Neuroreport, 1998 Dec 1, 9(17), 3893 - 5 Are aminoglycoside antibiotics excitotoxic? Sha SH, Schacht J. Guinea pigs received gentamicin to induce a profound hearing loss (61 dB auditory threshold shift at 18 kHz) . Concomitant administration of maleic or tartaric acid dissolved in dimethyl sulfoxide (DMSO) significantly reduced the threshold shift to < 40 dB . The results have several important implications . First, they support the hypothesis of a free-radical mechanism of gentamicin toxicity since the protective compounds are metal chelators and scavengers . Second, they caution against these and similar chemicals, commonly found in drug preparations, as vehicles in tests of aminoglycoside toxicity . For example, a recent study by others describing attenuation of aminoglycoside ototoxicity by NMDA antagonists may have been influenced by the presence of maleate, tartrate and DMSO . Third, they suggest simple antioxidants as a potentially efficient and inexpensive clinical prophylaxis of aminoglycoside-induced hearing loss. Arch Pharm Res, 1998 Apr, 21(2), 187 - 92 Synthesis of the 7,8-dihydro-7-deazapurine derivatives and their antibiotic activity; Sung SY et al.; The cis- and trans-diastereomers of the 7,8-dihydro-7-deazapurine derivatives were synthesized from the corresponding diastereomers of 4-trans-cyano-2-methyl-3-phenyl-5-oxopyrrolidine (5), which were reduced from the 2-cis- and 2-trans-diastereomers of 4-trans-cyano-2-hydroxymethyl-3-phenyl-5-oxopyrrolidine (2) via tosylation, iodination and following elimination, respectively . The prepared cis- and trans-diastereomers of 6-amino-2-mercapto-8-methyl-7-phenyl-7,8-dihydro-7(9H)-deazapurine (8) were transferred to the corresponding 2-methylthio-diastereomers 9 and following desulfurization with Raney-nickel leaded to the cis- and trans-diastereomers of 6-amino-8-methyl-7-phenyl-7,8-dihydro-7(9H)-deazapurine (10), respectively . The synthesized 7-deazapurine derivatives were tested for their antibiotic activity by the serial two-fold dilution method. Bioorg Med Chem Lett, 1998 Dec 1, 8(23), 3331 - 4 Synthesis and morphological reversion activity on srctsNRK cells of pyrimidinylpropanamide antibiotics, sparsomycin, sparoxomycin A1, A2, and their analogues; Nakajima N et al.; Three pyrimidinylpropanamide antibiotics sparsomycin (1), sparoxomycins A1, A2 (2, 3), and also six analogues (4-9) have been synthesized by employing asymmetric sulfide oxidation conditions as a key step . Sparsomycin (1) and its alkyl analogues (5-7) showed higher morphological reversion activities on srctsNRK cells than 2 and 3. Bioorg Med Chem Lett, 1998 Jul 7, 8(13), 1725 - 8 A free energy calculation can be used to predict K(+)-binding constants for new macrotetrolide antibiotics; Lee JW et al.; A free energy calculation technique was used to predict K+ binding constants for new macrotetrolides . The technique was validated by successfully predicting affinity constants for known, naturally produced, macrotetrolides. Bioorg Med Chem Lett, 1998 Feb 3, 8(3), 255 - 6 A practical synthesis of 3-{(1R)-1-t-butyldimethylsilyloxyethyl}-4-{(2R)- 4-halo-3-oxo-2-butyl}azetidinone, a versatile intermediate for carbapenem antibiotics; Yang C et al.; A key intermediate for 2-(functionalized-methyl)-1-beta-methylcarbapenems, 3-{(1R)-1-t-butyldimethylsilyloxyethyl}-4-{(2R)- 4-halo-3-oxo-2-butyl}azetidinone, was prepared efficiently from a commercially available carboxylic acid in 3 steps. Bioorg Med Chem Lett, 1998 Mar 3, 8(5), 535 - 8 DNA cleavage by 7-methylbenzopentathiepin: a simple analog of the antitumor antibiotic varacin; Chatterji T et al.; The compound 7-methylbenzopentathiepin, a simple analog of the benzopentathiepin antitumor antibiotic varacin, was shown to be a potent thiol-dependent DNA-cleaving agent . Biological experiments previously suggested that DNA cleavage might play a role in the cytotoxicity of varacin; however, this is the first direct evidence that benzopentathiepins can cause DNA strand breaks under physiologically relevant conditions. Arch Microbiol, 1998 Dec, 171(1), 50 - 8 Inhibition of colicin synthesis by the antibiotic globomycin; Cavard D; The antibiotic globomycin, an inhibitor of LspA (the lipoprotein signal peptidase), inhibited synthesis of colicin by Escherichia coli cells grown in rich medium . This inhibition was stronger in cells with mutation(s) within either the colicin operon, which is located on a plasmid, or the host chromosome . This phenotype was called Gbc (globomycin blocks colicin synthesis) . The Gbc phenotype was affected by growth conditions since it was partially or totally suppressed in cells subjected to high temperatures, treated with sodium azide, or grown in minimal medium . The Gbc phenotype observed with colicin-A-producing cells was more severe in strains carrying plasmids with a deletion within caa (the first gene of the colicin A operon), which encodes colicin A, than in cells with the wild-type caa gene . The Gbc phenotype was alleviated by a null mutation in the degP gene encoding the DegP/HtrA protease, abolished by a null mutation in the lpp gene encoding the murein-lipoprotein, and enhanced by a mutation in the pldA gene encoding the outer membrane phospholipase A . Transcription of the colicin A operon was blocked in cells exhibiting the Gbc phenotype as evidenced by rifampicin treatment of induced cells . This phenotype suggests that either a lipoprotein or a protein involved in lipoprotein metabolism might be involved in the regulation of the expression of the colicin operons and that the colicin A structural gene might play a role in the regulation of transcription of the colicin A operon. J Gastroenterol Hepatol, 1998 Nov, 13(11), 1115 - 8 Antibiotic-associated haemorrhagic colitis; Miller AM et al.; Antibiotic-associated haemorrhagic colitis is an uncommon cause of bloody diarrhoea in patients taking penicillin or penicillin-related antibiotics . Symptoms of abdominal pain and bloody diarrhoea occur within 1 week of antibiotic use and resolve without specific therapy within days of discontinuing the offending antibiotic . There is an apparent increased incidence of the disease in patients of Oriental ethnicity . The pathogenesis is unknown . We present two cases of haemorrhagic colitis in patients taking penicillin-related antibiotics who presented within 4 months of each other . One of the patients was being treated for Helicobacter pylori infection . The published literature is reviewed with particular emphasis on the histology and pathogenesis of the condition. Clin Infect Dis, 1998 Dec, 27(6), 1415 - 21 Medicare coverage of outpatient ambulatory intravenous antibiotic therapy: a program that pays for itself; Tice AD et al.; A number of studies have documented the safety, efficacy, and cost-effectiveness of outpatient intravenous (i.v.) antibiotic therapy for patients with infectious diseases . Nevertheless, Medicare policy prohibiting coverage of outpatient, self-administered drugs has severely limited access of Medicare patients to ambulatory i.v . therapy, thus forcing them to rely on more costly, impatient hospital care . To test the hypothesis that a new Medicare benefit providing coverage for ambulatory i.v . antibiotic therapy could significantly reduce the program's expenditures for the treatment of infectious diseases (including pneumonia, osteomyelitis, cellulitis, and endocarditis), a cost model was constructed with use of patient care information from the clinical literature as well as clinical experts, Medicare data, and other medical claims databases . The model shows cumulative 5-year savings of nearly $1.5 billion associated with the new Medicare benefit . Policy makers should consider implementing such a benefit. Minerva Stomatol, 1998 Oct, 47(10), 553 - 7 {A biocompatibility study and the effects of slow-release antibiotic materials in the treatment of periodontal disease . I . The biocompatibility of cellulose acetate charged with 25% tetracycline hydrochloride . A clinical and scanning microscopic study of a case}; Aronna G et al.; A clinical and microscopical (SEM) investigation has been carried out on the biocompatibility of cellulose acetate fiber tetracycline with 25% of tetracycline hydrochloride (Actisite R) . A subject with advanced periodontal disease was selected and a pocket of 8 mm of PD was chosen . A segment of fiber was inserted into the pocket for 8 days . After removal, PD and GI clinical parameters were detected and the fiber removed was analyzed at the scanning electronic microscope . The results showed clinical signs of inflammation after removal of fiber . SEM analysis showed macrophagic reaction, a typical sign of inflammatory response to material . The study suggests the need of more biocompatible materials, easier to use as delivery system of antibiotics in the treatment of periodontal disease. J Fam Pract, 1998 Dec, 47(6), 453 - 60 Are antibiotics effective treatment for acute bronchitis? A meta-analysis; Smucny JJ et al.; BACKGROUND: Most clinicians prescribe antibiotics for acute bronchitis in spite of recommendations against this practice . Because the results of individual clinical trials have been mixed, we conducted a meta-analysis to determine whether antibiotics are effective treatment for acute bronchitis . METHODS: We conducted a comprehensive search to identify all trials in which patients who had a diagnosis of acute bronchitis were randomly assigned to treatment with an antibiotic or placebo . Patient-oriented outcomes of importance that were reported in at least 3 studies were quantitatively summarized . RESULTS: Nine studies met the inclusion criteria, but not all trials provided data for each outcome . Patients given antibiotics were less likely to have a cough (relative risk {RR} = 0.69; 95% confidence interval {CI}, 0.49 -0.98) and be considered unimproved (RR = 0.51; 95% CI, 0.30-0.88) at a follow-up visit; but they were not less likely to have a productive cough (RR = 0.79; 95% CI, 0.60-1.03), activity limitations (RR = 0.59; 95% CI, 0.24-1.44), or feel ill (RR = 0.70; 95% CI, 0.31-1.58) . Antibiotic-treated patients had a slightly shorter duration of productive cough (weighted mean difference {WMD} = -0.56 days; 95% CI, -1.09 to -0.04), but not of overall cough (WMD = -0.94; 95% CI, -2.08 to 0.21) or activity limitations (WMD = -0.49; 95% CI, -1.07 to 0.10) . Patients treated with antibiotics did not report significantly more adverse effects (RR = 1.47; 95% CI, 0.82-2.65) . CONCLUSIONS: Antibiotics may be modestly effective for a minority of patients with acute bronchitis . It is not clear which patient subgroups might benefit, and the failure of some studies to report negative findings may have resulted in overestimates of the benefits of antibiotics . Antibiotics are not necessary for every patient with acute bronchitis. Br J Pharmacol, 1998 Nov, 125(6), 1150 - 7 The mechanism by which aminoglycoside antibiotics cause vasodilation of canine cerebral arteries; Gergawy M et al.; The effects of aminoglycoside antibiotics were examined in canine cerebral arteries and in cultured cerebrovascular smooth muscle cells stimulated with oxyhemoglobin (OxyHb), a blood constituent which has been implicated in the pathogenesis of cerebrovascular spasm . In cerebral arterial rings precontracted with OxyHb (10 microM), the aminoglycosides caused a concentration-dependent decrease in isometric tension . The EC50s for the relaxation were 0.46+/-0.1 mM (n=6), 0.53+/-0.08 mM (n=12), 1.6+/-0.3 mM (n=7) and 3.9+/-0.5 mM (n=5) for neomycin, gentamicin, streptomycin and kanamycin, respectively . This order of potency corresponds approximately to the number of positive charges in the molecules . The aminoglycosides also inhibited the contractions to prostaglandin F2alpha (1 microM) and depolarizing concentrations of potassium chloride (60 mM) . The order of potency was neomycin > gentamicin > streptomycin > kanamycin . The relaxation was maintained in vascular preparations denuded of endothelium . Neomycin (5 mM) abolished the Ca2+-independent contraction to PGF2alpha . In Fura-2-loaded cerebrovascular smooth muscle cells, OxyHb (1 microM) significantly enhanced the concentration of intracellular calcium ({Ca2+}i) by 330% . The administration of neomycin, gentamicin, kanamycin and streptomycin in concentrations corresponding to the EC50 from contractility studies, reduced the effects of OxyHb on {Ca2+}i by about 50% to 221+/-35 nM (n=7), 270+/-31 nM (n=7), 229+/-33 nM (n = 6) and 240+/-6 nM (n = 5), respectively . These results suggests that the effects of the aminoglycosides on the OxyHb-induced contraction and the long-term increase in {Ca2+}i, may arise from several effects, including inhibition of PLC, protection of calcium extrusion mechanisms, and interference with the process of {Ca2+}i accumulation. Radiat Med, 1998 Sep-Oct, 16(5), 347 - 51 In-111 labeled leukocyte scintigraphy in patients with suspected inflammation after failed antibiotic therapy; Nasu R et al.; In-111 labeled leukocyte scintigraphy (In-111 WBC scan) was performed in 16 patients with inflammation suspected on the basis of laboratory findings, symptoms, and diagnostic imaging, but who had failed antibiotic therapy . In-111 WBC scans revealed an abnormal focus of radiotracer activity (positive scans) in five of 16 patients . No correlation was found between the peripheral WBC count and accumulation of In-111 WBC . Inflammatory disease suspected on the basis of the CRP level should be considered when In-111 WBC scanning results in negative findings . Our results indicated that In-111 WBC scanning has low sensitivity after antibiotic therapy . Selection of patients on the basis of persistent elevation of CRP may be valuable. Eur J Clin Pharmacol, 1998 Oct, 54(8), 653 - 7 Intra-urban variation of antibiotic utilization in children: influence of socio-economic factors; Henricson K et al.; OBJECTIVE: The aim of this study was to investigate the intra-urban variation of antibiotic utilization in children in Malmo and to evaluate the influence of socio-economic factors on this variation . METHODS: In an ecological analysis, the variations in antibiotic utilization in children, expressed as defined daily dose (DDD) or as the number of prescriptions per 1000 inhabitants per day, were compared with variations in socio-economic and demographic factors in the 17 administrative districts of the Swedish city of Malmo (235000 inhabitants) . RESULTS: There were large between-area differences in antibiotic utilization, especially in children aged 0-6 years . Socio-economic factors reflecting a privileged situation correlated positively with antibiotic utilization . Thus, in districts with a high median family income and a high employment rate, the utilization of antibiotics was higher than in other districts . Conversely, in districts with a high proportion of blue-collar workers, people with foreign backgrounds and recipients of social benefit, antibiotic utilization was comparatively low . In contrast, the utilization of penicillin V relative to other antibiotics showed an opposite pattern, including positive correlations with the proportion of social benefit, immigrants and blue-collar workers and a negative correlation with employment rate . Conversely, the utilization of macrolides in relation to other antibiotics in children aged 0-6 years was highest in districts inhabited by those who were socio-economically privileged . INTERPRETATION: The findings suggest that utilization of antibiotics in children may vary considerably within a city, that it may increase with the degree of parental affluence, and that such affluence may reduce the utilization of penicillin V relative to other antibiotics. Acta Neurochir (Wien), 1998, 140(10), 1095 - 6 Systemic antibiotic therapy on multiple intracerebral abscesses of unknown origin; Sommer F et al.; A 68-year old patient presented with increasing right-sided weakness, dysarthria, pyrexia and a deteriorating general condition . CT and MRI showed about 20 round hyperdense lesions with peripheral enhancement of contrast material up to 1.5 cm in diameter . Antibiotic triple-therapy using ceftriaxone, gentamycin and metronidazole for 39 days and followed by antibiotic double-therapy using ceftriaxone and metronidazole for a further 22 days resulted in a radiologically proven reduction of the abscesses to very small remnants which disappeared completely during the follow-up period of two years . Simultaneously the general condition of the patient improved significantly . Repeated attempts at isolation of bacteria, fungi, protozoa and parasites from a subdural empyema failed . The histological examination of an abscess, which was entirely removed on occipital craniotomy, showed a structure resembling actinomycosis. J Bone Joint Surg Br, 1998 Nov, 80(6), 1045 - 50 The use of antibiotic-impregnated cement in infected reconstructions after resection for bone tumours; Donati D et al.; We have studied 35 patients with infected reconstructions after segmental resection for bone tumours . Two different regimes of treatment were employed both of which entailed debridement and the use of cement impregnated with antibiotic . In 25 patients gentamicin-PMMA beads were used and in ten an antibiotic-impregnated cement spacer . Better results were achieved with the second procedure in terms of cases healed, the number of operations, time of healing, time of recovery and the functional score . The use of vancomycin in the cement spacer gave better local control. Chem Biol Interact, 1998 Oct 2, 115(3), 247 - 60 Spectroscopy features of the binding of polyene antibiotics to human serum albumin; Romanini D et al.; The alteration in the fluorescence spectra observed for the polyene antibiotics nystatin and amphotericin B in the presence of human serum albumin is due to a decrease in the polar character of the antibiotic environment when these are bound to the protein . Amphotericin B showed two types of binding sites, the first having a very high affinity (5.8 x 10(7) M(-1)) and a secondary binding site with an affinity two orders lower than the primary site . This secondary binding site was very sensitive to temperature change . Nystatin yielded only one type of binding site with an affinity of 1.1 x 10(5) M(-1) . Nystatin was found to be bound to fatty acid binding sites in albumin, while amphotericin B was not, suggesting that the fatty acid binding sites are not simple, depending on the number of unsaturated bonds on the polyene antibiotic molecule . Both polyene antibiotics displaced bilirubin bound to albumin, which is in agreement with the similarities of the affinity values of this chromophore and the polyene antibiotics with albumin. Cancer Lett, 1998 Sep 25, 131(2), 137 - 43 Inhibition of tumor angiogenesis by roxithromycin, a 14-membered ring macrolide antibiotic; Yatsunami J et al.; We examined the effects of roxithromycin, a 14-membered ring macrolide antibiotic, on tumor angiogenesis using a mouse dorsal air sac model . The inhibitory effect of roxithromycin was dose-dependent and 100 mg/kg of roxithromycin administered intraperitoneally twice a day reduced the dense capillary network area to about 20% of the control . However, at concentrations of up to 50 microM, roxithromycin had no effect on lung cancer cells and human vascular endothelial cell growth and lung cancer cell production of the angiogenesis-inducing factors interleukin-8 and vascular endothelial growth factor . Roxithromycin at concentrations greater than 20 microM inhibited endothelial cell migration and tube formation. Eur J Obstet Gynecol Reprod Biol, 1998 Oct, 81(1), 1 - 8 Use of antibiotics during pregnancy; Czeizel AE et al.; OBJECTIVE: To describe the occurrence and distribution of antibiotic treatments, in addition their indications in control pregnant women in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996 . RESULTS: Of 38 151 control pregnant women who delivered later newborn infants without congenital abnormality, 6554 (17.2%) were treated by antibiotics . Most women (14.5%) had penicillin, while 1.2% and 0.7% of pregnant women were treated by cephalosporins and tetracyclines, respectively . More than 100 pregnant women used the following antibiotics: ampicillin (6.9%), penamecillin (5.9%), cefalexin (1.0%), phenoxymethylpenicillin (0.6%), oxytetracycline (0.5%), erythromycin (0.45%), benzylpenicillin-procain (0.4%) and benzylpenicillin+benzylpenicillin-procain (0.3%) . Different antibiotics had different indications for treatment . The mean birth weight was significantly lower in the treated group compared to the untreated group . PRACTICAL IMPLICATIONS: Different antibiotics have different chemical structures and indications for treatment . Therefore it is not appropriate to evaluate their teratogenic potential of combined antibiotic groups . There may be many interactions between underlying maternal diseases, other drug uses, further confounding factors and antibiotics studied, thus adequate controls are needed to estimate the adjusted teratogenic odds-risk ratios . European countries have different spectrum of antibiotic use . It would be necessary to know these baseline data of different populations . The anxiety and fear created by the notion that nearly all drugs cause congenital abnormalities may be more harmful than some proven human teratogenic drugs themselves . Thus a better risk-benefit estimation for antibiotic uses during pregnancy is an urgent and important task. Jpn J Antibiot, 1998 Sep, 51(9), 576 - 82 {Effects of prophylactic antibiotic agent on interleukin-6 level in open chest surgery--comparison between imipenem and flomoxef}; Sohma A et al.; Cytokines are known to increase in the patients subjected to open chest surgery . Those patients are usually administered with antibiotic agents for prophylaxis, while some of antibiotic agents might yield significantly higher level of cytokines than other agents especially in patients suffering from severe infections . It is believed that imipenem may yield lower interleukin-6 (IL6) level than cephem antibiotics . To study whether such difference could be observed in the patients who show no sign of severe infections, a total of 13 patients underwent scheduled open chest surgery were allocated at random into two groups, the imipenem-group and the flomoxef-group . The cytokine levels of the patients in the two groups were compared, while the prophylactic administration of imipenem or flomoxef . In both groups, IL6 increased immediately after the operation while endotoxin remained unchanged . Thereafter IL6 decreased gradually in both groups, however, the decrease of IL6 in the imipenem-group was faster and greater than the flomoxef-group resulting in the significantly lower level of IL6 on the 4th day after operation . One week after the operation, there existed no difference in the IL6 levels between these two groups . In conclusion, it was suggested that, depending on the choice of a prophylactic antibiotic agent, some invasive burden could be added to those patients underwent open chest surgery, a certain number of whom would develop severe infection. Rev Clin Esp, 1998 Oct, 198(10), 655 - 9 {Omeprazole plus 2 antibiotics for the eradication of H . pylori, are 5 days of treatment sufficient?}; Gisbert JP et al.; OBJECTIVE: Combinations of omeprazole plus two antibiotics for seven days have repeatedly been studied and high Helicobacter pylori eradication rates have been obtained, ranging from 80% and 90% in our country . Our objective was to verify whether length of such therapies (with omeprazole, metronidazole and clarithromycin or amoxicillin) can be shortened to five days with no loss of efficacy . METHODS: Design: randomized clinical trial . Patients: forty-eight consecutive patients with duodenal ulcer were prospectively studied . The exclusion criteria were previous administration of antibiotics, bismuth or gastroerosive drugs, and associated diseases . During the initial endoscopy biopsy specimens from antrum and corpus were obtained (haematoxylin-eosin) . Two therapies were administered for five days: omeprazole (20 mg/12 h) and clarithromycin (500 mg/12 h) plus metronidazole (500 mg/12 h) (n = 24) or amoxicillin (1 g/12 h) (n = 24) . One month after therapy was completed a new endoscopy was performed, biopsy specimens were obtained, and the 13C-urea breath test was performed . Compliance of therapy was assessed by questioning the patient and counting the residual medication . Data analysis: multiple logistic regression and "intention-to-treat" analysis . Outcome variable: eradication was defined as the absence of H . pylori by all diagnostic methods . RESULTS: Mean age +/- SD was 48 +/- 10 years, 73% were males . Twenty-three patients in each group completed the protocol and the distribution of investigated parameters was similar in both groups . Eradication was obtained in 91.7% (95% CI = 74%-98%) in the metronidazole group and 70.8% (51%-85%) in the amoxicillin group (chi 2 = 2.19; p = 0.13) . In the multivariate analysis, OR for the effect of type of therapy on eradication was 4.5 (CI = 0.83-24.7; p = 0.077) . No relevant secondary effects were reported . The most common secondary effect was a metallic taste of medication, which was perceived by half of patients in each group . CONCLUSION: The combination of omeprazole, clarithromycin, and metronidazole for only five days has a high eradicating efficacy (approximately 90%), similar to that obtained in previous studies with seven days of therapy . Nevertheless, the association of omeprazole, clarithromycin, and amoxicillin should probably be administered at least for one week to reach an optimal eradicating efficacy. World J Surg, 1999 Jan, 23(1), 75 - 9 Clinical relevance of antibiotic-induced endotoxin release in patients undergoing hepatic resection; Ishikawa M et al.; It has been proved that antibiotics binding to penicillin-binding protein 3 (PBP3) are associated with the greater release of endotoxin than those that bind to PBP2 in both in vitro and animal models . The aim of this study is to evaluate the potential clinical implications of antibiotic-induced endotoxin release after hepatic resection . Forty-five patients who underwent hepatic resection in our clinic were enrolled . The patients were divided into two groups . Group A (n = 26): antibiotics that bind primarily to PBP3, including cefmetazole (CMZ), latamoxef (LMOX), flomoxef (FMOX), were used . Group B (n = 19); antibiotics that bind to both PBP2 and PBP3, including cefazolin (CEZ), cefoperazone (CPZ), cefotiam (CTM) . Postoperative complications, liver functional tests, and chemical mediators {endotoxin, interleukins (IL-6, IL-8), tumor necrosis factor alpha (TNFalpha), granulocyte colony-stimulating factor (G-CSF), hepatotrophic growth factor (HGF) were examined after hepatic resection . There were no significant differences in the backgrounds of the two groups . Eight patients in each group developed postoperative complications; in particular, 9 of 13 patients with biliary tract carcinoma developed postoperative complications . No significant elevation of peripheral blood endotoxin was noted by the endospecy method, in any of the patients, although six died following sepsis . Pre- and postoperative levels of cytokines showed no significant difference between the two groups . Our data suggest that clinical antibiotic-induced endotoxin release would not occur after hepatic resection regardless of the antibiotic, probably owing to continuous scavenging of endotoxin from peripheral blood. Nucleic Acids Res, 1998 Dec 15, 26(24), 5551 - 61 Hairpin ribozyme cleavage catalyzed by aminoglycoside antibiotics and the polyamine spermine in the absence of metal ions; Earnshaw DJ et al.; The hairpin ribozyme is a small catalytic RNA that achieves an active configuration by docking of its two helical domains in an antiparallel fashion . Both docking and subsequent cleavage are dependent on the presence of divalent metal ions, such as magnesium, but there is no evidence to date for direct participation of such ions in the chemical cleavage step . We show that aminoglycoside antibiotics inhibit cleavage of the hairpin ribozyme in the presence of metal ions with the most effective being 5-epi-sisomicin and neomycin B . In contrast, in the absence of metal ions, a number of aminoglycoside antibiotics at 10 mM concentration promote hairpin cleavage with rates only 13-20-fold lower than the magnesium-dependent reaction . We show that neomycin B competes with metal ions by ion replacement with the postively charged amino groups of the antibiotic . In addition, we show that the polyamine spermine at 10 mM promotes efficient hairpin cleavage with rates similar to the magnesium-dependent reaction . Low concentrations of either spermine or the shorter polyamine spermidine synergize with 5 mM magnesium ions to boost cleavage rates considerably . In contrast, at 500 microM magnesium ions, 4 mM spermine, but not spermidine, boosts the cleavage rate . The results have significance both in understanding the role of ions in hairpin ribozyme cleavage and in potential therapeutic applications in mammalian cells. Antimicrob Agents Chemother, 1998 Dec, 42(12), 3282 - 4 Joint tolerance to beta-lactam and fluoroquinolone antibiotics in Escherichia coli results from overexpression of hipA; Falla TJ et al.; The basis of joint tolerance to beta-lactam and fluoroquinolone antibiotics in Escherichia coli mediated by hipA was examined . An antibiotic tolerance phenotype was produced by overexpression of hipA under conditions that did not affect the growth rate of the organism . Overexpressing hipA probably decreases the period in which bacteria are susceptible to the antibiotics by temporarily affecting some aspect of chromosome replication or cell division. Antimicrob Agents Chemother, 1998 Dec, 42(12), 3136 - 40 Possible mechanism by which the carbapenem antibiotic panipenem decreases the concentration of valproic acid in plasma in rats; Kojima S et al.; There is evidence indicating that the carbapenem antibiotic panipenem decreases plasma concentrations of valproic acid (VPA) in epileptic patients during VPA therapy . The mechanism for panipenem-induced changes in the pharmacokinetics of VPA was investigated in rats with and without bile duct cannulation . The effect of panipenem on the pharmacokinetics of diclofenac, which undergoes extensive enterohepatic recirculation, was also examined . VPA (50 mg/kg of body weight) or diclofenac (10 mg/kg of body weight) was administered intravenously under the steady-state plasma panipenem concentration of 4 microgram/ml, which had been achieved by a constant infusion rate . Panipenem decreased the plasma VPA concentrations in rats without bile duct cannulation but did not change the volume of the initial space and protein binding of VPA . However, panipenem had no effect on the plasma VPA concentrations and the biliary excretion of VPA in rats with bile duct cannulation . The secondary increase in plasma diclofenac concentration observed in the absence of panipenem was diminished in the presence of panipenem . These findings suggest that panipenem decreases plasma VPA concentrations by suppressing its enterohepatic recirculation, probably due to a panipenem-induced decrease in the numbers of enteric bacteria. Support Care Cancer, 1998 Nov, 6(6), 524 - 8 Economic aspects of empiric antibiotic therapy for febrile neutropenia in children with cancer; Castagnola E et al.; Several antibiotic regimens have been proposed worldwide for empiric treatment of febrile neutropenia in children with cancer, but none of them shows clear advantages in terms of clinical efficacy . Therefore, other parameters, including drug acquisition costs, should be considered in the selection of treatment . Children receive a "fraction" of a standard daily dose, and this fraction is generally calculated on the basis of body weight; therefore, the cost of each day of therapy is determined by the packages available for each single drug . We calculated the acquisition costs of various drugs proposed for the empiric treatment of febrile neutropenia in children with cancer, and then we estimated the daily cost of therapy referred to different patient weights . In general, the combination regimen with ceftriaxone plus aminoglycoside turned out to be less expensive than other regimens (including monotherapy with third-generation cephalosporins or carbapenems). J Fr Ophtalmol, 1998 Oct, 21(8), 577 - 82 {Amebicide activity of antiseptics and an antibiotic on 2 Acanthamoeba isolated from corneal ulcers}; Debbasch C et al.; PURPOSE: To study the in vitro amoebicidal activity of antiseptics and antibiotics . METHODS: Antiseptics (hexamidine, chlorhexidine, picloxydine, PHMB, polyvidone iodine) and an antibiotic (colimycine) were tested on two Acanthamoeba isolates from corneal ulcers under soft contact lenses . The appearence of trophozoits and the increase of the number of cysts show their viability . RESULTS: Four antiseptics and colimycin proved to be active in vitro on the two Acanthamoeba isolates: hexamidin 0.1% after 3 to 6 hours incubation, picloxydin 0.05% after 1 to 3 hours incubation (Wilcoxon test, p < 0.05), chlorhexidin 0.02% after 3 hours (Wilcoxon test, p < 0.01), PHBM 0.02% after 3 hours (Wilcoxon test, p < 0.01) and colimycin 125,000 Ul/ml after 1 to 3 hours incubation . Polyvidone iodine proved ineffective . CONCLUSION: Our results confirm that hexamidin, chlorhexidin and PHMB have an amoebicidal activity on the two stains, and show that colimycine, which has already been tested, has also an amoebicidal activity; picloxydine is effective after 1 to 3 hours; there is a considerable variability which exists between the isolates and the sensitivity of the isolates is time-dependent . Medical polytherapy is therefore necessary especially if the sensitivity of the Acanthamoeba has not been tested. Eur J Gastroenterol Hepatol, 1998 Oct, 10(10), 847 - 50 Continuous and more effective duodenal ulcer healing under therapy with bismuth and two antibiotics than with dual therapy comprising omeprazole and amoxicillin; Kashifard M et al.; OBJECTIVE: To determine the speed of the healing process of duodenal ulcers during eradication regimens with and without a high-dose anti-secretory drug . SETTING: An outpatient department of a university hospital as a community-based and referral centre . MATERIALS: A total of 101 patients with proven duodenal ulcer and a positive urease test were randomized into two groups: one group received the classic triple therapy (bismuth subnitrate 3 x 375 mg for 4 weeks + tetracycline 3 x 500 mg + metronidazole 3 x 250 mg daily, both for 2 weeks ), the other group received dual therapy comprising amoxicillin 2 x 1000 mg + omeprazole 2 x 20 mg daily, both for 2 weeks . All patients underwent a control endoscopy 2 and 6 weeks after the beginning of treatment . Eradication was assumed if a urease test and culture were negative in all specimens taken from antral and corpus mucosa . RESULTS: In total, 93 patients completed all 6 weeks of the study (45 patients in the triple therapy group and 48 patients in the dual therapy group) . The disappearance of ulcer pain was faster in the group under the regimen including omeprazole (dual therapy) than in the group with triple therapy (2.4+/-2.7 days versus 4.5+/-3.5 days; P< 0.01) . The two-week healing rate was significantly higher in the patients treated with dual therapy than in the group treated with triple therapy (77% versus 33.3%; P< 0.01); however, 12 out of 37 patients with a healed ulcer in the dual therapy group had an ulcer relapse at 6 weeks (six became symptomatic) . Only in one of these 12 patients was Helicobacter pylori eradicated . Fifteen of the 45 patients with triple therapy had healed ulcers at 2 weeks, and of these 14 remained healed at 6 weeks (H . pylori was eradicated in eight patients) . The six-week healing rate with dual therapy was the same as with classic triple therapy (64.6% versus 77.6%); the eradication rate was lower in the former group than in the latter (30.4% versus 51.1% respectively; P=0.056) . CONCLUSION: A high dose of a proton pump inhibitor (PPI) combined with amoxicillin results in rapid ulcer healing and pain disappearance, but is associated with early ulcer relapse due to lack of eradication of H . pylori . Its addition to regimens with bismuth and antibiotics is not necessary to achieve ulcer healing. Biochem Pharmacol, 1998 Dec 1, 56(11), 1471 - 9 Interaction of the antitumor antibiotic chromomycin A3 with glutathione, a sulfhydryl agent, and the effect upon its DNA binding properties; Chakrabarti S et al.; Chromomycin A3 (CHR), an anticancer antibiotic, blocks macromolecular synthesis via reversible interaction with DNA only in the presence of divalent cations like Mg2+ . In the absence of DNA, the antibiotic forms a dimer: Mg2+ complex {(CHR)2Mg2+} . It is the DNA-binding ligand . The antibiotic has potential reactive centers that could interact with GSH, the most abundant non-protein thiol in eukaryotic cells and a putative cofactor involved in the activation of many antibiotics in vivo . To understand the mode of action of CHR in vivo, we studied the interactions of CHR and the (CHR)2Mg2+ complex with GSH and the association of the resultant complexes with DNA by means of absorption, fluorescence, and circular dichroism spectroscopy . The novel finding was that GSH interacts non-covalently with CHR without a chemical modification of the antibiotic . The interaction was reversible in nature . The results are reported in two parts: the interaction of CHR with GSH in the absence and presence of Mg2+, and the effect of this interaction on the DNA-binding properties of the antibiotic . CHR forms a single type of complex with GSH . In contrast, (CHR)2Mg2+ forms two different types of complexes with GSH: a low GSH complex at approximately 12 mM GSH and a high GSH complex at > or = 16 mM GSH . Binding and thermodynamic parameters for the reversible association of the complexes with DNA demonstrated that they bind differently to the same DNA . The thermodynamic parameters indicate that the presence of GSH alters the mode of binding of the (CHR)2Mg2+ complex with DNA . The (CHR)2Mg2+ complex binds to DNA via an entropy-driven process, whereas in the presence of GSH the association is enthalpy-driven . The significance of these results in the understanding of the molecular basis of action of the antibiotic is discussed. Photochem Photobiol, 1998 Nov, 68(5), 666 - 74 Structure and medium-dependent photodecomposition of fluoroquinolone antibiotics; Fasani E et al.; The photochemical reactivity of four fluoroquinolone antibiotics is examined . For norfloxacin (NOR), enoxacin (ENX) and lomefloxacin (LOM), the only process occurring is defluorination (from position 6 for the first two drugs, from position 8 for the last one) . The quantum efficiency is both structure and medium dependent (phi close to 0.5 both in water and in 0.1 M phosphate buffer for LOM; 0.01 for ENX and 0.004 for NOR in buffer, but more than an order of magnitude higher in neat water) . Ofloxacin (OFL) is less light sensitive (phi 0.001) and undergoes, in part, reactions different from defluorination . The photoreaction involves heterolytic C-F bond fragmentation and its efficiency is determined by the internal charge-transfer character of the excited state (increasing in the series OFL < NOR < ENX < LOM according to the electronegativity of the substituent in position 8) and by the stabilization of the resulting aryl cation (larger for the 8-cation than for the 6-cation) . The relevance of these data for the rationalization of the known phototoxicity of these drugs is discussed. EMBO J, 1998 Nov 16, 17(22), 6437 - 48 Structural origins of gentamicin antibiotic action; Yoshizawa S et al.; Aminoglycoside antibiotics that bind to the ribosomal A site cause misreading of the genetic code and inhibit translocation . The clinically important aminoglycoside, gentamicin C, is a mixture of three components . Binding of each gentamicin component to the ribosome and to a model RNA oligonucleotide was studied biochemically and the structure of the RNA complexed to gentamicin C1a was solved using magnetic resonance nuclear spectroscopy . Gentamicin C1a binds in the major groove of the RNA . Rings I and II of gentamicin direct specific RNA-drug interactions . Ring III of gentamicin, which distinguishes this subclass of aminoglycosides, also directs specific RNA interactions with conserved base pairs . The structure leads to a general model for specific ribosome recognition by aminoglycoside antibiotics and a possible mechanism for translational inhibition and miscoding . This study provides a structural rationale for chemical synthesis of novel aminoglycosides. Am J Obstet Gynecol, 1998 Nov, 179(5), 1261 - 6 Chorioamnionitis: is continuation of antibiotic therapy necessary after cesarean section? Turnquest MA, How HY, Cook CR, O'Rourke TP, Cureton AC, Spinnato JA, Brown HL. OBJECTIVE: Our purpose was to determine whether the continuation of antibiotics postoperatively after cesarean section in patients whose labors were complicated by chorioamnionitis would reduce the incidence of endometritis . STUDY DESIGN: Patients with a clinical diagnosis of chorioamnionitis treated with ampicillin during labor and who required cesarean delivery for obstetric indications received preoperative intravenous clindamycin and gentamicin and were randomized into 2 groups . Group 1 received no scheduled postoperative antibiotics and group 2 continued to receive clindamycin 900 mg every 8 hours and gentamicin 1.5 mg/kg every 8 hours until afebrile for a minimum of 24 hours (temperature </=100 degreesF) . RESULTS: Sixty-one patients were randomized to group 1 and 55 patients were randomized to group 2 . The duration of labor, the duration of membrane rupture, and the number of intrapartum vaginal examinations were statistically insignificant between the 2 groups . The mean duration of maternal postoperative hospital stay was 4 days for both groups . There were no statistically significant differences in the rate of endometritis for group 1, 9 of 61 (14.8%), versus group 2, 12 of 55 (21.8%), P =.32 . CONCLUSIONS: In patients whose labors were complicated by chorioamnionitis and who underwent cesarean section, the continuation of preoperative clindamycin and gentamicin in the postoperative period did not reduce the risk of endometritis compared with a single preoperative dose. J Chemother, 1998 Oct, 10(5), 369 - 74 Clinical and economic outcomes of empiric parenteral antibiotic therapy for pneumonia: a retrospective study of 1,032 hospitalized patients; Bassi O et al.; The spiraling increase in pharmaceutical costs in hospitals means that the economic aspects of pharmacological therapy can no longer be ignored . The aim of the present study was to evaluate care and cost outcomes following initial therapy with parenteral antibiotics in a hospital setting for the treatment of lower respiratory tract infection (pneumonia and pleurisy with or without complications) . From January to December 1996, a total of 1,032 patients were reviewed . The mean age of the patients was 71.9 years (range, 16-100 years) . Piperacillin was most frequently prescribed (n=369), followed by ceftriaxone (n=324) and ceftazidime (n=161), among other antibiotics . The clinical success ranged from a maximum of 85.0% and 85.4% for piperacillin and ceftriaxone, respectively, to a minimum of 72.7% and 75.2% for cefodizime and ciprofloxacin, respectively . Differences between the antibiotic regimens emerged for mean prescribed daily doses, therefore the daily cost per administered dose was much lower for antibiotics such as piperacillin or ceftriaxone than for cefotaxime or ceftazidime . Ceftriaxone, at just over 177,840 Italian liras per success, was more cost-effective than other third-generation cephalosporins such as ceftazidime and cefotaxime, whose cost-effectiveness ratios were 420,590 and 272,030 Italian liras, respectively . A comparison of cost ratios for the seven antibiotic regimens evaluated indicates that using ceftriaxone led to a 57.72% cost savings per clinical success compared to using other third generation cephalosporins such as ceftazidime, and a 69.45% savings compared to therapy with ciprofloxacin. Biol Pharm Bull, 1998 Oct, 21(10), 1113 - 6 Effect of side chains including the N-methyl-tetrazole-thiol group of beta-lactam antibiotics on transport in cultured kidney epithelial cells LLC-PK1; Goto K et al.; In this study, the transcellular transport characteristics of four beta-lactam antibiotics (cefotaxime, cefmenoxime, cefmetazole, and cefotiam) were investigated in a kidney epithelial cell line LLC-PK1, especially focusing on the effect of the N-methyl-tetrazole-thiol (NMTT) group attached to 7-amino-cephalosporanic acid . There were no directional differences between the apical-to-basolateral and basolateral-to-apical transport of cefotaxime, cefmenoxime, and cefmetazole, suggesting that the NMTT group does not influence the transcellular transport behaviors of beta-lactam antibiotics . In contrast, cefotiam transport across LLC-PK1 cell monolayers was 1.3-fold greater in the basolateral-to-apical direction than in the apical-to-basolateral direction . It is considered that the ionization of nitrogen in the N-dimethylaminoethyl group attached to NMTT is a factor in the secretory-oriented movement of cefotiam . The transcellular transport of cefotiam in both directions was significantly depressed at a low temperature (4 degrees C) and by 2,4-dinitrophenol . The basolateral-to-apical transport of cefotiam was also shown to be concentration-dependent . These results suggest that a specialized transport process might participate in the transcellular transport of cefotiam . The lipophilicities of these beta-lactam antibiotics were not correlated to the degree of transcellular transport, directly. Biol Pharm Bull, 1998 Oct, 21(10), 1013 - 9 Action properties of HYI killer toxin from Williopsis saturnus var . saturnus, and antibiotics, aculeacin A and papulacandin B; Komiyama T et al.; The mechanism of the killing and cytocidal effects produced by HYI toxin from Williopsis saturnus var . saturnus, and by the amphiphilic antibiotics aculeacin A and papulacandin B on yeast Saccharomyces bayanus cells was studied . When the yeast cells were treated with these molecules, a discharge of cell materials at the budding position was observed by phase-contrast and scanning electron microscopy . The cytocidal effect of these molecules was most pronounced when the cells were in the logarithmic growth phase . Washing the HYI toxin incubation mixture completely eliminated the killing activity, but in the case of the antibiotics, it only partially reduced the cytocidal activity . Full recovery of the killing activity in the supernatant of the washing solution was observed after HYI toxin incubation, but in the case of the antibiotics, the recovery of cytocidal activity was time-dependent . The activity of membrane beta-1,3-glucan synthase was potently inhibited by HYI toxin, and the concentration of this enzyme in the budding tip was observed . These results suggest that HYI toxin exerts a cytocidal effect on the budding of sensitive yeast cells by inhibiting cell wall synthesis . This mechanism is similar to that of the HM-1 toxin of W . saturnus var . mrakii, and to aculeacin A and papulacandin B, although there are some differences from that of HYI toxin. J Pediatr, 1998 Nov, 133(5), 634 - 9 A multicenter, randomized, double-blind trial of 5 versus 10 days of antibiotic therapy for acute otitis media in young children; Cohen R et al.; BACKGROUND: All but 2 of the 15 published trials have failed to show a difference in efficacy between short (3 to 5 days) and standard (7 to 10 days) antibiotic regimens for acute otitis media (AOM) . These studies involved relatively few patients under 2 years of age, who are at a higher risk for treatment failure . METHODS: In a prospective, comparative, double-blind, randomized, multicenter trial, we compared amoxicillin/clavulanate in 3 divided doses for 10 days with an identical 5-day regimen, followed by a 5-day placebo period . RESULTS: Between February 1995 and May 1996, 385 children (mean age, 13.3 months) were enrolled, 194 in the 5-day treatment group and 191 in the 10-day treatment group . In the per protocol analysis, clinical success was obtained on days 12 to 14 after the beginning of treatment (main analysis) in 125 (76.7%) of the 163 children receiving the 5-day regimen and 148 (88.1%) of the 168 receiving the 10-day regimen (P = .006) . Clinical success persisted on days 28 to 42 among 57 (40.4%) of the 141 assessable patients in the 5-day group and 64 (46%) of the 139 assessable patients in the 10-day group . (P = .34) . Multivariate analysis showed that the 10-day course was statistically superior only among children cared for outside their homes (86.8% vs 70.8%; P = .008) . CONCLUSIONS: When assessed on days 12 to 14 after the outset of treatment, a 5-day regimen is not equivalent to a 10-day regimen among young children with AOM. J Antibiot (Tokyo), 1998 Sep, 51(9), 852 - 6 The mode of action of AKD-2C, an antifungal antibiotic from Streptomyces sp . OCU-42815; Ping X et al.; The mechanism of the antifungal action of AKD-2C was studied by using Torulaspora delbrueckii IFO 1621 as a model . AKD-2C slightly inhibited the incorporation of radioactive precursors into protein, RNA and lipid, but not into DNA . On the other hand, AKD-2C greatly enhanced the leakage of K+ ions from treated cells and showed a potent effect on liposomal glucose leakage . Using electron microscopic studies, though drastic morphological changes were not observed, an increase in cell membrane irregularities and swelling of the mitochondria caused by AKD-2C were demonstrated . These results suggest that the antifungal action of AKD-2C is due to effects on the yeast cell membrane. J Clin Microbiol, 1998 Dec, 36(12), 3731 - 3 Effectiveness of resins in neutralizing antibiotic activities in bactec plus Aerobic/F culture medium; Spaargaren J et al.; Incorporating resins in blood culture media can effectively reduce the activities of several antibiotics . It was shown that the activities of some generally used antibiotics decreased by 80 to 90% within 2 h in Bactec Plus Aerobic/F resin-containing culture medium . Bactec vials containing resins were still found to be positive for bacteria when antibiotics were present . The addition of beta-lactamase shortened the detection time irrespective of the presence of resins. Biochim Biophys Acta, 1998 Sep 23, 1374(1-2), 9 - 20 Anomalous solubility behavior of the antibiotic ciprofloxacin encapsulated in liposomes: a 1H-NMR study; Maurer N et al.; Many drugs are weak bases and can be accumulated into liposomes in response to a pH gradient to achieve high internal drug concentrations . This study is aimed at gaining an understanding of the relationship between the retention of the fluoroquinolone antibiotic ciprofloxacin in liposomes and the intraliposomal form and location of this drug . 1H-NMR spectroscopy was used to probe the interactions experienced by ciprofloxacin following uptake into large unilamellar liposomes (LUV) . It is shown that ciprofloxacin is located in the aqueous interior of the liposomes and is self-associated in the form of small stacks . It does not precipitate out of solution even though the intraliposomal ciprofloxacin concentration can exceed its solubility in aqueous solutions by almost two orders of magnitude . The results also indicate that little entrapped ciprofloxacin partitions into the inner monolayer of the LUV . As a result of the lack of precipitation and rapid exchange properties, ciprofloxacin can respond quickly to changes in electrochemical equilibria such as depletion of the pH gradient . This provides a rationale for the rapid leakage of this drug in response to serum destabilization or depletion of the pH gradient. Bull Hosp Jt Dis, 1998, 57(3), 125 - 9 Antibiotic-loaded porous hydroxyapatite blocks for the treatment of osteomyelitis and postoperative infection . A preliminary report; Itokazu M et al.; Hydroxyapatite blocks (HAB) can be used to administer antibiotics or anticancer drugs because its porous structure allows the gradual administration of the pharmacologic agents . A novel drug delivery system using hydroxyapatite blocks was developed for osteomyelitis and postoperative infections occurring after joint replacement . To load the antibiotics, hydroxyapatite blocks were mixed with an antibiotic solution and centrifuged at 1500 rpm for 15 minutes or decompressed in vacuum container at 5 to 10 in . Hg for 20 minutes . Fifteen patients with osteomyelitis including one with tuberculosis and four with infections subsequent to joint replacement were treated with antibiotic-loaded hydroxyapatite blocks in combination with intravenous injection . Except in one case, all of the foci had completely healed at follow-up (range: 13 to 71 months; average: 39.7 months) . These new methods are simple and can safely treat osteomyelitis in a one-stage operation. Enferm Infecc Microbiol Clin, 1998 Aug-Sep, 16(7), 328 - 33 {Analysis of automedication with antibiotics in Spain}; Orero Gonzalez A et al.; BACKGROUND: The aim of this study was to determine the incidence of automedication with antibiotics in Spain, analyzing the magnitude, importance and possible consequences of this problem . METHODS: A quantitative study was carried out in the pharmacies by personal interview with people who had acquired a pharmaceutical speciality . The study was performed according to territorial distribution proportional to the population of different autonomic communities and urban and rural environments . The questionnaires were done over one year with four cut offs, each coinciding with one of the annual seasons . RESULTS: Automedication with antibiotics was observed in 32.1% of the people who had acquired an antibiotic in a pharmacy, being 28.8% with pharmaceutical specialities acquired . In 20% of the cases (18.1% of the specialities), automedication was produced by direct request of the user, while in 12.1% of the cases (10.7% of the specialities) this was by recommendation by the pharmacist/ pharmaceutical auxillary . Of the people obtaining an antibiotic by self-medication, two out of three acquired a wide-ranging semisynthetic penicillin, while 23% acquired a macrolide . The remaining therapeutic subgroups acquired were tetracyclins (3.3%) and cephalosporins, quinolones and cotrimoxazoles being 1.6% each . Automedication was most frequent in people from 30 to 39 years of age (36.1%) followed by those from 40 to 49 years (29.5%) . Men showed a slightly greater incidence than women with 39% of the women acquiring an antibiotic directly doing so for someone other than themselves . Pharyngoamigdalitis was the most frequent process for which an antibiotic was acquired by automedication (34.5% of the cases) . The most frequent therapeutic schedule was three times a day for one week . There was little correspondence between the dosage schedule and length of treatment and the number of doses contained in the drug acquired . CONCLUSIONS: Antibiotic automedication is a widespread practice in Spain, specially in the treatment of infectious respiratory and bucal processes . Together with therapeutic unfulfillment and storage of antibiotics in the homes, automedication is currently one of the most serious problems in antibioticotherapy since it is frequently accompanied by bad usage . Health care education programs should be developed with the aim of making the public aware of the negative effects of automedication and orienting patients as to the rational use of antibiotics. Cell Biol Toxicol, 1998 Oct, 14(5), 333 - 43 In vitro toxic effects of certain antibiotics on the fibroblasts of two children with I-cell disease; Dumontel C et al.; Six antibiotics, pefloxacin (Peflacine), fosfomycin (Fosfocine), teicoplanin (Targocid), vancomycin (Vancocine), ceftazidime (Fortum), piperacillin (Piperilline), that may be used as a systematic coverage during bone marrow transplantation have been tested on dermal fibroblasts of one control subject and two I-cell disease patients, along with five subcultures, corresponding to 5 weeks of culture . The possible toxicity of these molecules was assessed . The evaluation of lysosomal enzyme sphingomyelinase activity, detection of free intracellular cholesterol and the light- and electron-microscopic examination of treated cells were used as measures of metabolic interference and cytotoxicity . Our study shows that despite a lack of any metabolic sign of interference (no modification in enzyme activity, no increase in free intracellular cholesterol), all the antibiotics tested induced a cytotoxic effect which was notably amplified in the I-cell populations . This may be due to the lysosomal lipid storage of these cells which modifies the relationship between the antibiotic and the cell by inducing a different kind of lipid-antibiotic interference. Drug Metab Dispos, 1998 Nov, 26(11), 1144 - 8 Transport of the beta-lactam antibiotic benzylpenicillin and the dipeptide glycylsarcosine by brain capillary endothelial cells in vitro; Torok M et al.; Peripherally administered beta-lactam antibiotics, which are structural analogs of tripeptides, may cause neurotoxic reactions or induce seizures . Previous in vivo studies provided evidence for brain uptake of these antibiotics . In the present work, we studied the extent and mechanism of the uptake of benzylpenicillin and glycylsarcosine by brain microvessel endothelial cells in vitro, using freshly isolated and cultured porcine brain capillary endothelial cells . Characterization of the cell culture model demonstrated the functional expression of the system transporting the neutral amino acids leucine and phenylalanine . The initial rate of uptake of benzylpenicillin was >3-fold greater than the rate of uptake of the extracellular marker sucrose (ratio, 3.29 +/- 0.37), whereas uptake of glycylsarcosine did not differ from that of sucrose . The differences in cellular uptake correlated with the octanol/buffer partition coefficients for glycylsarcosine and benzylpenicillin (1.16 x 10(-3) for glycylsarcosine and 6.83 x 10(-2) for benzylpenicillin) . The concentration-dependent uptake of benzylpenicillin (1-2000 microM) was not saturable and was not sensitive to shifts in pH or temperature . The permeability-surface area product for the uptake of benzylpenicillin at pH 7.4 was determined from these experiments and was found to be 8.1 x 10(-5) ml/sec/g of brain . This value was very close to the value determined in in vivo studies . Uptake of benzylpenicillin and glycylsarcosine was not reduced in the presence of 1 mM ceftibuten or 100 microM probenecid . The findings with cultured cell monolayers were confirmed using freshly isolated endothelial cells . These in vitro data are compatible with benzylpenicillin, but not glycylsarcosine, being able to penetrate endothelial cells . Uptake of benzylpenicillin by brain capillary endothelial cells occurs by a slow nonsaturable process, with no evidence for carrier-mediated transport. J Infect Dis, 1998 Oct, 178(4), 1075 - 80 A randomized controlled trial of filgrastim as an adjunct to antibiotics for treatment of hospitalized patients with community-acquired pneumonia . CAP Study Group; Nelson S et al.; Because of the critical role of neutrophils in host defenses, it was hypothesized that stimulation of neutrophil production and function with Filgrastim would improve the outcome of hospitalized patients with community-acquired pneumonia . To test this hypothesis, a randomized, placebo-controlled, multicenter trial of Filgrastim (300 micrograms/day up to 10 days) as an adjunct to antibiotics was conducted for these patients . Outcome measures included time to resolution of morbidity (TRM, a composite measure of temperature, respiratory rate, blood oxygenation, and chest radiograph), 28-day mortality, length of stay, and adverse events . Filgrastim increased blood neutrophils 3-fold, but TRM, mortality, and length of hospitalization were not affected . Treatment, however, accelerated radiologic improvement and appeared to reduce serious complications (e.g., empyema, adult respiratory distress syndrome, and disseminated intravascular coagulation) . Filgrastim administration was safe and well tolerated in these patients . Additional trials are needed to establish the value of this approach to treatment of infectious diseases. S D J Med, 1998 Oct, 51(10), 379 - 83 Acute coalescent mastoiditis caused by antibiotic resistant organisms; Collison PJ et al.; Two cases of acute coalescent mastoiditis with subperiosteal abscess are presented . Cultures from both abscesses resulted in bacteria resistant to commonly prescribed oral antibiotics . Historical perspectives on acute mastoiditis as well as the emergence of multi-drug resistant bacteria will be discussed . Current diagnostic evaluation and effective therapy for acute mastoiditis will also be reviewed. Aust Fam Physician, 1998 Oct, 27(10), 879 - 82 Choosing the right antibiotic; Kotsiou G; BACKGROUND: With the increasing complexity of the antibiotic armamentarium and the increasing prevalence of resistance, the choice of an appropriate antibiotic is more difficult than ever before . There is also increasing concern that overuse of broad spectrum antibiotics may help reduce their effectiveness in the future . In attempting to make rational antibiotic choices, competing interests must be balanced in order to preserve one of our most powerful medical tools . OBJECTIVE: The aim of this paper is to discuss some of the factors that should be considered when selecting an antibiotic and to provide general principles for use in day to day decision making . DISCUSSION: A knowledge of the patient combined with a working knowledge of the likely target organism and its predicted susceptibility profile is the basis of antibiotic selection. J Pept Sci, 1998 Sep, 4(6), 389 - 99 Conformation and membrane activity of an analogue of the peptaibol antibiotic trichogin GA IV with a lipophilic amino acid at the N-terminus; Locardi E et al.; We have synthesized by solution-phase methods two analogues of the 11-residue lipopeptaibol antibiotic trichogin GA IV in which the N-terminal n-octanoyl group is replaced either by an N-acetylated 2-amino-2-methyl-L-undecanoic acid or by an N-acetylated alpha-aminoisobutyric acid . CD, FTIR absorption . and NMR analyses unequivocally show that the main structural features of trichogin GA IV are preserved in these analogues . Since only the peptide containing the lipophilic chain exhibits membrane-modifying properties, these results strongly support the view that moving the long acyl moiety from the Nalpha-blocking group to the side chain of the N-terminal extra-residue does not affect the conformational properties or the membrane activity of trichogin GA IV. Int Orthop, 1998, 22(4), 247 - 51 Treatment of chronic osteomyelitis using calcium hydroxyapatite ceramic implants impregnated with antibiotic; Yamashita Y et al.; We treated eighteen patients with chronic osteomyelitis by implanting pieces of antibiotic-impregnated calcium hydroxyapatite ceramic into a cavity produced after thorough surgical excision of necrotic tissue . Within three months the infected sites had all healed . During follow-up ranging from 24 to 75 months there was no recurrence of infection . Two of the patients had infected prosthetic joints which were successfully revised . Infection was controlled and incorporation of the ceramic material into host bone was demonstrated radiographically . We recommend the use of porous pieces of calcium hydroxyapatite impregnated with antibiotic as a new system for drug delivery in the treatment of chronic osteomyelitis. Z Gastroenterol, 1998 Sep, 36(9), 803 - 9 Dual versus triple therapy: comparison of five antibiotic regimens for eradication of Helicobacter pylori in a prospective, randomized study; Kirstein FW et al.; We compared the efficacy of three dual and two triple therapies for eradication of Helicobacter pylori (HP), and evaluated the influence of smoking and omeprazole pretreatment on HP eradication . 220 patients with proven HP infection (histology and 13C-urea breath test {UBT}) were randomly allocated to one of the following regimes: BMT (bismuth subsalicylate 600 mg t . i . d . for 28 days, metronidazole 400 mg t . i . d . and tetracycline 500 mg q . i . d . for ten days) . OA (omeprazole 40 mg o . d . and amoxicillin 750 mq q . i . d . for 14 days), OC (omeprazole 40 mg o . d . and clarithromycin 500 mg b . i . d . for 14 days), OT (omeprazole 40 mg o . d . and tetracycline 500 mg q . i . d . for 14 days), OMC (omeprazole 40 mg o . d., metroinidazole 400 mg t . i . d . and clarithromycin 250 mg b . i . d . for seven days) . Eradication was defined as negative UBT six weeks after completion of the therapy . In an "all-patients-treated" ("per-protocol") analysis, the eradication rates were: BMT, 91% (93%); OA, 84% (90%); OC, 74% (74%); OT, 24% (24%); and OMC, 90% (93%) . Smoking impaired the success of OA and OT (p < 0.05), but the efficacy of the triple regimens was not affected . Omeprazole pretreatment did not influence eradication rates . Thus, highest eradication rates were achieved with the two triple therapies tested . However, OA, given at a daily antibiotic dose of 3 g amoxicillin for 14 d, was also highly effective . After failure of triple therapy, OA was successful in seven of ten patients (70%) . The efficacy of OC was lower than that of the triple therapies (p < 0.05) . In conclusion, metronidazole- and clarithromycin-based triple therapies are highly effective first line therapies . OA, given at a dose of 3 g per day over 14 days, should be considered as a possible second line therapy, e.g . in retherapy after failed triple therapy. Clin Pediatr (Phila), 1998 Oct, 37(10), 601 - 7 Study of skin rashes after antibiotic use in young children; Huang SW et al.; Immunoglobulin E (IgE)-mediated drug sensitivity in children is uncommon . However, undefined skin rash following antibiotic ingestion in younger children is commonly observed in clinical practice . We studied 86 consecutively referred patients to our allergy clinic over a 5-year period . We found that the majority of children (80%) with skin rashes were under 3 years of age . All the children had been treated with antibiotics for a bacterial upper respiratory infection (URI; otitis media, sinusitis, or pharyngitis), 73 (85%) had erythematous rash, 13 (15%) had urticaria occurring 3-5 days after the treatment, and 43 (50%) reported a repeated rash with the use of two or more different antibiotics . There were no reports of systemic reactions or histories of accompanying food allergy . When patients were given the suspected antibiotics while they were well, none developed rash . However, in the next bacterial infection, 62 (72%) chose to receive dye-free suspensions of the suspected antibiotics . Only three patients (3.5%) elected for the dye-containing suspension . Of the 62 patients who received dye-free suspensions, only eight developed a mild skin rash, which was managed successfully . We conclude that a practical approach for non-IgE-mediated skin rash needs to be evaluated . The current practice of complete avoidance of the suspected antibiotics without further evaluation may be unwarranted. Ann Med Interne (Paris), 1998 Sep, 149(5), 261 - 6 {Risk factor for antibiotic-associated diarrhea . A review of the literature}; McFarland LV; Antibiotic associated diarrhea (AAD) is a common adverse reaction to most types of antibiotics with frequencies ranging from 5-39%, depending upon the specific type of antibiotic and the presence of other risk factors . The pathogenesis of antibiotic associated diarrhea is mediated through the disruption of the normal flora and overgrowth of pathogens or through metabolic imbalances . Beside risk factors associated with the type and duration of antibiotic therapy, host factors include the extremes of age (< 6 years or > 65 years), severe underlying disease, presence of other chronic intestinal conditions, immunosuppression, prior history of AAD and exposures during recent hospitalizations (surgery, nasogastric tube feeding) . Factors which have not been significantly associated with antibiotic associated diarrhea include gender, dose or route of the inciting antibiotic and inflammatory bowel disease . The clinical impact of AAD is reflected by potential severity of the illness (PMC), possible consequences of the disruption in the treatment of the primary infection, higher medical costs, increased hospital stays and increased rates of morbidity and mortality . The key to decreasing these consequences is prompt diagnosis followed by effective treatment and institution of control measures and preventive treatments in patients at risk. Scand J Infect Dis, 1998, 30(3), 277 - 80 Antibiotic use in 3 European university hospitals; Kiivet RA et al.; The use of antibiotic drugs was studied in university teaching hospitals in Tartu, Estonia, Huddinge, Sweden and Badajoz, Spain . Data on drug deliveries to hospital wards during 1992 are presented in defined daily doses (DDD) per 100 bed-days (DDD/100 bed-days) . In addition, the time trends of antibiotic use in Tartu University Hospital from 1992 to 1995 are shown . The total amount of antibiotic drugs used for systemic treatment in 1992 was similar in the 3 hospitals, 41 DDD/100 bed-days in Tartu vs . 51 DDD/100 bed-days in Badajoz and 47 DDD/100 bed-days in Huddinge . The antibiotics used most frequently were tetracyclines and aminoglycosides in Tartu, broad-spectrum penicillins and cephalosporins in Badajoz and narrow-spectrum penicillins and cephalosporins in Huddinge . Injectable preparations accounted for one-half of the antibiotics used . Among the medical departments, the total use of antibiotics varied up to 3-fold (from 19 to 61 DDD/100 bed-days), less than among the surgical departments (18-94 DDD/100 bed-days) . The frequency of antibiotic use was very similar in departments of similar profile in the 3 hospitals (i.e . in departments of neurology, urology, etc.) . The use of antibiotic drugs in intensive care units was twice as high in Huddinge (243 DDD/100 bed-days) as in Badajoz (106 DDD/100 bed-days) and Tartu (135 DDD/100 bed-days) in 1992 . In conclusion, the international differences in the use of antibiotics in hospital were not in the frequency of use, but in the predominant prescription preferences in the hospital. Can Fam Physician, 1998 Sep, 44, 1850 - 6 Prospective study of antibiotic prescribing for children; Pennie RA; OBJECTIVES: To observe the frequency with which children in outpatient primary care settings are prescribed antibiotics and to investigate why these antibiotics are prescribed . To compare the prescribing behaviour of family doctors, primary care pediatricians, and urgent care physicians and to determine where refinements in management are most needed to reduce the number of antibiotic prescriptions appropriately . DESIGN: Prospective study using a data entry form with mostly closed-ended questions . SETTING: Ten primary care offices in urban south-central and eastern Ontario: five family practices, three pediatric practices, and two urgent care centres (UCC) . PARTICIPANTS: Every child younger than 16 years visiting these offices during a 3-week period in February and March 1997 . MAIN OUTCOME MEASURES: Frequency, clinical indications, and nature of the antibiotics prescribed . RESULTS: There were 4344 observed visits . Of 1706 antibiotic prescriptions, 1481 were for 10 days, and 1577 (92%) were for acute respiratory infections, 920 (53%) specifically for acute otitis media (AOM) . Full courses of antibiotics were given immediately (i.e., without test results) to 321 (76%) of 425 children with pharyngitis . Antibiotics were prescribed for 145 (90%) of 163 children with bronchitis . Urgent care physicians were significantly more likely than pediatricians or family physicians to prescribe immediate antibiotics and to disregard guidelines when choosing antibiotics for uncomplicated AOM . CONCLUSIONS: Three diagnoses accounted for 82% of antibiotic prescriptions: AOM, pharyngitis, and bronchitis . Physicians should be more selective when deciding whether, and for how long, to prescribe antibiotics for those three common conditions . Substantial reductions in antibiotic use will require changes in how physicians manage suspected AOM, the most common indication for antibiotics. Arch Gynecol Obstet, 1998, 261(4), 173 - 81 A review of randomized clinical trials of antibiotic therapy in preterm premature rupture of the membranes; Maymon E et al.; Rupture of membranes before 37 completed weeks of gestation, and before the onset of contractions occurs among 2-3% of pregnancies, and in about 30%-40% of women who deliver preterm . It is known as preterm premature rupture of membranes (PPROM) and is associated with maternal and neonatal morbidity . It has been postulated that antibiotic therapy may significantly decrease the complications associated with infection . The aim of the present review is to summarize the available data about the value of antibiotic therapy in PPROM. Arch Gynecol Obstet, 1998, 261(4), 167 - 72 A review of the role of trials of the use of antibiotics in women with preterm labor and intact membranes; Chaim W et al.; This updated review addresses the administration of antibiotics in women presenting with preterm labor and intact membranes as well as with bacterial vaginosis . 11 randomized controlled trials dealing with this question have been published since 1986 . The results are disappointing . The probable reasons are the small number of patients in the different studies and universal use of antibiotics without performing amniocentesis to isolate the organisms involved. Am Fam Physician, 1998 Oct 1, 58(5), 1113 - 8, 1123 Appropriate use of antibiotics for URIs in children: Part I . Otitis media and acute sinusitis . The Pediatric URI Consensus Team; Dowell SF et al.; Five conditions--otitis media, acute sinusitis, cough, pharyngitis and the common cold--account for most of the outpatient use of antibiotics in the United States . The first part of this two-part article presents guidelines that encourage physicians to make an appropriate distinction between acute otitis media and otitis media with effusion, to use shorter courses of antibiotic therapy in uncomplicated cases of otitis media and to limit prophylaxis to recurrence as defined strictly by number of episodes . Sinusitis in younger children is difficult to distinguish from the common cold, and the criterion for use of antibiotics should be duration of symptoms. South Med J, 1998 Oct, 91(10), 900 - 8 Perioperative antibiotics in nonemergency bowel surgery: a quality improvement project; Schell JA et al.; BACKGROUND: Guideline development has received considerable attention recently; guideline implementation less . For various reasons, reports of guideline implementations are not common in the published literature . In this paper, we report the results of a multisite quality improvement project undertaken as part of Health Care Financing Administration's Heath Care Quality Improvement Program . METHODS: Six acute care hospitals were selected for participation according to the number of procedures during the calendar year 1993 . Baseline and postintervention data were abstracted from the medical records of patients having bowel surgery . Performance feedback, education, and process improvement facilitation were the principal interventions used by the investigators; quality improvement plans varied by participant . Baseline and postintervention indicators were calculated . RESULTS: Statistically significant and practically meaningful improvement was observed in the primary indicator and in 4 of 11 subindicators . Conservative estimates indicated modest cost savings . CONCLUSIONS: Administration of perioperative antibiotics in bowel surgery can be improved by guideline implementations based on a continuous quality improvement model. Mol Microbiol, 1998 Oct, 30(1), 33 - 46 Pleiotropic effects of cAMP on germination, antibiotic biosynthesis and morphological development in Streptomyces coelicolor; Susstrunk U et al.; In wild-type Streptomyces coelicolor MT1110 cultures, cyclic adenosine 3',5' monophosphate (cAMP) was synthesized throughout the developmental programme with peaks of accumulation both during germination and later when aerial mycelium and actinorhodin were being produced . Construction and characterization of an adenylate cyclase disruption mutant (BZ1) demonstrated that cAMP facilitated these developmental processes . Although pulse-labelling experiments showed that a similar germination process was initiated in BZ1 and MT1110, germ-tube emergence was severely delayed in BZ1 and never occurred in more than 85% of the spores . Studies of growth and development on solid glucose minimal medium (SMMS, buffered or unbuffered) showed that MT1110 and BZ1 produced acid during the first rapid growth phase, which generated substrate mycelium . Thereafter, on unbuffered SMMS, only MT1110 resumed growth and produced aerial mycelium by switching to an alternative metabolism that neutralized its medium, probably by reincorporating and metabolizing extracellular acids . BZ1 was not able to neutralize its medium or produce aerial mycelium on unbuffered SMMS; these defects were suppressed by high concentrations (>1 mM) of cAMP during early growth or on buffered medium . Other developmental mutants (bldA, bldB, bldC, bldD, bldG) also irreversibly acidified this medium . However, these bald mutants were not suppressed by exogenous cAMP or neutralizing buffer . BZ1 also differentiated when it was cultured in close proximity to MT1110, a property observed in cross-feeding experiments between bald mutants and commonly thought to reflect diffusion of a discrete positively acting signalling molecule . In this case, MT1110 generated a more neutral pH environment that allowed BZ1 to reinitiate growth and form aerial mycelium . The fact that actinorhodin synthesis could be induced by concentrations of cAMP (< 20 microM) found in the medium of MT1110 cultures, suggested that it may serve as a diffusible signalling molecule to co-ordinate antibiotic biosynthesis. Can J Gastroenterol, 1998 Sep, 12(6), 390 - 1 Antibiotics; Borgaonkar MR et al.; Antibiotics may be a helpful addition to your therapy for IBD . Although it sounds as if there are a number of side effects, most patients do well, without any problems . If you develop new or worsening symptoms, or if you have other concerns, feel free to discuss them with your physician. J Trauma, 1998 Oct, 45(4), 758 - 64 Management of small infected tibial defects with antibiotic-impregnated autogenic cancellous bone grafting; Chan YS et al.; Between January of 1991 and December of 1993, 36 patients who had tibia fractures complicated by small infected tibia defects were treated at the authors' service . The group included 30 men and 6 women whose average age was 36.5 years (range, 18-72 years) . The average follow-up period was 3.7 years . By using the Cierney-Mader staging classification of chronic osteomyelitis, 26 of 36 patients (72%) were stage 4A and 10 of 36 patients (28%) were stage 4B . Ten patients required muscle transfer . All patients were treated with a two-stage protocol . In the first stage, antibiotic-impregnated polymethylmethacrylate bead chains were used to obliterate the debrided osseous defect . In the second stage, the beads were removed, and the defects were reconstructed with antibiotic-impregnated autogenic cancellous bone graft . The time between the first and second stage was 2 to 8 weeks for patients without muscle transfer and 8 to 12 weeks for the patients with muscle transfer . The bone defects ranged from 2 to 4 cm . Wound healing and bony union were achieved in all patients . Only two patients had recurrent infections . The infection arrest rate was 94.4% . Minor pin tract infection of the external skeletal fixation was seen in two patients . Two patients developed skin rashes secondary to antibiotic therapy . Radiographs at an average follow-up of 3.7 years showed good consolidation and hypertrophy of grafted bones in all patients . After 3 to 5 years of follow-up, our results suggest that the use of impregnating antibiotics have no adverse effects on autogenic cancellous bone graft incorporation and may help to eliminate infection . This treatment protocol provided rapid recovery from osteomyelitis . The use of antibiotic-impregnated autogenic bone graft seems to be an effective and safe method for the management of small infected tibial defects. J South Orthop Assoc, 1998 Fall, 7(3), 212 - 7 Prophylactic antibiotics for spine surgery: description of a regimen and its rationale; Riley LH 3rd; Cefazolin, an antibiotic commonly used for surgical prophylaxis, may not adequately penetrate the intervertebral disk or cerebrospinal fluid . The combination of gentamicin and cefuroxime has been found to penetrate both structures in adequate levels and was used in 40 consecutive elective spine cases without a postoperative infection or antibiotic-related complications. Clin Perinatol, 1998 Sep, 25(3), 659 - 85, x The role of antibiotic therapy in the prevention of prematurity; Mazor M et al.; Prematurity is the leading cause of perinatal morbidity and mortality in the industrial world, occurring in 4% to 9% of all deliveries, a rate that has remained unchanged during the past decades . Despite the relative minority of obstetric patients affected by this problem, prematurity is responsible for approximately 70% to 80% of perinatal morbidity and mortality corrected for congenital anomalies . To date, treatment modalities (tocolysis) that have been applied to patients who have preterm labor (PTL) and preterm premature rupture of membranes have been found to be of limited value in reducing both the rate of prematurity and of perinatal mortality and morbidity . A possible explanation for this failure in prevention of prematurity can be attributed to the poor understanding of the mechanisms of parturition in general and the pathophysiology of PTL in particular. J Clin Microbiol, 1998 Nov, 36(11), 3234 - 8 Comparison of the MB/BacT system with a revised antibiotic supplement kit to the BACTEC 460 system for detection of mycobacteria in clinical specimens; Benjamin WH Jr et al.; The MB/BacT system (MB/BacT) with a revised antibiotic supplement kit was compared with the BACTEC 460 system (BACTEC 460) in a test of 488 specimens submitted for mycobacterial culture from 302 patients . Twenty-four Mycobacterium tuberculosis isolates were detected by the BACTEC 460 versus 23 isolates by the MB/BacT . Mean time until detection of M . tuberculosis isolates identified by both systems was 11.9 days for the BACTEC 460 versus 13.7 days for the MB/BacT (P = 0.046) . M . avium complex was detected in 12 specimens by the MB/BacT versus 10 specimens by the BACTEC 460 . Only 8 of 14 (57%) M . avium isolates were detected by both systems, with a mean time until detection of 10.1 days for the BACTEC 460 and 14.2 days for the MB/BacT (P = 0.009) . The BACTEC 460 and the MB/BacT detected M . gordonae in four specimens, but only a single specimen was positive by both systems . One M . fortuitum isolate and one of five M . kansasii isolates were recovered only by the BACTEC 460 . The bacterial overgrowth rate was 7.0% for the MB/BacT versus 4.1% for the BACTEC 460 . We found the MB/BacT to be comparable to the BACTEC 460 for mycobacterial detection . Even though time until detection with the MB/BacT was slightly longer (1.8 days longer for M . tuberculosis and 4.1 days for M . avium {mean values}) and the bacterial overgrowth rate was somewhat higher, the decreased labor, the availability of a computerized data management system, and the noninvasive, nonradiometric aspects of the MB/BacT offset these relative disadvantages and make it an acceptable alternative for use in the diagnostic laboratory. Support Care Cancer, 1998 Sep, 6(5), 438 - 43 Statistical considerations in clinical trials testing empiric antibiotic regimens in patients with febrile neutropenia; Paesmans M; The Chalmers scoring system for assessing the quality of randomized controlled trials was applied to 19 papers (published in 1976-1984) reporting the results of trials of antibiotics in febrile neutropenic patients, it was found at the time of this survey (publication 1986) that statistical issues were inadequately addressed in the papers and that the scoring system was a measure of the quality of reporting in the papers rather than the quality of the actual trials . Some new items have been added to the system to improve the validity of results, and 15 more recent papers have been reviewed with reference to the updated scoring procedure, to find whether the quality of trials and of their reporting has improved since 1986 . Further discussion of statistical issues in clinical trials is recommended. Zhonghua Yi Xue Za Zhi, 1997 Sep, 77(9), 657 - 60 {Inhibition of angiogenesis by antitumor antibiotic C1027 and its effect on tumor metastasis}; Zhen H et al.; OBJECTIVE: To investigate the effect of C1027, an enediyne antitumor antibiotic, on angiogenesis and its anti-metastatic activity . METHODS: Chick embryo chorioallantoic membrane assay was used for anti-angiogenesis activity and bFGF receptor binding assay was used for the elucidation of the possible mechanism . Spontaneous pulmonary metastasis of Lewis carcinoma in mice was employed to evaluate the anti-metastatic effect . RESULTS: C1027 was highly potent in suppressing angiogenesis with a minimum effective dose of 0.01 microgram/egg . Enediyne chromophore moiety of the C1027 molecule was essential to anti-angiogenesis activity . Receptor binding assay showed that C1027 blocked bFGF binding to its receptor with an IC50 value of 2.3 x 10(-6) micrograms/ml . C1027 markedly inhibited pulmonary metastasis of Lewis carcinoma in mice . Compared at equitoxic dosage level (1/4 LD50), C1027 (0.01 mg/kg, i.v., x 2) was more effective than mitomycin (1.25 mg/kg, i.v., x 2) and the percent inhibition of metastatic foci in the lung was 98% and 78%, respectively . CONCLUSIONS: C1027 is a new potent anti-angiogenesis agent with markedly anti-metastatic activity . The mechanism of C1027 suppressing angiogenesis may be related to its blocking effect on bFGF binding to its receptor. Am J Gastroenterol, 1998 Oct, 93(10), 1909 - 13 Safety and efficacy of rabeprazole in combination with four antibiotic regimens for the eradication of Helicobacter pylori in patients with chronic gastritis with or without peptic ulceration; Stack WA et al.; OBJECTIVES: Rabeprazole is a new fast acting proton pump inhibitor that has recently been proven to be effective in the treatment of peptic ulceration and reflux esophagitis . The aim of this study was to evaluate rabeprazole in combination with antibiotics for the eradication of Helicobacter pylori (H . pylori) in patients with chronic active gastritis with or without peptic ulcer disease . METHODS: Seventy-five H . pylori-infected patients were randomized in a double-blind fashion to receive a 7-day treatment regimen consisting of: RAC, RAM, RCM, or RC (R=rabeprazole 20 mg b.d., A=amoxycillin 1 g b.d., C=clarithromycin 500 mg b.d., M=metronidazole 400 mg b.d.) . Randomized patients were H . pylori-positive by gastric biopsy urease test, histology and 13C urea breath test (13C-UBT) . H . pylori eradication was assessed by 13C-UBT, 4 and 8 wk after finishing treatment . Endoscopy with histology and culture for antibiotic sensitivity testing was performed pretreatment and if treatment failed . RESULTS: On an intention-to-treat analysis, treatment success was: RCM 100%, RAC 95%, RAM 90%, and RC 63% . The most common side effects were loose stools, headache, and taste disturbance, but there were no serious adverse events related to the study medication . The two patients failing RAM treatment had metronidazole-resistant strains before and after treatment . None of the pretreatment H . pylori isolates from six patients failing RC were clarithromycin resistant, but three of five successfully cultured posttreatment had developed clarithromycin resistance . CONCLUSION: Rabeprazole-based triple therapy with two antibiotics for 1 wk is safe and effective in eradicating H . pylori . Dual therapy with clarithromycin is less successful, and the majority of treatment failures develop clarithromycin resistance. J Chromatogr A, 1998 Aug 28, 818(1), 95 - 108 Development of a gas chromatography-mass spectrometry method for the analysis of aminoglycoside antibiotics using experimental design for the optimisation of the derivatisation reactions; Preu M et al.; A packed column GC-electron-capture detection method for the analysis of the aminoglycoside antibiotics kanamycin and gentamicin was adapted to capillary GC-MS . The analytes were derivatised using a two-step procedure involving trimethylsilylation of the hydroxyl groups with trimethylsilylimidazole and acylation of the amino groups with heptafluorobutyrylimidazole . Electron impact mass spectra of the resulting derivatives of kanamycin A and gentamicins C1, C1a and C2 are given and interpreted . The derivatisation procedure was optimised using experimental design . This chemometrical approach considers main effects as well as interactions of the influential parameters, thus conducting a more thorough investigation of the method than the common step-by-step approach . Optimisation using fractional factorial and Box Behnken Designs produced a derivatisation method featuring better yield than previously published methods while in many cases requiring less reagents and shorter reaction times. J Antibiot (Tokyo), 1998 Aug, 51(8), 699 - 707 Spirofungin, a new antifungal antibiotic from Streptomyces violaceusniger Tü 4113; Holtzel A et al.; A new secondary metabolite was detected in the culture filtrate and extracts of Streptomyces violaceusniger Tu 4113 by HPLC-diode-array and HPLC-electrospray-mass-spectrometry screening . The compound named spirofungin has a polyketide-spiroketal structure and shows various antifungal activities, particularly against yeasts. Int J STD AIDS, 1998 Sep, 9(9), 551 - 3 The availability and cost of antibiotics for treating PID in the Central Region of Ghana and implications for compliance with national treatment guidelines; Bosu WK et al.; The availability and cost of antibiotics for treating pelvic inflammatory disease (PID) were assessed in 17 drug-dispensing outlets in 5 districts of the Central Region, Ghana . The outlets included the dispensaries of 2 regional and 4 district hospitals, 4 privately-owned pharmacies and 7 chemical seller shops . The most common antibiotics available, including co-trimoxazole, metronidazole, benzylpenicillin, amoxycillin, chloramphenicol and gentamicin, were also the lowest-priced drugs . Conversely, the most expensive antibiotics including ceftriaxone, ciprofloxacin, cefuroxime and spectinomycin, were also the least commonly available . Recommended anti-gonococcal antibiotics (ciprofloxacin, ceftriaxone) may not be prescribed if they are not available in the districtsPIP: This paper assessed the availability and cost of antibiotics used for treating pelvic inflammatory disease in 17 drug-dispensing outlets in five districts of the Central Region, Ghana . The outlets included the dispensaries of 2 regional and 4 district hospitals, 4 privately owned pharmacies, and 7 chemical seller shops . The most common antibiotics available, including cotrimoxazole, metronidazole, benzylpenicillin, amoxycillin, chloramphenicol, and gentamicin, were also the lowest priced drugs . In contrast, the most expensive antibiotics, including ceftriaxone, ciprofloxacin, cefuroxime, and spectinomycin, were also the least commonly available . Recommended anti-gonococcal antibiotics (ciprofloxacin, ceftriaxone) may not be prescribed if they are not available in the districts . Adv Enzyme Regul, 1998, 38, 111 - 33 Exploring the mechanistic aspects of mitomycin antibiotic bioactivation in Chinese hamster ovary cells overexpressing NADPH:cytochrome C (P-450) reductase and DT-diaphorase; Belcourt MF et al.; We have directly demonstrated the involvement of human NADPH: cytochrome c (P-450) reductase in the aerobic/hypoxic differential toxicity of mitomycin C and porfiromycin in living cells by varying only this enzyme in a transfected cell line . In the same manner, we have implicated rat DT-diaphorase in the aerobic and hypoxic activation of mitomycin C, but found only a minor role for this enzyme in the aerobic activation of porfiromycin . DT-Diaphorase does not cause the production of an aerobic/hypoxic differential toxicity by mitomycin C, but rather activates this agent through an oxygen insensitive pathway . The evidence suggests that DT-diaphorase activates mitomycin C more effectively than porfiromycin, with porfiromycin being preferentially activated through a one-electron reductive pathway . The therapeutic potential of mitomycin antibiotics in the treatment of cancer can be envisioned to be enhanced for those tumors containing elevated levels of the bioreductive enzymes . However, cytogenetic heterogeneity within the tumor cell population and the various environmental factors which impact on bioreductive enzyme function, including pH and oxygen tension, may subvert this approach . Moreover, if high tumor levels of a drug activating enzyme reflect high levels in the normal tissues of the patient, normal tissue damage may also be enhanced with possibly no improvement in the therapeutic ratio . Approaches utilizing gene therapy, whereby a specific bioreductive catalyst is introduced into the tumor cell population via a targeting vehicle to activate a particular prodrug, may be more effective in that not only will the prodrug of choice be specifically activated in the tumor, but the source of the catalyst, be it bacterial, rodent, or human, will not be important . In fact, in the case of DT-diaphorase and mitomycin C, the rat form of the enzyme could be advantageous because it is more effective in activating mitomycin C than is the human form of this enzyme . Assuming targeted gene delivery to malignant cells, a non-host enzyme which is more effective at activating mitomycin C than the analogous host enzyme might also result in less drug activation in normal tissue and, hence, less normal tissue toxicity. Pharm Biotechnol, 1998, 11, 345 - 65 The use of esters as prodrugs for oral delivery of beta-lactam antibiotics; Mizen L et al.; It is apparent that the sequence of events that has been followed in the approach to the discovery and development of a new beta-lactam prodrug has been similar in many of the case histories we have studied and indeed similar to the approach we have followed . Initially, we select a suitable series of prodrug moieties, which either comprises totally novel structures or is deduced from the data bases available (bearing in mind reports of potential toxicity) or both . The successful preparation of these prodrugs and the studies undertaken to ensure they are of known purity and stability is not easy and, as would be expected, is the initial go/no-go decision . Usually, the next stage has involved the assessment of whether or not bioavailability of the parent molecule is increased after administration of the prodrug ester by gavage to laboratory animal species . The selection of which species to use has very often been made according to which has the most information available in those particular laboratories and in the literature . It is this process that can be dishearteningly misleading as was demonstrated in Table IV and Fig . 1 . Increasing the range of animal species does not lead to a better ability to predict bioavailability in humans . Hydrolysis studies are important to ensure that any novel prodrug will hydrolyze in human tissues, and also in the clarification of why a particular prodrug is not performing as expected in animals . After selection, it is essential to determine where and how rapidly hydrolysis takes place in the animal species to be used for safety evaluation prior to the first bioavailability studies in humans . The assessment of absolute oral bioavailability has not always been undertaken . This would seem critical for studies in not only the selected animal species but also in humans . In the absence of these data it is difficult to judge whether oral uptake can be increased further by modifying the ester moieties and at the development stage to determine whether or not modifications in formulation could increase bioavailability . When the prodrug is being developed for an injectable beta-lactam already available for humans, there would be no problem, but it would be an important consideration during the development of an entirely novel beta-lactam antibiotic for which no parenteral data are available in humans . Animal data are not totally predictive . The development of prodrugs is not easy, as a consequence of species differences in the properties of the prodrug superimposed on those of the parent compound during the evaluation . However, technical advances have enabled us to assay concentrations more precisely, determine basic physicochemical properties more efficiently, understand absorption processes by the use of in vitro systems, and analyze data far more comprehensively by the use of ever-evolving computer software . The prodrug approach to increasing the oral bioavailability of beta-lactam antibiotics has provided clinically valuable agents and continues . Despite the inherent difficulties, knowledge gained over the years, of the relationships between physicochemical and biological properties of the parent compound and the intact prodrug ester, has contributed to the design of novel prodrugs and a number of novel auxiliaries have been developed. Chirality, 1998, 10(7), 627 - 60 Evaluation of the macrocyclic antibiotic avoparcin as a new chiral selector for HPLC; Ekborg-Ott KH et al.; Avoparcin is a macrocyclic glycopeptide antibiotic structurally related to vancomycin, teicoplanin, and ristocetin A . When attached to 5-microns spherical silica gel, the avoparcin proved to be an effective chiral stationary phase (CSP) that could be used in the reversed-phase, normal-phase, and polar-organic modes . The avoparcin CSP was complimentary to the other macrocyclic glycopeptide CSPs in that it could resolve some racemates that the others could not, and vice versa . Some important compounds resolved on the avoparcin CSP include verapamil, thyroxine, mephenytoin, and 2-imidazolidone-4-carboxylic acid . The use of this CSP and the optimization of separations on it are discussed . Avoparcin appears to be a useful addition to this family of CSPs. J Biol Chem, 1998 Oct 9, 273(41), 26603 - 9 The role of residue 238 of TEM-1 beta-lactamase in the hydrolysis of extended-spectrum antibiotics; Cantu C 3rd et al.; beta-Lactamases inactivate beta-lactam antibiotics by catalyzing the hydrolysis of the amide bond in the beta-lactam ring . The plasmid-encoded class A TEM-1 beta-lactamase is a commonly encountered beta-lactamase . It is able to inactivate penicillins and cephalosporins but not extended-spectrum antibiotics . However, TEM-1-derived natural variants containing the G238S amino acid substitution display increased hydrolysis of extended-spectrum antibiotics . Two models have been proposed to explain the role of the G238S substitution in hydrolysis of extended-spectrum antibiotics . The first proposes a direct hydrogen bond of the Ser238 side chain to the oxime group of extended-spectrum antibiotics . The second proposes that steric conflict with surrounding residues, due to increased side chain volume, leads to a more accessible active site pocket . To assess the validity of each model, TEM-1 mutants with amino acids substitutions of Ala, Ser, Cys, Thr, Asn, and Val have been constructed . Kinetic analysis of these enzymes with penicillins and cephalosporins suggests that a hydrogen bond is necessary but not sufficient to achieve the hydrolytic activity of the G238S enzyme for the extended-spectrum antibiotics cefotaxime and ceftazidime . In addition, it appears that the new hydrogen bond interaction is to a site on the enzyme rather than directly to the extended-spectrum antibiotic . The data indicate that, for the G238S substitution, a combination of an optimal side chain volume and hydrogen bonding potential results in the most versatile and advantageous antibiotic hydrolytic spectrum for bacterial resistance to extended-spectrum antibiotics. Khirurgiia (Mosk), 1998, (8), 27 - 30 {The arteriolymphatic administration of antibiotics in treating patients with suppurative-inflammatory diseases of the abdominal cavity organs}; Buianov VM et al.; Experimental study of pharmacokinetics of Gentamicin was carried out in 23 dogs . Three different modes of its intralymphatic administration were used: intranodular inguinal, lymphotropic retroperineal and arterio-lymphatic . It has been established, that arterio-lymphatic mode of introduction of antibiotics (as well as regional endolymphatic and lymphotropic) warrants high concentration of antibiotics in venous blood and lymph . The peculiarity of arteriolymphatic administration is regional effect of accumulation of the antibiotic in organs and tissues of abdominal cavity of corresponding arterial region . Arteriolymphatic infusions of antibiotics have been introduced into complex of drug treatment of patients with pyogenic and inflammatory disorders of abdominal organs . The clinical testing has revealed high curative effect of this made of antibiotics administration. Mol Gen Genet, 1998 Aug, 259(3), 299 - 308 Analysis of a Streptomyces antibioticus chromosomal region involved in oleandomycin biosynthesis, which encodes two glycosyltransferases responsible for glycosylation of the macrolactone ring; Olano C et al.; A 6-kb region from the chromosome of Streptomyces antibioticus, an oleandomycin producer, was cloned and sequenced . This region was located between the 3' end of the gene encoding the third subunit of the oleandomycin type I polyketide synthase and the oleP and oleB genes, which encode a cytochrome P450 monooxygenase and an oleandomycin resistance gene, respectively . Analysis of the nucleotide sequence revealed the presence of five genes encoding a cytochrome P450-like protein (oleP1), two glycosyltransferases (oleG1 and oleG2) involved in the transfer of the two 6-deoxysugars (L-oleandrose and D-desosamine) to the oleandomycin macrolactone ring, a methyltransferase (oleM1), and a gene (oleY) of unknown function . Insertional inactivation of this region by gene disruption generated an oleandomycin non-producing mutant which accumulated a compound that, according to mass spectrometry analysis, could correspond to the oleandomycin macrolactone ring (oleandolide), suggesting that the mutation affects oleandrosyl glycosyltransferase. Biochemistry, 1998 Sep 22, 37(38), 13250 - 61 ATP/GTP hydrolysis is required for oxazole and thiazole biosynthesis in the peptide antibiotic microcin B17; Milne JC et al.; In the maturation of the Escherichia coli antibiotic Microcin B17, the product of the mcbA gene is modified posttranslationally by the multimeric Microcin synthetase complex (composed of McbB, C, and D) to cyclize four Cys and four Ser residues to four thiazoles and four oxazoles, respectively . The purified synthetase shows an absolute requirement for ATP or GTP in peptide substrate heterocyclization, with GTP one-third as effective as ATP in initial rate studies . The ATPase/GTPase activity of the synthetase complex is conditional in that ADP or GDP formation requires the presence of substrate; noncyclizable versions of McbA bind to synthetase, but do not induce the NTPase activity . The stoichiometry of ATP hydrolysis and heterocycle formation is 5:1 for a substrate that contains two potential sites of modification . However, at high substrate concentrations (>50Km) heterocycle formation is inhibited, while ATPase activity occurs undiminished, consistent with uncoupling of NTP hydrolysis and heterocycle formation at high substrate concentrations . Sequence homology reveals that the McbD subunit has motifs reminiscent of the Walker B box in ATP utilizing enzymes and of motifs found in small G protein GTPases . Mutagenesis of three aspartates to alanine in these motifs (D132, D147, and D199) reduced Microcin B17 production in vivo and heterocycle formation in vitro, suggesting that the 45 kDa McbD has a regulated ATPase/GTPase domain in its N-terminal region necessary for peptide heterocyclization. Southeast Asian J Trop Med Public Health, 1998 Mar, 29(1), 24 - 6 Indirect inhibition by antibiotics of nucleotide and deoxynucleotide biosynthesis in Plasmodium falciparum; Yeo AE et al.; The effects of the antibiotics, doxycycline, azithromycin, ciprofloxacin and chloramphenicol, upon levels of nucleoside-5'-triphosphates (NTPs) and 2'-deoxynucleoside-5'-triphosphates (dNTPs) have been compared in the malarial parasite, Plasmodium falciparum, and in human CCRF-CEM leukemia cells . All 4 antibiotics had more severe effects upon levels of NTPs and dNTPs in P . falciparum compared with leukemia cells providing an explanation for their selective toxicity against malaria and their utility as antimalarial drugs . In bacteria, the first 3 drugs inhibit protein synthesis while ciprofloxacin inhibits topoisomerase II . The observed depletions of NTPs and dNTPs would be a secondary effect of the drug but may result in death of the parasite. J Antimicrob Chemother, 1998 Aug, 42(2), 141 - 5 In-vitro activity of lytic peptides, inhibitors of ion transport systems