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 r