the-counter availability of antimicrobial agents, self-medication and patterns of resistance in Karachi, Pakistan; Sturm AW et al.; To determine whether the free availability of antimicrobial agents leads to misuse through self-medication, a house-to-house semi-structured interview was held in three different socio-economic areas of Karachi, Pakistan . Of the 2348 households visited, 1342 (57%) participated; this included 9209 individuals . Three hundred and twenty-two (3.5%) had used one or more antimicrobial in the previous 4 weeks, equivalent to 43 agents per 1000 persons per month . The most frequently used agents were amoxycillin (16.7%), co-trimoxazole (15.7%), erythromycin (10.9%), ampicillin/cloxacillin (Ampiclox, 9.1%) and metronidazole (4.5%) . Of these, 91.4% were prescribed by a physician, 2.3% were advised by a chemist and 6.3% were used as self-medication . Self-medication increased with socio-economic status . High levels of resistance were found to ampicillin, co-trimoxazole, chloramphenicol and erythromycin . If these high resistance levels are related to the high frequency of antimicrobial use, over-the-counter availability cannot be held responsible . Education of the medical profession seems to be the single most important tool to control misuse of antimicrobial agents . Innovative approaches for continuous medical education are urgently needed.

J Antimicrob Chemother, 1997 Apr, 39(4), 527 - 35
Indications for antibiotic use in ICU patients: a one-year prospective surveillance; Bergmans DC et al.; The high prevalence of nosocomial infections in critically ill ICU patients is associated with high antibiotic consumption . Besides its economic impact, there is the constant threat of selection and induction of antibiotic resistance . Surveillance studies recording the incidence of infections, antibiotic use, and antimicrobial susceptibilities of pathogens supply vital information regarding infection control and prevention of antibiotic resistance . In order to analyse antibiotic consumption we recorded antibiotic use in a general ICU during one year by categorizing the indications for antibiotic use into three groups; (i) prophylaxis; (ii) therapy for a bacteriologically proven infection (BPI); (iii) therapy for a non-bacteriologically proven infection (non-BPI) . Bronchoscopic techniques were used to diagnose pneumonia . In practice, BPI must be treated, but a proportion of antibiotics prescribed for non-BPI may be unnecessary . The subdivision in BPI and non-BPI may help to identify these cases . In all, 515 patients were admitted to ICU and 36% of these had at least one infection . Of all infections, 53% were ICU-acquired and 99% of these occurred in intubated patients . Antibiotics were prescribed in 61% of admissions . Of all antibiotics prescribed for therapy, 49% were for respiratory tract infections, 19% for abdominal infections and 13% for sepsis eci . Categorized by indication, 59% of all antibiotic prescriptions were for BPI, 28% for non-BPI and 13% for prophylaxis . A theoretical reduction of 25% in the number of non-BPI prescriptions would result only in a 7% decrease of total antibiotic use . We conclude that almost all antibiotics prescribed were for intubated patients and for BPI . Respiratory infections were the single most common infection and accounted for 49% of all antibiotics used . Therefore, in our setting, prevention of respiratory tract infections is probably the most effective mode to reduce antibiotic use.

Clin Infect Dis, 1997 Apr, 24(4), 713 - 6
Endophthalmitis due to Microbacterium species: case report and review of microbacterium infections; Funke G et al.; Microbacterium species (formerly CDC {Centers for Disease Control and Prevention} coryneform group A-4 and A-5 bacteria) are widely distributed in the environment and rarely cause infections in humans . We present a case of endophthalmitis due to Microbacterium species that occurred after accidental trauma and review the literature on microbacterium infections . If the infected tissue or medical device is removed and antimicrobial therapy (preferably with beta-lactams or glycopeptides) is instituted, the prognosis is usually favorable for patients with microbacterium infections.

Plant Cell, 1997 Apr, 9(4), 509 - 20
Overexpression of an endogenous thionin enhances resistance of Arabidopsis against Fusarium oxysporum; Epple P et al.; Thionins are antimicrobial proteins that are thought to be involved in plant defense . Concordant with this view, we have recently shown that the Arabidopsis thionin Thi2.1 gene is inducible by phytopathogenic fungi . Here, we demonstrate that constitutive overexpression of this thionin enhances the resistance of the susceptible ecotype Columbia (Col-2) against attack by Fusarium oxysporum f sp matthiolae . Transgenic lines had a reduced loss of chlorophyll after inoculation and supported significantly less fungal growth on the cotyledons, as evaluated by trypan blue staining . Moreover, fungi on cotyledons of transgenic lines had more hyphae with growth anomalies, including hyperbranching, than on cotyledons of the parental line . No transcripts for pathogenesis-related PR-1, PR-5, or the pathogen-inducible plant defensin Pdf1.2 could be detected in uninoculated transgenic seedlings, indicating that all of the observed effects of the overexpressing lines are most likely the result of the toxicity of the THI2.1 thionin . Our findings strongly support the view that thionins are defense proteins.

Pharm Res, 1997 Apr, 14(4), 450 - 7
Textural analysis and flow rheometry of novel, bioadhesive antimicrobial oral gels; Jones DS et al.; PURPOSE: This study examined the rheological and textural characteristics (hardness, compressibilty, adhesiveness and cohesiveness) of bioadhesive oral gels containing the antimicrobial agent chlorhexidine . METHODS: Textural analysis was performed using a Stable Micro Systems texture analyser (model TA-XT 2) in texture profile analysis (TPA) mode . In this, an analytical probe was twice compressed into each formulation to a defined depth (15 mm) and at defined rates (2, 4, 6, 8, 10 mm s-1), allowing a delay period (15 s) between the end of the first and beginning of the second compressions . Flow rheograms were performed using a Carri-Med CSL2-100 rheometer with parallel plate geometry under controlled shearing stresses at 20.0 +/- 0.1 degrees C . RESULTS: All formulations exhibited pseudoplastic flow with thixotropy . Increasing concentrations of each polymer significantly increased formulation hardness, compressibility, adhesiveness and zero-rate viscosity . Increased hardness and compressibility were due to the attendent increased viscosities of these formulations . Increased adhesiveness was related to the concentrations of the (bioadhesive) polymers employed in these formulations and, in addition, was dependent on the physical state of polycarbophil . Formulation viscosity contributed to product adhesiveness, reflecting the importance of product rheology on this parameter . Decreased formulation cohesiveness, observed as the concentrations of the PVP, PC and HEC (3-5% w/w) were increased, was due an increase in semi-solid character . Numerical values of hardness, compressibility and adhesiveness were affected by the choice of probe speed, a parameter related to rate of shear in flow rheometry . Statistical interactions were observed and were assigned to the effects of HEC on the physical state of PVP (dissolved or dispersed) and PC (swollen or unswollen) . CONCLUSIONS: This study has demonstrated both the applicability of textural analysis for the mechanical characterisation of bioadhesive semi-solid gel systems and, additionally, the direct influence of viscosity on the parameters defined by textural analysis, namely, hardness, compressibility and adhesiveness.

J Clin Periodontol, 1997 Apr, 24(4), 216 - 22
Inhibition of experimental gingivitis in beagle dogs with topical salivary histatins; Paquette DW et al.; Histatins, histidine-rich proteins found within parotid and submandibular secretions, are a novel class of endogenous peptides with antimicrobial properties . This masked, randomized, placebo-controlled preclinical investigation examined the effect of 3 topical histatins on the development of plaque and gingivitis in beagle dogs . 16, female, 1-year-old beagles were brought to optimal gingival health by mechanical scaling and polishing followed by rigorous daily tooth brushing . At the conclusion of this pretreatment period, dogs were randomly divided into 4 groups for the application of test formulations, and were placed on a plaque-promoting diet . Test agents included 3 synthetic salivary histatins (histatin 5, P-113 and P-113D) which were incorporated in hydroxypropyl methylcellulose gel at a concentration of 0.125%, and a placebo, or negative control, which was the gel vehicle alone . Throughout the 10-week treatment period, test formulations (2.0 ml) were applied 2 x daily to all premolar teeth using a Monojet syringe . Plaque formation and gingival inflammation were assessed using the plaque (PI) and gingival (GI) indices on days 0, 7, 14, 21, 28, 42, 56 and 70 . Furthermore, bleeding to probing was recorded as a percent of sites (%BOP) and according to the modified sulcus bleeding index (mSBI) . Comparisons among groups and between group pairs (active versus placebo) were made with Kruskal-Wallis tests with the average of data over the interval, days 14-42, being the primary focus of the analysis . From baseline to day 7, all groups expressed similar indices . Thereafter, overall significant differences among the groups were noted at day 42 for PI, at days 21, 28, 42 and 70 for GI, and at days 14 and 28 for %BOP (p < 0.05) . In particular, beagles treated with P-113 demonstrated significantly lower PI scores at day 42 (p < 0.05), significantly lower GI scores from days 21 through 42 (p < 0.05), and significantly lower %BOP scores at days 14 and 28 (p < 0.05) compared to beagles treated with placebo . Beagles treated with P-113D exhibited significantly lower GI at day 42 compared to the placebo (p < 0.05) . For the primary analysis conducted over the midtreatment interval (days 14-42), significant differences were detected for all parameters except mSBI (p < 0.05) . Accordingly, significantly lower PI scores were found for P-113, lower GI scores for P-113 and P-113D, and lower %BOP for P-113 and P-113D compared to placebo (p < 0.05) . These data indicate that in the beagle model, salivary histatins, P-113 and P-113D, topically applied, can significantly reduce clinical signs of plaque formation and gingival inflammation.

Am J Physiol, 1997 Apr, 272(4 Pt 1), G863 - 71
PSP expression in murine lacrimal glands and function as a bacteria binding protein in exocrine secretions; Robinson CP et al.; Nonobese diabetic (NOD) mice, an animal model for type I autoimmune diabetes and autoimmune sialoadenitis, abnormally express parotid secretory protein (PSP) in the submandibular glands (Robinson, C . P., H . Yamamoto, A . B . Peck, and M . G . Humphreys-Beher . Clin . Immunol . Immunopathol . 79: 50-59, 1996) . To evaluate possible PSP gene dysregulation in the NOD mouse, we have examined a number of organs and tissues for PSP mRNA transcripts and protein expression . Results indicate that PSP is produced in the lacrimal glands of NOD mice as well as most laboratory mouse strains . Although purified salivary PSP from C3H/HeJ or BALB/c mice fails to affect amylase enzyme activity in in vitro assays, PSP bound to whole bacteria in a Zn2+-dependent manner . Additionally, radiolabeled protein bound to specific bacterial membrane proteins using a ligand binding assay . PSP gene transcription, but not protein production, was observed in the heart and pancreas from NOD mice, indicating abnormal transcription of the PSP gene . Sequence analysis of PSP cDNA from NOD mice revealed numerous base differences (compared with the published PSP sequence) capable of leading to significant amino acid substitutions, suggestive of strain-specific differences for the protein in mice . Together these results suggest that there exists in the NOD mouse a dysregulation of PSP transcription in various tissues . However, except for C3H/HeJ mice, PSP appears as a normal product of the lacrimal glands where, as in saliva, it may function as a nonimmune antimicrobial agent in the protection of tissue surfaces exposed to the external environment.

J Periodontal Res, 1997 Apr, 32(3), 335 - 44
Effects of sanguinarium, chlorhexidine and tetracycline on neutrophil viability and functions in vitro; Agarwal S et al.; The effectiveness of an ideal antimicrobial agent depends on its ability to kill microbes with minimal toxicity to host cells . Depending on the treatment regimen, antimicrobial agents come into contact with host cells for various intervals of time . Sanguinarium (SANG), chlorhexidine (CHX) and tetracycline (TET) are 3 antimicrobial agents frequently used in the management of periodontal infections . However, their effects on host immune cells during different treatment regimens are not known . Due to their ability to serve as the first line of host defense against microbial infections, we have compared the effects of these antimicrobial agents on human neutrophil functions and viability . The results show that SANG is not lytic to neutrophils from peripheral blood or crevicular fluid, at all concentrations tested . However, exposures of neutrophils to very low concentrations of SANG (0.001%) inhibits neutrophil chemotaxis, oxidative metabolism and degranulation within 5 min . Increasing the exposure time results in a similar inhibition of neutrophil functions, albeit at 50-100 fold lower concentrations of SANG . CHX rapidly disrupts the cell membrane of both crevicular and peripheral blood neutrophils at concentrations above 0.005% within 5 min, and inhibition of all neutrophil functions is due to its lytic properties . While TET is least toxic to neutrophils, a dose dependent inhibition of neutrophil functions is dependent on the calcium concentrations of the cellular environment, and is observed only above 0.04% or higher concentrations in the absence of calcium . The data suggest that a critical cumulative concentration of these drugs is essential for their toxicity and inhibition of neutrophil functions . Therefore, both the length of exposure and the dose of the drug both are critical while considering the effectiveness of SANG, CHX or TET in the treatment of infections . Furthermore, due to differences in their mechanisms of action, the consequences of their effects on neutrophils may have significant bearing on tissue pathology as well as on their therapeutic efficacy.

J Vet Pharmacol Ther, 1997 Apr, 20(2), 105 - 10
Adverse reactions to veterinary drugs reported in Sweden during 1991-1995; Tjalve H; The present article gives a summary of suspected adverse reactions reported by Swedish veterinarians during the period 1991-1995 . The summary shows that severe adverse drug-reactions sometimes occur in Swedish veterinary practice . In horses, several cases of acute reactions in animals treated with procaine benzylpenicillin were reported and seven horses died within a few minutes after intramuscular injections of the drug . In cattle and swine most reports referred to the use of antimicrobial agents . In dogs reactions to vaccines were the most frequently reported adverse effects . The reactions were, however, usually rather mild . In dogs there were also several reports of severe reactions related to treatments with non-steroid anti-inflammatory drugs (NSAID) and alpha 2-receptor agonists . Amongst the reports six deaths were observed for each of these groups of drugs . In cats, as in dogs, adverse effects to vaccines were the most frequently reported reactions.

Infect Control Hosp Epidemiol, 1997 Apr, 18(4), 275 - 91
Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals; Shlaes DM et al.; Antimicrobial resistance results in increased morbidity, mortality, and costs of health care . Prevention of the emergence of resistance and the dissemination of resistant microorganisms will reduce these adverse effects and their attendant costs . Appropriate antimicrobial stewardship that includes optimal selection, dose, and duration of treatment, as well as control of antibiotic use, will prevent or slow the emergence of resistance among microorganisms . A comprehensively applied infection control program will interdict the dissemination of resistant strains.

Infect Control Hosp Epidemiol, 1997 Apr, 18(4), 260 - 6
Controlling use of antimicrobial agents; Duncan RA; Physicians and hospitals must curtail the excessive use of antimicrobial agents to limit the emergence and spread of multiply resistant organisms . This article describes how to organize an antimicrobial control program and provides options for hospitals working with a range of resources.

Infect Control Hosp Epidemiol, 1997 Apr, 18(4), 255 - 9
Changing the infection control paradigm from off-line to real time: the experience at Millard Fillmore Health System; Carr JR et al.; In 1993, several departments at Millard Fillmore Health System joined efforts to initiate a new approach to infection control . The main emphasis of this program is to move infection control to a real-time mode to manage patient outcomes daily . The principal objective was to decrease the number of nosocomial infections by 10%, with a particular emphasis on surgical-site infections . Besides real-time surveillance, we are critically evaluating several aspects of the management of nosocomial infections . High-level computer support has been the frame-work upon which this program was built . We have microcomputers that are linked directly to microbiology, pharmacy, billing, and admissions, downloading data several times daily . An expert software system merges all of the data, and from this we can target patients for real-time interventions . The computer system allows all inpatients to be screened for either infection control or antibiotic management interventions on a daily basis, with minimal time being spent on data collection and maximal efforts devoted to interventions at the bedside . Additionally, the infection management program will assist in maintaining the extraordinarily low expenditures on antimicrobial agents . During 1993, the Millard Fillmore Health System spent $924,884 on antibiotics, an amount approximately 50% that of comparably sized hospitals.

Am J Gastroenterol, 1997 Apr, 92(4 Suppl), 36S - 40S; discussion 40S-43S
Peptic ulcer disease: defining the treatment strategies in the era of Helicobacter pylori; Hunt RH; Peptic ulcer disease continues to be a major health care problem costing the public billions of dollars each year . Recent evidence confirms a major role for Helicobacter pylori infection in the natural history of most cases of peptic ulcer disease . The most established and effective antibiotic treatment for the eradication of H . pylori has been the classic bismuth "triple therapy" regimen containing bismuth, metronidazole, and tetracycline . However, pretreatment resistance to metronidazole, poor compliance, and side effects have limited the widespread acceptance of bismuth triple therapy for routine use . Recent studies suggest that the combination of one or two antibiotic agents and a proton pump inhibitor offers a better tolerated regimen than bismuth triple therapy . Efficacy is similar with respect to eradication of H . pylori, and the combined use of a proton pump inhibitor assures rapid symptom relief and ulcer healing . Although the mechanisms by which H . pylori eradication is effected, the optimal dosing schedules, and the specific antimicrobial agents to be administered require further study, the combination of a proton pump inhibitor and one or two antibiotics promises to be an appropriate first-line treatment for peptic ulcer disease.

Postgrad Med, 1997 Apr, 101(4), 243 - 4, 246-52, 254
Bite wounds . Early treatment and prophylaxis against infectious complications; Presutti RJ; Patient education is important for decreasing the incidence and morbidity of animal bites . When bites do occur, immediate treatment should be given according to established recommended guidelines . Copious irrigation may be the most important aspect of wound care . In addition, early initiation of antimicrobial therapy, particularly in patients at high risk for infection, can decrease morbidity and mortality . A patient's tetanus status and risk of rabies must also be identified and appropriate immunoprophylaxis administered.

Postgrad Med, 1997 Apr, 101(4), 111 - 2, 115-8, 122-3 passim
Intravenous-to-oral antibiotic switch therapy . A cost-effective approach; Cunha BA; Every attempt should be made to switch hospitalized infectious-disease patients from intravenous to oral antibiotic therapy as soon as clinical improvement makes it possible . In addition to tremendous cost savings, the advantages of oral therapy are impressive and include a decrease in the number of nosocomial infections, shorter length of hospital stay, and lower incidence of intravenous-line infections . The main barrier to the acceptance of switch therapy is a lack of understanding of its efficacy, safety, and cost advantages . The wide-scale institution of managed care has resulted in the dawning of the era of oral antimicrobial therapy . Everything from infective endocarditis in intravenous drug abusers to neuroborreliosis may be treated effectively by the oral route.

Am J Obstet Gynecol, 1997 Apr, 176(4), 887 - 8
First antenatal visits and metronidazole; McGregor JA et al.; OBJECTIVE: We evaluated the timing of initial antenatal visits to better characterize possible use of metronidazole or other antimicrobials for common reproductive tract infections in early pregnancy . STUDY DESIGN: We determined timing of initial antenatal evaluation in five busy and representative Denver, Colorado, practice settings (most recent 50 patients) . RESULTS: Most women were evaluated after completion of 9 weeks of pregnancy . Women seen in private settings received the initial visit earlier than did women in publicly supported clinics . CONCLUSION: Pregnant women with a common reproductive tract infection and bacterial vaginosis can be "screened and treated" at the initial antenatal examination.

Clin Pediatr (Phila), 1997 Apr, 36(4), 201 - 5
Parental issues in selection of antimicrobial agents for infants and children; Bauchner H et al.; The traditional American family has changed during the past several decades with increases in the number of single-parent households and working mothers . These changes have led to increased stress in the family when children become ill . Infectious diseases are the most common reasons parents seek care for ill children, and parents want effective and convenient treatment regimens so the child can recover quickly and return to day care or school . Issues that affect parental compliance and satisfaction with antimicrobial treatment regimens include efficacy, safety, cost, convenience, and previous experience . Parents are more involved in medical decision making than ever before and often want to be included in the selection of an antibiotic for their child . Physicians should be aware of the many issues impacting on parents' opinions about antibiotic therapy.

Clin Pediatr (Phila), 1997 Apr, 36(4), 193 - 9
A double-blind taste comparison of pediatric antibiotic suspensions; Steele RW et al.; This study examined the palatability of 22 antimicrobial suspensions by using five independent categories for scoring: appearance, smell, texture, taste, and aftertaste . The likely overall influence on patient compliance was also evaluated . Drugs were compared within their respective classes . The only antibiotics judged to be so unpalatable as to potentially jeopardize compliance were dicloxacillin, oxacillin, erythromycin/sulfisoxazole, and cefpodoxime . Among the penicillins, amoxicillin and ampicillin were preferred . Azithromycin was slightly superior to erythromycin and clarithromycin within the macrolide class . Many cephalosporins were ranked quite high, the best being loracarbef, cefadroxyl, cefprozil, and cefixime.

J Arthroplasty, 1997 Apr, 12(3), 317 - 21
Efficacy of closed wound drainage after total joint arthroplasty . A prospective randomized study; Ovadia D et al.; The efficacy of closed suction drains following joint arthroplasty operations was prospectively evaluated in a randomized manner . All 88 patients allotted to primary knee or hip arthroplasty operations during a 6-month period were included in the study . Drains were used in 32 of 58 patients following total knee arthroplasty and in 18 of 30 total hip arthroplasties . No statistical difference was found in the hemoglobin levels measured following surgery and in the number of patients requiring blood transfusions between the two groups after total hip arthroplasty (P = .06) . The power of the test to detect a difference of 2 g% in hemoglobin levels is 94% . Two patients from each group had a transient serous discharge for 3 to 4 days following surgery and none had wound infections . Significantly more blood transfusions were needed in patients with drains following total knee arthroplasty compared with patients without drains (0.7 unit per patient versus 0.2 unit per patient, P = .005) to maintain the same hemoglobin blood levels . Patients with no drains had significantly more transient sterile serous wound discharge than patients with drains (38.4% vs 12.5%, P = .02) . Superficial wound infection necessitating antimicrobial medication developed in one patient with drains and in no patients in the other group . These results suggest that drains may not be needed following total hip arthroplasty . The more common serous wound discharge may be of some concern when drains are not used following total knee arthroplasty.

Clin Pharmacokinet, 1997 Apr, 32(4), 324 - 43
Pharmacokinetic optimisation of cancer chemotherapy . Effect on outcomes; Masson E et al.; Cancer chemotherapy doses are empirical in that the majority are administered at a fixed dose (mg/m2 or mg/kg) . One reason for this is the intrinsic sensitivity of the tumour or host cells to one particular chemotherapy agent is unknown . Therefore, the likelihood of response or toxicity is unpredictable a priori . This contrasts with antimicrobial chemotherapy where sensitivity (minimum inhibitory concentration) can be determined for a specific bacterium . The pharmacokinetics of cancer chemotherapy agents is also highly variable between patients . In addition, the small therapeutic index of these drugs, combined with the lack of good surrogate markers of toxicity or response, adds to the empiricism of the administration of cancer chemotherapy . In the past few years, numerous studies have established good relationships between systemic exposure to cancer chemotherapy and both response and toxicity . These relationships have been used to individualise chemotherapy dose administration a priori and a posteriori . Some examples of drugs which are individualised based on their pharmacokinetics are methotrexate, busulfan and carboplatin . Other examples of antineoplastic agents which may eventually be individualised based on their pharmacokinetics are mercaptopurine, fluorouracil, etoposide and teniposide, topotecan and suramin . New strategies are being investigated to improve the therapeutic index of cancer chemotherapy agents such as biomodulation, pharmacogenetics, circadian administration and the modification of drug scheduling . Pharmacokinetic studies have also played a major role in these areas . Thus, despite the empiricism associate with cancer chemotherapy administration, some progress has been made and shown to have an impact on outcome . However, more studies are needed to improve cancer chemotherapy administration.

Am J Infect Control, 1997 Apr, 25(2), 117 - 20
Cost analysis and clinical impact of weekly ventilator circuit changes in patients in intensive care unit; Kotilainen HR et al.; BACKGROUND: The introduction of heated circuits and sealed, single-use humidifiers has prompted some investigators to question the traditional recommendations for changing ventilator circuits . We studied the clinical and cost impact of extending the circuit change interval from 72 hours to 7 days in our two intensive care units with 17 beds . METHODS: With standard surveillance definitions from the Centers for Disease Control and Prevention and the National Nosocomial Infections Surveillance System, baseline pneumonia rates were established for a 3-month period . After the institution of weekly circuit changes, daily surveillance of intubated patients was performed during 18 of 22 weeks from May through September 1993 . Standard microbiologic methods were used for the identification of patient and environmental isolates . RESULTS: Ventilator-associated pneumonia for the 72-hour circuit change group was 9.1% or 1.29 per 100 ventilator days . After the institution of weekly changes, pneumonia occurred in 9 of 146 patients (6.2% or 0.74 per 100 ventilator days chi 2 = 0.33, p = 0.44) . No common bacterial isolates were recovered as judged by phenotype, biochemical, or antimicrobial susceptibility patterns . Weekly changes reduced the number of circuits used from a predicted 469 to 214 . Estimating $26.46 per circuit change, annualized cost savings were $20,246.90 . CONCLUSIONS: Weekly circuited changes in patients undergoing ventilation therapy in the intensive care unit are cost-effective and do not contribute to increased rates of nosocomial pneumonia.

Urology, 1997 Apr, 49(4), 604 - 8
Management considerations for treating vesicoureteral reflux in children with solitary kidneys; Palmer LS et al.; OBJECTIVES: To evaluate the management approach for vesicoureteral reflux (reflux) into a solitary kidney . METHODS: Outcomes of all children with solitary kidneys and reflux managed between 1981 and 1996 were reviewed . Solitary kidneys were documented by nuclear renography and ultrasonography; reflux was graded after cystography . Management consisted of observation and antimicrobial prophylaxis or surgery by ureteroneocystostomy or subureteric injection of polytetrafluoroethylene (STING) . Follow-up ranged from 3 months to 14 years and included serial cystography, sonography, and serum creatinine measurement . RESULTS: Twenty-one patients with a median follow-up of 26 months were identified . Etiologies included contralateral renal agenesis (14 children), multicystic dysplastic kidney (5 children), or nonfunctioning ureteropelvic junction obstruction (2 children) . Low-grade (I to II) reflux was identified in 6 children, and high grade (III to V) was identified in 15 . Reflux resolved in 20 patients . Five children with low-grade reflux were managed without surgery and demonstrated reflux resolution after a mean of 20.5 months . Renal function deteriorated in only 1 child . Ureteroneocystostomy was performed in 13 children with grades III to V reflux, and STING was performed in 1 child with grade II reflux . Every surgical patient maintained stable renal function and was infection-free during a mean follow-up of 56 months . Management by observation in 2 children with grades IV to V reflux resulted in spontaneous resolution in one and stable grade IV in the other . CONCLUSIONS: Reflux into the solitary functioning kidney may be managed by the same strategies used to manage unilateral reflux in children with two normally functioning kidneys: low-grade reflux by observation/ chemoprophylaxis until spontaneous resolution occurs, and higher grades by surgery to protect renal function; however, chemoprophylaxis and serial imaging may be used until well-defined indications for surgery are satisfied . Renal function should be monitored diligently.

Pediatr Infect Dis J, 1997 Apr, 16(4), 438 - 43
Pharmacokinetics and pharmacodynamics of newer macrolides; Nightingale CH; Requirements for the antimicrobial activity of an antibiotic are: (1) binding of the drug to a specific site in the bacteria; (2) occupation of a critical number of binding sites; and (3) persistence at these binding sites for a sufficient time . With concentration-dependent antibiotics the ratio of the peak serum drug concentration to the MIC of a pathogen is the primary determinant of bacterial killing; with concentration-independent antibiotics it is the length of time serum concentration remains above the MIC, rather than the peak level . The pharmacokinetics of the new macrolides azithromycin and clarithromycin differ notably from those of conventional antibiotics in a more rapid and extensive distribution to body tissues . Because of these unique tissue pharmacokinetics, the pharmacodynamic models that apply to other classes of antibiotics may not explain the antimicrobial activity and clinical efficacy of azithromycin and clarithromycin.

Vet Clin North Am Equine Pract, 1997 Apr, 13(1), 79 - 96
Equine protozoal myeloencephalitis; MacKay RJ; Equine protozoal myeloencephalitis (EPM) is a common neurologic disease of horses in the Americas . Horses with EPM most commonly have abnormalities of gait, but they also may present with signs of brain disease . The disease ranges in severity from mild lameness to sudden recumbency, and clinical signs usually are progressive . A causative agent, Sarcocystis neurona, has been isolated from affected horses, and serologic surveys suggest that approximately 50% of horses in the United States have been exposed . EPM is considered a treatable disease, although the response to antimicrobial treatment often is incomplete . This article highlights new information about the life cycle of S . neurona and reviews the literature regarding diagnosis, clinical signs, and treatment of the disease.

Ann Pharmacother, 1997 Apr, 31(4), 492 - 4
Treatment of Rocky Mountain spotted fever in children; Cale DF et al.; RMSF is a potentially life-threatening disease that requires prompt diagnosis and empiric initiation of an appropriate antimicrobial agent . For the clinician treating young children with RMSF, there are few options . The safety and efficacy of fluoroquinolones and orally administered parenteral chloramphenicol have not been established in the pediatric population . Therefore, widespread and casual use of these agents is not recommended . Doxycycline is the most favorable agent for the treatment of RMSF in children younger than 9 years of age because of its documented effectiveness, broader margin of safety, reduced risk of drug-related adverse effects in young children, and convenient dosing schedule . For patients with RMSF reinfection, up to five courses of doxycycline may be administered with minimal risk of dental staining.

Va Med Q, 1997 Spring, 124(2), 108 - 11
The new antibiotics, 1997; Townsend GC et al.; Some of the antimicrobial agents released in the past few years possess characteristics suggesting real advantages over older agents (see Table I) . These advantages include broader spectrum of activity, favorable pharmacokinetic profile allowing for infrequent dosing, low toxicity and lower pricing . Although older agents and agents with narrower spectra should be considered first-line in most circumstances, there may be some clinical scenarios in which these newer agents should be contemplated as reasonable alternatives.

Am J Med Sci, 1997 Apr, 313(4), 247 - 8
The syndrome of inappropriate antidiuretic hormone secretion in a patient with Whipple's disease; Marinella MA et al.; We report the case of a patient with central nervous system Whipple's disease who developed the syndrome of inappropriate antidiuretic hormone secretion (SIADH) . The patient did not exhibit any gastrointestinal symptoms and initially was diagnosed based on neurologic findings and a duodenal biopsy that was positive for Tropheryma whippelii by the polymerase chain reaction . Radiologic involvement of the hypothalamus suggested Whipple's disease as the likely etiology of the syndrome of inappropriate antidiuretic hormone secretion . With antimicrobial therapy, the patient's serum sodium level and symptoms showed improvement.

Drugs, 1997 Apr, 53(4), 550 - 62
The System of Objectified Judgement Analysis (SOJA) . A tool in rational drug selection for formulary inclusion; Janknegt R et al.; Rational drug selection for formulary purposes is important . Besides rational selection criteria, other factors play a role in drug decision making, such as emotional, personal financial and even unconscious criteria . It is agreed that these factors should be excluded as much as possible in the decision making process . A model for drug decision making for formulary purposes is described, the System of Objectified Judgement Analysis (SOJA) . In the SOJA method, selection criteria for a given group of drugs are prospectively defined and the extent to which each drug fulfils the requirements for each criterion is determined . Each criterion is given a relative weight, i.e . the more important a given selection criterion is considered, the higher the relative weight . Both the relative scores for each drug per selection criterion and the relative weight of each criterion are determined by a panel of experts in this field . The following selection criteria are applied in all SOJA scores: clinical efficacy, incidence and severity of adverse effects, dosage frequency, drug interactions, acquisition cost, documentation, pharmacokinetics and pharmaceutical aspects . Besides these criteria, group specific criteria are also used, such as development of resistance when a SOJA score was made for antimicrobial agents . The relative weight that is assigned to each criterion will always be a subject of discussion . Therefore, interactive software programs for use on a personal computer have been developed, in which the user of the system may enter their own personal relative weight to each selection criterion and make their own personal SOJA score . The main advantage of the SOJA method is that all nonrational selection criteria are excluded and that drug decision making is based solely on rational criteria . The use of the interactive SOJA discs makes the decision process fully transparent as it becomes clear on which criteria and weighting decisions are based . We have seen that the use of this method for drug decision making greatly aids the discussion in the formulary committee, as discussion becomes much more concrete . The SOJA method is time dependent . Documentation on most products is still increasing and the score for this criterion will therefore change continuously . New products are introduced and prices are also subject to change . To overcome the time-dependence of the SOJA method, regular updates of interactive software programs are being made, in which changes in acquisition cost, documentation or a different weighting of criteria are included, as well as newly introduced products . The possibility of changing the official acquisition cost into the actual purchasing costs for the hospital in question provides a tailor-made interactive program.

J Am Acad Dermatol, 1997 Apr, 36(4), 513 - 26; quiz 527-30
Pediatric dermatology: advances in therapy; Chapel KL et al.; Several recent therapeutic advances in pediatric dermatology have been made . Of particular importance are new developments in the use of antimicrobials, antivirals, antifungals, retinoids, calcipotriene, and intravenous gamma globulin . We review safety and efficacy data of these drugs in their use in children with cutaneous disease.

Pediatr Nephrol, 1997 Apr, 11(2), 164 - 8
Catch-up growth in children with vesico-ureteric reflux; Polito C et al.; A longitudinal retrospective study of height Z score (HZ score) and weight-for-height index (WHI) was performed on 94 pre-pubertal children with vesico-ureteric reflux (VUR) and normal creatinine clearance followed for 1-6.8 years (mean 3.1 years) . Thirty patients had bilateral VUR with scintigraphic signs of renal scarring (B+), 17 had bilateral VUR without renal scarring (B-), 27 had unilateral VUR with (U+) and 20 unilateral VUR without (U-) renal scarring . Thirty-three patients received only antimicrobial medication and 61 underwent successful antireflux operation . The increase in HZ score and WHI during the 1st year of follow-up was significantly (P = 0.001 and 0.00003, respectively) higher than during the 2nd year . At first visit, B+ subjects had an average WHI and HZ score that were significantly (P = 0.02 and 0.04, respectively) lower than the other groups of patients together . At last visit this difference was not significant . In B+ subjects, the WHI and HZ score at last visit were significantly (P = 0.04 for both) higher than at the first visit . B+ patients fully recover their body growth deficit compared with other groups of VUR subjects after medical and/or surgical therapy.

J Infect Dis, 1997 Apr, 175(4), 901 - 4
Novel anti-Pneumocystis carinii effects of the immunosuppressant mycophenolate mofetil in contrast to provocative effects of tacrolimus, sirolimus, and dexamethasone; Oz HS et al.; The effects of three new immunosuppressive drugs used for organ transplantation, mycophenolate mofetil, tacrolimus, and sirolimus, were compared with those of dexamethasone in provocation of Pneumocystis carinii pneumonitis in virus-free Sprague-Dawley rats . Rats injected daily with tacrolimus showed a dose-related response to the point of severe P . carinii pneumonitis 4 weeks after initiation of drug administration identical to those animals treated with high-dose dexamethasone . Thirty percent of rats treated with sirolimus had mild P . carinii infection . Surprisingly, mycophenolate mofetil had an anti-P . carinii effect . None of the animals had discernible P . carinii infection when treated with mycophenolate mofetil alone or combined with dexamethasone . Mycophenolate mofetil is unique because of its dual activity as a potent immunosuppressant as well as an antimicrobial with action against P . carinii.

Biophys J, 1997 Apr, 72(4), 1762 - 6
Sizing membrane pores in lipid vesicles by leakage of co-encapsulated markers: pore formation by melittin; Ladokhin AS et al.; Many toxins and antimicrobial peptides permeabilize membrane vesicles by forming multimeric pores . Determination of the size of such pores is an important first step for understanding their structure and the mechanism of their self-assembly . We report a simple method for sizing pores in vesicles based on the differential release of co-encapsulated fluorescently labeled dextran markers of two different sizes . The method was tested using the bee venom peptide melittin, which was found to form pores of 25-30 A diameter in palmitoyloleoylphosphatidylcholine (POPC) vesicles at a lipid-to-peptide ratio of 50 . This result is consistent with observations on melittin pore formation in erythrocytes (Katsu, T., C . Ninomiya, M . Kuroko, H . Kobayashi, T . Hirota, and Y . Fujita 1988 . Action mechanism of amphipathic peptides gramicidin S and melittin on erythrocyte membrane Biochim . Biophys . Acta . 939:57-63).

Curr Opin Biotechnol, 1997 Apr 1, 8(2), 208 - 14
Genetic engineering for fungal and bacterial diseases; Shah DM; Significant new advances at the molecular level in the field of plant-pathogen interactions form the basis for novel transgenic approaches to crop protection . The cloning of disease resistance genes and the dissection of the signal transduction components of the hypersensitive response and systemic acquired resistance pathways have greatly increased the diversity of options available for transgenic disease resistance . These new approaches will supplement our rapidly increasing repertoire of antimicrobial peptides, defense-related proteins and antimicrobial compounds . The combinatorial deployment of these strategies will be exploited for engineering effective and durable resistance to pathogens in the field . The integration of transgenic approaches with classical resistance breeding offers a potentially chemical-free and environmentally friendly solution for controlling pathogens.

Aten Primaria, 1997 Mar 31, 19(5), 230 - 6
{Changes in the use of antibacterial agents in Catalonia, Impact of new marketed drugs}; Llop JC; OBJECTIVE: Due to the high morbidity of bacterial illnesses, there have been a lot of studies to assess the use of antibacterials . These studies usually focus on a small sample, whereas in the present study both the development of the use of antimicrobials in non-hospital care throughout Catalonia, and the extent to which new medicines are used, are examined . DESIGN: A retrospective, observational study . SETTING: Catalonia . MATERIAL AND METHODS: Using the data supplied by the pharmacy data base of the Catalan Health Service in DHD for 1992-1995, analyses were made of the development in the use of the different antibacterial subgroups, the effect of using new medicines and their impact on similar older antibacterials . MAIN RESULTS: The overall number of antibacterials taken in Catalonia remained fairly stable at high levels . CONCLUSIONS: Antibacterials are widely used . Three is a tendency to substitute newly marketed medicines for traditional medicines . A more prudent attitude should be adopted when starting antibacterials treatments and choosing the most suitable antibiotics for non-hospital care.

Aten Primaria, 1997 Mar 31, 19(5), 226 - 9
{Changes in the sensitivity of Escherichia coli to 6 antimicrobial agents during the last 12 years . Group of Microbiologists of County Hospitals of Catalonia}; Sauca G et al.; OBJECTIVE: To study the current state and development in the sensitivity of Escherichia coli during 12 years, in order to find the use of 6 antimicrobials . DESIGN: A descriptive study of the annual sensitivity percentages of E . coli strains isolated from clinical samples between 1984 and 1995 . SETTING: Microbiology Laboratories in 15 County Hospitals in the province of Barcelona . PATIENTS AND PARTICIPANTS: E . coli strains, isolated from clinically significant samples, were studied for sensitivity against antimicrobials . MEASUREMENTS AND MAIN RESULTS: Cefuroxime and Gentamicin had in vitro sensibility above 94% . Current sensitivity of E . coli to Norfloxacin was 85% . Amoxicillin-Clavulanic acid maintained its sensitivity at about 80% with few variations . Ampicillin and Co-trimoxazole had steady sensitivity figures, always below 50 and 70%, respectively . CONCLUSIONS: Progressive decrease in the sensitivity of E . coli strains to Norfloxacin was observed . There was excellent sensitivity to Cefuroxime and Gentamicin.

Cas Lek Cesk, 1997 Mar 19, 136(6), 191 - 5
{The present status and future perspectives of fluorinated quinolones from the aspect of clinical microbiology}; Lochmann O; The author presents a review on the contemporary position of fluoroquinolones from the microbiological and clinical aspect . He submits basic data on the mechanism of action of these drugs and development of resistance displayed by infectious agents . Favourable pharmacokinetics make wide clinical use of these drugs possible . Indiscriminate administration could debase these drugs possible . Indiscriminate administration could debase these very valuable antimicrobial drugs . This is why the author presents in his paper the main clinical indications for their therapeutic use . To complete the problem the author makes suggestions of suitable combinations and draws attention to possible therapeutic interactions and undesirable effects, incl . contraindications.

Eur J Biochem, 1997 Mar 15, 244(3), 743 - 9
Purification, characterisation and cDNA cloning of an antimicrobial peptide from Macadamia integrifolia; Marcus JP et al.; An antimicrobial peptide with no significant amino acid sequence similarity to previously described peptides has been isolated from the nut kernels of Macadcamia integrifolia . The peptide, termed MiAMP1, is highly basic with an estimated pI of 10.1, a mass of 8.1 kDa and contains 76 amino acids including 6 cysteine residues . A cDNA clone containing the entire coding region corresponding to the peptide was obtained . The deduced amino acid sequence of the cDNA indicated a 26-amino-acid signal peptide at the N-terminus of the preprotein . Purified MiAMP1 inhibited the growth of a variety of fungal, oomycete and gram-positive bacterial phytopathogens in vitro . Some pathogens exhibited close to 100% inhibition in less than 1 microM peptide (5 microg/ml) . Antimicrobial activity was diminished against most, but not all, microbes in the presence of calcium and potassium chloride salts (1 mM and 50 mM, respectively) . MiAMP1 was active against bakers yeast, was inactive against Escherichia coli and was non-toxic to plant and mammalian cells . Analysis of genomic DNA indicated that MiAMP1 was encoded on a single copy gene containing no introns . The MiAMP1 gene may prove useful in genetic manipulations to increase disease resistance in transgenic plants.

J Immunol, 1997 Mar 15, 158(6), 2731 - 5
Restoration of T cell-independent type 2 induction of Ig secretion by neonatal B cells in vitro; Snapper CM et al.; The humoral immune response of neonates to T cell-independent type 2 (TI-2) Ags is markedly defective . We previously demonstrated that multivalent membrane Ig cross-linking, using dextran-conjugated anti-Ig Abs (anti-Ig-dextran), is an in vitro model for membrane Ig-dependent TI-2 induction of Ig secretion . In this work, we demonstrate that highly purified neonatal B cells are intrinsically defective in IgM secretion in response to anti-Ig-dextran and cytokines in vitro, as well as other modes of B cell activation, relative to adult B cells . However, costimulation of anti-Ig-dextran-activated neonatal B cells with either CD40-ligand, a recombinant bacterial lipoprotein, or LPS restores the IgM secretory response of neonatal B cells to adult levels . Analysis of Ig isotype secretion indicates that neonatal B cells have an enhanced capacity to secrete IgE and IgA relative to other Ig isotypes . These data suggest that neonatal B cells are competent to secrete Ig in response to TI-2 Ags if adequate costimuli are provided, and thus may have particular relevance for the design of vaccine strategies in the immunodeficient host . The data also suggest that neonatal B cells are programmed to secrete relatively enhanced amounts of IgE and IgA, which may be relevant for antimicrobial resistance at mucosal surfaces.

J Med Chem, 1997 Mar 14, 40(6), 967 - 71
Semisynthetic derivatives of purpuromycin as potential topical agents for vaginal infections; Trani A et al.; Purpuromycin (1) is an antibiotic with a broad spectrum of antimicrobial activity, encompassing bacteria, fungi, and protozoa, particularly those involved in vaginal infections . With the aim of enhancing the solubility and reducing the serum binding, a chemical program of modifications was undertaken on the natural compound, and a new interesting series of derivatives at the naphthoquinone system was synthesized and evaluated as potential topical agents for vaginal infections . In particular three semisynthetic derivatives, 7'-amino (8a), 7'-methylamino (8b), 7'-ethylamino (8c), of 7'-demethoxypurpuromycin seemed to be the most promising . They were tested for in vitro activity against three of the most important vaginal pathogens and showed activity similar to that of purpuromycin against Candida isolates while they were significantly more active against Trichomonas vaginalis and Gardnerella vaginalis, which are cultured in media containing blood or serum . This is probably due to the fact that the activity of the derivatives is less antagonized by these supplements than that of purpuromycin.

Pharmacoeconomics, 1997 Apr, 11(4), 359 - 66
Cost-minimisation analysis of sequential treatment with ofloxacin or ciprofloxacin in hospitalised patients; Salewski E et al.; This study evaluated the cost of sequential treatment with once-daily ofloxacin or twice-daily ciprofloxacin in 474 hospitalised patients in different countries . The patients were treated intravenously for at least 3 days, then orally for 7 to 10 days or for 3 days beyond the disappearance of infection-related symptoms . The overall clinical cure rate (86.8% with ofloxacin and 89.6% with ciprofloxacin) and the overall bacteriological response rate (89.9 and 89.0%, respectively) were similar, and a cost-minimisation analysis was conducted . The acquisition costs for ofloxacin and ciprofloxacin in Greece, Israel, Slovenia and Turkey were used and converted to Deutschmarks (DM), and the costs of administration were analysed for each hospital . The different cost categories for oral and intravenous (IV) treatment (e.g . antimicrobial acquisition, drug monitoring, drug delivery costs) were used to identify any differences . The total costs per patient varied between the countries involved, but were higher for ciprofloxacin (ofloxacin: DM239 to DM724; ciprofloxacin: DM540 to DM976) . In a sensitivity analysis using identical daily acquisition costs for the 2 fluoroquinolones, the total cost of treatment was higher for ciprofloxacin, as a result of the lower cost of administration of ofloxacin in the once-daily regimen . Continuing IV therapy would be approximately 50% more expensive than switching to oral administration; however, whenever possible, both drugs can be switched from IV to oral treatment.

Biochem Biophys Res Commun, 1997 Mar 6, 232(1), 183 - 7
Superoxide scavenging activity of erythromycin-iron complex; Muranaka H et al.; We evaluated superoxide (O2-.) scavenging activity of erythromycin (EM) and of EM-iron complex by means of electron spin resonance spectroscopy, luminol-dependent chemiluminescence assay, and cytochrome c reduction assay . The EM-iron complex was produced by mixing EM with equal molar iron chloride and was stable in neutral buffer . The EM-iron complex reduced the amount of O2- . produced by xanthine oxidase/hypoxanthine without inhibiting the enzyme activity . It also reduced the amount of O2- . release from phorbor ester-stimulated human neutrophils and alveolar macrophages . EM alone showed few such effects . The scavenging activity of the complex was equal to that of L-ascorbic acid . These results in vitro suggest a possibility that the O2-.-scavenging effect of EM-iron complex contributes to the anti-inflammatory action of EM used in treating chronic inflammatory lung disease independent of its antimicrobial activity.

Curr Opin Pulm Med, 1997 Mar, 3(2), 170 - 4
Antibiotic penetration in the respiratory tract and implications for the selection of antimicrobial therapy; Honeybourne D; There has been an increasing amount of information published recently about the ability of different antimicrobial agents to penetrate specific areas of the lung . Initially, whole lung concentrations were reported, but this methodology has been refined so that levels are now measured in potential sites of infection, such as the bronchial mucosa, epithelial lining fluid, and alveolar macrophages, as well as in sputum . Distinct differences in the ability to concentrate in these sites have been shown among beta-lactams, quinolones, and macrolides . Considerable intracellular concentration of quinolones and macrolides, but not beta-lactams, occurs . This intracellular accumulation has been used for the treatment of atypical mycobacteria . The potential effects of high antibiotic levels on cellular function have also been investigated . The clinical relevance of these findings for the choice of antimicrobial agent, dosage, formulation (eg, liposomal), and route of administration (eg, nebulized) are increasingly being explored.

East Afr Med J, 1997 Mar, 74(3), 187 - 9
Rational approach to limiting emergence of antimicrobial drug resistance; Mbori-Ngacha DA; Microbial resistance to the available antimicrobial agents continues to be a major problem with regard to nosocomial and community acquired pathogens . The development of resistance to commonly used antimicrobials is of particular concern when it occurs in pathogenic organisms that cause invasive disease . This has implications on morbidity and mortality of infectious diseases, and will also result in escalated costs of care due to the use of alternative antimicrobials which are often more costly . The increasing frequency of drug resistance has been attributed to combinations of microbial characteristics, selective pressure of antimicrobial use and societal factors that enhance the transmission of drug resistant organisms . The emergence of antibiotic resistant bacteria has generally correlated with the rise and fall of specific antibiotic use in clinical practice . Although the discovery of a new drug temporarily confers therapeutic superiority over bacterial pathogens, the subsequent rapid evolution of resistance limits the duration of the effectiveness of specific agents against pathogens . Surveillance and the development of drug policies that encourage judicious use of antimicrobials will help to minimise the spread of resistant infections . This paper reviews how this dual strategy may be used to control antimicrobial resistance.

East Afr Med J, 1997 Mar, 74(3), 171 - 3
Antibiotic sale behaviour in Nairobi: a contributing factor to antimicrobial drug resistance; Indalo AA; A survey of antibiotic sale behaviour in retail chemist shops in Nairobi revealed that about 64% of chemists sell antibiotics without prescriptions from doctors . Most shops sold underdose drugs according to the request of the patient . The practice is more common in peri-urban than city centre chemists . Out of the 128 chemist shops visited, 82 sold the antibiotic, 33 sent the patients to go and see the doctors while 13 did both . Sixty eight per cent of the chemists in the city centre recommended the taking of full antibiotic course to the patients while only 46% in peri-urban centres did so . Even after the recommendation, some of the chemists still sold under dose drugs . Some of the drugs were sold in envelopes without any instruction at all and none of the drugs sold were fully labelled . Only seven chemists sold septrin, the brand of co-trimoxazole requested by the patients, the rest sold various brands of the drug some of whom still labelled the brands 'septrin'.

East Afr Med J, 1997 Mar, 74(3), 124 - 8
Epidemiological aspects of antimicrobial drug resistance; Kariuki SM et al.; Micro-organisms resistant to antimicrobial drugs are a problem for health workers worldwide . As scientists discover newer and more effective agents to manage emerging therapeutic challenges, the micro-organisms develop novel mechanisms of resistance hitherto unknown . The challenge in the present day is to understand the mechanisms of resistance in micro-organisms with a view to avoiding the emergence of resistance . For those in developing countries where health budgets are meagre and the cost of newer drugs ever increasing, there is need to develop effective policies to use the existing therapeutic choices in the most appropriate manner . This article highlights various epidemiological aspects of antimicrobial drug resistance in bacteria of medical importance that would be useful in the understanding of the basis for emergence and dissemination of resistance.

Z Gastroenterol, 1997 Mar, 35(3), 165 - 9
{Helicobacter pylori: pretherapeutic resistance status in Germany (Ruhr area)}; Tillenburg B et al.; BASIC PROBLEM AND OBJECTIVE OF STUDY: The situation of pretherapeutical antimicrobial drug resistance of Helicobacter pylori has therapeutical implications . For this reason the present study was designed to evaluate the frequency of resistance in Germany . MATERIAL AND METHODS: A total of 201 H . pylori isolates cultured on the basis of biopsies taken by routine gastroscopies were tested for resistance by E-test . The antibiotics examined were amoxicillin, tetracycline, clarithromycin and metronidazole . For further analysis the last 101 patients were asked for demographical and clinical data that were evaluated for a correlation with metronidazole resistance . RESULTS: Pretherapeutical resistance against amoxicillin and tetracycline was not detected . The rate of drug resistance against clarithromycin came to 3% and against metronidazole to 29% . There was a higher incidence of metronidazole resistance in female patients (Odds ratio 1.71; p = n.s.) . Reliable predictors for metronidazole resistance, however, could not be identified . CONCLUSIONS: About 30% of H . pylori isolates are pretherapeutically resistant to metronidazole . Resistance to clarithromycin is still rare, but further monitoring remains necessary to detect changes in the community.

Biofizika, 1997 Mar-Apr, 42(2), 472 - 9
{Photosensitizing properties and antioxidant activity of furagin--an antimicrobial drug that is a derivative of nitrofuran}; Makareeva EN et al.; Photosensitizing effect of antimicrobial drug nitrofuran derivative--furagin N-(5-nitro-2-furil)-allylidencamino-hydantoin) under irradiation with light longer than 280 nm was found . The method of investigation is based on photochemiluminescence of Gly-Trp peptide in aqueous solution . Maximum photosensitizing efficiency was observed at the furagin concentration 0.08 mM when chemiluminescence yield was 33 times greater than photochemiluminescence of Gly-Trp peptide in absence of drug . It was shown that photochemiluminescence sensitized by furagin occurred via free radical way . Life time of the triplet state of furagin determined by flash photolysis was 40 microseconds . A comparison of experimental data with kinetic calculation allowed us to estimate the rate constant of triplet quenching by oxygen ((2.2 +/- 0.3)10(8) M-1.s-1) and the total rate constants of physical quenching and chemical reaction with Gly-Trp peptide ((2.0 +/- 0.4)10(8) M-1.s-1) . It was also found in experiments with photochemiluminescence of Gly-Trp peptide sensitized by riboflavin (irradiation with monochromatic light 436 nm) that furagin possesses antioxidant properties twice reducing the intensity of chemiluminescence at the drug concentration 0.029 mM.

Semin Neurol, 1997 Mar, 17(1), 45 - 52
Treatment and prevention of Lyme disease, with emphasis on antimicrobial therapy for neuroborreliosis and vaccination; Wormser GP; Antibiotic therapy is recommended for all forms of neuroborreliosis . Although stage 2 neuroborreliosis will usually resolve without any treatment, antibiotic therapy has been associated with faster resolution of symptoms and may prevent additional non-neurologic disease manifestations . Ceftriaxone is the most convenient parenteral agent for stage 2 and 3 neuroborreliosis because of its once-daily dosage . Available data indicate that a 2-4-week treatment course is adequate for most patients . Patients with isolated seventh nerve palsy may be treated with an oral agent (for example, doxycycline) . Recombinant outer surface protein A of Borrelia burgdorferi is a highly protective immunogen for prevention of Lyme disease in experimental animals . Humoral immunity is sufficient for protection . A recombinant OspA vaccine has been licensed for prevention of Lyme disease in dogs . Licensure of an OspA vaccine for humans will depend on a critical analysis of the results of recently completed efficacy studies.

Semin Neurol, 1997 Mar, 17(1), 39 - 44
Lyme disease in children; Shapiro ED et al.; Neurologic manifestations of Lyme disease are common in children, among whom the incidence of Lyme disease is higher than among adults . Cranioneuropathies, in particular palsy of the facial nerve, occur in approximately 3-5% of children with Lyme disease, followed in frequency by meningitis (1% of symptomatic children) . Children with only non-specific symptoms such as headache, arthralgia or fatigue commonly are misdiagnosed as having Lyme disease . Although such non-specific symptoms often accompany more specific signs and symptoms (e.g., erythema migrans, arthritis) in children with Lyme disease, very rarely are non-specific symptoms the sole manifestation of Lyme disease . A number of carefully conducted follow-up studies have indicated that the prognosis is excellent for children with Lyme disease who have been treated with standard antimicrobial regimens.

Semin Neurol, 1997 Mar, 17(1), 19 - 24
Neuroborreliosis: central nervous system involvement; Halperin JJ; Despite rapid dissemination of Borrelia burgdorferi throughout the body following initial inoculation, the clinical manifestations of this illness tend to involve specific organ systems preferentially . The nervous system, in particular, is frequently affected; involvement usually follows one of several distinct patterns . Most commonly, patients develop a lymphocytic meningitis, radiculoneuritis or cranial neuropathy, occurring singly or in combination . Patients with radicular involvement often have a myelopathic component as well . At the other extreme, rare patients will develop focal inflammation of the central nervous system, an encephalomyelitis, that appears to involve white matter more often than grey . More commonly, patients may develop cognitive and memory impairment-a mild encephalopathy . In some patients this may represent a subtle form of encephalomyelitis, while in others it is probably a "toxic-metabolic" effect of systemic infection . Disease variability among patients probably is the result of multiple factors, including bacterial strain differences in virulence and organotropism, inoculum size, host immunity, and simultaneous co-infection with other tick-borne organisms . Accurate diagnosis remains somewhat problematic . The cerebrospinal fluid is almost always abnormal in the presence of active CNS infection . Intrathecal production of specific antibody can be demonstrated in over 90% of patients with meningitis or frank inflammatory encephalomyelitis; in patients with a milder encephalopathy this is less consistently observed . In most instances, diagnosis relies on a combination of demonstration of a specific immune response, and clinical judgment . In patients in whom the diagnosis is secure, appropriate antimicrobial therapy is highly effective in the vast majority of cases, although if there has been significant structural damage to the CNS, some residua may remain.

Lippincotts Prim Care Pract, 1997 Mar-Apr, 1(1), 40 - 9
Office management of minor burns; Parsons L; About 2 million people are burned in the United States each year . About 80% of these are treated as outpatients . Flame burns are the most common type of burn injury in adults, and scald burns are the primary type in children . Primary care providers must be familiar with burn assessment so burn injuries can be triaged appropriately to a regional burn center, an acute care (facility, or office management . Assessment includes extent and depth of burns, location of burns, patient reliability, and the home situation . Office management involves emergency care, debridement and dressings, topical antimicrobials, and pain control . Patient education for care in the home environment is essential for optimal healing.

Biol Chem, 1997 Mar-Apr, 378(3-4), 289 - 92
cDNA cloning, tissue distribution, and subcellular localization of horseshoe crab big defensin; Kawabata S et al.; A full-length cDNA for horseshoe crab big defensin with a strong antimicrobial activity was obtained from a hemocyte cDNA library . The open reading frame of the cDNA coded for an NH2-terminal signal sequence followed by a propeptide and the mature big defensin . The propeptide is linked to the mature protein through an -Arg-X-Lys/Arg-Arg- motif, the processing site for Kex2-like proteases . Northern blot analysis revealed that big defensin is expressed in all the tissues tested, suggesting that big defensin plays an important role not only in hemocytes but also in other tissues for host defense . The subcellular localization, determined by immunocytochemistry at ultrastructural level, confirmed the previous findings obtained by biochemical analysis that big defensin locates in both small and large granules in hemocytes . Big defensin is the first example to demonstrate the existence of broad tissue distribution in horseshoe crab.

Boll Chim Farm, 1997 Mar, 136(3), 266 - 71
Synthesis and biological activity studies of 1,3,4-thiadiazolo{2,3-c}-as-triazines; Kalluraya B et al.; Several new 1,3,4-thiadiazolo{2,3-c}-as-triazines were synthesized by the reaction of 6-substituted-4-amino-3-mercapto-1,3,4-triazon-5 (4H)-ones with appropriate aromatic and heterocyclic carboxylic acids in the presence of phosphorus oxychloride . The structures of the newly synthesized compounds were established on the basis of analytical, IR, NMR and mass spectral data . Some selected compounds from this series were subjected to both antimicrobial and pharmacological studies.

Boll Chim Farm, 1997 Mar, 136(3), 262 - 5
Synthesis and evaluation of some new substituted benzofuran derivatives as potentially active antimicrobial agents; Abdel-Rahman AH et al.; 6-(omega-Bromoacetyl)-2,3-diphenyl-5-methoxybenzofuran derivative (2) was synthesized and allowed to react with different reagents to get new benzofuran derivatives that are substituted with isolated or fused heterocyclic ring systems . The antimicrobial activity of the hitherto synthesized products was tested and evaluated.

Surv Ophthalmol, 1997 Mar-Apr, 41(5), 395 - 401
Antibiotic selection in the treatment of endophthalmitis: the significance of drug combinations and synergy; Roth DB et al.; Emerging resistance of organisms to standard antibiotic therapy has forced clinicians to continually evaluate the best intraocular antibiotics for the treatment of endophthalmitis . Early diagnosis and appropriate treatment with intraocular antibiotics are important factors in the successful management of endophthalmitis . Although drug combinations are necessary to cover the full range of bacteria causing endophthalmitis, antimicrobial synergy is probably less important in endophthalmitis treatment because of the high intravitreal concentration of individual antibiotics achieved by intravitreal injection . In the treatment of bacterial endophthalmitis, the combination of intravitreal vancomycin (1 mg/0.1 cc) and ceftazidime (2.25 mg/ 0.1 cc) is a reasonable alternative to the combination vancomycin and amikacin (0.4 mg/ 0.1 cc).

J Nat Prod, 1997 Mar, 60(3), 223 - 9
Massetolides A-H, antimycobacterial cyclic depsipeptides produced by two pseudomonads isolated from marine habitats; Gerard J et al.; Massetolides A-H (1-8), novel cyclic depsipeptides, and the known compound viscosin (9) have been isolated from cultures of two Pseudomonas sp . isolated from a marine alga and a marine tube worm, respectively . Massetolide A (1) and viscosin (9) exhibit in vitro antimicrobial activity against Mycobacterium tuberculosis and Mycobacterium avium-intracellulare . Precursor-directed biosynthesis has been used to generate unnatural massetolides 11-13 incorporating nonprotein amino acids.

Eur J Emerg Med, 1997 Mar, 4(1), 15 - 8
Prophylactic, empiric and therapeutic use of antibiotics . Do we need a guide: a universal edition or a local one?
Peetermans WE.
The goal of the antibiotic policy in hospitals is a correct and restrictive use of antimicrobial agents . Guidelines on antibiotic use aim to improve the quality of care, to reduce costs and to prevent the emergence of (multi-)resistant microorganisms . Strategic options and methods to reach these objectives are published by consensus committees of scientific societies and health care organizations . The local guidelines must be based upon the universal principles of prophylactic, empiric and therapeutic use of antimicrobial agents but they also take into account the local epidemiology of infectious diseases, microbiology and resistance patterns as well as the local clinical experience . Our experience on how an antibiotic policy was developed and implemented in our large university hospital is described.

Ann Periodontol, 1997 Mar, 2(1), 180 - 98
Design and implementation of clinical trials of antimicrobial drugs and devices used in periodontal disease treatment; Newman MG; The design and implementation of clinical trials (CTs) carried out to evaluate antimicrobial and anti-infective drugs and devices are one of the most difficult challenges in contemporary periodontal research and product development . The overwhelming amount of evidence which has established a microbial etiology for periodontitis is the basis for developing and testing antimicrobial treatments . Well-designed antimicrobial CTs start with a carefully crafted hypothesis and a protocol which explicitly integrates the requirements of the patient, the clinician, the sponsor, and regulatory authorities . Surrogate variables for effectiveness must be clinically relevant, scientifically sound, and statistically valid . Currently, clinical attachment level measurements and alveolar bone assessments are accepted as proof of effectiveness . Indication and claim support of the antimicrobial product guide the design and implementation of the CT . Adverse microbiologic consequences, such as lack of antimicrobial susceptibility, wrong spectrum, incorrect dosage, non-compliance, and drug interference, must be monitored . Successful CTs balance a large group of variables used to screen, randomize, and assign subjects to experimental and control groups to ensure that prognostic and risk factors are properly accounted for.

Am J Rhinol, 1997 Mar-Apr, 11(2), 123 - 32
Recurrent sinusitis: examining medical treatment options; Kaliner MA; Recurrent sinusitis is an increasingly important disease in its own right and is an often overlooked underlying trigger for chronic asthma and/or bronchitis . The complications of unresolved recurrent sinusitis may include intracranial conditions with significant clinical implications . Patients failing conventional therapy require more aggressive therapy to avoid the necessity for invasive measures, and extensive patient education may help increase compliance with the regimen . Invasive measures (surgery) for the treatment of recurrent sinusitis carry a serious complication rate of 0.5% in 200,000 cases/ year . For this reason, aggressive medical management of these patients is an essential effort . This article explores recurrent sinusitis and its pathophysiology, and suggests a medical treatment regimen using nasally inhaled corticosteroids together with antimicrobial and supportive therapy.

Am J Trop Med Hyg, 1997 Mar, 56(3), 307 - 10
Outcome of leptospirosis in children; Marotto PC et al.; We conducted a retrospective analysis of 43 consecutive children (35 boys and 8 girls), 4-14 years of age and living in an urban area, who were hospitalized at the Instituto de Infectologia Emilio Ribas (Sao Paulo, Brazil) from January 1989 to December 1995 with an acute illness subsequently diagnosed as leptospirosis . Epidemiologic data indicated contact with contaminated water in most cases (88%) . The patient sera reacted most strongly with Leptospira interrogans serovars copenhageni (45%) and icterohaemorrhagiae (32.7%) . Jaundice was present in 70% of the patients, elevated transaminase levels in 56%, renal failure in 79%, meningitis in 23%, thrombocytopenia in 65%, and hemorrhagic manifestations in 11.6% . Three children had pulmonary hemorrhage with respiratory failure and one death occurred as a consequence of respiratory failure . We also observed that antimicrobial therapy reduced the extent of renal failure and thrombocytopenia . These data indicate that antibiotics benefit children with late, severe leptospirosis and that severe disease also occurs in children and should be considered in the differential diagnosis.

Lepr Rev, 1997 Mar, 68(1), 10 - 5
Leucocytopenia after rifampicin and ofloxacin therapy in leprosy; Vijayakumaran P et al.; New antimycobacterial agents and combined treatment regimens are being introduced for the treatment of leprosy . Ofloxacin is one such broad spectrum antimicrobial agent . In this study rifampicin plus ofloxacin were administered daily for 4 weeks (daily supervised dose) . Two patients (and possibly a third patient who refused all investigations) out of 125 patients developed leucocytopenia during the third week of therapy . It was associated with fever, malaise, nausea and loss of appetite . They recovered after cessation of drug treatment . Patients receiving ofloxacin should be monitored for constitutional symptoms suggestive of this complication even though the risk of such complication may be minimal.

Phytochemistry, 1997 Mar, 44(5), 887 - 9
Antimicrobial constituents of Angelica dahurica roots; Kwon YS et al.; One novel coumarin from Angelica dahurica roots was elucidated to be 5,8-di(2,3-dihydroxy-3-methylbutoxy)-psoralen . It occurs together with six other known coumarins and ferulic acid . The antimicrobial activity of the coumarins and ferulic acid were compared.

Clin Infect Dis, 1997 Mar, 24(3), 471 - 85
Programmatic role of the infectious diseases physician in controlling antimicrobial costs in the hospital; John JF Jr et al.; Controlling antimicrobial costs has preoccupied infectious diseases physicians (IDPs) . IDPs have controlled antimicrobial costs by the use of eight strategies: education, formulary restriction, pharmacy justification, formulary substitution, computer surveillance, laboratory item cost listing, purchase plans, and multidisciplinary approaches . Most strategies had input from IDPs and resulted in cost savings (up to $500,000 annually), particularly during the initiation periods . Educational efforts were successful in reducing costs but needed continual intervention . Formulary restriction was the most straightforward cost-control mechanism . Restriction of "target antimicrobials" has given way to "switch" therapy between expensive and less costly agents or between parenteral and oral regimens . Switch therapy is facilitated through the use of innovative order forms and on-line computer interaction . Computer surveillance has a capacity for interactive controls . Purchase plans may give way to centralized pharmacy monitoring, a strategy that is attractive to managed care organizations . Multidisciplinary antimicrobial management programs (AMPs) offer the best potential for sustaining savings in antimicrobial costs . Ten recommendations lay a groundwork for IDPs to translate their expertise into leadership of AMPs.

J Am Optom Assoc, 1997 Mar, 68(3), 178 - 87
Treatment of ocular bacterial infections: an update; Hammond RW et al.; BACKGROUND: Because of increased bacterial resistance and the addition of new antimicrobial medications, the current and appropriate treatment of ocular bacterial infections is an important issue for eye care practitioners . METHODS: The literature on the antimicrobial treatment of ocular bacterial infections is reviewed to provide the practicing optometrist with an overview of the issues and medications involved in therapy . RESULTS: New topical, oral, and parenteral antibiotic medications continuously become available to eye care practitioners . Clinicians must routinely reassess the conventional antimicrobial therapy in light of the drugs available for the treatment of bacterial eye infections . The clinician must be familiar with distinct protocols and medications for the management of different ocular bacterial infections . CONCLUSIONS: Knowledge of the results of controlled antimicrobial studies and a review of standard practices in managing bacterial eye disease can provide the necessary background to help the eye care clinician make appropriate antimicrobial therapeutic decisions in patient care.

Pharmazie, 1997 Mar, 52(3), 189 - 94
Synthesis and antimicrobial activity of some bis-quinazoline derivatives; Shiba SA et al.; The hitherto unknown bis{quinazolin-4-one-2-yl}-m-phenylene (2d), and its 3-N-substituted derivatives were prepared from the corresponding bis{3,1-benzoxazin-4-one-2-yl}-m-phenylene (1) as precursor . The quinazolinone derivative 2d was converted into bis{quinazolin-4-thioxo-2-yl}-m-phenylene (3) via different routes, bis{4-chloroquinazolin-2-yl}-m-phenylene (8) and bis{4-hydrazinoquinazolin-2-yl}-m-phenylene (11), respectively . The structures of the compounds 2, 3, 8, and 11 were supported by elemental, spectroscopic analysis as well as, chemical proofs . Biological activities of some of the produced compounds were evaluated.

J Intraven Nurs, 1997 Mar-Apr, 20(2), 101 - 8
Antimicrobial drug resistance: a danger to world health; Dugger B; Antimicrobial drug resistance threatens control of infectious disease throughout the world . Antimicrobial susceptibility patterns have changed to the extent that some pathogens are not responsive to the most powerful drug therapies available . IV nurses have the opportunity to educate the public and other health care workers about the importance of infection control practices and appropriate antimicrobial management.

Clin Perinatol, 1997 Mar, 24(1), 251 - 66
Antibacterial therapy in pregnancy and neonates; Edwards MS; This article reviews the effects of the physiologic changes accompanying pregnancy on the pharmacokinetics of antimicrobials commonly employed during pregnancy . The possible adverse effects on the fetus from maternal use of antibacterials and their excretion into breast milk are reviewed . Principles of antibiotic pharmacology in newborn infants are summarized . The indications for use, dosages, and potential for adverse effects are reviewed for antibiotics currently in use and for several agents for which approval is pending for use in the newborn.

Clin Perinatol, 1997 Mar, 24(1), 91 - 105
Ureaplasma urealyticum infections in the perinatal period; Wang EE et al.; Good evidence indicates the widespread carriage of U . urealyticum among sexually active females . Colonization of the upper genital tract appears to be a risk factor for adverse pregnancy outcomes, though this is not the case for lower-genital-tract colonization . Based on studies in which amniotic fluid obtained from amniocenteses was already positive for U . urealyticum, and its high prevalence in very-LBW neonates, it is likely that the infection is acquired during early pregnancy . A number of observational studies have linked this organism to pulmonary infections, meningeal infections, and bacteremias, particularly in LBW neonates . It is difficult, however, to separate the morbidity that is directly attributable to infection with the organism from morbidity owing to extreme prematurity . Problems in measuring the burden of illness resulting from this organism are compounded by difficulties in its diagnosis . The organism's fastidious nature prevents many laboratories from isolating it from specimens . Rapid and practical methods for identifying the organism are urgently needed . These need to be followed by RCTs to determine if outcomes of pregnant women and babies with various conditions, from whom the organism has been isolated, can be improved through treatment with antimicrobial agents.

J Antimicrob Chemother, 1997 Mar, 39(3), 401 - 4
In-vitro ranking of the efficacy of antimicrobial agents; Tajima Y; A new 'drug efficacy score' was devised to compare the in-vitro efficacy of various drugs . The score is easily calculated from an MIC correlogram; strains positioned above the diagonal of the correlogram are positively scored and those positioned below are given negative scores . Each score is multiplied by the number of corresponding strains, and all such products are summed.

J Nat Prod, 1997 Mar, 60(3), 315 - 8
Triterpene saponins from Cyclamen mirabile and their biological activities; Calis T et al.; Six saponins, cyclaminorin (1), deglucocyclamin (2), cyclacoumin (3), cyclamin (4), isocyclamin (5), and mirabilin (6) were isolated from the tubers of Cyclamen mirabile . Compound 6 is a new natural compound, and its structure was established as 3-{O-beta-{{beta-D-xylopyranosyl-(1-->2)}- {beta-D-glycopyranosyl-(1-->6)}-beta-D-glucopyranosyl-(1-->4)}-{be ta-D- glucopyranosyl-(1-->2)}-alpha-L-arabinopyranosyl}-3 beta,16 alpha,28-trihydroxyolean-12-en-30-oic acid (6) . The structure elucidation of this compound was accomplished using both spectral and chemical methods . Antimicrobial and uterocontractile activities of the saponins were also investigated.

Pharmacotherapy, 1997 Mar-Apr, 17(2), 302 - 7
Cost of oral antibiotic therapy; Nightingale CH et al.; Many bacterial infections can be managed effectively with oral agents rather than parenteral therapy, significantly reducing treatment costs . With renewed interest in oral therapy, and with the importance of cost containment in the managed care environment, it is necessary to evaluate costs associated with different oral antimicrobials . Comparison of per-dose cost and baseline treatment cost (cost/dose x doses/day x days of treatment) is straightforward . More difficult to determine is the overall treatment cost, which is influenced by probabilities that therapy will be effective, safe, and complete . Tolerability, complexity of dosage regimen, and potential for drug-drug interactions may all affect therapeutic efficacy and overall cost . Compared with older agents, newer antibiotics are generally better tolerated and less likely to produce adverse reactions, resulting in better patient compliance, greater efficacy, and often lower overall cost of antimicrobial therapy.

Pharmacotherapy, 1997 Mar-Apr, 17(2), 271 - 6
A pharmacist-initiated program of intravenous to oral antibiotic conversion; Przybylski KG et al.; A prospective program to convert patients from parenteral to oral antibiotics was evaluated over 12 months to determine its pharmacoeconomic impact on antibiotic acquisition and length of hospital stay . Physicians of patients meeting predetermined clinical criteria for mild and moderate infections were contacted to discuss potential oral alternative therapy . Clinical end points and economic data were followed in 242 patients (200 converted and 42 not converted but meeting criteria) . No significant differences were noted between the groups with regard to demographic data, infection diagnosis, clinical outcome, or adverse effects . The average number of days of therapy for patients converted was 1.53 days shorter than that of patients who were not converted to oral therapy (p < 0.003) . Cost savings for drug acquisition and length of stay were $15,149.24 and $161,071.88, respectively . The intervention program appeared to provide a cost-effective conversion from parenteral to oral antimicrobial administration without compromising patient care . It is anticipated that expansion of the program to include additional antibiotics will result in even greater cost savings for the institution.

J Clin Periodontol, 1997 Mar, 24(3), 171 - 9
A logistic regression model for the decision to perform access surgery; Loesche WJ et al.; Access surgery may be recommended to about 80% of patients who present with advanced forms of periodontal disease . In this report, a multivariate logistic regression analysis which incorporated several clinical parameters for each tooth examined, i.e., tooth type, furcation involvement, bleeding on probing, attachment level, probing depth, mobility and BANA test score, was conducted using generalized estimating equations (GEE) . This approach identified parameters that were significantly associated at p < 0.05 level with the need for access surgery or extraction for periodontal purposes . The estimated probabilities derived from the GEE model were plotted over the complete spectrum of operating conditions to obtain a receiver-operator characteristic (ROC) curve . At a probability cutpoint of 0.8, the decision threshold for surgery/extraction at the pretreatment examination would have a sensitivity of 76.1% and a specificity of 75.3% . We have taken this 0.8 cut point to look at specific clinical decisions made by our examiners after the patients had received scaling and root planing plus 2 weeks unsupervised usage of systemic antimicrobials . The clinicians' decision was taken as the primary reference standard . The model's estimated decision agreed with the clinicians' decision in 226 of the 284 teeth, for an accuracy of 80% . The specificity was 90% and the sensitivity was 43%.

Photochem Photobiol, 1997 Mar, 65(3), 599 - 602
Photogeneration of fluoride by the fluoroquinolone antimicrobial agents lomefloxacin and fleroxacin; Martinez LJ et al.; The photolysis (> 320 nm) of the fluoroquinolone antibacterial agents lomefloxacin and fleroxacin results in the loss of their F3 atoms as fluoride . The quantum yield for lomefloxacin was 0.98 at pH 7.4 . The mechanism probably involves aryl-F heterolysis from the S1 state with the concomitant generation of a carbene at C-8 . In contrast, the monofluorinated fluoroquinolones norfloxacin and ciprofloxacin do not generate fluoride upon irradiation . Carbenes are highly reactive species that undergo addition, insertion and abstraction reactions and can cause DNA cleavage . These findings may explain why lomefloxacin and fleroxacin are more photomutagenic and photocarcinogenic than fluoroquinolones in which C-8 is either unsubstituted or bears a substituent other than fluorine.

Pediatr Infect Dis J, 1997 Mar, 16(3), 297 - 305
Susceptibility of pneumococcal carriage isolates to penicillin provides a conservative estimate of susceptibility of invasive pneumococci; Lehmann D et al.; OBJECTIVE: Because of its practical importance for public health monitoring in developing countries, we aimed to determine whether susceptibility to penicillin of pneumococci isolated from the upper respiratory tract (URT) is representative of the susceptibility of pneumococci causing pneumonia in children . METHOD: The serogroup distribution and minimum inhibitory concentration of penicillin for 56 and 90 isolates from blood and cerebrospinal fluid, respectively, were compared with those of 833 pneumococcal carriage isolates from Papua New Guinean children . These included 154 and 98 strains from bacteremic and nonbacteremic hospitalized patients with pneumonia, respectively, 350 from outpatients with respiratory infections and 176 and 55, respectively, from children in a community-based study who were healthy or sick with pneumonia . RESULTS: Proportions of pneumococci intermediately resistant to penicillin were comparable in the URT and blood (60%) in 1985 through 1987 when serogroup distributions in the two sites were similar . However, penicillin resistance was higher in the URT (75%) than blood (44%) in 1980 through 1984 when the less frequently carried, less resistant serogroups (1 to 5, 7 to 12, 45 and 46) accounted for a high proportion of bacteremic strains . CONCLUSIONS: URT isolates from any group of sick or healthy children could provide a conservative estimate of antimicrobial susceptibility of invasive strains and is a practical way of monitoring susceptibility as well as evaluating the continued effectiveness of standard antibiotic therapy . If there was cause for concern, it would then be necessary to examine invasive isolates.

Arch Fam Med, 1997 Mar-Apr, 6(2), 173 - 80
Antimicrobial management of Helicobacter pylori-associated gastrointestinal tract disease; Guay DR et al.; Since the identification of Helicobacter pylori in 1983, this pathogen has become the dominant focus of investigation in a variety of gastrointestinal tract disorders, including peptic ulcer disease, nonulcer dyspepsia, and gastric carcinoma . During the past 7 years, the efficacy of a variety of antimicrobial single, dual, and triple therapy regimens--including the use of acid-suppressive agents, such as proton pump inhibitors, and histamine2-receptor antagonists--in the eradication of H pylori have been investigated . Newer treatment approaches, such as dual therapy (proton pump inhibitor + 1 antimicrobial agent) and 7-day regimens have shown a high degree of success and have the potential to improve compliance . However, the optimal regimen, in terms of cost, efficacy, and tolerability, and optimal length of treatment still remains to be determined.

Am J Respir Cell Mol Biol, 1997 Mar, 16(3), 343 - 9
Human airway epithelia express a beta-defensin; McCray PB Jr et al.; Recent evidence suggests that the surface fluid secreted by human airway epithelial cells contains antimicrobial activity . The identification of the factor(s) responsible for the antibacterial activity in airway surface fluid may bring new insights into lung defense mechanisms and the pathogenesis of disease . Defensins are small cationic peptides with broad-spectrum antimicrobial activity, and are therefore candidates for the bacterial killing factor in airway surface fluid . They are produced in mucosal epithelia and neutrophils of several species . To date no defensins have been isolated from human airway epithelia; however, such peptides are produced by bovine airway epithelia . A cDNA fragment for a human beta-defensin-1 (hBD-1) was recently cloned from the kidney . We cloned the full-length coding sequence for hBD-1 from human airway epithelia . The amino acid sequence for hBD-1 shared homology with the signal/propiece and mature peptides of other beta-defensins, including bovine tracheal antimicrobial peptide and lingual antimicrobial peptide . By Northern analysis, a single approximately 400-nt hBD-1 transcript was expressed in airway epithelia . Ribonuclease protection analysis demonstrated that hBD-1 transcripts were more abundant in the conducting airways than the gas exchange regions of human lung and that the expression was developmentally regulated . Human beta-defensin-1 may contribute to the antimicrobial activity of airway surface fluid and play a role in the mucosal defenses of the lung.

CMAJ, 1997 Mar 1, 156(5), S703 - 11
A practical guide for the diagnosis and treatment of pediatric pneumonia; Jadavji T et al.; OBJECTIVE: To develop guidelines for the diagnosis and management of community-acquired pediatric pneumonia . OPTIONS: Clinical assessment, radiography, laboratory testing, and empirical antimicrobial therapy . OUTCOMES: Increased awareness of age-related causes, improved accuracy of clinical diagnosis, better utilization of diagnostic testing and the rational use of empirical antimicrobial therapy resulting in more rapid diagnosis, initiation of appropriate therapy and decreased morbidity and mortality . EVIDENCE: A MEDLINE search for relevant articles published from 1996 to September 1996 using the MeSH terms "pediatric," "pneumonia," "respiratory tract infection," "pneumonitis," "etiology," "diagnosis," "therapy," "antibiotics," "resistance," "radiology," "microbiology" and "biochemistry." VALUES: A hierarchical evaluation of the strength of evidence modified from the methods of the Canadian Task Force on the Periodic Health Examination was used . When application of the hierarchy was not feasible or appropriate, different evaluation criteria were used . BENEFITS, HARMS AND COSTS: Increased awareness of the causes of pneumonia, accurate diagnosis and prompt treatment should reduce costs associated with unnecessary investigations and complications due to inappropriate treatment . RECOMMENDATIONS: Age is the best predictor of the cause of pediatric pneumonia, viral pneumonia being most common during the first 2 years of life . The absence of a symptom cluster of respiratory distress, tachypnea, crackles and decreased breath sounds accurately excludes the presence of pneumonia (level II evidence) . Bacterial cultures of samples from the nasopharynx and throat have no predictive value; however, Gram staining and culture of sputum from older children and adolescents are useful (level III evidence) . Oral antimicrobial therapy will provide adequate coverage for most mild to moderate forms of pneumonia in children (level III evidence) . Parenteral therapy is typically reserved for neonates and patients with severe pneumonia admitted to hospital (level III evidence) . VALIDATION: These recommendations are based on consensus of Canadian experts in infectious diseases and microbiology . They are the only guidelines to address antimicrobial treatment from an age-related, etiologic perspective . SPONSOR: The development of these guidelines and the technical support and assistance of Core Health Inc . in preparing this manuscript were funded through an unrestricted educational grant from Abbott Laboratories Canada . The sponsoring company was not involved in determining the membership of the consensus group or the content of the guidelines.

Infect Dis Clin North Am, 1997 Mar, 11(1), 119 - 33
Pneumonia and tuberculosis in pregnancy; Riley L; Antepartum pneumonia requires prompt evaluation and empiric antimicrobial therapy . The choice of antimicrobial therapy depends on maternal risk factors, symptoms, and clinical presentation . Although laboratory studies such as culture and serology should be obtained, they may not always yield a specific etiologic agent . However, prompt empiric treatment and supportive care should lead to good maternal and fetal outcomes . Similarly, in most cases, proper diagnosis and treatment of TB during pregnancy yield good maternal and fetal outcomes . TB screening is essential for the growing population of individuals with HIV infection and recent immigrants from areas where tuberculosis is endemic.

Clin Diagn Lab Immunol, 1997 Mar, 4(2), 138 - 41
Depletion of endogenous interleukin-10 augments interleukin-1 beta secretion by Mycobacterium bovis BCG-reactive human cells; Mendez-Samperio P et al.; In this study, we found evidence that the interleukin-10 (IL-10) protein is functionally relevant in Mycobacterium bovis BCG-induced cytokine synthesis, as neutralization of endogenously synthesized IL-10 in human cells activated with BCG resulted in a two- to threefold increase in the level of IL-1 beta . When exogenous recombinant human IL-10 was added to human mononuclear cells, a significant reduction of BCG-induced IL-1 beta secretion was observed . This inhibitory effect was not attributed to a cytotoxic effect, since trypan blue exclusion studies indicated no loss of cell viability in the presence of IL-10, and it was specific, as it was completely abolished in the presence of anti-IL-10 neutralizing monoclonal antibody while an irrelevant antibody used as a control had no effect . Taken together, these are the first studies that demonstrate that the depletion of endogenous IL-10 via anti-IL-10 antibody results in a very significantly enhanced BCG-induced IL-1 beta secretion and that the addition of exogenous IL-10 to human mononuclear cells stimulated with BCG inhibits IL-1 beta production . Further experimental work is needed to determine if the neutralization of IL-10 activity via anti-IL-10 antibody indeed enhances cytokine synthesis in vivo . However, the present results may be of importance, since the use of anti-IL-10 antibody could presumably contribute to the protective immunity induced by BCG against tuberculosis via an increase in cytokine synthesis that would amplify antimicrobial systems.

Am J Pathol, 1997 Mar, 150(3), 1009 - 20
Immunohistochemical localization of defensin in human coronary vessels; Barnathan ES et al.; Neutrophil defensins comprise a family of cationic peptides that possess potent antimicrobial activity . Defensins are normally sequestered in cytoplasmic granules with their primary site of action in phagolysosomes, although some peptide is released into the circulation during the course of infection or inflammation . In view of the fact that neutrophils adhere to the endothelium and that defensins have been reported to bind to human endothelial cells in vitro, we used immunohistochemistry to study the distribution of these peptides in normal and in atherosclerotic human coronary arteries . Defensin was found primarily in the intima of normal and atherosclerotic vessels, most prominently in association with intimal smooth muscle cells . Both large- and small-vessel endothelium stained focally for defensin . Defensin was also found in the media near the external elastic lamina and in some periadventitial vessels . The same distribution was seen in vessels that had been perfusion fixed immediately upon procurement, excluding diffusion of defensin from PMNs ex vivo . These data indicate that neutrophil defensin is present in the walls of human coronary arteries . The deposition of defensin in vessels may contribute to the pathophysiological consequences of inflammation in addition to their role in host defense.

Am J Pathol, 1997 Mar, 150(3), 889 - 900
Apoptosis and expression of inducible nitric oxide synthase are mutually exclusive in renal mesangial cells; Nitsch DD et al.; Nitric oxide (NO) is a multipurpose messenger molecule, important for blood vessel relaxation, neuronal communication, and antimicrobial activities . The generation of NO from L-arginine is catalyzed by NO synthase (NOS) . An inducible form of NOS, iNOS, was first characterized in macrophages and then in many other tissues and cells, including renal mesangial cells . Mesangial cells play a crucial role in the regulation of the glomerular filtration rate as well as in the pathophysiology of certain forms of glomerulonephritis in which mesangial cells and macrophages produce NO in high amounts . Because reports have associated NO production with apoptotic cell death in macrophages and we recently demonstrated NO-mediated apoptosis in mesangial cells, we searched for the relationship between in situ iNOS induction and apoptosis by iNOS immunocytochemistry and terminal desoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining . RAW 264.7 macrophages exhibited homogeneous iNOS expression and apoptotic nuclei in the iNOS-containing cells upon stimulation with interferon-gamma and lipopolysaccharide . In contrast, stimulated rat mesangial cells stained heterogeneously for iNOS, depending on cell passage and iNOS-stimulating pathway . Mesangial cells expressing iNOS did not display signs of apoptosis and, vice versa, cells showing characteristic features of apoptosis did not stain for iNOS . Thus, our study suggests that mesangial cells react to stimulation by interleukin-1 and/or cAMP-elevating compounds with mutually exclusive responses, either by expression of iNOS or by undergoing programmed cell death.

Antimicrob Agents Chemother, 1997 Mar, 41(3), 717 - 9
Direct evidence for uptake of intact liposomes encapsulating silver sulfadiazine by cultured human keratinocytes based on combined transmission electron microscopy and X-ray microanalysis; Schaller M et al.; Cultured human keratinocytes were exposed to liposomally encapsulated silver sulfadiazine, free silver sulfadiazine, silver sulfadiazine cream, and a corresponding vehicle for 5 min to 24 h . Phagocytosis of intact liposomes by keratinocytes was demonstrated in vitro by combined X-ray microanalysis and electron microscopy . Silver as an active part of the antimicrobial served as an electron-dense marker.

Antimicrob Agents Chemother, 1997 Mar, 41(3), 647 - 53
Evolution of extended-spectrum beta-lactam resistance (SHV-8) in a strain of Escherichia coli during multiple episodes of bacteremia; Rasheed JK et al.; Nine isolates of Escherichia coli were recovered from seven blood cultures over a period of 3 months from a 19-month-old female with aplastic anemia . Initial isolates were susceptible to extended-spectrum cephalosporins, including ceftazidime (MIC, < or = 0.25 microgram/ml), but gradually became resistant to this drug (MICs, > or = 128 micrograms/ml) and other cephalosporins and the monobactam aztreonam . Molecular typing methods, including plasmid profile analysis, pulsed-field gel electrophoresis, and arbitrarily primed PCR, indicated that the nine isolates were derived from a common ancestor . Dot blot hybridization and PCR analysis of total bacterial DNA using blaSHV- and blaTEM-specific DNA probes and primers identified the presence of a blaTEM beta-lactamase gene in all of the isolates and a blaSHV gene in the isolates with elevated ceftazidime MICs . Isoelectric focusing analysis of crude lysates showed that all nine isolates contained an enzyme with a pI of 5.4 corresponding to the TEM-1 beta-lactamase, and those isolates containing an SHV-type beta-lactamase demonstrated an additional band with a pI of 7.6 . The first of the ceftazidime-resistant isolates appeared to hyperproduce the SHV enzyme compared to the other resistant isolates . DNA sequencing revealed a blaSHV-1 gene in the first ceftazidime-resistant isolate and a novel blaSHV gene, blaSHV-8, with an Asp-to-Asn substitution at amino acid position 179 in the remaining four isolates . Three of the ceftazidime-resistant isolates also showed a change in porin profile . The patient had received multiple courses of antimicrobial agents during her illness, including multiple courses of ceftazidime . This collection of blood isolates from the same patient appears to represent the in vivo evolution of resistance under selective pressure of treatment with various cephalosporins.

Antimicrob Agents Chemother, 1997 Mar, 41(3), 624 - 9
Antimicrobial action of rabbit leukocyte CAP18(106-137); Mason DJ et al.; CAP18 is a cationic antimicrobial protein originally isolated from rabbit neutrophils, of which a 32-mer sequence from its C-terminal and (CAP18(106-137)) has been found to be the most active . The bactericidal action of this peptide has been characterized by conventional culture techniques and flow cytometry . Cultures of Escherichia coli NCTC10418 were exposed to the MBC (12 microM) of the peptide for up to 60 min and stained with a fluorochrome sensitive to changes in either membrane potential (bis-(1,3-dibutylbarbituric acid)trimethine oxonol {DiBAC4(3)), or membrane integrity (propidium iodide {PI}) before flow cytometric analysis . Addition of CAP18(106-137) to E . coli in broth culture resulted in immediate collapse of membrane potential {as determined by uptake of DiBAC4(3)} and loss of membrane integrity (as indicated by uptake of PI), with a corresponding 6- to 8-log decrease in viable counts as determined by colony formation on solid media . In identical experiments, the presence of Mg2+ (1 to 10 mM), K+ (50 to 250 mM), or EDTA (5 mM) or incubation in nutrient-free buffer or at 4 degrees C had no effect on peptide-induced dye uptake . In contrast, addition of Ca2+ (1 to 10 mM) or the respiratory chain poison carbonyl cyanide m-chlorophenylhydrazone (CCCP) (50 microM) inhibited the uptake of both dyes . These findings, however, did not relate to bacterial recovery on solid media, where (unless in the presence of K+ 150 to 250 mM) CAP18(106-137) at 12 microM fulfilled the MBC criteria (99.9% killing) . We conclude that CAP18(106-137) exerts a rapid and profound action on E . coli cytoplasmic membranes and viability as measured by colony formation . The results suggest, however, that CAP18(106-137) may exert its action at sites additional to the cell membrane and that its activity profile is unique among cationic antimicrobial proteins.

Obstet Gynecol, 1997 Mar, 89(3), 409 - 12
Necrotizing fasciitis after cesarean delivery; Goepfert AR et al.; OBJECTIVE: To review our experience with the diagnosis and management of necrotizing fasciitis after cesarean delivery . METHODS: We reviewed medical records of women with serious post-cesarean wound infections at the University of Alabama at Birmingham between 1987 and 1994 to identify women with necrotizing fasciitis . The diagnosis of necrotizing fasciitis required intraoperative identification of necrotic fascia in febrile women undergoing post-cesarean wound debridement . RESULTS: During the study period, 5048 women had cesarean deliveries, nine of which were complicated by necrotizing fasciitis . The mean (+/-standard deviation) maternal age was 27 +/- 6 years, and the mean maternal weight was 199 +/- 64 lb . None of the patients had insulin-dependent diabetes mellitus, and none had known peripheral vascular disease . There were no intraoperative complications at cesarean delivery . The mean time from cesarean delivery to the diagnosis of necrotizing fasciitis and reoperation was 10 +/- 4 days (range 5-17) . All patients had surgical debridement upon consideration of the diagnosis, and all received broad-spectrum antimicrobial therapy . Results of wound cultures were available in seven of the women, and all seven were found to have polymicrobial infections . There were two mortalities, one as a result of metastatic breast cancer and another with complications of sepsis . CONCLUSION: Necrotizing fasciitis is infrequent (1.8 per 1000 women) after cesarean delivery at our institution, but it does result in appreciable morbidity and mortality.

J Infect Dis, 1997 Mar, 175(3), 648 - 54
Effects of doxycycline and antiinflammatory agents on experimentally induced chlamydial upper genital tract infection in female macaques; Patton DL et al.; To evaluate the effects of antimicrobial and antiinflammatory drugs on oviductal pathology in chronic chlamydial upper genital tract infection, the fallopian tubes of 40 female Macaca nemestrina were inoculated with Chlamydia trachomatis and randomly assigned to treatment with doxycycline (n = 10), doxycycline plus ibuprofen (n = 10), doxycycline plus triamcinolone (n = 10), or placebo (n = 10) . Before therapy, all animals were positive for culture or ligase chain reaction (or both), and laparoscopy demonstrated the presence of upper genital tract pathology . After therapy, cervical cultures remained positive in 5 animals given placebo versus 0 given doxycycline alone (P = .03), 0 given doxycycline plus ibuprofen (P = .03), and 1 given doxycycline plus triamcinolone (P = .14) . At hysterectomy, neither gross nor histologic pathology was affected by any of the treatment regimens, but immunocytochemistry and in situ hybridization evidence of persistent tubal infection was significantly more frequent among animals given placebo or doxycycline plus antiinflammatory agents than among those given doxycycline alone.

Biochemistry, 1997 Feb 25, 36(8), 2104 - 11
Modulation of magainin 2-lipid bilayer interactions by peptide charge; Matsuzaki K et al.; Magainin 2, an antimicrobial peptide from Xenopus skin, assumes an amphiphilic helix when bound to acidic phospholipids, forming a pore composed of a dynamic, peptide-lipid supramolecular complex {Matsuzaki et al . (1996) Biochemistry 35, 11361-11368} . Upon the disintegration of the pore, a fraction of the peptide molecules stochastically translocates across the bilayer (Matsuzaki, et al., 1995) . In order to investigate the effects of peptide charge on the magainin 2-lipid bilayer interactions, we synthesized four magainin 2 analogs with different charges (0-6+) . MG0: K10E, K11E, F12W-magainin 2 . MG2+: K10E, F12W-magainin 2 . MG4+: F12W-magainin 2 . MG6+: F12W, E19Q-magainin 2 amide . An increase in charge resulted in a stronger binding of the peptide to the negatively charged membranes, suggesting that electrostatic attractions play a crucial role in the binding process . The helical stability in a trifluoroethanol/buffer mixture was decreased with increasing positive charge because of electrostatic repulsions between the closely spaced positive side chains, whereas the helicity in the lipid bilayer was much higher and appeared to be independent of the peptide charge . However, enhanced repulsions between the highly positively charged helices destabilized the pore . Therefore, the efficiency of the most basic peptide (MG6+) to translocate across the bilayer was the greatest by virtue of the short life span of its pore and the very tight membrane binding . The charge distribution of wild-type magainin 2 was found to be so designed as to exhibit the maximal lytic activity by simultaneously achieving a strong binding and a moderate pore stability.

Orv Hetil, 1997 Feb 23, 138(8), 473 - 8
{Simple parameters of antibiotic utilization and diagnostic background of antimicrobial therapy in Hungarian hospitals in 1995}; Almasi I et al.; This paper is published as second part of a survey on antibiotic utilisation of 8 Hungarian hospitals in January, 1995 . The length of hospital stay of the patients receiving systemic antibiotic treatment was significantly higher (P < 0.0001) than those of not receiving such treatment . After exclusion of the patients suffering from nosocomial infections, average of the excess of hospital days was 4.65 . Comparing the figures of patients receiving one or more antibiotic/one hospital stay and the rate of monotherapy and combined therapy and number of used antibiotics/100 discharged patients or/100 patients treated with antibiotics it was found that these indexes were most favourable in that hospital, where antibiotic policy was in function . Examining diagnoses (perioperative profilaxis 32.7%, pneumonia 13.3% of the 753 diagnoses) and drugs (metronidazol 26.3%, aminoglycosides 20% of the 1455 antibiotics) most frequently found in cases of combined antibiotic therapy it was concluded that parallel treatment with two or more antibiotic was often unjustified . Only 11% of antibiotics was used as directed against known bacteria . It was found that the rate of the achieved microbiological examinations and targeted therapy was low even if microbiological samples were easy to obtain . It was not the main purpose of the survey to get data of the clinical diagnostic background of antibiotic therapy, but indirect signs showed that these drugs were often used without sufficient clinical evidences (anamnesis, physical status, labor, X-ray and other tests) of infection . Authors recommend further survey in order to find out the causes of insufficiency of diagnoses . They also propose elaboration of diagnostic protocols.

Cell, 1997 Feb 21, 88(4), 553 - 60
Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis; Goldman MJ et al.; A human bronchial xenograft model was used to characterize the molecular basis for the previously described defect in bacterial killing that is present in the cystic fibrosis (CF) lung . Airway surface fluid from CF grafts contained abnormally high NaCl and failed to kill bacteria, defects that were corrected with adenoviral vectors . A full-length clone for the only known human beta-defensin (i.e., hBD-1) was isolated . This gene is expressed throughout the respiratory epithelia of non-CF and CF lungs, and its protein product shows salt-dependent antimicrobial activity to P . aeruginosa . Antisense oligonucleotides to hBD-1 ablated the antimicrobial activity in airway surface fluid from non-CF grafts . These data suggest that hBD-1 plays an important role in innate immunity that is compromised in CF by its salt-dependent inactivation.

Lancet, 1997 Feb 15, 349(9050), 490 - 5
Chemokines: leucocyte recruitment and activation cytokines; Adams DH et al.; Chemokines are a family of structurally related proteins that share the ability to induce migration of specific subsets of leucocytes . These specialised cytokines play a critical part in the generation of cellular inflammation, both in the protective responses to invading pathogens and in the pathological processes associated with infection and immune-mediated diseases . Chemokines are more than simple chemotactic factors, since they are also implicated in leucocyte activation, angiogenesis, and antimicrobial functions, including a protective role in HIV infection . These molecules provide potentially valuable targets for therapeutic intervention in a wide range of diseases.

Ann Intern Med, 1997 Feb 15, 126(4), 280 - 91
Management strategies for Helicobacter pylori-seropositive patients with dyspepsia: clinical and economic consequences; Ofman JJ et al.; BACKGROUND: Noninvasive testing for Helicobacter pylori is widely available and has been considered as an initial management strategy for uninvestigated dyspepsia . However, data to guide clinicians in the management of patients with dyspepsia who are seropositive for H . pylori are lacking . OBJECTIVE: To examine the economic, clinical, and policy implications of alternative initial management strategies for patients with uninvestigated dyspepsia who are seropositive for H . pylori . DESIGN: Decision analysis comparing the costs and outcomes of initial anti-H . pylori therapy and initial endoscopy . PATIENTS: Helicobacter pylori-seropositive patients with dyspepsia . MEASUREMENTS: Cost estimates were obtained from the Medicare reimbursement schedule and a health maintenance organization pharmacy . Probability estimates were derived from the medical literature . RESULTS: Initial endoscopy costs an average of $1276 per patient, whereas initial anti-H, pylori therapy costs $820 per patient; the average saving is $456 per patient treated . The financial effect of a 252% increase in the use of antibiotics for initial H . pylori therapy is more than offset by reducing the endoscopy workload by 53% . Endoscopy-related costs must be reduced by 96% before the two strategies become equally cost-effective . In patients with nonulcer dyspepsia, the financial benefits of initial anti-H . pylori therapy are not substantially affected by varying the rates of H . pylori eradication, the complications of antibiotics, or the response of symptoms to cure of H . pylori infection . CONCLUSIONS: In H . pylori-seropositive patients with dyspepsia, initial anti-H . pylori therapy is the most cost, effective management strategy . Randomized studies of these strategies that evaluate outcomes and patient preferences are needed to optimize management decisions . In the meantime, unless physicians are concerned about resistance to antimicrobial agents or the lack of proven benefit of anti-H . pylori therapy in nonucler dyspepsia, the strategy outlined in this analysis can be used as a basis for management and policy decisions about H . pylori-seropositive patients with dyspepsia.

J Inorg Biochem, 1997 Feb 15, 65(3), 183 - 9
Structural and biological aspects of copper (II) complexes with 2-methyl-3-amino-(3H)-quinazolin-4-one; Ramadan AM; A series of new copper (II) complexes with 2-methyl-3-amino(3H)-quinazolin-4-one (MAQ) and various anions (Cl-, Br-, ClO(-)4, NO(-)3, SCN-, and SO(2-)4 was prepared . Their structures and properties were characterized by elemental analysis, IR, UV-Vis and ESR spectroscopy, molar conductivity, and magnetic moment measurements . The square-planar complex was only obtained in the presence of perchlorate anion, whereas the five coordinate species, which have a square-pyramidal structure, were obtained for chloro and bromo complexes . In the case of hexa coordinate complexes, in which nitrate, sulphate, or thiocyanate is attached to a copper(II) ion in a 1:2 (metal:ligand) ratio, a distorted octahedral geometry around copper(II) is proposed . The antimicrobial activity of the free ligand and its copper(II) complexes clearly illustrates that the compounds have both an antibacterial and antifungal potency against the organisms tested . In most cases, the complexes were found to be more active than the free ligand, but in some cases, an equal activity was displayed . To further elucidate the biological activity of the complexes, their activities towards active oxygen species, such as H2O2 and O(-)2, were investigated . A probable mechanism for the cytotoxic reaction with the different organisms is proposed.

J Biol Chem, 1997 Feb 7, 272(6), 3384 - 8
Effect of amino acid substitutions on the activity of carnobacteriocin B2 . Overproduction of the antimicrobial peptide, its engineered variants, and its precursor in Escherichia coli; Quadri LE et al.; Carnobacteriocin B2, a 48-amino acid antimicrobial peptide containing a YGNGV motif that is produced by the lactic acid bacterium Carnobacterium piscicola LV17B, was overexpressed as fusion with maltose-binding protein in Escherichia coli . This fusion protein was cleaved with Factor Xa to allow isolation of the mature bacteriocin that was identical in all respects to that obtained from C . piscicola . Similar methodology permitted production of the precursor precarnobacteriocin B2 (CbnB2P), which has an 18-amino acid leader, as well as six mutants of the mature peptide: CbnF3 (Tyr3 --> Phe), CbnS33 (Phe33 --> Ser), CbnI34 (Val34 --> Ile), CbnI37 (Val37 --> Ile), CbnG46 (Arg46 --> Gly), and Cbn28 (truncated frameshift mutation: (carnobacteriocin B2 1-28) + ELTHL) . Examination of these compounds for antimicrobial activity showed that although CbnI34, CbnI37, and CbnG46 were fully active, CbnB2P, CbnF3, CbnS33, Cbn28, and all of the fusion proteins had greatly reduced or no antimicrobial activity . Expression of the immunity protein that protects against the action of the parent carnobacteriocin B2 in a previously sensitive organism also protects against the active mutants . Because carnobacteriocin B2 also acts as an inducer of bacteriocin production in C . piscicola, the ability of the precursor CbnB2P and the mutants to exert this effect was examined . All were able to induce Bac- cultures and reestablish the Bac+ phenotype except for the truncated Cbn28 . The results demonstrate that very minor changes in the peptide sequence may drastically alter antimicrobial activity but that the induction of bacteriocin production is much more tolerant of structural modification, especially at the N terminus.

Cesk Slov Oftalmol, 1997 Feb, 53(1), 49 - 56
{Clinical experience with Spersadex comp . gtt.}; Bodnar M et al.; The preparation Spersadex comp . gtt . was tested on three groups of patients (60 patients, 109 eyes) in order to assess its effectiveness in indications outlined by the manufacturer . The preparation has a very favourable antimicrobial, and antiphlogistic action . It proved very effective also in the treatment of chlamydial infections and in the postoperative treatment the combination of the antiphlogistic effect and the antibiotic action proved very useful, though tested only in small groups of patients . Spersadex comp . gtt . is a very effective preparation, well tolerated by patients and it supplements in a useful way the range of eye drops by a new antibiotic-corticoid combination.

Clin Infect Dis, 1997 Feb, 24 Suppl 2, S256 - 65
Empirical treatment of febrile neutropenia: evolution of current therapeutic approaches; Hathorn JW et al.; Administration of empirical antibiotic therapy is now standard practice in the management of febrile neutropenia, but there has been considerable debate about the selection of an efficacious empirical antimicrobial regimen over the past 2 decades . A variety of approaches, including both monotherapeutic and multidrug regimens, have been demonstrated to be effective, although no one regimen has been proven to be superior to another . Changes in the epidemiology of infectious organisms and the growing emergence of highly drug-resistant strains make it necessary to continually reevaluate the therapeutic options . Fortunately, the number of therapeutic options has also been broadening as new antimicrobial agents, including third-generation cephalosporins and carbapenem antibiotics such as imipenem and meropenem, become available . Optimal management is directed by the findings of a clinical evaluation of the patient as well as an awareness of institutional patterns of infection and susceptibility of likely infecting organisms.

Clin Infect Dis, 1997 Feb, 24 Suppl 2, S231 - 7
Streamlining antimicrobial therapy for lower respiratory tract infections; Hitt CM et al.; Antimicrobial streamlining is the practice of converting a broad-spectrum empirical regimen to therapy with either a single, narrow-spectrum parenteral agent or an oral agent as soon as possible . This practice results in many benefits for the patient and the hospital . When intravenous catheters can be removed early, the frequencies of catheter-associated bacteremias and phlebitis are reduced, thus making it possible to avoid incurring major costs . With the availability of newer oral agents with favorable pharmacokinetic, pharmacodynamic, and microbiological profiles, such as the fluoroquinolones, the macrolides/azalides, and the cephalosporins, the clinician has greater opportunity to employ streamlining tactics . The patient who is hospitalized with a lower respiratory tract infection (LRTI) often requires empirical antimicrobial therapy before the pathogen is identified . By day 3 of the hospital course, the pathogen is often known, the patient's condition may have stabilized, or both events may have occurred . At this point, streamlining is possible . At present, data suggest that rapid conversion from intravenous to oral antimicrobial therapy is safe and efficacious and should be considered for appropriate patients requiring hospitalization for LRTIs.

Acta Paediatr Jpn, 1997 Feb, 39(1), 98 - 104
Clinical trials of new antibiotics in children in Japan; Fujii R; Japan is the most advanced of the industrialized nations in the development of antibiotics . Compared to the United States and countries of the European Union, there is a rich selection and availability of new and appropriate antibiotics for patients with infectious diseases in Japan that is unchallenged under a medical system where its people are all covered by a national health insurance plan . This can also be said in the area of antimicrobial treatment of children and newborns . In Japan, the turning point (T-point), which the author defines as the point when the average life expectancy of newborns equals that of 1 year olds, was in 1970 . Keeping infant deaths from infectious diseases under control was indispensable for this achievement, to which antibiotics had greatly contributed . After the T-point, another methodology was needed in pediatrics . The situation in Japan, where most newly developed antibiotics are equipped with statements concerning methods of administration, dosage and safety for children or newborns, differs considerably from overseas situation . The procedures and methods of the clinical trials on children that were performed in strict compliance with good clinical practice are described . Trial studies cannot be performed easily in Japan . Next, the reason why the clinical trials of the antibiotics in pediatrics were performed and accurately evaluated without incident over 50 years by comparatively small numbers of specialists and facilities is described historically and retrospectively . During the 30 years since modern methods were established, clinical trials of antibiotics with children and newborns have been performed only on essential agents; about one-half and one-third, respectively, of the 91 new antibiotics on which clinical trials with adults were conducted . The author has recently published evaluation criteria for clinical studies on antibiotics in the pediatric field . In addition, as the trial's director/administrator, the author states his concept for future clinical development of new antibiotics for children.

Infect Control Hosp Epidemiol, 1997 Feb, 18(2), 84 - 92
Modeling the spread of resistant nosocomial pathogens in an intensive-care unit; Sebille V et al.; OBJECTIVES: To show the value of mathematical modeling in simulating the spread of nosocomial pathogens in an intensive-care unit (ICU), to provide a framework for listing available knowledge; to predict the benefits of various control measures; and to supplement the epidemiological assessment of these measures . DESIGN: Simulated outbreak of a nosocomial pathogen in an ICU, based on a deterministic compartmental model describing both person-to-person spread and indirect spread between patients through staff members . INTERVENTIONS: Stimulation of three typical colonization control measures: effective handwashing compliance among staff members, ICU antimicrobial policy, and curtailing ICU admission of colonized patients . RESULTS: In controlling colonization, effective handwashing compliance reduced staff member colonization, but only moderately limited patient colonization unless the ICU was isolated strictly by curtailing the admission of colonized patients . The impact of antibiotic policy was very slight . CONCLUSIONS: In the field of nosocomial infection, mathematical modeling appears to be valuable tool that can be used to evaluate the magnitude of the expected effects of control strategies and to guide the selection of the best randomized clinical trials to pursue.

Clin Infect Dis, 1997 Feb, 24(2), 235 - 47
Development of interpretive breakpoints for antifungal susceptibility testing: conceptual framework and analysis of in vitro-in vivo correlation data for fluconazole, itraconazole, and candida infections . Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards; Rex JH et al.; The availability of reproducible antifungal susceptibility testing methods now permits analysis of data correlating susceptibility in vitro with outcome in vivo in order to define interpretive breakpoints . In this paper, we have examined the conceptual framework underlying interpretation of antimicrobial susceptibility testing results and then used these ideas to drive analysis of data packages developed by the respective manufacturers that correlate fluconazole and itraconazole MICs with outcome of candidal infections . Tentative fluconazole interpretive breakpoints for MICs determined by the National Committee for Clinical Laboratory Standards' M27-T broth macrodilution methodology are proposed: isolates for which MICs are < or = 8 microg/mL are susceptible to fluconazole, whereas those for which MICs are > or = 64 microg/mL appear resistant . Isolates for which the MIC of fluconazole is 16-32 microg/mL are considered susceptible dependent upon dose (S-DD), on the basis of data indicating clinical response when > 100 mg of fluconazole per day is given . These breakpoints do not, however, apply to Candida krusei, as it is considered inherently resistant to fluconazole . Tentative interpretive MIC breakpoints for itraconazole apply only to mucosal candidal infections and are as follows: susceptible, < or = 0.125 microg/mL; S-DD, 0.25-0.5 microg/mL; and resistant, > or = 1.0 microg/mL . These tentative breakpoints are now open for public commentary.

APMIS, 1997 Feb, 105(2), 89 - 98
The effect of human cytomegalovirus on selected functions of peripheral blood monocytes; Holberg-Petersen M et al.; The effect of in vitro infection of human cytomegalovirus (HCMV) on various monocyte functions relevant to antimicrobial defence mechanisms has been investigated: the phagocytic activity of monocytes, the release of lysozyme and intracellular concentration of acid phosphatase, and the release of the cytokines interleukin-1 (IL-1), IL-6, and tumour necrosis factor-alpha (TNF-alpha) . HCMV significantly inhibited the release of lysozyme and intracellular concentration of acid phosphatase . Regarding the phagocytic activity and the release of cytokines, there was considerable variation in the HCMV effect among the different blood donors tested . There was no clear tendency in the observed results; both stimulation and inhibition were seen . The HCMV-specific pp65 was detected in the nucleus of about 1% of the monocytes 3 h after infection and HCMV-specific IE antigens were found in about 0.1% of the monocytes 2 days postinfection . No E- or L-gene expression was observed and no infectious virus was produced in the monocytes . Our results indicate that HCMV infection may influence monocyte functions in spite of no productive infection of these cells.

J Antibiot (Tokyo), 1997 Feb, 50(2), 111 - 8
Aflastatin A, a novel inhibitor of aflatoxin production by aflatoxigenic fungi; Ono M et al.; Aflastatin A, a novel inhibitor of the production of aflatoxin by aflatoxigenic fungi, has been isolated from the solvent extract of mycelial cake of Streptomyces sp . and its molecular formula was determined as C62H115NO24 . Aflastatin A completely inhibited aflatoxin production by Aspergillus parasiticus NRRL 2999 in liquid medium or on agar plate at a concentration of 0.5 microgram/ml . The mycelial growth of this fungus was not affected in the liquid medium at the same concentration, while the hyphal extension rate was reduced on the plate together with some morphological changes . The growth of the fungus was not completely inhibited even at a concentration of 100 micrograms/ml . Aflastatin A exhibits antimicrobial activity against some bacteria, yeasts and fungi as well as antitumor activity.

Community Dent Oral Epidemiol, 1997 Feb, 25(1), 82 - 6
Salivary parameters of relevance for assessing caries activity in individuals and populations; Tenovuo J; A review of the non-microbial salivary parameters with respect to their possible association with caries activity is presented . The parameters are limited to those which already are or at least in the near future will obviously be simple enough, also for clinical purposes . Salivary flow rate is undoubtedly the most important single parameter since the cariostatic activity or efficacy of practically all other salivary parameters depends on the flow rate . Flow rate as such has no linear association with dental caries but there seems to exist an individual "threshold" limit which is decisive for enhanced caries activity . This threshold limit varies among different individuals and therefore the so-called normal values for unstimulated or stimulated flow rate are more reliable on a population level than among individuals for screening purposes . In any individual a regular and longitudinal follow-up of the flow rate is of higher clinical value than only a single cross-sectional measurement . Salivary buffer effect has only a weak negative association with caries activity and again, this effect is of greater clinical significance on a population level . Since the decisive processes in caries attack occur within or under the dental plaque, the buffering effect of saliva is limited and obviously more important to screen for erosion-than caries-prone individuals . Although important for dental health, none of the salivary antimicrobial agents as such has shown any strong association with caries activity . The only ones with some evidence of a regulatory role are secretory IgA antibodies, hypothiocyanite ions, and agglutinins . However, the data are controversial and it seems that instead of measuring individual parameters, the assessment of saliva's functional properties (such as the ability to aggregate bacteria, prevent their adhesion to hydroxyapatite or sugar metabolism etc.) is more important for clinical purposes . Of the parameters involved in de- and remineralization process, only salivary fluoride content has some association with caries susceptibility but its diagnostic or predictive value is questionable.

Zentralbl Bakteriol, 1997 Feb, 285(3), 341 - 67
Host/parasite interactions in bacterial endophthalmitis; Jett BD et al.; Bacterial infections within the eye arise as complications of intraocular surgery, penetrating injury, or hematogenous spread from distant anatomical sites . Because: 1) the interior surfaces of the eye are lined with sensitive, nonregenerating tissues, 2) the inner chambers of the eye are relatively sequestered from circulating immunological components, 3) the integrity of blood-ocular barriers provides poor penetration of systemically administered antibiotics, and 4) aqueous and vitreous humor represent rich, relatively acellular culture media; endophthalmitis often progresses rapidly and total loss of vision frequently results . Years of clinical experience have shown that current therapies for endophthalmitis, including antimicrobials, antiinflammatory agents, and vitrectomy, are frequently unsuccessful in ameliorating destruction of intraocular tissues . While bacterial and host factors were thought to play key roles in the course and severity of endophthalmitis, it is only recently that their contributions have been experimentally defined . Molecular-based techniques are gaining increased use in the study of infectious eye diseases . Current findings regarding the host/parasite interactions within the eye are reviewed, and a resulting integrative model of the natural course of endophthalmitis proposed . A molecular-level understanding of the roles of both bacterial and host factors during endophthalmitis will likely reveal potential targets for therapeutic intervention aimed at salvaging vision.

Kansenshogaku Zasshi, 1997 Feb, 71(2), 130 - 5
{Evaluation of antibiotics used for enterohemorrhagic Escherichia coli O157 enteritis--effect of various antibiotics on extracellular release of verotoxin}; Ito T et al.; We tested antimicrobial activities of ten oral antibiotics; ampicillin (ABPC), cefdinir (CFDN), cefaclor (CCL), fosfomycin (FOM), norfloxacin (NFLX), nalidixic acid (NA), kanamycin (KM), minocycline (MINO), doxycycline (DOXY), and tetracycline (TC) against eleven enterohemorrhagic Esherichia coli (EHEC) O157 clinical strains . Two strains were resistant to ABPC and TC . Other strains were sensitive to all the ten antibiotics . To investigate the effect of antibiotics on extracellular release of verotoxin (VT), strain EHEC TT10 was grown in 10 ml of LB containing various concentrations of the antibiotics for 2 h . Number of viable cells were counted and the amounts of VT1 and VT2 released in the supernatants were measured with reverse passive latex agglutination (RPLA) using serially diluted sterilized culture supernatants . The amount of VT1 and VT2 was evidently increased with ABPC, CFDN, CCL, and FOM, the inhibitors of cell wall biosynthesis . In the case of quinolons, VT2 was markedly increased, but VT1 was not released to the supernatant . KM killed the bacteria efficiently, but no release of VT1 or VT2 was observed in the supernatant . Tetracyclines (MINO, DOXY, and TC) did not make the bacteria release either VT1 or VT2, but could not kill the bacteria appreciably . These results indicated that the inhibitors of protein synthesis (KM, MINO, DOXY, TC) are the safe antibiotics not causing the release of verotoxin from the cells and thus preventing development of hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpra (TTP), the important sequelae of the enteritis.

J Small Anim Pract, 1997 Feb, 38(2), 81 - 4
Bone fracture and sequestration as complications of external skeletal fixation; Seguin B et al.; A transverse tibial fracture and bone sequestrum at the pin-bone interface were diagnosed in a dog treated with external skeletal fixation for tarsal arthrodesis . The causes of the bone fracture were improper use of external fixator pins and trauma after the fixator became entangled in a fence . After removal of the original fixator, the tibial fracture was successfully repaired with an intramedullary pin, a type II external skeletal fixator and an autogenous cancellous bone graft . Bone sequestration and draining sinuses were successfully treated with curettage and antimicrobial therapy.

Ann Surg, 1997 Feb, 225(2), 172 - 80
The prevention of anastomotic leakage after total gastrectomy with local decontamination . A prospective, randomized, double-blind, placebo-controlled multicenter trial; Schardey HM et al.; OBJECTIVE: A prospective, randomized, double-blind, placebo controlled multicenter trial was undertaken in 205 patients treated with total gastrectomy for gastric malignancies to evaluate whether local antimicrobial measures reduce the incidence of esophagojejunal anastomotic leakage . SUMMARY BACKGROUND DATA: Anastomotic leakage of the esophagojejunostomy is always a septic complication of total gastrectomy for gastric malignancies, but it never has been attempted to prevent this complication with the administration of topical antimicrobial agents during the critical phase of anastomotic wound healing . METHODS: To evaluate the efficacy and safety of topical decontamination, the study was carried out as a prospective, randomized, double-blind and placebo-controlled clinical multicenter trial in patients with total gastrectomy for gastric cancer . Patients received either placebo or decontamination with polymyxin B (100 mg), tobramycin (80 mg), vancomycin (125 mg), and amphotericin B (500 mg) four times per day orally from the day before the operation until the seventh postoperative day . All patients received a perioperative intravenous prophylaxis with cefotaxime 2 x 2 g . Other interventions including the administration of antibiotics and fluids, were not affected by the study protocol . RESULTS: Of 260 patients who were randomized, total gastrectomy was not carried out in 55 patients . They dropped out of the study . Patients receiving an esophagojejunostomy were observed until day 42, when they were discharged from the clinic or died . An intention-to-treat analysis of the data was carried out . Among the 103 recipients of placebo, there were 11 (10.6%) with an anastomotic leakage of the esophagojejunostomy, and among the 102 recipients of decontamination, there were 3 (2.9%) with an anastomotic leakage of the esophagojejunostomy (p = 0.0492) . Pulmonary infections were observed in 23 patients (22.3%) receiving placebo and in 9 patients (8.8%) who were decontaminated (p = 0.02) . There were 11 deaths (10.6%) among the recipients of placebo and 5 deaths (4.9%) among the recipients of decontamination (p = 0.1) . CONCLUSIONS: Decontamination with polymyxin, tobramycin, vancomycin, and amphotericin B during anastomotic wound healing is safe and effective in the prevention of esophagojejunal anastomotic leakage after total gastrectomy.

Am J Obstet Gynecol, 1997 Feb, 176(2), 470 - 5
Detection of human defensin 5 in reproductive tissues; Svinarich DM et al.; OBJECTIVES: This study was undertaken to determine whether tissue-specific defensins are expressed within female reproductive tissues . STUDY DESIGN: Messenger ribonucleic acid from amnion, chorion, endometrium, endocervix, myometrium, placenta, small intestine, peripheral blood lymphocytes, and cervical, endometrial, and trophoblast cell lines was reverse transcribed with a 3'-RACE adapter . 3'-RACE polymerase chain reaction was conducted with an upstream human defensin 5 primer and 3'-RACE adapter primer . Polymerase chain reaction products hybridizing to a human defensin 5 probe were cloned for sequence analysis . Sequence data were compared against a nucleotide sequence database, and secondary structure predictions were made . RESULTS: Chorionic tissue, endocervical tissue, endometrial tissue, and an endometrial cell line all demonstrated a single hybridizing 362 bp polymerase chain reaction product . Sequence analysis of all clones demonstrated near-perfect identity with human defensin 5 . CONCLUSIONS: Human endocervix, endometrium, and chorion express defensin 5 at the level of transcription . These findings suggest that a previously unrecognized mechanism of protecting female reproductive tissues against infection, by means of a natural antimicrobial system (defensins), may be present.

J Clin Periodontol, 1997 Feb, 24(2), 86 - 91
Studies on stannous fluoride toothpaste and gel (2) . Effects on salivary bacterial counts and plaque regrowth in vivo; Addy M et al.; There has been a resurgence of interest in stannous fluoride (SF) products in particular to provide oral hygiene and gingival health benefits . The aim of this study was to assess the persistence of antimicrobial action of a number of SF formulations in the mouth and relate these to plaque inhibitory activity . The formulations were 2 SF toothpastes (SF1, SF2), 2 SF plus stannous pyrophosphate toothpastes (SFSP1, SFSP2), a SF gel (G), a NaF toothpaste (C) and saline (S) as control . Both studies involve 2 different groups of 21 healthy dentate volunteers . The studies were single, blind, randomised, crossover designs balanced for residual effects, with a minimum 2 1/2 day washout period . Salivary bacterial counts were determined before and to 7 h after a single rinse with the formulations . Plaque regrowth from a zero baseline (day 1) was measured by index and area on day 5, after 2x daily rinsing with slurries of the formulations or saline . For bacterial counts, highly significant treatment differences were found . Bacterial counts were variably reduced by all treatments to 30 min then showed a variable rate of return towards baseline . All test agents were significantly better than S at some timepoints . The order for greatest persistence of action downwards was; (1) SFSP2; (2) SFSP1, G, and SF1; (3) SF2; (4) C; (5) S . Highly significant differences in plaque regrowth between treatments were found with similar mean ordering of efficacy as for salivary bacterial counts from most effective downwards namely; (1) SFSP1 and SFSP2; (2) SF1; (3) SF2; G and C; (4) S . The results were consistent with a parallel study measuring tea staining in vitro, whereby formulations causing the most staining produced the greatest persistence of action and plaque inhibitory activity . This suggests the availability of stannous ions was important for the clinical effects . It is concluded that stannous ions can enhance the plaque inhibitory action of toothpaste via a persistent antimicrobial action.

J Clin Periodontol, 1997 Feb, 24(2), 81 - 5
Studies on stannous fluoride toothpaste and gel (1) . Antimicrobial properties and staining potential in vitro; Wade W et al.; Stannous fluoride (SF) in a toothpaste vehicle has the potential to provide anticaries and plaque inhibitory benefits through the fluoride and antimicrobial stannous moieties respectively . Dental staining, however, can occur by precipitation of dietary chromogens onto the tooth surface by stannous ions . These studies in vitro compare the antimicrobial profile and propensity to cause tea staining of a number of stannous fluoride formulations . The formulations used were 2 SF toothpaste products (SF1, SF2), 2 experimental SF plus stannous pyrophosphate toothpastes (SFSP1, SFSP2), a SF gel (G) and a NaF toothpaste (C) . Maximum inhibitory dilution values against a range of oral bacteria were determined by agar dilution . Tea staining was measured spectrophotometrically on saliva coated clear acrylic blocks exposed to slurries of the paste or gel . All formulations showed antimicrobial activity with the order of greatest activity downwards being C, SF2, SF1, SFSP1, SFSP2 and G . Tea staining at 10 exposures was in the following descending order of optical density SFSP1, SFSP2, G . C, SF1, SF2, water control . The antimicrobial profile of G was similar to that of SF, whereas that of the other formulations were varied but similar to a detergent profile . The difference in staining suggested considerable variation in availability of stannous ions in the formulations . However, the propensity for stannous ions to stain must be balanced against the stain removal propensity of the contained detergents in the toothpaste formulations . In conclusion, the variation in antimicrobial activity and more particularly staining activity of the formulations suggest the products will vary in activity in vivo.

Plant Cell, 1997 Feb, 9(2), 209 - 21
Localization of hydrogen peroxide accumulation during the hypersensitive reaction of lettuce cells to Pseudomonas syringae pv phaseolicola; Bestwick CS et al.; The active oxygen species hydrogen peroxide (H2O2) was detected cytochemically by its reaction with cerium chloride to produce electron-dense deposits of cerium perhydroxides . In uninoculated lettuce leaves, H2O2 was typically present within the secondary thickened walls of xylem vessels . Inoculation with wild-type cells of Pseudomonas syringae pv phaseolicola caused a rapid hypersensitive reaction (HR) during which highly localized accumulation of H2O2 was found in plant cell walls adjacent to attached bacteria . Quantitative analysis indicated a prolonged burst of H2O2 occurring between 5 to 8 hr after inoculation in cells undergoing the HR during this example of non-host resistance . Cell wall alterations and papilla deposition, which occurred in response to both the wild-type strain and a nonpathogenic hrpD mutant, were not associated with intense staining for H2O2, unless the responding cell was undergoing the HR . Catalase treatment to decompose H2O2 almost entirely eliminated staining, but 3-amino-1,2,4-triazole (catalase inhibitor) did not affect the pattern of distribution of H2O2 detected . H2O2 production was reduced more by the inhibition of plant peroxidases (with potassium cyanide and sodium azide) than by inhibition of neutrophil-like NADPH oxidase (with diphenylene iodonium chloride) . Results suggest that CeCl3 reacts with excess H2O2 that is not rapidly metabolized during cross-linking reactions occurring in cell walls; such an excess of H2O2 in the early stages of the plant-bacterium interaction was only produced during the HR . The highly localized accumulation of H2O2 is consistent with its direct role as an antimicrobial agent and as the cause of localized membrane damage at sites of bacterial attachment.

J Hand Surg {Br}, 1997 Feb, 22(1), 135 - 7
Antimicrobial treatment of fish tank granuloma; Laing RB et al.; Three patients with fish tank granuloma of the hand and forearm are reported . Each patient was treated with antimicrobial regimes which have rarely or never been previously used in this condition . Two patients responded well to treatment, one who received ciprofloxacin plus clarithromycin and another who was given clarithromycin plus ethambutol . The third patient received six different antimicrobial regimes before responding to a combination of rifabutin and ciprofloxacin . Our experience suggests that there now exist a number of effective alternatives to antimicrobials which have been traditionally used in the treatment of cutaneous Mycobacterium marinum infection.

J Periodontol, 1997 Feb, 68(2), 172 - 9
Bacterial adherence to guided tissue regeneration barrier membranes exposed to the oral environment; Chen YT et al.; Microbial colonization of barrier materials used in guided tissue regeneration (GTR) is known to adversely affect treatment outcomes . The purpose of this study was to compare the rate at which 11 commonly-occurring oral bacteria species colonize three different barrier materials (collagen, expanded polytetrafluoroethylene, and polylactic acid) . The study group consisted of 10 systemically healthy individuals with no history of periodontal disease and absence of antimicrobial therapy within the previous 3 months . In each patient, 4 teeth per quadrant (P1, P2, M1, M2) were selected and 3 teeth were randomly assigned as test teeth while the remaining tooth acted as a control site (i.e., natural colonization of the tooth surface) . These teeth were then randomly assigned to receive one of the three barrier types (i.e., each patient received 4 barriers of each type, 1 per quadrant) . A 2 x 5 mm piece of barrier material was positioned over the oral surface of the buccal marginal gingiva and secured with an external sling suture . With oral hygiene procedures suspended, one barrier of each type was collected at 1, 3, 7, and 14 days . Slot immunoblot assay demonstrated that all species types (A . actinomycetemcomitans, A . viscosus, B . melaninogenicus, F . nucleatum, P . gingivalis, P . intermedia, S . mutans, S . sanguis, Selenomonas sputigena, T . denticola, and T . vincentii) were present . Semi-quantitative scoring (scale 0 to 3) of slot blot results and analysis by chi-square ratio and Pearson correlation test indicated that while total bacteria adherence increased over time (P < 0.05), the 3 barrier types and the control sites did not differ in numbers or species of colonizing bacteria detected per time point . These results suggest that under these experimental conditions the barrier materials tested do not differ in bacteria adherence or antimicrobial properties.

Am J Infect Control, 1997 Feb, 25(1), 51 - 64
Microbial resistance to drug therapy: a review; Cohen FL et al.; Microbial resistance to the antimicrobials in standard use is becoming more prevalent . A historical perspective frames further discussion . Bacterial resistance is most common, but resistance has been identified in fungi, viruses, and parasites . Resistance is a complex phenomenon that involves the microorganism, the environment, and the patient-separately and interactively . Resistance may be a characteristic of the microbe before exposure to a given drug or may arise as a consequence of therapy . Mechanisms of resistance to antibiotics are discussed . Antibiotic resistance is considered in both hospital and community settings, as ecosystems that are separate yet blending, and the major organisms demonstrating significant resistance problems are presented . A review of existing guidelines, strategies, and plans for addressing resistance and some recommendations conclude this review.

Scand J Gastroenterol, 1997 Feb, 32(2), 112 - 7
Usefulness of the 14C urea breath test as a semi-quantitative monitoring instrument after therapy for Helicobacter pylori infection; van de Wouw BA et al.; BACKGROUND: We evaluated the reliability and usefulness of the 14C urea breath test (UBT) in confirming eradication of Helicobacter pylori 4 to 6 weeks after cessation of antimicrobial therapy . METHODS: We investigated 57 patients, who underwent both an upper endoscopy with multiple biopsy specimens taken for histopathology, culture and/or CLO test, and a 14C UBT . Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the breath test were calculated against the combined biopsy-based test results . Values for sensitivity, specificity, PPV, and NPV were also calculated after excluding results in a grey zone containing equivocal test results . RESULTS: Sensitivity, specificity, PPV, and NPV of the 14C UBT were 92%, 78%, 52%, and 97%, respectively . After introduction of a grey zone concept, these values were 89%, 100%, 100%, and 97% respectively . CONCLUSIONS: We conclude that for research, upper gastrointestinal endoscopy with multiple biopsy specimens and using different diagnostic techniques should remain the 'gold standard' to test for cure.

J Vet Pharmacol Ther, 1997 Feb, 20(1), 21 - 3
Minimum inhibitory concentrations for selected antimicrobial agents against Fusobacterium necrophorum isolated from hepatic abscesses in cattle and sheep; Mateos E et al.; Minimum inhibitory concentrations for 35 antimicrobial agents against 100 Fusobacterium necrophorum isolates from hepatic abscesses in sheep and cattle were determined . Twelve of the thirteen beta-lactam antibiotics tested inhibited growth of 100% of strains tested . Of the remaining antimicrobial agents, extensive susceptibility was found for: spiramycin, josamycin, lincomycin, tylosin, oxytetracycline, chlortetracycline, rufloxacin, metronidazole, cotrimoxazole, sulfadimethoxine, virginiamycin and fosfomycin.

Aliment Pharmacol Ther, 1997 Feb, 11(1), 109 - 12
One-day intensified lansoprazole-quadruple therapy for cure of Helicobacter pylori infection; de Boer WA et al.; BACKGROUND: Peptic ulcer patients need to be treated with antimicrobials to cure Helicobacter pylori infection . Seven-day quadruple therapy is the regimen with the highest cure rates . An ultra-short quadruple therapy was evaluated prospectively . METHODS: Forty-six consecutive H . pylori positive patients (33 had proven ulcer disease) were prescribed lansoprazole 30 mg b.d . on days 1-4, and on day 4 they received in addition tripotassium dicitrato bismuthate 120 mg, tetracycline 250 mg and metronidazole 250 mg at 09.00, 11.00, 13.00, 15.00, 17.00, 19.00, 21.00, 23.00 hours . Repeat endoscopy with biopsies for CLOtest, Giemsa stain and culture was carried out 6 weeks later . RESULTS: Follow-up was complete . Overall cure rate (all three biopsy-based tests negative) was 26/46 (57%; 95% CI: 41-71%) . Antibiotic sensitivity was available in 42 . Thirty-nine carried a metronidazole sensitive strain and 23/39 (59%) were cured, three carried a resistant strain and therapy failed in all . Three out of four in whom susceptibility was unknown were cured . Metronidazole resistance was induced in 8 out of 16 with a sensitive strain . Only one patient (3%) reported severe side effects . CONCLUSIONS: This convenient quadruple regimen showed that a short contact time is sufficient to kill H . pylori in vivo . Since 57% of patients are cured with a 14-h treatment, a slightly longer treatment duration may increase the cure rate to above 90%.

Pediatr Infect Dis J, 1997 Feb, 16(2 Suppl), S27 - 9
Pharmacoeconomic impact of factors affecting compliance with antibiotic regimens in the treatment of acute otitis media; Wandstrat TL et al.; BACKGROUND: The total cost of treating otitis media in the United States alone is estimated at > 3.5 billion dollars annually . Therefore treatment approaches that reduce the cost of managing otitis media can have a large impact on overall health care costs . METHODS: In this study cost effectiveness factors of various antimicrobial agents, such as adverse events and overall patient acceptance, were examined . RESULTS: Decreased patient acceptance and higher incidence of adverse events had a negative impact on the cost of treatment . Amoxicillin/clavulanate, cefprozil, erythromycin/sulfisoxazole and trimethoprim/sulfamethoxazole were found to be associated with decreased patient acceptance compared with cefixime . Cefixime also had the lowest number of adverse events of any of the drugs used . Amoxicillin had the lowest total cost for a single course of treatment, exclusive of costs of recurrence, which were examined in a previous study . CONCLUSION: This study concluded that in cases in which several antibiotics may be clinically effective, comparative tolerability and patient acceptance data should be considered for selection of appropriate therapy . High compliance and lower morbidity can result in lower costs and better quality of life.

Pediatr Infect Dis J, 1997 Feb, 16(2 Suppl), S9 - 11
Overall cost in the treatment of otitis media; Kaplan B et al.; BACKGROUND: Numerous antimicrobial agents are available for treatment of otitis media (OM); however, little is known about the relative cost effectiveness of these drugs . METHODS: We developed a noninvasive, observational model to assess the total costs (direct and indirect) associated with commonly used antibiotics in the therapy of OM . We also gathered data on recurrence rates, which can significantly affect costs . RESULTS: The average total cost of treating an episode of OM in this study was $115.80 . Treatment of a recurrent OM episode was significantly more costly than treatment of an initial episode ($124.64 vs . $107.81, P = 0.0001) . This study suggests that significant costs are associated with OM treatment and that antibiotic price constitutes only a small portion of this cost . Recurrence rates appeared to vary with various antibiotic treatments . CONCLUSION: We conclude that recurrence is a major determinant of OM treatment costs . Drugs associated with lower rates of recurrence will usually be the most cost-effective treatment options.

Pediatr Infect Dis J, 1997 Feb, 16(2), 185 - 90
Antimicrobial prescribing for acute purulent rhinitis in children: a survey of pediatricians and family practitioners; Schwartz RH et al.; BACKGROUND: The tenet that children with acute purulent rhinitis need not be treated with antibiotics unless drainage persists for 7 to 10 days is taught to medical students and residents in primary care specialties but may not be adhered to in actual clinical practice . Because of the global increase in bacterial resistance stemming largely from the overuse of antibiotics, we sought to determine how acute purulent rhinitis is managed in the primary care setting . METHODS: We surveyed all 450 pediatricians (PD) and family practitioners (FP) in northern Virginia who were in active practice in 1994 . The survey instrument was a questionnaire containing two clinical vignettes followed by a series of multiple choice or fill-in-the-blanks questions . Initial nonresponders received up to three additional mailings of the same questionnaire . RESULTS: There were 346 (77%) evaluable responses . Seventy-one percent of FP and 53% of PD (P = 0.001) immediately prescribed antibiotics for infants with scant, green nasal mucopurulent secretions of 1 day duration; fewer treated an older child immediately (50% FP vs . 24% PD, P < 0.00001) . Only 15% of FP vs . 23% of PD (P = 0.07) waited for 7 to 10 days of persistent purulent nasal drainage in infants before prescribing antibiotics . Ninety-four percent of FP and 95% of PD (P = 0.8) indicated that they would prescribe antibiotics immediately for infants with acute purulent rhinitis who attended day care . For otitis-prone children who were not in day care, 86% of FP and 78% of PD (P = 0.02) would also treat without delay . The reasons given for prompt antibiotic therapy were (1) the belief that many untreated patients would develop persistent purulent nasal drainage, (2) concern that acute otitis media would develop, (3) pressure from mothers to prescribe an antibiotic and/or (4) the desire to allow employed parents to return to work earlier . Amoxicillin was the initial choice for 89% of FP vs . 76% of PD (P = 0.003) . Most FP (89%) and PD (97%) were concerned about the increase in bacterial resistance rates arising from unnecessary antibiotic prescribing (P = 0.01) . CONCLUSIONS: Most infants and children with acute purulent rhinitis of short duration were treated with antibiotics despite professed concerns over the spread of bacterial resistance; the practice was more prevalent among FP.

Drugs, 1997 Feb, 53(2), 245 - 56
Recognition and optimum treatment of brucellosis; Solera J et al.; Brucellosis (infection with Brucella spp.) is a common zoonosis in many parts of the world . Human brucellosis is a multisystem disease that may present with a broad spectrum of clinical manifestations . Treatment of brucellosis must effectively control acute illness and prevent complications and relapse . The choice of regimen and duration of antimicrobial therapy should be based on the presence of focal disease and underlying conditions which contraindicate certain specific antibiotics . The regimen of first choice is combination therapy with doxycycline for 45 days and streptomycin for 14 days . Gentamicin or netilmicin for the first 7 days may be substituted for streptomycin . Second-choice regimens consist of combinations of doxycycline and rifampicin (rifampin) for 45 days, or monotherapy with doxycycline for 45 days . Surgery should be considered for patients with endocarditis, cerebral or epidural abscess, spleen abscess or other abscesses which are antibiotic-resistant . Tetracyclines are generally contraindicated for pregnant patients and children < 8 years old . Rifampicin 900 mg once daily for 6 weeks is considered the drug of choice for treating brucellosis in pregnant women . In children < 8 years old the preferred regimen is rifampicin with cotrimoxazole (trimethoprim-sulfamethoxazole) for 45 days . An alternative regimen consists of a combination of rifampicin for 45 days with gentamicin 5 to 6 mg/kg/day for the first 5 days.

Laryngoscope, 1997 Feb, 107(2), 273 - 6
Kikuchi's disease: report of three cases and an overview; Nikanne E et al.; We describe, to our knowledge, the first native Finnish patients with Kikuchi's histiocytic necrotizing lymphadenitis . The diagnosis was based in all cases on histopathological findings in open biopsy . The disease was first detected in Japan in 1972, but in Scandinavia, until this decade, there had been no cases reported . Our patients were young, otherwise healthy women who had cervical lymphadenopathy, fever, and fatigue as their main symptoms . In two of them, the disease was mild and subsided spontaneously within 2-6 months . One patient with more fulminant lymphadenopathy was treated with antimicrobial and antiinflammatory drugs . She became symptomless in 3 months . The cause of Kikuchi's disease is unknown . A viral or postviral hyperimmune reaction has been proposed as its etiology . Malignant lymphoma and systemic lupus erythematosus are differential diagnoses . Histopathological findings are pathognomonic and pathologists must be aware of its typical characteristics.

Antimicrob Agents Chemother, 1997 Feb, 41(2), 363 - 73
The population dynamics of antimicrobial chemotherapy; Lipsitch M et al.; We present and analyze a series of mathematical models for the emergence of resistance during antibiotic treatment of an infected host . The models consider the population dynamics of antibiotic-sensitive and -resistant bacteria during the course of treatment and addresses the following problems: (i) the probability of obtaining a resistant mutant during the course of treatment as a function of antibiotic exposure; (ii) the conditions under which high, infrequent doses of an antibiotic are predicted to succeed in preventing the emergence of resistance; (iii) the conditions for the success of multiple drug treatment in suppressing the emergence of resistance and the relationship between antibiotic synergism and suppression of resistance; and (iv) the conditions under which nonadherence to the prescribed treatment regimen is predicted to result in treatment failure due to resistance . We analyze the predictions of the model for interpreting and extrapolating existing experimental studies of treatment efficacy and for optimizing treatment protocols to prevent the emergence of resistance.

Antimicrob Agents Chemother, 1997 Feb, 41(2), 357 - 62
Effects of benzoxazinorifamycin KRM-1648 on cytokine production at sites of Mycobacterium avium complex infection induced in mice; Tomioka H et al.; Although various antimicrobial agents exhibit appreciable microbicidal activity in the early phase (weeks 2 t0 4) of Mycobacterium avium complex (MAC) infection induced in mice, progressive bacterial regrowth subsequently occurs . To clarify the reason for this pattern of changes, we studied changes in the levels of various cytokines in tissue at sites of infection (spleens and lungs) of MAC-infected mice which were or were not given a benzoxazinorifamycin, KRM-1648 (KRM) . Levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) in tissues temporarily increased at around weeks 2 to 4 after infection, rapidly decreased thereafter, and returned to normal by week 8 . Similar but somewhat delayed changes were noted for levels of interleukin 10 (IL-10) and transforming growth factor beta (TGF-beta), immunosuppressive cytokines with macrophage (M phi)-deactivating activity, in tissue, except that TGF-beta levels in the spleen remained high during weeks 4 to 8 . KRM treatment blocked the increase in the levels of all of those cytokines in tissue in the early phase of infection, most strongly at week 4 . IL-6 levels were beneath the limit of detection throughout the observation period . Bacterial loads in the visceral organs decreased during the first 2 weeks, and KRM treatment markedly promoted this decrease . However, regrowth of MAC organisms began at weeks 2 to 4 and continued thereafter, even in KRM-treated mice . Splenocytes and splenic M phi s of MAC-infected mice (week 2) produced and/or released into the culture fluid significant amounts of TNF-alpha (in a cell-bound form), IFN-gamma, and IL-10, but not TGF-beta, during 3 days of cultivation . A substantial amount of TGF-beta was produced during 2 weeks of cultivation of peritoneal M phi s . KRM itself did not significantly affect the IL-10- and TGF-beta-producing ability of cultured M phi s . These findings suggest that IL-10 and TGF-beta play important roles in the regrowth of MAC organisms seen during the course of KRM treatment.

Antimicrob Agents Chemother, 1997 Feb, 41(2), 242 - 50
Clinically used antimicrobial drugs against experimental pneumocystosis, singly and in combination: analysis of drug interactions and efficacies; Walzer PD et al.; We analyzed single drugs and combinations of drugs used clinically in the treatment of opportunistic infections and other conditions for their activities against Pneumocystis carinii pneumonia in immunosuppressed rats . When they were used alone, atovaquone, rifabutin, and dapsone were more active than clarithromycin or trimethoprim . Drug combinations were evaluated for synergistic activity by an analysis of variance model for two-way factorial experiments and a response surface model . Atovaquone combined with trimethoprim trimethoprim and some combinations of dapsone and clarithromycin was synergistic; however, the activities of combinations of atovaquone and rifabutin, atovaquone and clarithromycin, and atovaquone and dapsone were simply additive . Lovastatin, which inhibits 3-hydroxy-methylglutaryl coenzyme A reductase, was inactive whether it was used alone or in combination with other agents . None of the synergistic drug combinations was as effective as trimethoprim-sulfamethoxazole . We conclude that the rat model can be used to test combinations of anti-P . carinii agents for synergistic activity by well-established statistical techniques . While some combinations of clinically used antimicrobial drugs have enhanced anti-P . carinii activity, further studies are needed before clinical trials can be contemplated.

Biophys J, 1997 Feb, 72(2 Pt 1), 794 - 805
Bilayer interactions of indolicidin, a small antimicrobial peptide rich in tryptophan, proline, and basic amino acids; Ladokhin AS et al.; Tryptophan, proline, and basic amino acids have all been implicated as being important in the assembly and structure of membrane proteins . Indolicidin, an antimicrobial 13-residue peptide-amide isolated from the cytoplasmic granules of bovine neutrophils, is highly enriched in these amino acids: five tryptophans, three prolines, three basic residues, and no acidic residues . Consistent with the likely importance of these amino acids in membrane protein assembly, indolicidin is known to be highly membrane-active and is believed to act by disruption of cell membranes . We have, therefore, examined the interactions of native indolicidin with large unilamellar vesicles (LUV) formed from palmitoyloleoylphosphatidylcholine (POPC), and palmitoyloleoylphosphatidylglycerol (POPG), in order to use it as a model system for studying membrane protein insertion and for evaluating the relative contributions of hydrophobic and electrostatic forces in peptide-bilayer interactions . Equilibrium dialysis measurements indicate that indolicidin binds strongly, but reversibly, to both neutral POPC and anionic POPG vesicles with free energies of transfer of -8.8 +/- 0.2 and -11.5 +/- 0.4 kcal/mol, respectively . The extremely strong partitioning into POPG vesicles necessitated the development of a new equilibrium dialysis method that is described in detail . Tryptophan fluorescence measurements show that indolicidin is located in the bilayer interface and that indole fluorescence is affected by the type of lipid used to form the LUVs . Circular dichroism (CD) measurements reveal unordered conformations in aqueous and bulk organic solutions and a somewhat more ordered, but not alpha-helical, conformation in SDS micelles and lipid bilayers . Fluorescence requenching measurements (Ladokhin et al . 1995 . Biophys . J . 69:1964-1971) on vesicles loaded with the fluorophore/quencher pair 8-aminonapthalene-1,3,6 trisulfonic acid (ANTS)/p-xylene-bis-pyridinium bromide (DPX), show that indolicidin induces membrane permeabilization . For anionic POPG, leakage is graded with a high preference for the release of cationic DPX over anionic ANTS . For neutral POPC vesicles no such preference is observed . Leakage induction is more effective with POPG vesicles than with POPC vesicles, as judged by three quantitative measures that are developed in the Appendix.

J Chromatogr B Biomed Sci Appl, 1997 Jan 24, 688(2), 319 - 24
High-performance liquid chromatographic assay detects pentamidine metabolism by Fisher rat liver microsomes; Tuttle RH et al.; Fisher rat liver microsomes metabolized the antimicrobial drug pentamidine to four new compounds detected by gradient elution reversed-phase high-performance liquid chromatography with variable wavelength detection . Coelution experiments with pentamidine metabolite standards determined the new peaks to be previously identified hydroxylated metabolites of pentamidine, with 1,5-bis(4'-amidinophenoxy)-3-pentanol and 1,5-di-(4'-amidinophenoxy)-2-pentanol formed in the greatest amount . The data contradict a previous report that Fisher rat liver homogenates do not metabolize pentamidine . Pentamidine and its known primary metabolites have almost identical absorption spectra; thus, pentamidine metabolism must be evaluated using gradient elution HPLC to resolve pentamidine from its metabolites . The current assay has now been used to demonstrate that Fisher and Sprague-Dawley rat, mouse, rabbit and human liver microsomes all metabolize pentamidine in vitro.

Am J Health Syst Pharm, 1997 Jan 15, 54(2), 185 - 9
Compatibility of filgrastim with selected antimicrobial drugs during simulated Y-site administration; Hall PD et al.; The compatibility of filgrastim with imipenem-cilastatin, ceftazidime, fluconazole, gentamicin, tobramycin, and amikacin was studied . Filgrastim 40 micrograms/mL or filgrastim 10 micrograms/mL (with human albumin) was combined with (1) imipenem-cilastatin 5 mg/mL (in terms of imipenem content), (2) ceftazidime 10 mg/mL (as the sodium salt), (3) fluconazole 2 mg/ mL, (4) gentamicin 1.6 mg/ mL (as the sulfate), (5) tobramycin 1.6 mg/mL (as the sulfate), or (6) amikacin 5 mg/ mL (as the sulfate) . Equal volumes (5 mL) of the test-agent solutions were added in pairs to glass containers (simulating Y-site administration) in triplicate . Samples were analyzed for filgrastim activity, drug concentration, pH, and visible physical changes during storage at approximately 25 degrees C for up to four hours . Filgrastim activity was measured by the in vitro bioassay, and antimicrobial drug concentrations were measured by stability-indicating high-performance liquid chromatography or fluorescence polarization immunoassay . Filgrastim retained its activity, except for the combination of filgrastim at the lower concentration with gentamicin or at the higher concentration with imipenem-cilastatin . Antimicrobial drug concentrations did not change significantly during the study . No precipitation, color change, or haze was noted in any mixture . Changes in pH were negligible except for an increase in the mixture of filgrastim at either concentration with ceftazidime . In most cases, filgrastim retained its activity in the presence of a variety of antimicrobial drugs for up to four hours; in all cases, the antimicrobial drugs remained stable.

Blood, 1997 Jan 15, 89(2), 672 - 9
p15s (15-kD antimicrobial proteins) are stored in the secondary granules of Rabbit granulocytes: implications for antibacterial synergy with the bactericidal/permeability-increasing protein in inflammatory fluids; Zarember K et al.; The bactericidal potency toward complement-resistant Escherichia coli of bactericidal/permeability-increasing protein (BPI) released from polymorphonuclear leukocytes (PMNs) in glycogen-induced inflammatory peritoneal exudates of rabbits is dependent on synergy with extracellular p15s . This synergy depends on the high molar ratio of p15s to BPI in the extracellular fluid (approximately 50:1), which greatly exceeds the intracellular ratio (approximately 5:1) . To explore the possible basis of the greater accumulation of p15s in inflammatory fluid, we examined the subcellular localization of BPI and p15 in PMNs . Immunogold electron microscopy confirmed the storage of BPI in primary granules and showed that p15s are stored in secondary granules . Reverse-transcription polymerase chain reaction of density-fractionated rabbit bone marrow cells verified that p15s are expressed later than BPI during myeloid differentiation . As the inflammatory response evolves, p15 mRNA appears earlier in blood and exudate cells than mRNA for BPI, consistent with release of progressively less mature precursors from bone marrow . Finally, Ca(2+)-ionophore-mediated exocytosis of p15s occurs more readily than release of BPI . We therefore propose that localization of a synergistic partner of BPI (p15s) in more readily released secondary granules allows the neutrophil to mobilize potent BPI-dependent antibacterial activity extracellularly without significant depletion of intracellular BPI stores.

Arch Intern Med, 1997 Jan 13, 157(1), 47 - 56
The hospital discharge decision for patients with community-acquired pneumonia . Results from the Pneumonia Patient Outcomes Research Team cohort study; Fine MJ et al.; BACKGROUND: The hospital discharge decision directly influences the length of stay in patients with community-acquired pneumonia, yet no information exists on how physicians make this decision . OBJECTIVES: To identify the factors physicians considered the factors responsible for extending length of hospital stay in clinically stable patients, and the outpatient medical services that would allow earlier hospital discharge for patients with community-acquired pneumonia . METHODS: Physicians responsible for the hospital discharge decision of patients with community-acquired pneumonia were asked to identify the factors responsible for extending stay in patients hospitalized beyond stability, and the medical services that could have allowed earlier hospital discharge to occur . RESULTS: For the 418 eligible patients with community-acquired pneumonia identified during the study, 332 questionnaires (79%) were completed by 168 physicians . Physicians believed 71 patients (22%) were discharged from the hospital 1 day or more (median, 2.5 days) after reaching clinical stability . The most common factors rated as being "very important" in delaying discharge were diagnostic evaluation or treatment of comorbid illness (56%), completion of a "standard course" of antimicrobials (15%), and delays with arrangements for long-term care (14%) . Among the 302 patients with available information on both length of hospital stay and stability at discharge, median length of stay was 7.0 days for the 29 low-risk patients hospitalized beyond reaching clinical stability and 5.0 days for the remaining 128 low-risk patients (P < .005); median length of stay was 12.5 days for the 42 medium- and high-risk patients hospitalized beyond reaching clinical stability and 8.0 days in the remaining 113 medium- and high-risk patients (P < .001) . Frequently cited medical services that "probably" or "definitely" would have allowed earlier discharge to occur included availability of home intravenous antimicrobial infusion (26%) and home visits by nurses (20%) . CONCLUSIONS: Physicians believed that diagnostic evaluation or treatment of comorbid illness, completion of a standard course of antimicrobial therapy, and delays with arrangements for long-term care delayed hospital discharge in clinically stable patients . Addressing the efficiency of these aspects of inpatient medical care, as well as providing home treatment programs, could decrease the length of hospital stay in patients with community-acquired pneumonia.

Arch Intern Med, 1997 Jan 13, 157(1), 36 - 44
The hospital admission decision for patients with community-acquired pneumonia . Results from the pneumonia Patient Outcomes Research Team cohort study; Fine MJ et al.; BACKGROUND: The hospital admission decision directly influences the magnitude of resource use in patients with community-acquired pneumonia, yet little information exists on how medical practitioners make this decision . OBJECTIVES: To determine which factors medical practitioners consider in making the hospital admission decision and which health care services they believe would allow ambulatory treatment of low-risk hospitalized patients with community-acquired pneumonia . METHODS: Medical practitioners responsible for the hospital admission decision for low-risk patients with community-acquired pneumonia were asked to describe patient characteristics at initial examination that influenced the hospitalization decision, and to identify the health care services that would have allowed initial outpatient treatment of hospitalized patients . RESULTS: A total of 292 medical practitioners completed questionnaires for 472 (76%) of the 624 low-risk patients eligible for this study . Although all patients had a predicted probability of death of less than 4%, practitioners estimated that 5% of outpatients and 41% of inpatients had an expected 30-day risk of death of more than 5% . Univariate analyses identified 3 practitioner-rated factors that were nearly universally associated with hospitalization: hypoxemia (odds ratio, 173.3; 95% confidence interval, 23.8-1265.0), inability to maintain oral intake (odds ratio, 53.3; 95% confidence interval, 12.8-222.5), and lack of patient home care support (odds ratio, 54.4; 95% confidence interval, 7.3-402.6) . In patients without these 3 factors, logistic regression analysis demonstrated that practitioner-estimated risk of death of more than 5% had a strong independent association with hospitalization (odds ratio, 18.4; 95% confidence interval, 6.1-55.7) . Practitioners identified home intravenous antibiotic therapy and home nursing observation as services that would have allowed outpatient treatment of more than half (68% and 59%, respectively) of the patients initially hospitalized for treatment . CONCLUSIONS: Practitioners' survey responses suggest that the availability of outpatient intravenous antimicrobial therapy and home nursing care would allow outpatient care for a large proportion of low-risk patients who are hospitalized for community-acquired pneumonia . These data also suggest that methods to improve practitioners' identification of low-risk patients with community-acquired pneumonia could decrease the hospitalization of such patients . Future studies are required to help physicians identify which low-risk patients could safely be treated in the outpatient setting on the basis of clinical information readily available at presentation.

Br J Nurs, 1997 Jan 23-Feb 12, 6(2), 114 - 5
Arglaes controlled release dressing in the control of bacteria; Williams C; It has been known for many years that silver has antimicrobial properties . Arglaes is a film dressing that provides a continuous and controlled release of silver ions and is produced by Maersk Medical . The name is derived from argentum, which is Latin for silver, and Ag, the chemical symbol for silver . Since the emergence of resistant organisms, topical antibiotics are best avoided . Arglaes has been developed in the light of this and appears to control the bacteria in wounds and prevent bacterial contamination . Arglaes also provides a moist environment for the healing process and is suitable for many wound types.

J Biol Chem, 1997 Jan 10, 272(2), 875 - 82
Regulation of Src homology 2-containing tyrosine phosphatase 1 during activation of human neutrophils . Role of protein kinase C; Brumell JH et al.; The tyrosine phosphorylation of several proteins induced in neutrophils by soluble and particulate stimuli is thought to be crucial for initiating antimicrobial responses . Although activation of tyrosine kinases is thought to mediate this event, the role of tyrosine phosphatases in the initiation and modulation of neutrophil responses remains largely undefined . We investigated the role of Src homology 2-containing tyrosine phosphatase 1 (SHP-1; also known as protein tyrosine phosphatase 1C (PTP1C), hematopoetic cell phosphatase, PTP-N6, and SHPTP-1), a phosphatase expressed primarily in hemopoietic cells, in the activation of human neutrophils . SHP-1 mRNA and protein were detected in these cells, and the enzyme was found to be predominantly localized to the cytosol in unstimulated cells . Following stimulation with neutrophil agonists such as phorbol ester, chemotactic peptide, or opsonized zymosan, a fraction of the phosphatase redistributed to the cytoskeleton . Agonist treatment also induced significant decreases (30-60%) in SHP-1 activity, which correlated temporally with increases in the cellular phosphotyrosine content . Phosphorylation of SHP-1 on serine residues was associated with the inhibition of its enzymatic activity, suggesting a causal relationship . Accordingly, both the agonist-evoked phosphorylation of SHP-1 and the inhibition of its catalytic activity were blocked by treatment with bisindolylmaleimide I, a potent and specific inhibitor of protein kinase C (PKC) activity . Immunoprecipitated SHP-1 was found to be phosphorylated efficiently by purified PKC in vitro . Such phosphorylation also caused a decrease in the phosphatase activity of SHP-1 . Together, these data suggest that inhibition of SHP-1 by PKC-mediated serine phosphorylation plays a role in facilitating the accumulation of tyrosine-phosphorylated proteins following neutrophil stimulation . These findings provide a new link between the PKC and tyrosine phosphorylation branches of the signaling cascade that triggers antimicrobial responses in human neutrophils.

Pharmacoeconomics, 1997 Feb, 11(2), 169 - 74
An economic evaluation of the use of granulocyte colony-stimulating factor after bone marrow transplantation in children; Duncan N et al.; Studies that have assessed the use of granulocyte colony-stimulating factor (G-CSF) following bone marrow transplantation have shown a significantly reduced time to neutrophil recovery with the use of this agent, which may translate into a reduced duration of antimicrobial therapy and hospitalisation . We performed a pharmacoeconomic study evaluating the elective use of G-CSF after bone marrow transplantation in children . 22 consecutive children who underwent bone marrow transplantation and received G-CSF 5 micrograms/kg/day were compared with 18 such children (control group) who did not receive G-CSF . Despite a significant reduction in time to recovery of the absolute neutrophil count (ANC) to > 0.5 x 10(9)/L in G-CSF recipients compared with the control group (14 days vs 20.9 days; p < 0.0001), there was only a trend towards a reduction in the duration of intravenous antimicrobial therapy (14.5 days vs 18.6 days; p = 0.15), and there was no significant difference in the duration of hospitalisation (25.3 days vs 29.8 days) . Reasons for prolonged hospitalisation beyond ANC recovery included continued use of total parenteral nutrition, treatment of graft-versus-host disease and treatment of ongoing infection . Overall, the mean total cost for patients receiving G-CSF was Pounds 15001, compared with Pounds 15482 for the control group (1995 values) . In conclusion, while there appears to be no benefit in financial terms, the release of a child from strict isolation as a result of early ANC recovery must be taken into consideration.

FEBS Lett, 1997 Jan 6, 400(3), 289 - 92
Identification of the region that plays an important role in determining antibacterial activity of bovine seminalplasmin; Sitaram N et al.; Seminalplasmin (SPLN) is a 47-residue protein isolated from bovine seminal plasma having potent antimicrobial activity against a broad spectrum of microorganisms . SPLN, also known as caltrin, acts as a calcium transport regulator in bovine sperms . Analysis of the sequence of SPLN reveals a 27-residue stretch with the sequence SLSRYAKLANRLANPKLLETFLSKWIG more hydrophobic than the rest of the protein . It is demonstrated that a synthetic peptide corresponding to this 27-residue segment has antimicrobial activity comparable to that of SPLN . It does not exhibit hemolytic activity at concentrations where antibacterial activity is observed . Since P27 can be conveniently obtained in large amounts by chemical synthesis, it could serve not only as a starting compound to obtain peptides with improved antibacterial activity but also to understand the role of SPLN in reproductive physiology.

FEBS Lett, 1997 Jan 3, 400(2), 168 - 72
ESTs reveal a multigene family for plant defensins in Arabidopsis thaliana; Epple P et al.; Plant defensins, formerly named gamma-thionins, are a group of small, cysteine-rich, basic, and antimicrobial plant proteins . Random sequencing of expressed sequence tags (ESTs) in Arabidopsis thaliana has revealed several different plant defensin genes in this plant species which can be grouped into two subfamilies . We have used one EST of each subfamily to study the expression of the corresponding genes in A . thaliana . Pdf2.3 is constitutively expressed in seedlings, rosettes, flowers, and siliques and is not inducible in seedlings either by methyl jasmonate, salicylate, ethephon, and silver nitrate or by several different phytopathogenic fungi . The expression of a second gene, Pdf1.2, is in untreated plants only detectable in rosettes . In seedlings, it is inducible by methyl jasmonate, silver nitrate, and different phytopathogenic fungi, notably Fusarium oxysporum f . sp . matthiolae . The regulation of Pdf1.2 resembles that of the pathogen-inducible thionin gene Thi2.1.

FEBS Lett, 1997 Jan 3, 400(2), 158 - 62
Clavanins, alpha-helical antimicrobial peptides from tunicate hemocytes; Lee IH et al.; Hemocytes from the invertebrate Styela clava, a solitary tunicate, contained a family of four alpha-helical antimicrobial peptides that were purified, sequenced and named clavanins A, B, C and D . Each clavanin contained 23 amino acid residues and was C-terminally amidated . The tunicate peptides resembled magainins in size, primary sequence and antibacterial activity . Synthetic clavanin A was prepared and displayed comparable antimicrobial activity to magainins and cecropins . The presence of alpha-helical antimicrobial peptides in the hemocytes of a urochordate suggests that such peptides are primeval effectors of innate immunity in the vertebrate lineage.

Acta Otolaryngol Suppl, 1997, 529, 116 - 8
Pediatric facial paralysis--a spirochetal infection with good prognosis?
Peltomaa M, Saxen H, Pyykko I.
The aim of the study was to investigate the possible signs of chronic spirochetal infection in 27 children with a history of facial paralysis with onset of symptoms during May-October 1985-1993 . These children had not been studied at the time of facial paralysis for possible Lyme borreliosis and none of these children had received antimicrobial therapy at that time . The patients were interviewed with special reference to symptoms and signs of Lyme borreliosis and thereafter examined clinically and with laboratory tests . None of the patients showed signs or symptoms of chronic Lyme borreliosis . One child-now a 14-year old girl-had a 4-fold rise in serum Borrelia burgdorferi antibodies as a sign of a recent infection . According to our prospective studies on pediatric facial paralysis in Finland (over 50% of children presenting with facial paralysis during May-October have Lyme borreliosis), we have a reason to assume that at least some in our study group had a facial paralysis caused by Borrelia burgdorferi infection . The results of our study indicate that facial paralysis has a favorable prognosis and in short-term follow-up the children do not have symptoms or signs of chronic Lyme borreliosis.

Dev Biol Stand, 1997, 90, 3 - 12
A historical review of fish vaccinology; Evelyn TP; The first report on fish vaccination to appear in a widely read international scientific journal was that by Duff {5} dealing with his results obtained with anti-furunculosis vaccines . Duff's report did not result in an immediate landslide of fish vaccination trials in other laboratories because, in the years following the second world war, the preoccupation was with disease control using the newly discovered antibiotics . In fish culture, the ensuing 30 to 40 years might accurately have been termed the "era of chemotherapy" because large numbers of antibiotics, sulpha drugs, and even mercury-based antimicrobial agents were routinely used . It was only in the mid to late 1970s, with an increased interest in fish farming, particularly marine fish farming, that attention was once again turned to the possibility of vaccination as a means of preventing/ controlling fish diseases and to the development of commercially available vaccines . The reasons for this turn of events were varied: the high cost of using chemotherapy, the short-term nature of the protection obtained with antibiotics, the increasing appearance of antibiotic resistant fish pathogens, and, to some extent, concerns about the environmental impacts of antibiotic use . This paper briefly outlines the success that has attended efforts to develop vaccines against some of the more important bacterial diseases of cultured fish and the progress made in developing vaccines against important viral fish pathogens . In the process, an attempt will be made to show how fish vaccine development has benefited from an improved knowledge of the fish's immune system and from a better understanding of the virulence factors possessed by particular fish pathogens.

Scand J Infect Dis Suppl, 1997, 104, 15 - 7
Animal models for Chlamydia pneumoniae infection; Laitinen K et al.; There is accumulating evidence that persistent Chlamydia pneumoniae infections occur in vivo . Animal studies are necessary in order to evaluate the effects of different treatment regimens for eradication of such infections . A mouse model was found to be efficacious for the study of the effects of cortisone and antimicrobial agents on C . pneumoniae infection.

Antibiot Khimioter, 1997, 42(5), 24 - 8
{A conjugate of ristomycin A ristosaminylaglycon-polymyxin B: the spectrum of its antimicrobial action and its membranolytic activity}; Polin AN et al.; Antimicrobial activity of a conjugate based on two antibiotics, i.e . ristomycin A and polymyxin B was studied . The conjugate was shown to have a broad antimicrobial spectrum . In concentrations of 5 to 30 micrograms/ml it inhibited the growth of gram-positive and gram-negative bacteria and in concentrations of 5 to 40 micrograms/ml it inhibited the growth of the pathogenic clinical strains . An insignificant membranolytic action of the conjugate with respect to membranes of the susceptible bacteria and no hemolytic action on human red blood cells were detected.

Dermatology, 1997, 194(4), 383 - 7
Healing rate and bacterial necrotizing vasculitis in venous leg ulcers; Pierard-Franchimont C et al.; Morbidity associated with venous leg ulcers is important in the elderly . The biological processes involved during attempts at healing are much more complex than in most models of experimental wounds . In addition, there is still controversy on deleterious effects elicited by both microorganisms and antiseptics on cells involved in the healing process . Using histology, immunohistochemistry and iterative computerized planimetry, we evaluated the bacterial load, the inflammatory aspects and the healing rate of leg ulcers present in 15 eligible women aged from 57 to 73 years . Each patient had at least 2 chronic ulcers treated with hydrocolloid dressing alone or in combination with daily applications of povidone-iodine solution (PVP-I) . The weekly reduction in wound area was superior for hydrocolloid+PVP-I treatment than in hydrocolloid-treated ulcers . After a 4-week treatment, hydrocolloid-treated ulcers contained clumps of microorganisms and showed massive infiltration by phagocytes including Mac 387+ and factor XIIIa+ cells . Leukocytoclastic vasculitis was present as well . These features were less pronounced in ulcers treated with hydrocolloid+PVP-I . In sum, a broad-spectrum antimicrobial such as PVP-I may be beneficial in reducing deleterious bacteria-related inflammation . As a result, the healing rate leg ulcers is enhanced.

Morfologiia, 1997, 111(2), 7 - 16
{The functional morphology of the Langerhans cells in the female reproductive tract}; Bykov VL; The modern views on the distribution, morphological and functional characteristics of Langerhans cells (LCs) and their role in the immunological defense system in female genital tract are summarised . Within this tract, LCs are situated mainly in the mucosal epithelia of vagina and uterine cervix . They are surrounded by hormone-dependent and cyclically changing epithelium and are highly sensitive to hormonal and deleterious factors . LCs function as a component of afferent limb of the local immune system . which has special properties as it is modulated by the changing hormonal levels, provides the antimicrobial immunity and is tolerant to multiple immunization with sperm antigens . Perspectives in the study of LCs in female genital tract are discussed.

Annu Rev Biochem, 1997, 66, 337 - 45
D-amino acids in animal peptides; Kreil G; D-amino acids have been detected in a variety of peptides synthesized by animal cells . These include opiate and antimicrobial peptides from amphibian skin, neuropeptides from snail ganglia, a hormone from crustaceans, and a constituent of a spider venom . cDNA cloning has shown that at those positions where a D-amino acid is found in the end-product, a normal codon for the corresponding L-amino acid is present . This implies that the D-residues are formed from L-amino acids by a posttranslational reaction . A prototype enzyme catalyzing such a reaction has recently been isolated from the venom of the funnel web spider.

J Clin Dent, 1997, 8(2 Spec No), 39 - 45
A comparison of stabilized stannous fluoride dentifrice and triclosan/copolymer dentifrice for efficacy in the reduction of gingivitis and gingival bleeding: six-month clinical results; McClanahan SF et al.; This parallel-group, double-blind, placebo-controlled clinical trial directly compared the efficacy of two antimicrobial dentifrice formulations for the control of plaque, gingivitis and gingival bleeding during six months of use following a pre-test randomization period . Test antimicrobial dentifrices for the study included: a stabilized stannous fluoride formulation (Crest Plus Gum Care-currently marketed in U.S.) comprised of 0.454% SnF2 in a stabilized silica abrasive base; and a formulation containing triclosan (Colgate Total, currently marketed outside the U.S . in numerous countries) comprised of 0.30% triclosan . 2.0% Gantrez co-polymer and 0.243% NaF in a silica abrasive base . The control dentifrice was a conventional fluoride dentifrice comprised of 0.243% NaF in a silica abrasive base . Clinical evaluations included Turesky et al . plaque, Loe-Silness gingivitis and gingival bleeding, and Meckel stain . The stabilized stannous fluoride dentifrice exhibited significant efficacy in the reduction of both gingivitis (20.5%) and gingival bleeding (33.4%) after six months relative to the placebo control (p < 0.05) . In direct comparison, the stabilized stannous fluoride dentifrice reduced gingivitis and gingival bleeding significantly relative to the triclosan/copolymer dentifrice (p < 0.05) . These results establish: 1) the superior clinical efficacy of a stabilized stannous fluoride dentifrice relative to a triclosan/copolymer dentifrice in the chemotherapeutic control of gingivitis and gingival bleeding; 2) the important contribution of clinical test design/sensitivity in assessing the therapeutic efficacy of antimicrobial agents; and 3) the value of head-to-head comparative studies in establishing the therapeutic relevance of clinical effects of formulations for the reduction of gingivitis.

Rev Assoc Med Bras, 1997 Jan-Mar, 43(1), 47 - 52
{In vitro activity of cefetamet compared with other antimicrobial agents against bacteria isolated from respiratory tract infections}; Mendes CM; Cefetamet pivoxil is a new beta lactamase orally stable administered cephalosporin . Antimicrobial resistance among respiratory pathogens has become an important problem for both the physician and the microbiologist and the patterns of resistance vary greatly depending on geographic location, often requiring in vitro susceptibility testing of isolates . PURPOSE: The in vitro activity of cefetamet, the microbiologically active metabolite of the prodrug cefetamet pivoxil, was compared with other 11 drugs against 376 bacterial strains recently isolated from patients with respiratory tract infections . METHODS: The comparative activity in vitro of cefetamet and other 11 antimicrobial agents was measured against 376 bacterial strains isolated from patients with respiratory tract infections, during a six month period . Through the determination of minimum inhibitory concentration by the microdilution technique, patterns of antimicrobial resistance were reported . RESULTS: Cefetamet showed high in vitro activity against all the bacterial tested, possessing a spectrum of activity similar to that other recently developed oral cephalosporins . The good activity of cefetamet against beta-lactamase producing isolates, like Moraxella catarrhalis, can be due to its beta-lactamase stability . At a concentration of 1.0 microgram/mL, cefetamet inhibited 97% of all the tested bacteria . CONCLUSION: The MIC90 of the cumulative susceptibility results of the 12 antimicrobics tested in the 376 strains studied, confirm the excellent activity of cefetamet against the common respiratory tract pathogens.

Fold Des, 1997, 2(3), 183 - 92
Homology modelling of an antimicrobial protein, Ace-AMP1, from lipid transfer protein structures; Gomar J et al.; BACKGROUND: Plant nonspecific lipid transfer proteins (ns-LTPs) are small basic proteins that facilitate lipid shuttling between membranes in vitro . The function of ns-LTPs in vivo is still unknown . It has been suggested, in relation to their lipid binding ability, that they may be involved in cutin formation . Alternatively, they may act in the plant defence system against pathogenic agents . Ace-AMP1 is an antimicrobial protein extracted from onion seed that shows sequence homology with ns-LTPs but that is unable to transfer lipids . We have recently determined the three-dimensional structure of wheat and maize ns-LTPs . In order to compare the structural features of Ace-AMP1 and ns-LTPs, we have used the comparative modelling software MODELLER to predict the structure of Ace-AMP1 . RESULTS: The global fold of Ace-AMP1 is very similar to those of ns-LTPs, involving four helices and a C-terminal tail without secondary structure elements . The structure of maize and wheat ns-LTP is characterized by the existence of a tunnel-like hydrophobic cavity in which a lipid molecule can be inserted . In the Ace-AMP1 structure, this cavity is blocked by a number of bulky residues . Similarly, the electrostatic potential contours of ns-LTPs show some common features that were not observed in Ace-AMP1 . CONCLUSIONS: Although Ace-AMP1 displays a similar global fold to ns-LTPs, it does not present a hydrophobic cavity, which may explain why Ace-AMP1 cannot shuttle lipids between membranes in vitro . The large differences in the electrostatic properties of Ace-AMP1 and ns-LTPs suggest a different mode of interaction with membranes.

Microbios, 1997, 89(358), 39 - 46
Antibacterial and antifungal activity of aromatic constituents of essential oils; Pattnaik S et al.; Five aromatic constituents of essential oils (cineole, citral, geraniol, linalool and menthol) were tested for antimicrobial activity against eighteen bacteria (including Gram-positive cocci and rods, and Gram-negative rods) and twelve fungi (three yeast-like and nine filamentous) . In terms of antibacterial activity linalool was the most effective and inhibited seventeen bacteria, followed by cineole, geraniol (each of which inhibited sixteen bacteria), menthol and citral aromatic compounds, which inhibited fifteen and fourteen bacteria, respectively . Against fungi the citral and geraniol oils were the most effective (inhibiting all twelve fungi), followed by linalool (inhibiting ten fungi), cineole and menthol (each of which inhibited seven fungi) compounds.

Biopolymers, 1997, 43(2), 119 - 28
Biochemical properties of regulatory peptides derived from milk proteins; Meisel H; Biologically active peptides derived from milk proteins are inactive within the sequence of the precursor proteins but can be released by enzymatic proteolysis . Based on structure-activity studies, peptides with a defined bioactivity show common structural features . Moreover, many milk protein-derived peptides reveal multifunctional bioactivities . Bioactive peptide fragments originating from milk proteins should be taken into account as potential modulators of various regulatory processes in the body . Opioid peptides are opioid receptor ligands with agonistic or antagonistic activities . Angiotensin converting enzyme (ACE) inhibitory peptides can exert an antihypertensive effect . Immunomodulating casein peptides have been found to stimulate the proliferation of human lymphocytes and the phagocytic activities of macrophages . Antimicrobial peptides have been shown to kill sensitive microorganisms . Antithrombotic peptides inhibit the fibrinogen binding to a specific receptor region on the platelet surface and also inhibit aggregation of platelets . Casein phosphopeptides can form soluble organophosphate salts and may function as carriers for different minerals, especially calcium . In relation to their mode of action, bioactive peptides may reach target sites (e.g., receptors, enzymes) at the luminal side of the intestinal tract or after absorption, in peripheral organs . The physiological significance of bioactive peptides as exogenous regulatory substances is not yet fully understood . Nevertheless, several bioactive peptides derived from milk proteins have been shown to exert beneficial physiological effects . Milk-derived peptides were already produced on an industrial scale and as a consequence these peptides have been considered for application both as dietary supplements in "functional foods" and as drugs.

Vopr Pitan, 1997, (2), 38 - 40
{Cranberries: chemical composition, nutritional and medicinal properties}; Zaitsev AN et al.; The contents of protein, fats, carbohydrates (glucose, fructose, sucrose, dietary cellulose), some vitamin (ascorbic acid, riboflavin, beta-carotene, vitamin E), polyphenolic compounds, organic acids, pectin, glycosides, macro- and microelements in red bilberry are presented . Antimicrobial effect and other effect of red bilberry and its use in traditional medicine and dietetics are also outlined.

Rapid Commun Mass Spectrom, 1997, 11(9), 997 - 1000
New caerin antibacterial peptides from the skin glands of the Australian tree frog Litoria xanthomera . Part 2 . Sequence determination using mass spectrometry and associated techniques; Steinborner ST et al.; Mass spectrometric sequencing, enzymic digestion and Edman degradation provide the structures of the two antimicrobial peptides from the skin glands of the Australian tree frog Litoria xanthomera as:- Gly Leu Phe Ser Val Leu Gly Ala Val Ala Lys His Val Leu Pro His Val Val Pro Val Ile Ala Glu Lys Leu (NH2) (caerin 1.6), and Gly Leu Phe Lys Val Leu Gly Ser Val Ala Lys His Leu Leu Pro His Val Ala Pro Val Ile Ala Glu Lys Leu (NH2) (caerin 1.7).

Microbiol Immunol, 1997, 41(5), 427 - 30
Levels of endogenous interleukin-1, interleukin-6, and tumor necrosis factor in congenic mice infected with Borrelia garinii; Isogai H et al.; This study describes the levels of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) in the sera and parenchymal organs of various congenic mouse strains infected with Borrelia garinii . A significant elevation of inflammatory cytokine levels was found in the organs of C3H/HeN (H-2k) and B10.BR (H-2k) mice but not in those of BALB/c mice (H-2d) . Focally produced cytokines can contribute to antimicrobial defense against these organisms . High levels of IL-1 alpha were observed in the sera of C3H/HeN, B10.BR and B10 (H-2b) mice infected with B . garinii and they were associated with the presence of spirochetes in the skin . Thus, susceptible mice demonstrated a stronger cytokine response than resistant mice . This study presents in vivo evidence that B . garinii infection affects the immunopathogenesis of Lyme disease.

Ciba Found Symp, 1997, 207, 152 - 63; discussion 163-6
The evolution of beta-lactamases; Bush K; beta-lactamases, the enzymes often associated with resistance to beta-lactam antibiotics, are found in most bacterial species . Although these enzymes protected bacteria from naturally occurring beta-lactams long before the introduction of synthetic antimicrobial agents, the numbers and varieties of beta-lactamases have increased dramatically with the introduction of modern penicillins and cephalosporins . Over the past twenty years it has become apparent that families of beta-lactamases have been selected as the result of antimicrobial usage . Outbreaks of beta-lactam-resistant bacteria can be traced to the introduction of specific classes of beta-lactams or to the introduction of a specific agent . Many of the most serious epidemics can be related to transferable beta-lactamase genes that are harboured on multidrug-resistant plasmids . The separation of beta-lactamases into three major functional groups or four structural classes has been proposed . Stepwise selection of variants within several of these classes has been documented both in the clinical setting and in the laboratory, e.g . the extended-spectrum (TEM and SHV) beta-lactamases and the inhibitor-resistant (TEM) beta-lactamases . Close relationships among the recently described plasmid-mediated 'cephamycinases' and the common chromosomal cephalosporinases have been identified . Carbapenem-hydrolysing metallo-beta-lactamases with broad spectrum hydrolysing activity have become serious concerns as they begin to be described on plasmids . Factors contributing to selection of beta-lactam-resistant strains include decreased outer membrane permeability and increased beta-lactamase production.

Ciba Found Symp, 1997, 207, 112 - 27; discussion 127-30
The within-host population dynamics of antibacterial chemotherapy: conditions for the evolution of resistance; Lipsitch M et al.; For tuberculosis and number of other bacterial infections, treatment with a single antimicrobial drug frequently fails due to the ascent of mutants resistant to that drug . To minimize the likelihood of this occurrence, multiple drugs with independent resistance mechanisms are used simultaneously . None the less, multiply resistant bacteria sometimes emerge even when patients are simultaneously treated with two or more drugs, and the ascent of these multiply-resistant mutants may result in treatment failure in the patient and spread of these resistant bacteria to other hosts . We consider two mathematical models of antibacterial chemotherapy which can account for the ascent of multiple antibiotic resistance within hosts treated with multiple antibiotics . In both, multiple resistance evolves because of selection favouring mutants resistant to fewer than all of the chemotherapeutic agents employed, intermediates . In one model, this occurs because of temporal fluctuations in the concentrations of the antibiotics in the course of normal treatment and/or because of non-adherence to the treatment regime . In the other, intermediates are favoured and multiple resistance evolves because of tissue and somatic cell heterogeneity . In the effective concentrations of the antibiotics and physiological variation in the sensitivity of subpopulations of bacteria to different antibiotics . We discuss the limitations (and assets) of this model and approach and the implications for the design of antibiotic treatment regimes . Finally, we consider how the assumptions behind this model and the predictions made from its analysis could be tested experimentally.

Ciba Found Symp, 1997, 207, 47 - 56; discussion 56-60
The contribution of antibiotic use on the frequency of antibiotic resistance in hospitals; Gaynes R et al.; Abundant evidence suggests a relationship between antibiotic resistance and use, including animal models, consistent associations between resistance and antibiotic use in hospitals, concomitant variation in resistance as antibiotic use varies, and a dose-response relationship for many pathogen/antibiotic combinations . Much of the evidence has come from studies performed in single hospitals . Most multicentre studies on resistance have not included data on antibiotic usage . Despite this substantial body of evidence, some studies have failed to demonstrate an association between antibiotic resistance and use, suggesting other contributing factors such as cross-transmission, inter-hospital transfer of resistance, a community contribution to resistance, or a complex relationship between resistance and the use of a variety of antibiotics . A multicentre study, project ICARE (Intensive Care Antimicrobial Resistance Epidemiology), implemented in 1994 by Centers for Disease Control and Prevention and Rollins School of Public Health, Emory University, has found dramatic differences in the patterns of antibiotic usage and resistance in US hospitals . The findings suggest that antibiotic usage is the major risk factor in development of antibiotic resistance in hospitals but the relationship can be complex with additional factors involved . Understanding the problem of antibiotic resistance in a hospital cannot be achieved without knowledge of the hospital's pattern of antibiotic use.

Vestn Ross Akad Med Nauk, 1997, (3), 19 - 22
{Factors of intestinal microflora persistence in dysbacteriosis}; Bukharin OV et al.; The persistent properties of the intestinal microflora as a mechanism of adaptation to the host's antimicrobial factors are substantiated . The results of determination of antilysozyme and anticomplementary activities and the inactivating abilities of the bactericidal component of interferon in enteric bacteria isolated in intestinal dysbacteriosis are outlined . Changes were found in the population structure of the Escherichia flora in relation to the severity of dysbacteriosis and a high prevalence of persistent signs were revealed in enteric bacteria . There was a correlation between the persistent signs of bacteria and the severity of intestinal microbiocenotic abnormalities . The factors of microbial persistence are proposed to be used as markers of a dysbiotic process.

Farmaco, 1997 Jan, 52(1), 67 - 9
Pyridazine N-oxides . II . Synthesis and in vitro antimicrobial evaluation of 3-chloro-4-carbamoyl-5-aryl-6-methyl-pyridazine N-oxides; Gavini E et al.; As a part of a research project on antimicrobial agents, various novel carbamoyl derivatives of pyridazine-N-oxides 7a-j were prepared in moderate to good yields from 3-chloro-4-ethoxycarbonyl-5-aryl-6-methyl-3-pyridazine . All compounds synthesized were ineffective against Gram+, Gram- bacteria and fungi while 7e and 7j exhibited a fairly good activity against Trichomonas vaginalis.

Farmaco, 1997 Jan, 52(1), 21 - 4
Synthesis and antimicrobial activity of N-(1,2-benzisothiazol-3-yl)amidines; Vicini P et al.; Several N-(1,2-benzisothiazol-3-yl)amidines were synthesized and examined for their in vitro antimicrobial activity . Some of the compounds studied were effective against bacteria and fungi . Amidines carrying unsaturated alkylic chains showed the highest antimicrobial activity, the propenyl derivative 7 proving to be the most potent with minimum inhibitory concentrations of 25 micrograms/ml against Gram positive bacteria and mould and of 3-12 micrograms/ml against yeasts . The results indicate that an unsaturated moiety is an important function for enhancing the antimicrobial activity in the compounds under investigation.

Scand J Infect Dis, 1997, 29(2), 147 - 51
The diagnostic value of enzyme immunoassay and immunoblot in monitoring eradication of Helicobacter pylori; Sorberg M et al.; 55 patients with severe ulcer disease and H . pylori infection, successfully treated with antimicrobials, were followed-up with repeated blood samples for up to 32 months . Sera were analysed by enzyme immunoassay (EIA) for IgG and IgA antibodies and by IgG immunoblot . The EIA for IgG antibodies showed a high sensitivity (100%), while IgA antibodies above the cut-off level were found in 55% of the patients . At a median of 77 days after onset of treatment, approximately 50% of the patients showed a significant decrease (> or = 50%) of IgG or had titres below the cut-off level . All patients but 1 had a significant decrease of IgG after 6-12 months . The decrease was slower for IgA . The H . pylori-specific 116 kDa and 19.5 kDa bands were found in all pre-treatment samples, but the decrease in median intensity of the bands was slower than for the IgG EIA . In the 32-months post-treatment samples, both bonds had an intensity still above 50% of the pre-treatment value . The study showed that the IgG EIA is a useful method for monitoring eradication of H . pylori . Immunoblot can detect previous H . pylori infection in EIA negative Individuals.

Transpl Int, 1997, 10(3), 241 - 4
Liver transplantation in patients with Caroli's disease and recurrent cholangitis; Sans M et al.; Caroli's disease is an uncommon congenital disorder of the intrahepatic biliary tree . It is characterized by multiple and segmental dilatations of the bile ducts . The clinical course of Caroli's disease is often complicated by recurrent episodes of bacterial cholangitis that seriously impair the patient's quality of life . Despite wide spectrum antimicrobial agents, medical treatment of cholangitis is frequently unsuccessful in patients with Caroli's disease due to the persistence of bacteria in dilatated bile ducts . Other therapies, including internal or external biliary drainages and various surgical or endoscopic procedures, have been used in the treatment of Caroli's disease, with poor results . There are no previous reports in the literature of liver transplantation for recurrent cholangitis in patients with Caroli's disease . We present two such cases, in which cholangitis is resolved.

Biol Trace Elem Res, 1997 Jan, 56(1), 107 - 16
Reactive oxygen species and nitric oxide in viral diseases; Peterhans E; Metabolites derived from superoxide (O2.-) and nitric oxide (NO.) play an important role in antimicrobial and antitumoral defense, but may also harm the host . Low levels of such metabolites can also facilitate viral replication because of their mitogenic effects on cells . Most viruses grow better in proliferating cells, and indeed, many viruses induce in their host cell changes similar to those seen early after treatment with mitogenic lectins . Influenza and paramyxo-viruses activate in phagocytes in the generation of superoxide by a mechanism involving the interaction between the viral surface glycoproteins and the phagocyte's plasma membrane . Interestingly, viruses that activate this host defense mechanism are toxic when injected in the bloodstream of animals . Mice infected with influenza virus undergo oxidative stress . In addition, a wide array of cytokines are formed in the lung, contributing to the systemic effects of influenza . Oxidative stress is seen also in chronic viral infections, such as AIDS and viral hepatitis . Oxidant production in viral hepatitis may contribute to the emergence of hepatocellular carcinoma, a tumor seen in patients after years of chronic inflammation of the liver . Antioxidants and agents that downregulate proinflammatory cytokines and lipid mediators may be a useful complement to specific antiviral drugs in the therapy of viral diseases.

Annu Rev Immunol, 1997, 15, 323 - 50
Nitric oxide and macrophage function; MacMicking J et al.; At the interface between the innate and adaptive immune systems lies the high-output isoform of nitric oxide synthase (NOS2 or iNOS) . This remarkable molecular machine requires at least 17 binding reactions to assemble a functional dimer . Sustained catalysis results from the ability of NOS2 to attach calmodulin without dependence on elevated Ca2+ . Expression of NOS2 in macrophages is controlled by cytokines and microbial products, primarily by transcriptional induction . NOS2 has been documented in macrophages from human, horse, cow, goat, sheep, rat, mouse, and chicken . Human NOS2 is most readily observed in monocytes or macrophages from patients with infectious or inflammatory diseases . Sustained production of NO endows macrophages with cytostatic or cytotoxic activity against viruses, bacteria, fungi, protozoa, helminths, and tumor cells . The antimicrobial and cytotoxic actions of NO are enhanced by other macrophage products such as acid, glutathione, cysteine, hydrogen peroxide, or superoxide . Although the high-output NO pathway probably evolved to protect the host from infection, suppressive effects on lymphocyte proliferation and damage to other normal host cells confer upon NOS2 the same protective/destructive duality inherent in every other major component of the immune response.

Boll Chim Farm, 1997 Jan, 136(1), 28 - 38
{Microbiological control of drugs with antimicrobial properties with membrane filtration: problems, proposals, prospects}; Negretti F; The attention to the difficulty to performing the control of sterility (and also of contamination) of pharmaceuticals with antimicrobial activity (antibiotics, chemotherapeutic agents, etc.) or containing preservatives is called . On the basis of our and others investigations, the technique of the membrane filtration (employed usually) is unable to eliminate the interferences on the microbial growth . The membranes used for the filtration of antimicrobial agents acquire antimicrobial properties, resulting in: a) appearance of inhibition zones onto agar plates previously inoculated with microbial strains; b) decrease of the number of CFU after artificial contamination of the membranes (more sensitive method); c) absence or partial growth into culture broths of microbial strains contaminant the membranes; d) antimicrobial activity of the culture broths inoculated with used membranes . The separate washing with 300 ml and upper volumes of peptone water does not eliminate completely the antimicrobial activity of the membranes . If the filtration is associated to treatments with suitable neutralisant substances, it is possible to eliminate partially the antimicrobial activity of the membranes . In No . 10 antibiotics, a total neutralization of the antimicrobial activity was obtained in No . 4 cases (40%) . In No . 14 chemotherapeutic agents, We have obtained a total neutralization of the antimicrobial activity in No . 11 cases (78.57%) and a partial remission in No . 3 cases (21.43%) . In No . 18 disinfectant, We have obtained a complete disappearance of the drawback in No . 16 (88.8%) cases and a partial disappearance in No . 2 (11.2%) cases . Only in the case of the preservatives (No . 3 single and 16 associations), we have obtained a total remission of the interferences in all cases . For the neutralization, some classic neutralizers (albumin, p-aminobenzoic acid, beta-lactamase, cysteine, Ca+2, egg yolk, Fe+3, heparin, hydroxylamine, thymidine, Tween 20) and a new neutralizing agent (ascorbic acid) were employed . Thus, it is necessary to find suitable neutralizing agents or to research new types of filtering membranes . In the meantime, the production of chemo-antibiotic agents should be carried out according to stingent criteria of asepsis.

Diagn Microbiol Infect Dis, 1997 Jan-Feb, 27(1-2), 49 - 53
The future--can we learn from the past?
Craig WA.
We know that the current problems of resistance among bacterial pathogens to commonly prescribed antibiotics is, in part, attributable to inappropriate prescribing . If we are to rectify matters, we must learn from past mistakes and take appropriate measures to ensure that community-acquired infections do not become as untreatable as certain nosocomial infections are now . This means that we must be able to predict efficacy outcomes better so that we can make more effective use of available antibiotics . Animal studies suggest that the duration of time that an antibiotic exceeds the MIC of the causative pathogen (i.e., at least 40 to 50% of the dosing interval) is a good prognostic indicator for the efficacy of beta-lactam antibiotics . Clinical studies are now being published that confirm the value of time above MIC . Use of this information should enhance efficacy and may delay the pace of developing antibiotic resistance, allowing time for new antimicrobial agents to be researched and brought to market.

Diagn Microbiol Infect Dis, 1997 Jan-Feb, 27(1-2), 41 - 7
Role of oral antibiotics in treatment of community-acquired lower respiratory tract infections; Legnani D; Amoxicillin/clavulanic acid has been one of the first choice treatments for community-acquired lower respiratory tract infection since its introduction nearly 15 years ago . Since then, it has become the "gold standard" against which most new oral antimicrobials are compared, but none of these newer agents has demonstrated a superior efficacy . To the contrary, two recent studies comparing amoxicillin/clavulanic acid with azithromycin, cefixime, or ciprofloxacin in the treatment of acute exacerbations of chronic bronchitis have demonstrated a higher efficacy rate for amoxicillin/clavulanic acid.

Diagn Microbiol Infect Dis, 1997 Jan-Feb, 27(1-2), 1 - 5
Validation of Etest for seven antimicrobial agents using regulatory criteria for the assessment of antimicrobial susceptibility devices; Biedenbach DJ et al.; Etest, a stable-gradient antimicrobial susceptibility test method (AB Biodisk, Solna, Sweden), was compared to the agar dilution method for tests with amikacin, tobramycin, aztreonam, cefdinir, cefprozil, ceftazidime and sparfloxacin . The study design followed recommended guidelines for 510(k) application by the U.S . Food and Drug Administration (FDA) . Results demonstrated Etest accuracy (MIC +/- 1.0 log2 dilutions compared to agar dilution MIC) to be 90.4% with only one of 1150 comparisons showing a reproducible variation of 2 log2 dilutions . Categorical equivalency was > or = 92% for all drugs except ceftazidime (82 to 89%), but false-susceptible error was rare (< 0.1%) . Etest was very reproducible (100% of results +/- 1.0 log2 dilution) and quality control results conformed to published MIC ranges . The Etest seems to render accurate results for these seven antimicrobial agents evaluated.

Antibiot Khimioter, 1997, 42(2), 38 - 40
{Effectiveness of piperacillin/tazobactam in the treatment of fever of unknown etiology in patients with granulocytopenia}; Maschan AA et al.; Piperacillin/tazobactam (P/T) was used in the treatment of 14 patients at the age of 5 to 15 years: 5 patients with acute lymphoblastic leukemia, 3 with acute nonlymphoblastic leukemia, 4 with severe aplastic anemia, 1 with lymphoma and 1 with neuroblastoma . P/T was administered as intravenous infusions in a daily dose of 200-300/25-37.5 mg/kg body weight divided into 3 or 4 portions . All the patients were subjected to intestine selective antimicrobial decontamination . In 7 patients the afebrile condition was recorded before elimination of agranulocytosis without correction of the therapy i.e . without combination of P/T with some other antibiotics such as amphotericin B, vancomycin or aminoglycosides . In 5 patients the effect was stated after correction of the regimen by its supplementing with amphotericin B . 2 patients died . No side effects of P/T was observed . The afebrile condition was provided in 1 to 7 days . P/T is recommended for the treatment of fever of obscure etiology in patients with agranulocytosis and for effective control of infection in such patients.

Ann Trop Med Parasitol, 1997 Jan, 91(1), 87 - 94
Plasmid diversity of multi-drug-resistant Escherichia coli isolated from children with diarrhoea in a poultry-farming area in Kenya; Kariuki S et al.; Biotin-labelled DNA probes and restriction-endonuclease digestion (RED) with HindIII were used to study the diversity of resistance plasmids (R-plasmids) from 414 Escherichia coli isolates: 168 from children living in close contact with antibiotic-fed poultry and 246 from the chickens . Full sensitivity to all 10 antimicrobials tested was more common in the isolates from poultry than in those from the children (36.2% v . 9.5%; P < 0.001) . Multi-drug resistance, to at least two of the antimicrobials, was relatively common in the isolates from the children (85.5% v . 26.00%; P < 0.001) . Overall, 31% of the poultry isolates were resistant to tetracycline alone . Resistance to amoxycillin was due to production of TEM-1 (89%) and TEM-2 (11%) . In > 71% of the isolates from children and 79% of those from poultry, resistance was encoded on a 100-110-kb transferable plasmid belonging to incompatibility group FII . However, RED patterns of R-plasmids from the two groups of isolates were highly diverse and not indicative of any close relatedness . This difference in patterns and in the levels of multi-drug resistance indicate that the isolates from the children and those from the poultry represent two distinct pools of resistance plasmids.

Ostomy Wound Manage, 1997 Jan-Feb, 43(1), 56 - 60, 62, 64-6
Malignant cutaneous wounds: a management protocol; Haisfield-Wolfe ME et al.; Malignant cutaneous wounds are emotionally traumatic and difficult to manage lesions which occur secondary to infiltration of cancer into the skin . They occur in patients with end-stage disease and are highly exudative, malodorous, and bleed easily . Quality of life is the goal for treatment, which includes radiation, chemotherapy, surgery, and local wound care . Odor is addressed with varying levels of success through wound cleansing, external deodorizers, charcoal-impregnated dressings, topical antimicrobial therapy, and metronidazole . Exudate is managed with highly absorbent dressing materials, topical steroids or hyoscine (a drying agent) . Light bleeding is controlled with local pressure and hemostatic dressings; heavier bleeding may require ligation or cauterization . Cosmetic appearance and other psychosocial issues must be assessed on an ongoing basis . Creative dressing techniques can help restore the look of symmetry to the patient's body . Effective wound management, debridement, and antimicrobial therapy can reduce the risk of infection . Wound cleansing, through irrigation or flushing, should not cause pain, further trauma or bleeding . Dressings should maintain a moist wound environment and not traumatize the wound upon removal . A protocol is included which can be individualized to the needs of each patient and addresses assessment, interventions, patient teaching, documentation, and expected outcomes.

Pharmazie, 1997 Jan, 52(1), 34 - 40
{Evaluation of pharmacopoeia methods for determination of antimicrobial agents, especially of natural substances}; Brantner A; Microbiological assays referring to antibiotics were first mentioned in 1955 in the US Pharmacopedia XV and in the Pharmacopedia of India I . In the pharmacopedias two general methods are employed: The first group of methods is grounded on diffusion (disc assay, cylinder-plate and hole-plate assay), the second one is based on the determination of optical density (turbidimetric method) . Both methods involve certain problems, particularly with respect to the testing of low-active natural substances . In the course of our investigations those test methods were evaluated and the advantages and disadvantages discussed . The methods were compared to test systems not being described in the pharmacopedias (microdilution test, bioautographic TLC assay) . In addition to that we examined spectrophotometrically (OD580nm) the influence of an antimicrobial substance and of a solutizer on the bacterial growth . Tetracycline hydrochloride was used as reference and naringenin as test substance . The results were analyzed with statistical methods cited in the pharmacopedias, e.g . straight-line method and compared to other common methods, e.g . analysis of variance.

Allergy Asthma Proc, 1997 Jan-Feb, 18(1), 29 - 32
Outpatient management of Stevens-Johnson syndrome: a report of four cases and management strategy; Noskin GA et al.; Stevens-Johnson syndrome is a severe form of erythema multiforme with or without bullous lesions . This is a potentially life-threatening condition that has traditionally required hospitalization for optimal management . We report the successful management of four patients who developed this syndrome following administration of antimicrobial agents . In our experience, for individuals with mild to moderate disease, Stevens-Johnson syndrome can be managed with corticosteroids as an outpatient.

J Antibiot (Tokyo), 1997 Jan, 50(1), 22 - 6
Targeted screening for elongation factor Tu binding antibiotics; Selva E et al.; The development of a screen targeted to antibiotics which bind elongation factor Tu (EF-Tu) is described . The method was based on selection of antimicrobial activities which were antagonized by exogenous EF-Tu . Kirromycin, a known inhibitor of EF-Tu, was positive in this screen . Among 47,000 microorganisms screened, several producers of kirromycin-type antibiotics were detected and the novel antibiotics GE2270 and GE37468 were discovered . These thiopeptide molecules constitute, along with amithiamycin, a novel class of antibiotics acting on EF-Tu.

Ophthalmologica, 1997, 211 Suppl 1, 77 - 80
Local antimicrobial prophylaxis in cataract surgery: recent controversies and clinical guidelines; Adenis JP et al.; The best prevention of endophthamitis is the use of strict surgical hygiene . Supplementing the irrigating solution with aminoglycosides and/or vancomycin is a rational, convenient and cost effective method of antimicrobial prophylaxis . However emerging resistance to vancomycin entails restrictions to its daily use . In conclusion, two options are possible: limit the use of prophylaxis in the irrigating solution to only those patients at high risk of injection, or use topical and general antibioprophylaxis with low cost drugs.

Curr Opin Hematol, 1997 Jan, 4(1), 53 - 8
Antimicrobial peptides of leukocytes; Ganz T et al.; Leukocytes use an array of antimicrobial peptides and proteins to help them destroy invading microorganisms . These endogenous antibiotic molecules are remarkable for their structural variety, rapid evolutionary divergence, intraspecies variation, and complex yet subtle interactions with their targets . This arsenal has been studied most extensively in neutrophils, where its members include lactoferrin, secretory phospholipase A2, lysozyme, and the cathelicidins in the secretory granule compartment; defensins, bactericidal permeability inducing protein, serprocidins, and (again) lysozyme in the azurophil granule compartment; and calprotectin in the cytosolic compartment . That antimicrobial peptides and proteins are not limited to neutrophils and other phagocytes was made clear by the recent discovery of a microbicidal protein, NK lysin, in porcine natural killer cells and cytotoxic T lymphocytes . The structural homology of NK-lysin to amebapore, an antimicrobial cytolytic peptide of the parasitic protozoan Entamoeba histolytica, provides remarkable support for a long-suspected evolutionary connection between the leukocytes of higher animals and their unicellular, protozoan ancestors.

Vet Microbiol, 1997 Jan, 54(1), 63 - 72
Antimicrobial susceptibility of Bordetella bronchiseptica isolates from cats and a comparison of the agar dilution and E-test methods; Speakman AJ et al.; One hundred and fifty-two predominantly feline isolates of Bordetella bronchiseptica were tested for their susceptibility to seven antimicrobial agents using an agar dilution method . The majority of isolates tested by the agar dilution method were resistant to trimethoprim (MIC90 500 micrograms/ml) and ampicillin (MIC90 > 32 micrograms/ml) but sensitive to tetracycline, doxycycline and enrofloxacin (MIC90 2 micrograms/ml for all three agents) . The isolates showed a spectrum of susceptibility to sulphadiazine and clavulanate potentiated amoxycillin . The MIC's of twenty-nine of the 152 isolates were then compared for five of the antimicrobial agents using the E-test (AB Biodisk, Sweden), a recently introduced method for measuring the MIC's of antimicrobial agents based on the diffusion of a pre-defined antibiotic gradient from a plastic strip . Comparisons with the E-test demonstrated an overall agreement (+/- 1 log2 dilution) with the agar dilution method of 79.4% and an agreement within +/- 2 log2 dilutions of 96.2%.

Pediatr Pathol Lab Med, 1997 Jan-Feb, 17(1), 27 - 42
Histologic features of chorioamnion membrane rupture: development of methodology; Bendon RW et al.; This study developed a set of histologic features that will allow subclassification of placentas with preterm premature rupture of membranes . Placentas were obtained from patients participating in a multi-institutional NICHD Maternal-Fetal Medicine Unit Network study of antimicrobial therapy after preterm premature rupture of membranes . The rupture site was sampled by inking the open sac margin and rolling a membrane strip in four quadrants from the ink to the placental margin . Independently, four pathologists used a provisional feature list to score the slides from 15 placentas . A concordance analysis was performed on those results . With those results, the slides were reviewed concurrently to discover the source of disagreements and to revise the feature list . The sampling method frequently demonstrated a rupture site with histology distinct from that of the remainder of the membranes . After review of the preliminary scoring results, 29 features of membrane histology present in preterm premature rupture could be objectively described with agreement among four pathologists . The feature list allows both novel and commonly recognized histologic features of fetal membranes to be recorded with objectivity . This list, with the described sampling technique, is presented as a tool for clinical correlation in studies of membrane rupture, especially in preterm, premature rupture.

Hinyokika Kiyo, 1997 Jan, 43(1), 19 - 23
{Electron microscopic study on the surface of long-term indwelling silver-protein-coated urethral catheters (Urotopic Ag Protein)}; Konishi T et al.; In order to determine the bacterial and crystal adherence to long-term indwelling urethral catheters, we performed a scanning electron microscopic study utilizing commercially available silver-protein-coated latex (Urotopic Ag Protein) and silicone urethral catheters that were left in place for over 4 weeks . Microorganisms and crystals frequently were associated with fibrillar materials . On the surface of silicone catheters bacteria often were embedded in the amorphous matrix . In contrast we found no bacteria adhering to the antimicrobial urethral catheter surface coated with silver-protein . Crystal formation was similar in both catheters, but no catheteral obstruction was observed in this study . We suggested that antimicrobial urethral catheter coated with silver-protein is applicable to patients who tend to form encrustations on long-term indwelling catheters.

J Antimicrob Chemother, 1997 Jan, 39(1), 5 - 12
The stability of amoxycillin, clarithromycin and metronidazole in gastric juice: relevance to the treatment of Helicobacter pylori infection; Erah PO et al.; Although omeprazole is an important component in anti-Helicobacter pylori therapeutic regimes using clarithromycin, amoxycillin and metronidazole, the mechanism by which it enhances antimicrobial action is unknown . One potential explanation for this effect is increased antibiotic chemical stability resulting from gastric pH changes induced by co-administration of omeprazole . The chemical stability of clarithromycin, amoxycillin and metronidazole was investigated in aqueous solutions and in human gastric juice collected before and after a 7-day course of omeprazole . Amoxycillin, clarithromycin and metronidazole were prepared in buffered aqueous solutions of pH 1.0 to 8.0 and in gastric juice of pH 2.0 and 7.0 . The gastric juice samples were obtained from fasted H . pylori-negative volunteers before and after they had received a 7-day course of omeprazole . All the samples were incubated at 37 degrees C and analysed at intervals by HPLC . Amoxycillin, clarithromycin and metronidazole were stable in aqueous solutions of pH 4.0-7.0, pH 5.0-8.0 and pH 2.0-7.0, respectively . At pH 2.0, the degradation half-lives were 19.0 +/- 0.2 h, 1.3 +/- 0.05 h and 2200 +/- 1100 h, respectively . In gastric juice samples of pH 2.0, the degradation half-lives were 15.2 +/- 0.3 h, 1.0 +/- 0.04 h and > or = 800 h, respectively . The half-lives of the drugs in the gastric juice samples of pH 7.0 were all > 68 h . The co-administration of omeprazole with amoxycillin or clarithromycin is likely to increase the chemical stability of amoxycillin and clarithromycin in gastric juice . Clarithromycin degrades rapidly at normal gastric pH (1.0-2.0) but amoxycillin and metronidazole are sufficiently stable at this pH to maintain an antibacterial concentration in the stomach.

Immunopharmacology, 1997 Jan, 35(3), 265 - 71
Vancomycin down-regulates lipopolysaccharide-induced tumour necrosis factor alpha (TNF alpha) production and TNF alpha-mRNA accumulation in human blood monocytes; Siedlar M et al.; The cytokines play an important role in the cascade of the pathological events leading to septic shock . The TNF alpha produced by monocytes/macrophages upon stimulation with bacterial fragments may contribute to induction of this cytokine cascade . Moreover, the antibiotics used for antimicrobial therapy may cause the increase of TNF alpha production due to massive bacterial killing and exposure of monocytes/macrophages to bacterial cell constituents . To investigate the effect of Vancomycin on TNF alpha production, an in vitro model of LPS-stimulated monocytes was used . The level of TNF alpha protein or TNF biological activity were tested in the culture supernatants of monocytes with LPS . Vancomycin down-regulated, in dose-dependent manner, the TNF alpha production . Vancomycin also inhibited TNF alpha-mRNA accumulation in LPS-stimulated monocytes, as assessed by fluorescence in situ hybridization (FISH) in cell suspension . The down-regulation of TNF alpha production in LPS-stimulated monocytes may indicate that inhibition of this cytokine release is one of the important therapeutic effects of Vancomycin in sepsis.

New Microbiol, 1997 Jan, 20(1), 35 - 45
Evaluation of the in vitro activity of seven selected antimicrobial agents to be used for the isolation of human intestinal spirochaetes; Calderaro A et al.; This study aimed at making a comparative assessment of the growth of pure cultures of Human Intestinal Spirochaetes (HIS) in a control medium without antibiotics and in media including antibiotics (spectinomycin, rifampin, colistin, polymyxin B, amphotericin B, vancomycin, spiramycin) whose use had been indicated in the literature in connection with the isolation of HIS or animal intestinal spirochaetes . All the strains of HIS tested grew in media to which appropriate concentrations of those drugs had been added giving a final number of CFU/ml +/- 10 times the number of CFU/ml observed in the control medium . These results indicate that a selective medium to be used for the isolation of HIS may include appropriate concentrations of one or more of the following antibiotics: spectinomycin (100-1,000 micrograms/ml), rifampin (10-30 micrograms/ml), vancomycin (6.25 micrograms/ml), colistin (6.25 micrograms/ml), polymyxin B (5 micrograms/ml), spiramycin (1-10 micrograms/ml) and amphotericin B (0.05-35 micrograms/ml).

J Hosp Infect, 1997 Jan, 35(1), 47 - 57
Evaluation of the efficacy of a 3.2% glutaraldehyde product for disinfection of fibreoptic endoscopes with an automatic machine; Akamatsu T et al.; The efficacy of 'Cidex Plus' 3.2% alkaline glutaraldehyde was evaluated for the disinfection of fibreoptic endoscopes . The glutaraldehyde concentration in 'Cidex Plus', stored in an automatic machine (Olympus EW-20), remained higher than 2% (2.21%) even after a total of 102 disinfection cycles during 28 consecutive days . The results of the in-vitro study on antimicrobial activity showed that this alkaline glutaraldehyde product had a greater activity against 20 test organisms, including vegetative bacteria, bacterial spores, mycobacteria, and fungi, than 2% glutaraldehyde alone . The presence of 10 or 30% human serum did not appear to affect the activity of glutaraldehyde adversely . Instrument samples made from a variety of materials such as stainless steel, glass, teflon, etc . were not damaged after 168 h of immersion in alkaline glutaraldehyde, although it contained approximately 1.7 times more glutaraldehyde than 2% glutaraldehyde alone . Based on these results, 3.2% alkaline glutaraldehyde is considered to be a more effective disinfectant for fibreoptic endoscopes, with the use of an automatic machine, than 2% glutaraldehyde.

J Periodontol, 1997 Jan, 68(1), 2 - 6
Oral carriage of Helicobacter pylori: a review; Madinier IM et al.; Helicobacter pylori is a microaerophilic, motile bacterium, especially adapted to life in the human stomach . The presence of H . pylori in the stomach is strongly associated with chronic gastritis and ulcer disease and is a risk factor for gastric cancers . The microorganism may be transmitted orally and has been detected in dental plaque, saliva, and feces, but the hypothesis that oral microflora may be a permanent reservoir of H . pylori is still controversial . A review of the literature suggests that the recovery of H . pylori in the mouth is probably intermittent, associated with gastroesophageal reflux but not with specific oral disease . Nonetheless, the PCR identification of oral H . pylori may become helpful, particularly in cases of gastritis or ulcer relapse after antimicrobial therapy . Eradication of oral H . pylori by local medication or periodontal procedures would rely on the precise identification of its ecological niche . Within family groups, prophylactic methods should be practiced to avoid oral carriage of H . pylori . The risk of iatrogenic transmission during dental care, however, is already circumscribed by standard professional hygiene procedures.

J Toxicol Clin Toxicol, 1997, 35(1), 89 - 92
Effect of charcoal hemoperfusion on clearance of pentamidine isethionate after accidental overdose; Watts RG et al.; BACKGROUND: Pentamidine isethionate is an antimicrobial agent effective in the treatment of Pneumocystis carinii pneumonia, trypanosomiasis and leishmaniasis . Severe and fatal toxicity is reported with pentamidine use . CASE REPORT: A patient received an accidental overdose (40 times the prescribed dose) of intravenous pentamidine due to a pharmacy mixing error . Charcoal hemoperfusion was utilized to attempt to lower the serum concentration of pentamidine and lessen toxicity . RESULTS: Measurement of pentamidine concentrations in the patient's blood demonstrates a beneficial effect of hemoperfusion . CONCLUSIONS: Charcoal hemoperfusion may represent a useful modality in the management of pentamidine isethionate overdosage.

Infect Control Hosp Epidemiol, 1997 Jan, 18(1), 32 - 7
Use of electrophoretic karyotyping in the evaluation of Candida infections in a neonatal intensive-care unit; Vazquez JA et al.; OBJECTIVE: To evaluate a possible common-source outbreak of Candida infections in the neonatal intensive-care unit . Systemic Candida infections increased from 6 to 11 cases (0.71 to 1.34 per 1,000 patient-days) . In addition, Candida parapsilosis infections increased from 1 in 1992 to 10 in 1993 . DESIGN AND SETTING: Tertiary-care, teaching, pediatric institution with a 40-bed neonatal intensive-care unit (NICU) . Clinical characteristics, associated conditions, and antimicrobial therapy were obtained from the medical records of all NICU patients with positive blood cultures for Candida during 1992 and 1993 . Nineteen Candida isolates from 15 infants were studied retrospectively using contour-clamped homogeneous electric-field (CHEF) electrophoresis . RESULTS: CHEF revealed eight karyotypes of C parapsilosis . Five isolates recovered from four patients shared one karyotype . The remaining isolates from seven infants all had distinctly different karyotypes . CONCLUSIONS: The evidence was insufficient to implicate a single source of infection, even though four patients in the same unit had identical strain types . However, identical strains of C parapsilosis were associated geographically, suggesting that nosocomial acquisition of C parapsilosis through indirect patient contact in the NICU was possible . The CHEF technique yields unique patterns that may be used to delineate clinical isolates and to study the molecular epidemiology of candidal infections.

Nurse Pract, 1997 Jan, 22(1), 104, 107 - 8, 113-7; quiz 117-9
Acute bronchitis in adults: commonly diagnosed but poorly defined; Leiner S; This article reviews the existing literature about acute bronchitis, a condition commonly diagnosed but poorly defined . The little epidemiologic research that has been done has failed to identify a microbiologic etiology approximately 60% to 85% of the time . The majority of cases appear to be caused by viruses, but 25% of adults with nonspecific lower respiratory symptoms may actually have pertussis . Mycoplasma pneumoniae and Chlamydia pneumoniae probably play minor roles . Although clinicians frequently prescribe antibiotics to patients they have diagnosed with acute bronchitis, there is little evidence in support . General treatment studies have failed to demonstrate benefit, and the natural history of even potentially curable pathogens is not altered by antimicrobial therapy . Some recent studies suggest that albuterol may be the best treatment choice for acute bronchitis; it can successfully ameliorate symptoms, and does not pose the same public health risk as inappropriate antibiotics do . Erythromycin may occasionally be indicated for patients in frequent contact with small infants not yet immunized against pertussis, but careful surveillance of the child is probably more effective than treating the contagious adult.

Mol Microbiol, 1997 Jan, 23(1), 161 - 8
The leader peptide is essential for the post-translational modification of the DNA-gyrase inhibitor microcin B17; Madison LL et al.; Microcin B17 (MccB17) is a ribosomally encoded DNA-gyrase inhibitor . Ribosomally encoded antibiotics are derived from precursors containing an N-terminal leader, which is removed during maturation, and a C-terminal structural peptide . PreMccB17, the translational product of mcbA, is modified into proMccB17 by the action of three enzymes, McbB, McbC, and McbD . A chromosomally encoded peptidase then converts proMccB17 into MccB17 . The role of McbB, McbC, and McbD is to convert glycine, cysteine, and serine residues present in preMccB17 into four thiazole and four oxazole rings . Using a modification-specific antibody rather than antimicrobial activity, we show that the 26-amino-acid N-terminal leader of preMccB17 is essential for the conversion of preMccB17 into proMccB17 . Neither a preMccB17 peptide lacking the leader nor a preMccB17-beta-galactosidase fusion lacking the leader are post-translationally modified.

Pediatr Infect Dis J, 1997 Jan, 16(1), 147 - 9; discussion 160-2
Risk-benefit experience of ciprofloxacin use in pediatric patients in the United Kingdom; Redmond AO; BACKGROUND: Selection of the most appropriate therapeutic regimen in the management of an infectious disease in a small child or infant is often difficult . Many antimicrobial agents have side effects, thus stressing the importance of risk vs . benefit assessment in the younger patient population . Frequent use of an antimicrobial agent provides the practitioner with critical data regarding the relative rate and intensity of specific adverse events . In addition the benefits of therapy in terms of rapidity of cure, return to normal life and economic outcomes may also be appreciated . Oral ciprofloxacin, although not currently indicated for use in children, has been available to practitioners for > 10 years . OBJECTIVE: Compassionate use experience with ciprofloxacin for the treatment of acute, serious infections (i.e . Pseudomonas species) in pediatrics is described . RESULTS: To date ciprofloxacin has been a very useful agent for the management of serious infections in children and has been associated with little risk of permanent joint damage . CONCLUSION: These data support the use of ciprofloxacin in children in selected situations where the efficacy outweighs any considerable risk, thereby minimizing misuse and overuse of this antimicrobial agent.

Pediatr Infect Dis J, 1997 Jan, 16(1), 140 - 5; discussion 145-6, 160-2
Use of fluoroquinolones for empirical management of febrile neutropenia in pediatric cancer patients; Freifeld A et al.; BACKGROUND: Empiric antibiotic therapy has become a standard of care for the febrile neutropenic patient . Many clinical trials over the previous three decades have demonstrated that a variety of antibiotic combinations and more recently potent antibiotic monotherapies may preserve the patient through the critical time of fever and neutropenia . Recently attempts have been made to identify "low risk" patients who may not require traditional, intensive, hospitalized intravenous antimicrobial therapy . Therefore the need for new treatment alternatives for the febrile neutropenic pediatric cancer patient in particular revolves around the desire for less complex regimens, agents with minimal toxicity and expense and the option of an oral formulation for outpatient management . OBJECTIVE: Fluoroquinolones, especially ciprofloxacin and ofloxacin, are examined in this paper as potential oral alternatives for managing the low risk neutropenic pediatric cancer patient population . Attention must be paid to their antibacterial spectra, however, and in some cases fluoroquinolones should be combined with a second agent for additional Gram-positive coverage . RESULTS: Several studies, including one ongoing trial at the National Cancer Institute, have shown the potential benefits of oral fluoroquinolone therapy among low risk febrile neutropenic patients . Joint complaints in children after ciprofloxacin therapy in the National Cancer Institute trial thus far have been minimal, reversible and felt to be unrelated to ciprofloxacin treatment . CONCLUSION: The use of outpatient therapy, such as the fluoroquinolones, to manage febrile neutropenic episodes must be approached with caution and should be undertaken only in selected low risk patients.

Psychother Psychosom, 1997, 66(1), 3 - 26
Psychological stress, neuroimmunomodulation, and susceptibility to infectious diseases in animals and man: a review; Biondi M et al.; This article reviews research on the role of psychological stress, personality, social support and other psychosocial factors in bacterial, viral and parasitic infections . After 100 years of research on man and animals, psychological stress is considered as a potential cofactor in the pathogenesis of infectious disease . Psychological stress seems able to alter the susceptibility of animals and man to infectious agents, influencing the onset, course and outcome of certain infectious pathologies . Many experiments have identified in neuroimmunomodulation the principal mediator of the alterations associated with conditions of stress . The development of psychoneuroimmunology has fostered in-depth study of the complex relationship between psychosocial factors, the central nervous system, the immune system and infectious disease . Although antimicrobial drugs have certainly remained the basis of all anti-infective therapy, this type of study has already led some authors to propose and experiment protocols of psychological intervention or psychoimmunotherapy in pathologies such as tuberculosis, or herpes simplex virus or human immunodeficiency virus infections . The psychoneuroimmunological approach to infectious diseases will probably grow in importance in the future not only in the setting of research in psychosomatic medicine but also in that of clinical microbiology.

Clin Infect Dis, 1997 Jan, 24 Suppl 1, S169 - 75
Reports on surveillance of antimicrobial resistance in individual countries; Rahal K et al.; In preparation for the meeting of the World Health Organization Working Group on Monitoring and Management of Bacterial Resistance to Antimicrobial Agents, representatives of 10 countries were asked to provide brief reports on the status of surveillance in their countries . Some gave extensive information on the methods used to test susceptibility of nosocomial pathogens to a variety of antibiotics; some described in detail the network of reference laboratories available to hospitals and individual clinicians for monitoring, identifying, and testing infectious agents; others chose to describe how their countries deal with the resistance of the most frequently isolated pathogen to a commonly used drug . The following summary of these reports shows the broad range of problems encountered and solutions undertaken by these 10 countries in dealing with the increasingly alarming problem of bacterial resistance to antimicrobial agents.

Clin Infect Dis, 1997 Jan, 24 Suppl 1, S157 - 68
Surveillance of antimicrobial resistance: the WHONET program; Stelling JM et al.; Genes expressing resistance to each antimicrobial agent emerged after each agent became widely used . More than a hundred such genes now spread selectively through global networks of populations of bacteria in humans or animals treated with those agents . Information to monitor and manage this spread exists in the susceptibility test results of tens of thousands of laboratories around the world . The comparability of those results is uncertain, however, and their storage in paper files or in computer files with diverse codes and formats has made them inaccessible for analysis . The WHONET program puts each laboratory's data into a common code and file format at that laboratory, either by serving as or by translating from its own computer reporting system . It then enables each medical center to analyze its files in ways that help it monitor and manage resistance locally and to merge them with files of other centers for collaborative national or global surveillance of resistance.

Clin Infect Dis, 1997 Jan, 24 Suppl 1, S154 - 6
Strategies for the rational use of antimicrobials; Couper MR; The World Health Organization's (WHO) policy on drugs is based on the essential-drug concept . In order that this policy specifically encompasses antimicrobials, several steps must be taken . Adequate information on the management of infectious diseases should be readily available to prescribers . Continuing education of prescribers, provision of treatment guidelines, and accurate product labeling are important as well . Unethical promotion of antimicrobial products by pharmaceutical companies should be prohibited . Patterns of drug resistance in important pathogens should be monitored . Attempts should be made to monitor drug use in terms of both prescription and consumption . Systematic interchange of information at the national and international levels within defined networks is necessary . The pharmaceutical quality of antimicrobials must be ensured through rigorous registration and enforcement procedures . Collaboration between the pharmaceutical industry and academics must be ongoing . The WHO is prepared to assist countries in developing strategies on the rational use of antimicrobials.

Clin Infect Dis, 1997 Jan, 24 Suppl 1, S148 - 50
The role of fundamental research and biotechnology in finding solutions to the global problem of antibiotic resistance; Hancock RE; Resistance to antibiotics is becoming a major problem worldwide . Exacerbating this situation is the fact that few new antibiotics are in the development pipeline, and, indeed, no novel class of antibiotics has been introduced into medical practice in more than 20 years . It is proposed that the solutions to the problem of antibiotic resistance will be found only through fundamental research that will probably use biotechnology as a tool . A variety of novel approaches being utilized in university laboratories and biotechnology companies are outlined . Two approaches in particular, namely, Synsorbs and recombinant cationic peptide antimicrobials, that have been developed through the Canadian Bacterial Diseases Network, a national research consortium, are discussed.

Clin Infect Dis, 1997 Jan, 24 Suppl 1, S139 - 45
Control of nosocomial antimicrobial-resistant bacteria: a strategic priority for hospitals worldwide; Goldmann DA et al.; The rapid emergence and dissemination of antimicrobial-resistant microorganisms in hospitals worldwide is a problem of crisis dimensions . The root causes of this problem are multifactorial, but the core issues are clear . The emergence of antimicrobial resistance is highly correlated with selective pressure that results from inappropriate use of antimicrobial agents . Dissemination of resistant organisms is facilitated by person-to-person transmission due to inconsistent application of basic infection control practices by hospital personnel . While control strategies exist, the interventions are not likely to be successful unless hospital leaders assume the responsibility for control of antimicrobial resistance . Strategic goals for the control of resistant organisms should be formulated on the basis of multidisciplinary input from hospital personnel . Processes and outcomes relevant to these strategic goals should be measured, and the resultant data should be used to design, implement, and evaluate systematic measures to increase the appropriate use of antimicrobial agents and basic infection control practices . This approach is as relevant to hospitals in countries with limited resources as it is to in fully industrialized countries.

Clin Infect Dis, 1997 Jan, 24 Suppl 1, S2 - 8
The global epidemic nature of antimicrobial resistance and the need to monitor and manage it locally; O'Brien TF; An antimicrobial agent may be used for years before a gene expressing resistance to it emerges in a strain of bacteria somewhere . Progeny of that strain, or of others to which the gene is transferred, may then disseminate preferentially through global networks of bacterial populations on people or animals treated with that agent or with other agents as the gene becomes linked to genes expressing resistance to them . Over 100 resistance genes-varying in their frequency of emergence, vectors, linkages, and pathways-have thus emerged, reemerged, converged, and disseminated irregularly through the world's bacterial ecosystems over the last 60 years to reach infecting strains and block treatment of infection . We may delay emergence by using agents less and retard dissemination by good hygiene, infection control measures, and avoidance of agents that select for resistance genes in contiguous populations . Local monitoring and management of resistance appear essential because of the intricacies of tracing and targeting the problems at each place and because national or global surveillance and strategy develop from local information and understanding.

Mov Disord, 1997 Jan, 12(1), 111 - 4
Ophthalmoplegia and leg myorhythmia in Whipple's disease: report of a case; Rajput AH et al.; Whipple's disease (WD) is a rare disorder that is more common in males than in females . Progressive supranuclear ophthalmoplegia (SNO) in conjunction with oculomasticatory myorhythmia (OMM) or oculofacioskeletal myorhythmia are characteristic movement abnormalities when WD involves the nervous system . Limb myorhythmia without facial or ocular myorhythmia has not been reported in WD . We report such a case who had SNO and leg myorhythmia but no facial or ocular myorhythmia . She had onset of WD at age 28 and 16 years later developed SNO and leg myorhythmia . The neurological manifestations did not respond to antimicrobial agents or to the drugs used for parkinsonism or essential tremor . Valproate produced a remarkable improvement in leg myorhythmia, but the efficacy declined after 3 months . Because WD may infest as a neurological disorder without gastrointestinal symptoms, all SNO cases, with or without OMM, and those with skeletal myorhythmia should be suspected of WD . These patients should be treated vigorously and followed carefully since neurological involvement is the most disabling feature and it has a propensity to relapse.

Am J Vet Res, 1997 Jan, 58(1), 83 - 8
Endotoxemia associated with experimentally induced multiple portosystemic shunts in dogs; Howe LM et al.; OBJECTIVE: To document presence of endotoxin in portal and systemic blood in a model of canine multiple portosystemic shunts (PSS), and compare values in clinically normal dogs, before and after vena caval banding . ANIMALS: 6 control dogs and 10 dogs with dimethylnitrosamine-induced multiple PSS that were subjected to vena caval banding . PROCEDURE: Dimethylnitrosamine was administered orally (2 mg/kg of body weight, twice weekly) to the 10 dogs in the diseased group until multiple PSS developed . Surgery was then performed on all 16 dogs (both groups), and shunts were confirmed in the diseased dogs . Blood was collected from the portal vein, hepatic vein, and caudal vena cava baseline endotoxin determination and aerobic and anaerobic blood culturing . Baseline pressure measurements were taken from the portal venous catheter; then vena caval banding was performed . Blood for endotoxin determinations was taken from all vessels 20, 40, 60, 120, 240, and 360 minutes after banding; portal pressure measurements were taken at the same time as sample acquisition . Blood for culturing was taken from the portal and hepatic venous catheters at 120, 240, and 360 minutes after banding . RESULTS: Dogs in the diseased group had significantly greater overall presence of endotoxin in the portal vein (P < or = 0.0002), hepatic vein (P < or = 0.0001), and caudal vena cava (P < or = 0.0004) than did control dogs . With respect to time, endotoxin presence was greater in the diseased group before banding (P < or = 0.0002), and at 20 (P < or = 0.0008), 40 (P < or = 0.002), 60 (P < or = 0.006), and 120 (P < or = 0.01) minutes after banding . CONCLUSIONS: Endotoxemia is more frequently present in catheterized dogs with dimethylnitrosamine-induced hepatic disease and multiple PSS, compared with clinically normal dogs . Additionally, portal pressure changes induced by vena caval banding did not affect endotoxemia . CLINICAL RELEVANCE: Endotoxemia may exist in dogs with hepatic disease and multiple PSS, and should be kept in mind when formulating treatment (particularly antimicrobial selection) for dogs with suspected endotoxemia.

Cornea, 1997 Jan, 16(1), 94 - 100
In vitro amoebicidal activity of propamidine and pentamidine isethionate against Acanthamoeba species and toxicity to corneal tissues; Alizadeh H et al.; Effective chemotherapy for Acanthamoeba keratitis has been hampered because of the marked resistance of the parasites to a variety of antimicrobial agents . In view of the fact that topical Brolene (propamidine isethionate) and neosporin are currently considered to be the medical treatment of choice in Europe, we sought to determine whether pentamidine may be equally effective, because the drug is more readily available to ophthalmologists in the United States . In this study, we compared the amoebicidal activity of the Brolene (commercial product), propamidine isethionate and pentamidine isethionate (Pentam) in vitro against three different species of Acanthamoeba, and the drugs' corresponding biocompatibility with rabbit corneal epithelial and endothelial cell cultures . The results indicated that there were significant species differences in drug sensitivity . Propamidine (> 1,000 micrograms/ml) was clearly less effective than pentamidine (> 125 micrograms/ml) against A . castellanii, although equivalent potency (> 250 micrograms/ml) was observed against A . polyphaga . On the other hand, propamidine (> 31.25 micrograms/ml) was slightly more effective than pentamidine (> 62.5 micrograms/ml) against A . hatchetti . Both drugs were also relatively nontoxic after short-term contact with cell cultures, even though the highest concentration of pentamidine caused low-grade injury to the superficial epithelium and reversible membrane damage to the endothelium . Steady-state levels of propamidine at effective amoebicidal concentrations, however, were much more toxic than pentamidine, which indicated that the drug has a much lower therapeutic index . Our data suggest that pentamidine may be an effective therapeutic option because of its potency and low toxicity.

Antimicrob Agents Chemother, 1997 Jan, 41(1), 117 - 21
Intraperitoneal injection of tetracyclines protects mice from lethal endotoxemia downregulating inducible nitric oxide synthase in various organs and cytokine and nitrate secretion in blood; Milano S et al.; We have tested whether tetracyclines (TETs) are able to protect mice from lipopolysaccharide (LPS)-induced shock, a cytokine-mediated inflammatory reaction . Mice, injected with a single dose of tetracycline base (TETb; 1.5, 10 and 20 mg/kg of body weight) or doxycycline (DOXY; 1.5 mg/kg), were significantly protected from a lethal intraperitoneal injection of LPS (500 micrograms per mouse) . TETs acted in early events triggered in response to LSP; in fact, they were no longer significantly protective if injected more than 1 h after the injection of endotoxin . LPS-treated mice protected by TETs showed a significant inhibition of tumor necrosis factor alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), and nitrate secretion in the blood, events that were directly related with the survival . In mice treated with TETs a significant decrease of inducible nitric oxide synthase (iNOS) activity was observed in spleen and peritoneal cells compared with that detected in mice treated with LPS alone . Furthermore, TETs were found to inhibit NO synthesis by peritoneal macrophages stimulated in vitro with LPS . On the contrary, TETs were unable to decrease the ability of the macrophages to synthesize IL-1 alpha and TNF-alpha in vitro . These results indicate that TETs are not able to act directly on the synthesis of these cytokines, but they may modulate other pathways that could in turn be responsible for the inhibition of IL-1 alpha and TNF-alpha synthesis . Altogether, these results indicate that TETs are advantageous candidates for the prophylaxis and treatment of septic shock in mice, having both antimicrobial activity and the ability to inhibit endogenous TNF-alpha, IL-1 alpha, and iNOS, hence, exerting, potent anti-inflammatory effects.

Antimicrob Agents Chemother, 1997 Jan, 41(1), 7 - 12
Net effect of inoculum size on antimicrobial action of ampicillin-sulbactam: studies using an in vitro dynamic model; Firsov AA et al.; To examine the predictable effect of inoculum size on the kinetics of the antimicrobial action of ampicillin-sulbactam, five TEM-1 beta-lactamase-producing Escherichia coli strains were studied in an in vitro dynamic model at two different initial inocula (N0S) . All bacteria were exposed to ampicillin-sulbactam in a simulated system reflecting the pharmacokinetic profiles in human tissue after the administration of a single intravenous dose of ampicillin (2 g) plus sulbactam (1 g) . Each strain was studied at low (4.0 to 5.2 log CFU/ml) and high (5.0 to 7.1 log CFU/ml) N0S . Despite pronounced differences in susceptibilities, the patterns of the killing curves observed with a given strain at different N0S were similar . As expected, viable bacterial counts increased with inoculum size . Striking visual contrasts in the respective curves for each organism were reflected by the area under the bacterial count-time curve (AUBC) but not by the difference between the N0 and the lowest bacterial counts (Nmin) at the nadir of the killing curve: the N0-associated changes in the AUBC on average were 75%, versus 2.5% for log N0--logNmin . To examine qualitative differences in antimicrobial effects at different N0S (i.e., the net effect of the inoculum), the difference in the high and low N0S was subtracted from each point on the killing curve obtained at the higher N0 for each strain . These adjusted curves were virtually superimposable on the observed killing curves obtained at the lower N0 . Moreover, by using adjusted data, the AUBC values were similar at the two inocula, although slight (average, 11%) but systematic increases in the AUBC occurred at high N0S . Thus, there was only a weak net effect of inoculum size on the antibacterial effect of ampicillin-sulbactam . Due to similar slopes of the AUBC-log N0 plots, the antibacterial action at different N0S may be easily predicted by an approximate equation; the predicted AUBCs were unbiased and well correlated with the observed AUBCs (r = 0.997) . Compiled data obtained with normalized AUBCs for different strains at different N0S yielded a positive correlation (r = 0.963) between the N0-normalized AUBC and the MIC of ampicillin-sulbactam . The adjustment and normalization procedure described might be a useful tool for revealing the net effect of the inoculum and to predict the inoculum effect if there are no qualitative differences in antimicrobial action at different inocula.

J Am Vet Med Assoc, 1997 Jan 1, 210(1), 87 - 92
Survey of diplomates of the American College of Veterinary Internal Medicine and the American College of Veterinary Surgeons regarding clinical aspects and treatment of endotoxemia in horses; Shuster R et al.; A questionnaire designed to elicit information concerning prevalence, underlying causes, diagnosis, prevention, treatment, and complications of endotoxemia in horses was mailed to diplomates of the American College of Veterinary Internal Medicine and the American College of Veterinary Surgeons who identified themselves as equine practitioners . Gastrointestinal tract compromise, conditions associated with foaling, and grain overload were reported to be the most common clinical conditions that led to endotoxemia . Most of the respondents diagnosed endotoxemia on the basis of the following clinical and laboratory findings: neutropenia, leukopenia, hyperemic mucous membranes, tachycardia, and fever . Treatments used to attempt to prevent development of endotoxemia or to treat horses with endotoxemia included i.v . fluids and administration of broad-spectrum antimicrobials and flunixin meglumine.

Eur J Biochem, 1996 Dec 15, 242(3), 788 - 92
Temporins, antimicrobial peptides from the European red frog Rana temporaria; Simmaco M et al.; A cDNA library from the skin of Rana temporaria has been screened using a cDNA fragment probe that encodes the signal peptide of the precursor of esculentin from the skin secretion of Rana esculenta . With this approach, the cDNAs encoding the precursors of three peptides were isolated . Subsequently, the peptides predicted from the sequence of the cloned cDNAs as well as several structurally related peptides could be isolated from the skin secretion of R . temporaria . These peptides, which were named temporins, have a length of 10-13 residues and show some sequence similarity to hemolytic peptides isolated from Vespa venom {Argiolas, A . & Pisano, J . J . (1984) J . Biol . Chem . 259, 10106-10111} . Natural and synthetic temporins have antibacterial activity against gram-positive bacteria, but they are not hemolytic . Temporins are the smallest antibacterial peptides hitherto found in nature.

Am J Health Syst Pharm, 1996 Dec 15, 53(24), 2963 - 9
Antimicrobials prescribed for otitis media in a pediatric Medicaid population; White LL et al.; Antimicrobial prescribing patterns for Tennessee Medicaid children having their first case of otitis media (OM) in at least nine months were studied . Tennessee Medicaid claims data for patients under 11 years whose first documented OM diagnosis in 1993 occurred in the fourth quarter and who had had an antimicrobial claim filed within two days of diagnosis were studied to determine antimicrobial prescribing patterns . Of 7357 children meeting the study criteria, 70% were less than three years of age, 65% were Caucasian, and 60% had a rural address . Twenty antimicrobials were prescribed . Amoxicillin was prescribed most frequently (53% of the time), followed by cefaclor; all first-line therapies (amoxicillin, ampicillin, erythromycin-sulfisoxazole, and trimethoprim-sulfamethoxazole) accounted for 64% of the prescriptions, but only one fourth of the costs . The highest use of first-line therapy was associated with children under three years of age; children without prior antimicrobial therapy, recent upper respiratory infection (URI), or recent sinusitis; children seen by emergency department physicians; and children seen by urban physicians . Tennessee Medicaid would have saved +68,250 if first-line therapy had been used for all children having their first occurrence of OM in the fourth quarter alone . The savings to the state were estimated at +300,000 or more in 1993 had first-line therapy been used for most first occurrences of OM in all four quarters plus even a small percentage of the estimated 30,000 remaining repeat OM cases . Amoxicillin was prescribed 53% of the time, and all first-line therapies 64% of the time, for children with their first case of OM in at least nine months . In children without recent antimicrobial therapy, URI, or sinusitis, first-line therapy was still used only 72% of the time.

Presse Med, 1996 Dec 14, 25(39), 1923 - 8
{Prophylaxis of infectious endocarditis}; Delahaye F et al.; Prophylaxis of infective endocarditis has been the subject of recommendations from most countries for several years . The basis of the recommendations is the administration of prophylactic antibiotics preceding a procedure at risk for patients with a known at risk cardiac disease . The antimicrobial agent is selected to be active against the main microorganisms causing bacteremia according to the type of at risk procedure . Furthermore, the choice and modalities of antibiotic prophylaxis are adapted to take into account a possible documented allergy to penicillin, the type of predisposing cardiac disease, the number of performed procedures and the requirement for general anesthesia . Future advances should concern the diffusion and application of these recommendations, and the appropriateness of these practices in terms of general cost benefit assessment.

BMJ, 1996 Dec 14, 313(7071), 1541 - 3
Intravenous antimicrobial therapy in the community: underused, inadequately resourced, or irrelevant to health care in Britain?
Nathwani D, Davey P.
The NHS Executive is keen to promote "hospital at home" services in Britain, as part of its philosophy of keeping more care in the community and also to relieve the increasing demand for hospital beds . One such service is the provision of intravenous antimicrobial therapy in the community . Yet, compared with the United States, where home or outpatient intravenous antimicrobial therapy programmes are well developed, experience in Britain and Europe is limited, reflecting a difference in cultural attitudes and healthcare structures between the two continents . Only a few units in Britain currently run home intravenous antimicrobial therapy programmes, and several issues need to be addressed if more treatment is to be provided outside hospital . These include an assessment of the need for community intravenous antibiotic treatment and which patient groups many benefit . The main motive for community intravenous treatment should be better patient care and not simply a reduction in healthcare costs . At present the pace of change is being set by a few clinical enthusiasts and by commercial organisations, whereas the NHS deserves a more organised strategy for purchasing treatment with intravenous antibiotics in the community.

Biochem Biophys Res Commun, 1996 Dec 13, 229(2), 381 - 7
cDNA cloning and characterization of buforin I, an antimicrobial peptide: a cleavage product of histone H2A; Kim HS et al.; A cDNA containing coding information for buforin I, the toad stomach antimicrobial peptide, was identified by PCR . The cloned cDNA encoded a protein of 129 amino acids whose 39-amino-acid N-terminus was identical to buforin I . Nucleotide sequence analysis of the cloned cDNA revealed that it had over 90% amino acid homology with histone H2A, the replication-dependent protein . Both Northern and Southern blot analysis of the toad genome suggested that histone H2A and buforin I were encoded by the same gene . A specific protease responsible for the generation of buforin I from histone H2A was found to be present in the crude extracts of the toad stomach . These results suggest that there exists a specific regulation mechanism which converts the toad histone H2A to the antimicrobial peptide buforin I.

FEBS Lett, 1996 Dec 2, 398(2-3), 146 - 50
Limulus factor D, a 43-kDa protein isolated from horseshoe crab hemocytes, is a serine protease homologue with antimicrobial activity; Kawabata S et al.; A glycoprotein (Mr = 43,000) from horseshoe crab hemocytes with antimicrobial activity against Gram-negative bacteria was purified . The internal peptide sequences coincided exactly with the deduced amino acid sequence of a cDNA clone, designated limulus factor D, which was isolated by screening a hemocyte cDNA library with an anti-human plasminogen antibody . The open reading frame codes for a precursor of factor D of 394 amino acid residues, including an NH2-terminal signal sequence . The COOH-terminal domain of factor D has significant sequence homology with the catalytic domain of mammalian serine proteases, in particular with human tissue plasminogen activator (32% identity), except for the substitution of Ser of the active site triad to Gly . Factor D has a unique NH2-terminal domain with weak sequence homology with part of the mammalian interleukin-6 receptor alpha-chain . Factor D is likely to have an important role in host defense mechanisms.

Clin Oral Implants Res, 1996 Dec, 7(4), 366 - 72
Guided bone regeneration in the treatment of periimplantitis; Persson LG et al.; The objective of the present experiment was to study the soft and hard tissue healing following treatment of experimentally induced periimplantitis . 5 labrador dogs about 1-year old were used . The mandibular right and left 1st molars, 4th and 3rd premolars were removed, titanium fixtures (Branemark System) were installed, and standard abutments were connected in a 2nd stage procedure . After 3 months experimental periimplantitis was induced by the placement of cotton floss ligatures in a submarginal position . 6 weeks later the ligatures were removed . 1 month after ligature removal, an antibiotic regimen was initiated . During a 3-week period, each dog was given tablets of amoxicillin and metronidazole . In the left side of the mandible, buccal and lingual mucoperiosteal flaps were elevated and granulation tissue within the bone craters curetted . The abutments were removed . The exposed outer surfaces and the internal part of the fixtures were carefully cleaned with a detergent (delmopinol HC1) . An e-PTFE membrane was placed over each fixture and adjusted to cover the bone crater . New cover screws were fitted through the membranes to the cleaned fixtures . The implants were submerged and the flaps sutured . In the right side of the mandible no local treatment was performed . The dogs were sacrificed after 4 months and biopsies prepared for histological examination . The findings indicated that treatment of a periimplantitis lesion, including comprehensive systemic antimicrobial therapy and cleaning of submerged implants resulted in (i) the elimination of the inflammatory process in the periimplant tissues and (ii) the establishment of a dense connective tissue capsule in direct contact with the previously exposed surface of the implant system . It was also observed that (iii) new bone was frequently laid down on the pristine cover screws.

Clin Oral Implants Res, 1996 Dec, 7(4), 320 - 8
The effect of antimicrobial therapy on periimplantitis lesions . An experimental study in the dog; Ericsson I et al.; The objective of the present study was to evaluate the effect of systemic antibiotics and local debridement in the treatment of experimentally induced periimplantitis lesions . 5 Labrador dogs, and about 1-year old, were included in the study . In order to establish bilateral recipient sites for implants the mandibular right and left 1st molars, 4th and 3rd premolars were removed . 6 titanium fixtures (Branemark System Nobelpharma AB, Goteborg, Sweden) were installed and standard abutments were connected 3 months after fixture installation . Cotton floss ligatures were placed in a submarginal position around the neck of the abutments and the animals were placed on a diet which allowed plaque accumulation . After 6-8 weeks, when the tissue destruction amounted to about 20% of the fixture length, the ligatures were removed . 1 month after ligature removal, an antibiotic regimen (amoxicillin and metronidazole) was initiated and maintained for 3 weeks . In the left side of the mandible, buccal and lingual mucoperiosteal flaps were elevated, the granulation tissue within the bone craters adjacent to the implants was curetted, and the abutments were removed . The exposed outer surface, the internal part of the fixtures, as well as the abutments were treated with a detergent, delmopinol . The cleaned abutments were autoclaved, and connected to the clean fixtures . The mucoperiosteal flaps were replaced to their original position, adapted to the abutments and sutured . A careful plaque control program was initiated for the left jaw quadrants . In the right side of the mandible no local treatment was given to the fixtures and the abutments following ligature removal . Furthermore, no plaque control was provided to the implant segments in the right jaws . After 4 months of healing block biopsies including one implant with adjacent hard and soft tissue were harvested and prepared for light microscopy . It was observed that systemic antimicrobial therapy, combined with implant cleaning, curettage of the bone defect and regular plaque control resulted in (i) resolution of the periimplantitis lesion, (ii) a significant recession of the marginal periimplant mucosa, and (iii) a minor additional apical shift of the base of the bone defect . In the untreated sites the plaque associated infiltrate remained and was in several sites examined in contact with the adjacent bone tissue.

Arch Latinoam Nutr, 1996 Dec, 44(4 Suppl 1), 26S - 30S
Protein proteinase inhibitors in legume seeds--overview; Birk Y; Protein proteinase inhibitors are widely distributed in plant seeds, particularly in legumes . The specificity and potency of inhibition depend on defined inhibitory sites and on the animal species of the target proteinase . Feeding experiments on diets containing isolated soybean trypsin inhibitors (the Kunitz soybean trypsin inhibitor STI and the Bowman-Birk trypsinchymotrypsin inhibitor BBI) caused insignificant growth depression in rats and chicks, but induced enlargement of the pancreas in rats, chicks and mice but not in pigs, dogs, calves, monkeys and presumably humans . The trypsin-inhibitory site has been responsible for induction of the pancreatic enlargement . The trypsin-chymotrypsin inhibitors from soybeans and from chickpeas inhibit insect midgut proteinases, supporting the hypothesis that proteinase inhibitors comprise a built-in defense mechanism of the seed against insects . Findings on the involvement of proteinase inhibitors, such as BBI, in prevention of tumorigenesis suggest a possible positive contribution of the inhibitors to the nutritional value of legume seeds . BBI is also an effective inhibitor of nephrotoxicity induced by the antibiotic gentamicin . BBI does not cause side effects and does affect the antimicrobial activity . The in vitro effects of proteinase inhibitors on animals should be interpreted with caution when related to humans.

Rinsho Shinkeigaku, 1996 Dec, 36(12), 1324 - 5
{A possibility of therapeutic trial with tetrahydrobiopterin, which was suggested by the administration of sulfamethoxazole-trimethoprim}; Sakai T; In 1988, Mello and Abbott incidentally found an effectiveness of sulfamethoxazole-trimethoprim (S-T), an antimicrobial combination which was prescribed for the treatment of dysuria, on neurologic dysfunction in a patient with MJD . However, the mechanism by which S-T exerts its pharmacological actions on the central nervous system was not delineated . The purposes of the present studies are to investigate whether or not S-T is effective in alleviating the neurological symptoms and signs in MJD, and then to clarify the mechanism how S-T exerts its pharmacological actions on the neurological deficits, and finally to test the effectiveness of tetrahydrobiopterin (BH4) as a treatment . (1) Sulfamethoxazole-trimethoprim double-blind, placebo-controlled, crossover trial . The clinical results were as follows; mild improvements of hyperreflexia of knee jerks and of rigospasticity of the legs during S-T treatment period . In addition, S-T significantly reduced the times of 8 motor activities on the timed tests . The biochemical results showed that basal levels of all biopterins and homovanillic acid in the cerebrospinal fluid(CSF) were reduced to less than half the levels of controls with other neurological diseases . After S-T treatment, total and oxidized form of biopterins in the CSF increased significantly . Therefore, S-T may be effective to neurologic deficits through its mechanism of increasing the level of brain biopterins in MJD . The present study prompted us to investigate whether or not tetrahydrobiopterin (BH4) is useful as a therapeutic strategy . (2) Tetrahydrobiopterin double-blind, placebo-controlled, crossover trial . The results were as follows: 1 . Questionnaire . Choking was mildly improved on the first tetrahydrobiopterin (BH4) treatment day, though not significant (p < 0.10) . 2 . Neurologic examinations . Hyperreflexia of the knee jerks was mildly improved on the 10th day of BH4 treatment, but it was not significant (p < 0.10) . 3 . Timed tests . Significant improvements were seen on several timed tests . These results, though preliminary, implied that BH4 showed mild improvements of neurologic deficits.

Antimicrob Agents Chemother, 1996 Dec, 40(12), 2859 - 64
Stenotrophomonas maltophilia: emergence of multidrug-resistant strains during therapy and in an in vitro pharmacodynamic chamber model; Garrison MW et al.; Emergence of Stenotrophomonas maltophilia as a nosocomial pathogen is becoming increasingly apparent . Pleiotropic resistance characterizes S . maltophilia . Furthermore, a slow growth rate and an increased mutation rate generate discordance between in vitro susceptibility testing and clinical outcome . Despite original susceptibility, drug-resistant strains of S . maltophilia are often recovered from patients receiving beta-lactams, quinolones, or aminoglycosides . Given the disparity among various in vitro susceptibility methods, this study incorporated a unique pharmacodynamic model to more accurately characterize the bacterial time-kill curves and mutation rates of four clinical isolates of S . maltophilia following exposure to simulated multidose regimens of ceftazidime, ciprofloxacin, gentamicin, and ticarcillin-clavulanate . Time-kill data demonstrated regrowth of S . maltophilia with all four agents . With the exception of ticarcillin-clavulanate, viable bacterial counts at the end of 24 h exceeded the starting inoculum . Ciprofloxacin only reduced bacterial counts by less than 1.0 log prior to rapid bacterial regrowth . Resistant mutant strains, identical to their parent strain by pulsed-field gel electrophoresis, were observed following exposure to each class of antibiotic . Mutant strains also had distinct susceptibility patterns . These data are consistent with previous reports which suggest that S . maltophilia, despite susceptibility data that imply that the organism is sensitive, develops multiple forms of resistance quickly and against several classes of antimicrobial agents . Standard in vitro susceptibility methods are not completely reliable for detecting resistant S . maltophilia strains; and therefore, interpretation of these results should be done with caution . In vivo studies are needed to determine optimal therapy against S . maltophilia infections.

Antimicrob Agents Chemother, 1996 Dec, 40(12), 2732 - 6
Comparative study of once-weekly azithromycin and once-daily amoxicillin treatments in prevention of recurrent acute otitis media in children; Marchisio P et al.; Continuous chemoprophylaxis is effective in the prevention of new episodes of acute otitis media (AOM) in otitis-prone children, but compliance can be a problem and thus efficacy can be decreased . Intermittent chemoprophylaxis has so far shown conflicting results . Azithromycin, which has a peculiar pharmacokinetics, resulting, even after a single dose, in persistently elevated concentrations in respiratory tissues, could permit a periodic administration with higher compliance . We compared a 6-month course of once-weekly azithromycin (5 or 10 mg/kg of body weight) with that of once-daily amoxicillin (20 mg/kg) in a single-blind, randomized study of prophylaxis for recurrent AOM in 159 children aged 6 months to 5 years with at least three episodes of AOM in the preceding 6 months . In the amoxicillin group, 23 (31.1%) of 74 children developed 29 episodes of AOM, while in the 10-mg/kg azithromycin group, 11 (14.9%) of 74 children experienced 15 episodes . The 5-mg/kg/week azithromycin trial was prematurely interrupted after nine cases, due to the high occurrence rate of AOM (55.5%) . During the 6-month prophylaxis period, the proportion of children with middle ear effusion declined similarly in both groups . No substantial modification of the nasopharyngeal flora was noted at the end of prophylaxis in both antimicrobial groups . In the 6-month-postprophylaxis follow-up period, about 40% of children in both groups again developed AOM . Azithromycin at 10 mg/kg once weekly can be regarded as a valid alternative to once-daily low-dose amoxicillin for the prophylaxis of AOM . Although in the present study no microbiological drawback was noted, accurate selection of children eligible for prophylaxis is mandatory to avoid the risk of emergence of resistant strains.

Genet Anal, 1996 Dec, 13(6), 139 - 45
Sequential amplification of cloned DNA as tandem multimers using class-IIS restriction enzymes; Lee JH et al.; In order to make high-copy-number multimers of DNA fragments in a tandem unit, two different gene amplification vectors (pSK9 and pBBS1) were developed . Two identical class-IIS restriction enzyme sites (BspMI for pSK9 and BbsI for pBBSI) were inversely oriented in each vector with the same cut site, creating asymmetric and complementary cohesive ends (5'-CCCC and 5'-GGGG) . Multimers were made by: (i) cloning a target DNA into the class-IIS restriction enzyme cut site of each vector; (ii) excision of the monomeric insert by digestion with the class-IIS restriction enzyme; (iii) isolation of the fragments; (iv) self-ligation of the fragments; (v) cloning into the original vector digested with the class-IIS restriction enzyme; and (vi) repeating steps (i) through (v) to generate higher-order multimers . Various-sized multimers of a 93-bp DNA fragment encoding magainin, an antimicrobial peptide, were obtained with the gene amplification vector, pBBS1 . Larger multimers, up to about 108 copies, were constructed from the monomer by the sequential amplification procedure . Of six different Escherichia coli hosts examined for the stability of multimers, the multimers were the most stable in E . coli D1210 . The gene amplification vector system described here is very efficient and can be applied in the construction of tandem multimers of any kind of DNA, as long as the cloned DNA does not contain the cut site of the class-IIS restriction enzyme to be utilized.

Epidemiol Mikrobiol Imunol, 1996 Dec, 45(4), 148 - 52
{Antimicrobial and physico-chemical aspects of antiseptics based on the iodine-polyvinylpyrrolidone complex}; Hartmanova M et al.; Antimicrobial efficacy of modern antiseptics-iodophores based on the iodine-polyvinylpyrrolidone complex using standard suspension tests and their modifications and screening methods with bacteriophage phi X 174 was studied . The study was completed with molecular modelling of structural and spatial distribution of these substances with the help of computer programme HyperChem 2.0 . Using calculation methods of quantum and molecular mechanics the conditions and results of the antimicrobial efficacy of these antiseptics were described.

J Emerg Nurs, 1996 Dec, 22(6), 570 - 6; quiz 576-8
The treatment of minor burns in rural Alabama emergency departments; Hill MG et al.; OBJECTIVE: The purposes of this descriptive survey were to determine the treatments for minor burns in rural Alabama emergency departments, to assess how closely those treatments correspond with recommendations for burn therapy noted in the literature, and to identify specific deficits in the burn research literature . DESIGN: A descriptive survey consisting of open-ended questions was used to gather data on current practices for treating outpatient burn wounds . METHODS: A researcher-developed questionnaire organized into seven categories of burn care was pilot-tested in an urban burn center; the questionnaire was then mailed to 96 rural Alabama hospitals, addressed to the ED nurse manager . The seven categories--initial cooling, analgesics, cleansing agents, topical antimicrobial therapy, wound dressings, blister debridement, and referrals--were identified from both major and minor burn care literature, because little research has been published about minor burns . Simple frequencies were used to analyze results from the 20% (n = 21) of the sample that responded . RESULTS: Seven categories of burn care are common to all respondent facilities, with wide variation in the details . Most practices proceed logically from the treatments recommended for major burn care, with a few notable and potentially dangerous exceptions, but there is no definitive research available to guide the clinician in the care of outpatient burns . Research questions were generated that can provide direction for measurement of outcomes in the care of minor burns treated on an outpatient basis.

Farmaco, 1996 Dec, 51(12), 825 - 7
Synthesis of some 1-(2-arylvinyl)-3-arylpyrazino{1,2-a}benzimidazole derivatives and their antimicrobial activities; Demirayak S et al.; Some 1-(2-arylvinyl)-3-arylhyrazino{1,2-a}benzimidazole derivatives were synthesized, their structures were elucidated, and their antibacterial and antifungal activities were examined . None of the compounds proved to be sufficiently active.

Farmaco, 1996 Dec, 51(12), 811 - 4
Synthesis and antimicrobial activity of some 1,4-disubstituted thiosemicarbazide and 2,5-disubstituted 1,3,4-thiadiazole derivatives; Rollas S et al.; Various new 1,4-disubstituted thiosemicarbazide and 2,5-disubstituted-1,3,4-thiadiazole derivatives were synthesized and evaluated for their in vitro antimicrobial activity . The structure of compounds was confirmed by elemental analyses and spectroscopic techniques . Some of the synthesized compounds were found to be active against C . Albicans.

Ann Trop Med Parasitol, 1996 Dec, 90(6), 603 - 15
Efficacy of 101 antimicrobials and other agents on the development of Cryptosporidium parvum in vitro; Woods KM et al.; An in-situ ELISA was used as a primary screen to test the effects of 101 antimicrobials and other agents on the development of Cryptosporidium parvum in vitro . Over 40 of the compounds displayed some form of anticryptosporidial activity, and dose-response curves were generated for 40 of these . The in-situ ELISA makes a highly effective primary, pharmaceutical screen for C parvum, to be used prior to more detailed microscopical, toxicological or in-vivo assays.

Nippon Geka Gakkai Zasshi, 1996 Dec, 97(12), 1048 - 53
{The pathophysiology and treatment of severe intra-abdominal abscess}; Shinagawa N; Formation of an abscess within the peritoneal cavity is a dynamic process, representing the body's success at localizing the contamination but its ultimate failure to completely destroy the bacteria and neutralize their toxic products . In most instances, the origin of the microbial insult is from bacteria which colonize the intestinal lumen . The therapeutic means are prompt surgical drainage and appropriately administered antimicrobial agents . Surgical drainage of abscess are accompanied by either (1) an extraperitoneal approach, (2) an intra-abdominal exploration, or (3) ultrasound-guided needle aspiration of the abscess . Choice of antimicrobial agents is frequently based upon prediction of pathogens from normal flora of bowel contents contaminating a normally sterile area, or from knowledge of pathogens expected in certain conditions, rather than on results of cultures and susceptibility tests . This selection frequently calls for the choice of agents effective against multiple organisms . Patients with prolonged septic courses die from a combination of the infection itself and the malnutrition resulting from the associated hypercatabolism and starvation . Nutritional therapy also of clinical importance in halting the progression toward a fatal outcome.

Jpn J Antibiot, 1996 Dec, 49(12), 1049 - 61
{Comparison between monotherapy with imipenem/cilastatin sodium (IPM/CS) and combinations of IPM/CS and other drugs for treating bacterial infections in patients with hematopoietic disorders}; Sawae Y et al.; One hundred and nine patients with infections concurrent with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS) either alone (IPM/CS monotherapy) or in combination with other antimicrobial drugs (IPM/CS combination therapy) . The following results were obtained . 1 . One hundred and nine patients were allocated at random to two groups: 53 patients to IPM/CS monotherapy and 56 patients to IPM/CS combination therapy . Fourteen patients (6 and 8 in the 2 groups, respectively) were excluded from the clinical evaluation . There were not significant differences between the two groups with respect to the background . 2 . The efficacy rates of the 2 treatments against bacterial infections were as follows: in the IPM/CS monotherapy group, 62.5% in 8 patients with sepsis, 75.0% in 23 patients with fever of undetermined origin (FUO), 50.0% in 10 patients with pneumonia, and 68.3% in the 47 patients, and in the IPM/CS combination group, 85.7% in 7 patients with sepsis, 63.6% in 24 patients with FUO, 50.5% in 8 patients with pneumonia, and 67.4% in the 48 patients . The differences between the two groups were not significant . 3 . Among the drugs used in combination with IPM/CS, antibiotics other than penicillins, cephalosporins, and aminoglycosides were used in 12 patients and a high efficacy rate of 91.7% was obtained . 4 . Bacteriologically, 19 and 17 strains were isolated from the IPM/CS monotherapy and combination therapy groups respectively, and the eradication rates were 100% and 88.9% respectively . 5 . Side effects were noted in 2 patients in the IPM/CS monotherapy group and 7 in the combination therapy group, but all of these resolved after discontinuation or completion of the treatment . The efficacies against severe bacterial infections in the presence of hematopoietic disorders were not different between IPM/CS alone and IPM/CS in combination with other antibiotics . Adverse reactions were uncommon with the monotherapy.

Eur J Clin Microbiol Infect Dis, 1996 Dec, 15(12), 937 - 40
In vitro activity of omeprazole in combination with several antimicrobial agents against clinical isolates of Helicobacter pylori; Alarcon T et al.; An agar dilution checkerboard method was used to evaluate the in vitro activity of omeprazole combined with clarithromycin, amoxicillin, and ceftibuten, respectively, against clinical isolates of Helicobacter pylori . Mueller-Hinton agar plus 5% horse blood, an inoculum of 10(6) cfu/ml, and incubation of 72 h in a CO2 atmosphere were used . With the omeprazole and clarithromycin combination, synergism was observed in 51.5% and partial synergism in 39.3% of 33 strains; with omeprazole and amoxicillin, synergism was observed in 3% and partial synergism in 60.6% of 33 strains; and with omeprazole and ceftibuten, synergism was observed in 33.3% and partial synergism in 50% of 24 strains . Antagonism between omeprazole and each antibiotic was exhibited in 0%, 6.1%, and 4.1% of these groups of strains, respectively . Of the antibiotic combinations tested, omeprazole plus clarithromycin exhibited synergism (partial or total) in the highest percentage of strains.

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