Antibiotics

J Vet Med B Infect Dis Vet Public Health, 2000 Aug, 47(6), 453 - 60
Influence of antibiotics used as feed additives on the immune effect of erysipelas live vaccine in swine; Yamamoto K et al.; To investigate the influence of antibiotics used as feed additives on the immune response to erysipelas live vaccine, the pig inoculation test was applied . Avilamycin, oxytetracycline quaternary salt, enramycin, virginiamycin and tylosin phosphate were selected as test antibiotics . Five experimental feeds containing each antibiotic at the highest concentration permitted for feed additives in Japan, and the basal diet lacking antibiotics were examined . Twenty-nine pigs were divided into six groups . At first all the groups were fed with the antibiotic-free basal diet for 7 days, and then each group received the experimental feeds . On the 14th day after feeding with test feeds all the pigs, except for one control pig in each group, were immunized with the vaccine and all the pigs were then challenge-exposed to a virulent strain of Erysipelothrix rhusiopathiae 14 days after vaccination . The clinical response was observed every day for 14 days . In all the groups, most of the vaccinated pigs did not develop any clinical signs of acute erysipelas after the challenge exposure, whereas non-vaccinated control pigs died or showed severe generalized erythema with profound depression and anorexia . No differences in the protection against the challenge exposure were observed among the groups . Therefore, the present results suggest that these selected antibiotics would not interfere with the immune effect of the vaccine if given at the usual concentrations used for feed additives.

Cornea, 2000 Sep, 19(5), 659 - 72
The evolution of antibiotic therapy for bacterial conjunctivitis and keratitis: 1970-2000; Baum J et al.; The editors of this Festschrift asked us to review the use of antibiotics for the treatment of bacterial conjunctivitis and keratitis over the past 25 years, a period coinciding with the life of the Castroviejo Corneal Society . We believe it is more appropriate to begin our review in the late 1960s . about the time that experimental and clinical studies and algorithms for the clinical care derived from these studies helped shape a more rigorous approach to therapy . Those years saw the introduction of antibiotics that were adapted for ophthalmic use, many of which are still being used today . We will give more weight to our review of keratitis than conjunctivitis.

An Esp Pediatr, 2000 Feb, 52(2), 157 - 63
{Antibiotic prescribing patterns in primary health care . Do pediatricians use antibiotics rationally?}; Calvo Rey C et al.; OBJECTIVES: To determine antibiotic prescribing patterns in the pediatric (infants and children) population attended to at a primary health care centre in the community of Madrid . We also wanted to determine the necessity or otherwise of antibiotic therapy and whether the selected antibiotic drug was appropriate for the pathology diagnosed . METHODS: Retrospective study of all infectious or respiratory processes diagnosed during 1 year and of the respective antibiotic cycles prescribed in all patients under the age of 4 years . The prescribing physician and the appropriateness of all therapeutic decisions, including those where the decision was not to treat with antibiotic drugs, were analyzed . RESULTS: We evaluated 910 children under the age of 4 years with a total of 3, 847 processes (mean of 4.55 +/-3.6 processes per child per year) . Sixty-three percent of the children received at least one cycle of antibiotic drugs per year (mean 1.63+/-1.69 cycles of treatment per child per year) . Of all therapeutic decisions, 85.2% were considered appropriate . In 36% of the processes antibiotics were prescribed (1,386 cycles), 46% of which were considered inappropriate either because no antibiotic therapy should have been given (71.6%) or because the chosen drug was not appropriate for the pathology (28.4%) . There were significant differences among the evaluated physicians . The most correct decisions were taken by the pediatrician in the outpatient clinic, especially when compared with physicians in the emergency ward (p<0.0001) . The most frequently prescribed antibiotic drugs were amoxicillin (41.2%) and amoxicillin combined with clavulanic acid (33%) . Cephalosporin accounted only for 6.9% of the prescriptions . CONCLUSIONS: Antibiotic therapy is overprescribed in children, a situation that should be corrected.

J Pharm Sci, 1987 Aug, 76(8), 596 - 8
Intestinal absorption of acidic beta-lactam antibiotics: contribution of ionized and un-ionized forms; Prieto JG et al.; The effect of the pH of dissolutions of weakly acidic beta-lactam antibiotics on their intestinal absorption has been studied by quantification of the contribution of the ionized and un-ionized antibiotic forms to the whole absorptive process . In vivo recirculation in both sexes of adult Wistar rats was performed with buffer solutions at different pH values and samples were analyzed by high-performance liquid chromatography (HPLC).

Pediatr Infect Dis J, 2000 Sep, 19(9), 929 - 37
Short course antibiotic therapy for respiratory infections: a review of the evidence; Pichichero ME; BACKGROUND: The judicious use of antibiotics entails achieving the appropriate balance between prescribing them with sufficient frequency and duration to effect a clinical cure for bacterial infections and overprescribing them, a practice that increases prescription drug costs as well as the risks of bacterial resistance, noncompliance with therapy and side effects . The recognition that the traditional 10-day or greater duration of therapy for acute otitis media, tonsillopharyngitis and sinusitis does not derive from a strong scientific or medical rationale (with the exception of penicillin therapy for tonsillopharyngitis) and the increasing awareness of the adverse sequelae of long-duration antibiotic therapy have led some clinicians to call for shortening the duration of antibiotic therapy in these infections . The soundness of this recommendation hinges on the demonstration that shortened courses of antibiotic therapy are at least as effective as traditional courses of therapy . SYNOPSIS: Data relevant to determining the optimum duration of therapy in acute otitis media, tonsillopharyngitis and sinusitis are reviewed in this article . The review demonstrates particularly strong justification for shortening the duration of therapy from the standard 10 days to 5 days in acute otitis media, in which numerous open label and controlled studies have shown equivalent efficacy of the two durations of regimen . A growing body of evidence indicates that tonsillopharyngitis, too, can be effectively treated with non-penicillin antibiotics given for fewer than 10 days . Although sinusitis data are less plentiful than those for acute otitis media and tonsillopharyngitis, the results available to date are encouraging in suggesting that shortened courses of therapy may also be appropriate for acute maxillary sinusitis.

Adv Surg, 2000, 34, 121 - 35
Duodenal ulcer disease: treatment by surgery, antibiotics, or both; Kauffman GL Jr; Peptic ulcer disease is a function of derangements in intraluminal aggressive factors and defects in endogenous defense mechanisms . Some of these previously described abnormalities may be caused by the presence of H pylori colonization of the antral mucosa and antral mucosal metaplasia of the proximal duodenum . In vivo and in vitro data are being accrued that support this concept, particularly with reference to the mechanisms of H pylori-induced aberrations in gastric and duodenal mucosal function . Standard medical therapy for PUD includes antisecretory medications as well as antibiotics designed to eradicate H pylori colonization . It is rare for patients with an asymptomatic but nonhealed DU to come to surgical attention . Those who do, along with those with a symptomatic DU refractory to all forms of medical therapy, should be offered a proximal gastric vagotomy . Life-threatening bleeding from a DU requires secure suture ligation of the base of the ulcer combined with truncal vagotomy and pyloroplasty . Those patients with non-life-threatening hemorrhage most likely will have been treated with intensive medical therapy, including antibiotics, and should be treated with truncal vagotomy and antrectomy . If H pylori is still present histologically in the antral specimen, sensitivity testing of the bacteria should lead to the use of appropriate antibiotic therapy . Both of these populations of patients with bleeding DU will likely have a lower rebleeding rate if H pylori is eradicated than if they are treated with surgery alone . Perforated DU should be treated with omental patch closure and antisecretory medications and antibiotics to eradicate H pylori, particularly when there are comorbid conditions such as shock, perforation for more than 24 hours, or if the patient has not had significant symptoms for 3 months preperforation . Those patients with perforated DU who are appropriate candidates for proximal gastric vagotomy in addition to omental patch closure and antibiotic therapy do well; however, the true benefit of proximal gastric vagotomy over omental patch closure with antibiotic therapy, in this population, has yet to be clearly demonstrated.

Biochemistry, 2000 Sep 26, 39(38), 11621 - 8
Kinetic studies on the interaction between a ribosomal complex active in peptide bond formation and the macrolide antibiotics tylosin and erythromycin; Dinos GP et al.; The inhibition of peptide bond formation by tylosin, a 16-membered ring macrolide, was studied in a model system derived from Escherichia coli . In this cell-free system, a peptide bond is formed between puromycin (acceptor substrate) and AcPhe-tRNA (donor substrate) bound at the P-site of poly(U)-programmed ribosomes . It is shown that tylosin inhibits puromycin reaction as a slow-binding, slowly reversible inhibitor . Detailed kinetic analysis reveals that tylosin (I) reacts rapidly with complex C, i.e., the AcPhe-tRNA . poly(U).70S ribosome complex, to form the encounter complex CI, which then undergoes a slow isomerization and is converted to a tight complex, CI, inactive toward puromycin . These events are described by the scheme C + I <==> (K(i)) CI <==> (k(4), k(5)) CI . The K(i), k(4), and k(5) values are equal to 3 microM, 1.5 min(-1), and 2.5 x 10(-3) min(-1), respectively . The extremely low value of k(5) implies that the inactivation of complex C by tylosin is almost irreversible . The irreversibility of the tylosin effect on peptide bond formation is significant for the interpretation of this antibiotic's therapeutic properties; it also renders the tylosin reaction a useful tool in the study of other macrolides failing to inhibit the puromycin reaction but competing with tylosin for common binding sites on the ribosome . Thus, the tylosin reaction, in conjunction with the puromycin reaction, was applied to investigate the erythromycin mode of action . It is shown that erythromycin (Er), like tylosin, interacts with complex C according to the kinetic scheme C + Er <==> (K(er)) CEr <==> (k(6), k(7)) C*Er and forms a tight complex, CEr, which remains active toward puromycin . The determination of K(er), k(6), and k(7) enables us to classify erythromycin as a slow-binding ligand of ribosomes.

Am Surg, 2000 Sep, 66(9), 887 - 90
Complicated appendicitis: is there a minimum intravenous antibiotic requirement? A prospective randomized trial; Taylor E et al.; The proper duration of postoperative intravenous (IV) antibiotics in patients suffering complicated (perforated or gangrenous) appendicitis is debatable . Some advocate a set minimum number of IV antibiotic days whereas others discontinue IV antibiotics depending on the patient's clinical course regardless of the length of therapy . Our objective was to determine whether there are differences in morbidity and resource utilization between the two treatment methodologies . Ninety-four patients with intraoperative findings of complicated appendicitis were included . In all patients IV antibiotics were discontinued on the basis of clinical factors . However, Group 1 patients were given a minimum 5-day IV antibiotic course whereas Group 2 patients had no minimum IV antibiotic requirement . Group 1 patients received more IV antibiotics than Group 2 patients did (5.9 vs 4.3 days; P = 0.014) . Infectious complications were not statistically different between the two groups (13.0% in Group 1 and 12.5% in Group 2) . Average hospital stay was also not statistically different between the two groups . The data suggest that a protocol with no minimum IV antibiotic requirement in patients with complicated appendicitis does not increase morbidity . Furthermore, the protocol arm with no minimum IV antibiotic requirement led to less IV antibiotic use but did not significantly decrease hospital stay.

Biosci Biotechnol Biochem, 2000 Aug, 64(8), 1671 - 4
Synthesis of (+/-)-methyl bishomononactate, a monomeric component of polynactin antibiotics; Hanadate T et al.; The synthesis of (+/-)-methyl bishomononactate, one of the monomeric components of polynactin antibiotics (macrotetrolides), was achieved via cis-selective iodoetherification as the key step.

J Bone Joint Surg Br, 2000 Aug, 82(6), 807 - 12
The PROSTALAC functional spacer in two-stage revision for infected knee replacements . Prosthesis of antibiotic-loaded acrylic cement; Haddad FS et al.; The PROSTALAC functional spacer is made of antibiotic-loaded acrylic cement but has a small metal-on-polythene articular surface . We have used it as an interim spacer in two-stage exchange arthroplasty for infected total knee replacement . PROSTALAC allows continuous rehabilitation between stages as it maintains good alignment and stability of the knee and a reasonable range of movement . It also helps to maintain the soft-tissue planes, which facilitates the second-stage procedure . We reviewed 45 consecutive patients, treated over a period of nine years . The mean follow-up was for 48 months (20 to 112) . At final review, there was no evidence of infection in 41 patients (91%); only one had a recurrent infection with the same organism . There was improvement in the Hospital for Special Surgery knee score between stages and at final review . The range of movement was maintained between stages . Complications were primarily related to the extensor mechanism and stability of the knee between stages . Both of these problems decreased with refinement of the design of the implant . The rate of cure of the infection in our patients was similar to that using other methods . Movement of the knee does not appear to hinder control of infection.

Microb Drug Resist, 2000 Summer, 6(2), 119 - 26
Antibiotic susceptibility of Escherichia coli dnaK and dnaJ mutants; Wolska KI et al.; The role of two chaperone proteins, DnaK and the cooperating factor DnaJ, in Escherichia coli antibiotic susceptibility to three antibiotics (a beta-lactam, chloramphenicol, tetracycline) has been studied . It was found that null dnaJ and dnaKdnaJ mutants are impaired in the functions leading to antibiotic susceptibility . The secretion of beta-lactamase to the periplasmic space is diminished in both mutants, and the additive effect of the two mutations was observed . The activity of chloramphenicol acetyltransferase is also impaired in an additive manner in both mutant strains . Tetracycline uptake is changed only in the double deletion mutant . These defects were observed only during incubation at high temperature (42 degrees C) . Efficient complementation of some of these defects by the wild-type alleles introduced on low-copy number plasmid was achieved . Minimal inhibitory concentrations and the titer of the wild-type strains, delta dnaJ and delta dnaKdnaJ mutants treated with ampicillin, chloramphenicol, and tetracycline were also determined . Higher susceptibility of both mutants to chloramphenicol and tetracycline, as compared to their wild-type parent, was observed only after 1 h preincubation of cultures at 42 degrees C . On the contrary, both mutants were less susceptible to ampicillin than their parent strain.

Pharmacol Toxicol, 2000 Aug, 87(2), 84 - 8
Effects of different periods of lithium pretreatment and aminoglycoside antibiotics on apomorphine-induced yawning in rats; Sharifzadeh M et al.; Interactive effects of intracerebroventricular administration of the aminoglycoside antibiotics, amikacin and gentamicin, and different duration of lithium pretreatment on apomorphine-induced yawning were investigated in male rats . The study was designed to investigate whether the hypothesis that the aminoglycoside antibiotics, amikacin and gentamicin, via their effects on phosphoinositide pathways and calcium channel might influence dopaminergic mechanisms as manifested in the yawning effect . Lithium is known to interact with phosphoinositide metabolism and was also tested after chronic studies on the apomorphine yawning model . Subcutaneous administration of apomorphine (0.1, 0.2 and 0.4 mg/kg) to rats induced yawning in a biphasic manner . However the maximum response was obtained by 0.2 mg/kg of the drug . Intracerebroventricular administration of aminoglycoside antibiotics amikacin (25 microg/rat) increased and gentamicin (10 and 20 microg/rat) decreased apomorphine-induced yawning . Pretreatment of animals with lithium (600 mg/l) in drinking water for 7, 14 and 21 days reduced yawning induced by apomorphine . Administration of lithium for 28 days did not induce any significant effect on yawning response . Amikacin and gentamicin function via the same mechanism on phosphoinositide cascade . Since amikacin and gentamicin did not affect the yawning response similarly, they apparently do not involve inositol trisphosphate level in the alterations of dopaminergic-induced yawning . Probably, the effect of lithium pretreatment on the number of yawns is also time-dependent and some tolerance to the inhibitory effect of lithium might occur after 28 days' treatment.

Antibiot Khimioter, 2000, 45(8), 12 - 6
{Evaluation of modern antibiotics efficacy at experimental Northern Asia rickettsiosis}; D'iakov SI et al.; Comparative investigation of antibiotics therapy efficacy at experimental murine Northern Asia rickettsiosis was performed . The efficacy was evaluated by the determination of protective activity in per cent and by the pathogen erradication . The investigated antibiotics may be ranged in the following order (by the diminishing efficacy): ansamycins (azorif, rifapentine, rifampicin), tetracyclines (doxycycline), macrolides (azitromycin, sumamed), carbapenems (imipenem/cilastatin), fluoroquinolones (lomefloxacin, pefloxacin) . Rifampicin and its derivatives--azorif, rifapentine, along with doxycycline and azitromycm can be recommended for clinical trials at experimental rickettsiosis profilaxy and treatment in natural infection focus.

Bull Acad Natl Med, 2000, 184(4), 761 - 74
{Update on drug allergies induced by antibiotics and anti-retroviral agents}; Demoly P et al.; Allergic reactions to antibiotics have raised considerable concerns, and are still underevaluated . It is a daily problem for general practitioners and allergologists . Their clinical manifestations are numerous, ranging from mild maculo-papular eruptions to sometimes deadly anaphylactic shocks or epidermal necrolisis . Atopy is not a risk factor, but concomitant viral infections, including Epstein-Barr virus and HIV infections are . HIV-infected patients indeed suffer more frequently from drug-induced hypersensitivity reactions than immunocompetent subjects or even non-HIV immunodeficient patients . We are lacking clinical and biological tools and the available ones still need to be validated . However, a precise diagnosis is required in order to set up prevention measures . In some cases, graded challenges (desensitization when an IgE mechanism is involved) is possible and efficacious (quinolones for cystic fibrosis, sulfonamides for HIV-infected patients).

Bioorg Med Chem Lett, 2000 Sep 4, 10(17), 1897 - 9
DNA triple helix stabilization by aminoglycoside antibiotics; Arya DP et al.; The stabilization of the poly(dA) x 2poly(dT) triple helix by neomycin is reported . Preliminary results indicate that neomycin stabilizes DNA triple helices and the double helical structures composed of poly(dA) x poly(dT) are virtually unaffected . This is the first report of the interaction of aminoglycoside antibiotics with DNA triple helices.

Proc Natl Acad Sci U S A, 2000 Sep 12, 97(19), 10613 - 8
A common polymorphism associated with antibiotic-induced cardiac arrhythmia; Sesti F et al.; Drug-induced long QT syndrome (LQTS) is a prevalent disorder of uncertain etiology that predisposes to sudden death . KCNE2 encodes MinK-related peptide 1 (MiRP1), a subunit of the cardiac potassium channel I(Kr) that has been associated previously with inherited LQTS . Here, we examine KCNE2 in 98 patients with drug-induced LQTS, identifying three individuals with sporadic mutations and a patient with sulfamethoxazole-associated LQTS who carried a single-nucleotide polymorphism (SNP) found in approximately 1.6% of the general population . While mutant channels showed diminished potassium flux at baseline and wild-type drug sensitivity, channels with the SNP were normal at baseline but inhibited by sulfamethoxazole at therapeutic levels that did not affect wild-type channels . We conclude that allelic variants of MiRP1 contribute to a significant fraction of cases of drug-induced LQTS through multiple mechanisms and that common sequence variations that increase the risk of life-threatening drug reactions can be clinically silent before drug exposure.

Ann Pharmacother, 2000 Sep, 34(9), 996 - 1001
Compatibility and stability of linezolid injection admixed with three quinolone antibiotics; Zhang Y et al.; OBJECTIVE: To evaluate the physical compatibility and chemical stability of linezolid 200 mg/100 mL admixed with ciprofloxacin 400 mg, ofloxacin 400 mg, and levofloxacin 500 mg for seven days at 4 and 23 degrees C . METHODS: The test samples were prepared by adding the required amount of the quinolone antibiotic to bags of linezolid injection . Evaluations for physical and chemical stability were performed initially and after one, three, five, and seven days of storage at temperatures of 4 and 23 degrees C . Physical stability was assessed using visual observation in normal light and using a high-intensity monodirectional light beam . In addition, turbidity and particle content were measured electronically . Chemical stability of the drugs was evaluated by using stability-indicating HPLC analytical techniques . RESULTS: The linezolid admixtures with levofloxacin and ofloxacin were clear and pale yellow when viewed in normal fluorescent room light, and slightly hazy with a green cast when viewed using a Tyndall beam . Measured turbidity and particulate content were low and exhibited little change . HPLC analysis found no loss of the drugs in any sample stored at either temperature throughout the study . The linezolid admixtures with ciprofloxacin stored at room temperature (23 degrees C) were clear and nearly colorless in normal room light and when viewed using a Tyndall beam . They exhibited little or no change in measured turbidity or particulate content during the study period . HPLC analysis found no loss of either drug in seven days . However, the refrigerated samples were only compatible for 24 hours and developed a gross white precipitate thereafter . CONCLUSIONS: Admixtures of linezolid 200 mg/100 mL with levofloxacin 500 mg and with ofloxacin 400 mg were physically compatible and chemically stable for at least seven days stored at 4 and 23 degrees C . Admixtures of linezolid with ciprofloxacin 400 mg were compatible and stable for seven days at 23 degrees C, but ciprofloxacin precipitation occurred after 24 hours stored under refrigeration . Linezolid/ciprofloxacin admixtures should not be stored under refrigeration.

J Antimicrob Chemother, 2000 Sep, 46(3), 509 - 12
Practice factors that influence antibiotic prescribing in general practice in Tayside; Steinke DT et al.; A cohort design was used to evaluate antibiotic prescribing in relation to patient and general practice characteristics . The study included prescribing to all subjects resident in Tayside, from January to December 1994 and found 215217 antibiotic prescriptions dispensed to 118596 people . Training status of general practitioners (GPs) was found to be the characteristic most associated with prescribing . Adjusting for other GP characteristics had little effect on these results . Training practice status was the dominant factor associated with significant differences in rates of antibiotic prescribing, in class of antibiotic prescribed and in performance indicators of antibiotic prescribing.

Vopr Onkol, 2000, 46(3), 285 - 9
{A comparative randomized phase-II study of Xeloda (capecitabine) and paclitaxel in patients with breast cancer progressing after anthracycline antibiotics}; Moiseenko VM et al.; A randomized study of the effectiveness of treatment with capecitabine (Xeloda) (22) and paclitaxel (taxol) (19) was carried out in breast cancer patients resistant to anthracycline antibiotic drugs . Capecitabine and paclitaxel showed comparable effectiveness, although the former appeared less toxic, particularly, in hematologic complication situations . Therefore, it may be administered to out-patients who previously received several courses of chemotherapy.

J Mass Spectrom, 2000 Aug, 35(8), 1011 - 24
Analysis of protonated and alkali metal cationized aminoglycoside antibiotics by collision-activated dissociation and infrared multi-photon dissociation in the quadrupole ion trap; Goolsby BJ et al.; Nine aminoglycoside antibiotics were analyzed in two quadrupole ion trap mass spectrometers using electrospray ionization . Structural information was obtained via collision-activated dissociation (CAD) and infrared multi-photon dissociation (IRMPD) of the protonated species . Several of the compounds, having multiple basic sites, preferred the doubly protonated form while some existed in the singly charged state or were distributed between single and doubly protonated species, allowing comparison of the fragmentation patterns of the two charge states . In general, IRMPD is as efficient as CAD, produces more low-mass fragment ions, and is more universally applied owing to its low dependence on trapping, pressure and tuning conditions . Alkali metal complexation using Li(+) and Na(+) was probed as a means of producing different fragmentation patterns, but in most cases the resulting fragmentation patterns were simplified versions of those obtained for the protonated analogs .

Mol Microbiol, 2000 Sep, 37(5), 995 - 1004
A single amino acid substitution in region 1.2 of the principal sigma factor of Streptomyces coelicolor A3(2) results in pleiotropic loss of antibiotic production; Aigle B et al.; Antibiotic production in streptomycetes generally occurs in a growth phase-dependent and developmentally co-ordinated manner, and is subject to pathway-specific and pleiotropic control . Streptomyces coelicolor A3(2) produces at least four chemically distinct antibiotics, including actinorhodin (Act) and undecylprodigiosin (Red) . afsB mutants of S . coelicolor are deficient in the production of both compounds and in the synthesis of a diffusible gamma-butyrolactone, SCB1, that can elicit precocious Act and Red production . Clones encoding the principal and essential sigma factor (sigmaHrdB) of S . coelicolor restored Act and Red production in the afsB mutant BH5 . A highly conserved glycine (G) at position 243 of sigmaHrdB was shown to be replaced by aspartate (D) in BH5 . Replacement of G243 by D in the afsB+ strain M145 reproduced the afsB phenotype . The antibiotic deficiency correlated with reduced transcription of actII-ORF4 and redD, pathway-specific regulatory genes for Act and Red production respectively . Exogenous addition of SCB1 to the G-243D mutants failed to restore Act and Red synthesis, indicating that loss of antibiotic production was not a result of the deficiency in SCB1 synthesis . The G-243D substitution, which lies in the highly conserved 1.2 region of undefined function, had no effect on growth rate or morphological differentiation, and appears specifically to affect antibiotic production.

Aliment Pharmacol Ther, 2000 Sep, 14(9), 1151 - 7
Eradication of Helicobacter pylori with pantoprazole and two antibiotics: a comparison of two short-term regimens; Frevel M et al.; BACKGROUND: High rates of Helicobacter pylori eradication can be achieved by combining proton pump inhibitors with two antibiotics . However, in the search for an optimal therapy a direct comparison of different regimens is necessary . METHODS: For this open study, 331 patients with duodenal ulcer were screened and randomly allocated to either pantoprazole 40 mg b.d., clarithromycin 500 mg b.d., and metronidazole 500 mg b.d . (PCM) or pantoprazole 40 mg b.d., amoxycillin 1000 mg b.d., and clarithromycin 500 mg b.d . (PAC) for 7 days . Both combinations were followed by a 7-day therapy with pantoprazole 40 mg o.d . alone . Eradication of H . pylori was assessed by use of a 13C-urea breath test 4 weeks after the intake of the last medication . RESULTS: Eradication rates were 90% in intention-to-treat patients from the PCM (132 out of 147; 95% CI: 84-94%) and the PAC group (135 out of 150; 95% CI: 84-94%) . H . pylori was eradicated in 112 out of 117 per protocol patients of the PCM group (96%; 95% CI: 90-99%) and in 119 out of 126 patients of the PAC group (94%; 95% CI: 89-98%) . Rapid relief from ulcer pain and a decrease in the mean intensity of other gastrointestinal symptoms was observed . Sixty-nine patients reported adverse events, none of which were related to the intake of pantoprazole . Four serious adverse events, none related to the trial medication, were observed . CONCLUSIONS: Both pantoprazole-based short-term triple therapies are highly effective and well-tolerated treatment regimens in the eradication of H . pylori.

Aliment Pharmacol Ther, 2000 Sep, 14(9), 1141 - 50
Helicobacter pylori eradication: proton pump inhibitor vs . ranitidine bismuth citrate plus two antibiotics for 1 week-a meta-analysis of efficacy; Gisbert JP et al.; OBJECTIVE: To compare the efficacy of proton pump inhibitor vs . ranitidine bismuth citrate (RBC) with two antibiotics for 1 week in Helicobacter pylori eradication . METHODS: Randomized trials comparing 1-week regimens with (i) proton pump inhibitor plus two antibiotics {clarithromycin (C) and amoxycillin (A) or a nitroimidazole (N)}; or (ii) RBC plus the same antibiotics . Eradication was confirmed by histology or 13C-urea breath test at least 4 weeks after therapy . Data sources included PubMed database and abstracts from congresses until October 1999 . Statistical analysis was by meta-analysis combining the odds ratios (OR) of the individual studies in a global OR (Peto method) . RESULTS: Twelve studies met the selection criteria . Nine compared proton pump inhibitor vs . RBC plus C and A, and five compared proton pump inhibitor vs . RBC plus C and N . With RBC, C and A, mean H . pylori eradication efficacy by intention-to-treat analysis (pooled data) was 76.6% (95% CI: 72-81%) and 73.7% (95% CI: 69-78%) with proton pump inhibitor, C and A . The OR for the effect of RBC vs . proton pump inhibitor (plus C and A) on H . pylori eradication was 1.15 (95% CI: 0.8-1.64%) . Mean H . pylori eradication with RBC, C and N was 87 . 2% (95% CI: 83-91%), and 74.9% (95% CI: 74-84%) with proton pump inhibitor plus these two antibiotics . The OR for the effect of RBC vs . proton pump inhibitor (plus C and N) on H . pylori eradication was 1.76 (95% CI: 1.08-2.85%) . CONCLUSION: RBC and proton pump inhibitor have similar efficacy for H . pylori eradication when given with C and A for 1 week, but RBC seems to have a higher efficacy than proton pump inhibitor when C and N are the co-prescribed antibiotics.

Physiol Chem Phys Med NMR, 2000, 32(1), 49 - 56; discussion 56
Modified antibiotics-methylated ampicillin and ethylated ampicillin-inhibit growth of ampicillin-resistant strain of bacteria; Bartzatt R et al.; Bacterial resistance to antibiotics is a significant problem in health facilities and results in higher costs for health care and increased fatalities due to infection . The work presented here suggests that antibiotic molecular structure can be altered in a selected manner, which will revive the bacterial growth inhibiting capability . A bacterial strain PKK3535(DH1), which is resistant to the antibiotic ampicillin, was found to be highly growth inhibited by these altered forms of ampicillin when tested in tissue culture . The level of growth inhibition of bacterial strain PKK3535(DHI) was greater than 50%, for both molecular variants of ampicillin that were investigated . The bacteria strain used for testing was a clinical isolate obtained from the University Hospital of the University of Nebraska, Omaha . These two antibiotic variants were methylated ampicillin and ethylated ampicillin . The synthetic procedure for generating these variants is presented as well as the molecular structure . The methylated and ethylated ampicillin were found to be stable at 0 degrees C for many weeks, were somewhat less soluble than normal ampicillin, but dissolved in LB plate media . The resistant bacteria strain was plated onto LB media with altered ampicillin and profound inhibition of bacteria growth was seen within the first 24 hours of incubation . These molecular variants of ampicillin provide evidence of a means to combat the proliferation of resistant bacterial strains . The molecular alteration of antibiotics may provide a suitable means to study and combat the appearance of antibiotic-resistant bacteria.

Med J Malaysia, 1997 Dec, 52(4), 409 - 11
Prevalence and antibiotic susceptibility of Ureaplasma urealyticum in Malaysian neonates with respiratory distress; Tay ST et al.; Ureaplasma urealyticum was isolated from the endotracheal aspirates of 39 (21.4%) of 182 neonates with respiratory distress requiring ventilatory support . Mycoplasma hominis was isolated from one (0.5%) neonate . Bacterial cultures were negative in 123 (67.6%) neonates . Antibiotic susceptibility test carried out on ten isolates of U . urealyticum showed that all the organisms were sensitive to erythromycin but resistant to lincomycin and sulfamethoxazole trimethoprim . All, except one, U . urealyticum were sensitive to tetracycline and minocycline . Two isolates were resistant to ciprofloxacin . This study showed that U.urealyticum was a common organism isolated from the endotracheal aspirates of neonates with respiratory distress.

Biologicals, 2000 Sep, 28(3), 155 - 67
Evaluation of the applicability of the bacterial endotoxin test to antibiotic products; Yamamoto A et al.; Fundamental conditions for applying the bacterial endotoxin test to antibiotic products were investigated so as not to affect the level of regulation by the rabbit pyrogen test . According to accuracy evaluation of test methods, the kinetic-turbidimetric and kinetic-colourimetric assays were shown to allow more accurate measurement and, therefore, more sensitive detection of interference to the bacterial endotoxin test than the gel-clot method . In total, 102 antibiotic products were evaluated on their interfering effect to show that the antibiotics could be categorized into three groups depending on intensity of the interference . Although the test was shown to be applicable even to the group showing the strongest interference, it was assumed to be crucial to use appropriate reagents and an accurate test method for avoiding approval of a pyrogenic product . Accordingly, lists of antibiotics are presented to provide limits of concentration for eliminating interference and endotoxin limits for approval to facilitate effective bacterial endotoxin tests .

Acta Biochim Pol, 2000, 47(1), 1 - 9
A simple model for predicting the free energy of binding between anthracycline antibiotics and DNA; Rudnicki WR et al.; A theoretical model for predicting the free energy of binding between anthracycline antibiotics and DNA was developed using the electron density functional (DFT) and molecular mechanics (MM) methods . Partial DFT-ESP charges were used in calculating the MM binding energies for complexes formed between anthracycline antibiotics and oligodeoxynucleotides . These energies were then compared with experimental binding free energies . The good correlation between the experimental and theoretical energies allowed us to propose a model for predicting the binding free energy for derivatives of anthracycline antibiotics and for quickly screening new anthracycline derivatives.

J Org Chem, 2000 Aug 11, 65(16), 4883 - 7
Attractive through-space S-O interaction in the DNA-cleaving antitumor antibiotic leinamycin; Wu S et al.; We describe here a study on the intramolecular nonbonded 1, 5-sulfur-oxygen (S-O) interaction in the antitumor antibiotic leinamycin 1 . The results from density-functional theoretical and semiempirical calculations on leinamycin 1 and model systems 2-5 provide evidence for the 1,5-S-O nonbonded interaction . Our results are used to explain previous experimental data on the X-ray structure of leinamycin 1 (Hirayama, N.; Matsuzawa, E . S . Chem . Lett . 1993, 1957) . The amide oxygen (O5) alters the thiosulfinate ester conformation and stabilizes the 1,2-dithiolan-3-one 1-oxide heterocycle . The attractive interaction induces S1 of leinamycin to adopt a distorted trigonal bipyramidal geometry . The magnitude of this stabilizing interaction is approximately 6 kcal/mol.

Antimicrob Agents Chemother, 2000 Sep, 44(9), 2581 - 4
Mutant prevention concentration as a measure of antibiotic potency: studies with clinical isolates of Mycobacterium tuberculosis; Dong Y et al.; The mutant prevention concentration (MPC) of a C-8-methoxy fluoroquinolone exhibited a narrow distribution for 14 genetically diverse clinical isolates of Mycobacterium tuberculosis, indicating that results from single-isolate studies are likely to be representative . When one isolate was challenged with a variety of antituberculosis agents, C-8-methoxy fluoroquinolones were exceptional in having MPCs below the maximum concentration attained in serum by use of commonly recommended doses.

Drug Metab Dispos, 2000 Sep, 28(9), 1014 - 7
Oxidation of the novel oxazolidinone antibiotic linezolid in human liver microsomes; Wynalda MA et al.; In vitro studies were conducted to identify the hepatic enzyme(s) responsible for the oxidative metabolism of linezolid . In human liver microsomes, linezolid was oxidized to a single metabolite, hydroxylinezolid (M1) . Formation of M1 was determined to be dependent upon microsomal protein and NADPH . Over a concentration range of 2 to 700 microM, the rate of M1 formation conformed to first-order (nonsaturable) kinetics . Application of conventional in vitro techniques were unable to identify the molecular origin of M1 based on the following experiments: a) inhibitor/substrates for various cytochrome P-450 (CYP) enzymes were unable to inhibit M1 formation; b) formation of M1 did not correlate (r(2) < 0.23) with any of the measured catalytic activities across a population of human livers (n = 14); c) M1 formation was not detectable in incubations using microsomes prepared from a baculovirus insect cell line expressing CYPs 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4, 3A5, and 4A11 . In addition, results obtained from an in vitro P-450 inhibition screen revealed that linezolid was devoid of any inhibitory activity toward the following CYP enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) . Additional in vitro studies excluded the possibility of flavin-containing monooxygenase and monoamine oxidase as potential enzymes responsible for metabolite formation . However, metabolite formation was found to be optimal under basic (pH 9.0) conditions, which suggests the potential involvement of either an uncharacterized P-450 enzyme or an alternative microsomal mediated oxidative pathway.

J Pharm Pharm Sci, 1998 Sep-Dec, 1(3), 95 - 101
Prediction of plasma levels of aminoglycoside antibiotic in patients with severe illness by means of an artificial neural network simulator; Yamamura S et al.; PURPOSE: The purpose of this work was to predict plasma peak and trough levels of an aminoglycoside antibiotic in patients with severe illness in an intensive care unit by a novel approach . Plasma levels were predicted based on the values of 15 physiological measurements using an artificial neural network (ANN) simulator . METHOD: A data set of 15 physiological measurements for 30 patients was used to develop the model . The ANN structure consisted of three layers: an input layer comprised of 15 processing elements, a hidden layer comprised of 10 processing elements with a sigmoid function as an activation function, and an output layer of two processing elements (peak and trough levels) . The weight between neurons was trained according to the delta rule back-propagation of errors algorithm . Predicted values were obtained by "leave-one-out" experiments by both ANN and multiple linear regression analysis (MLRA) . RESULTS: The correlation coefficients between observed and predicted values obtained by ANN prediction using standardized data sets were r=0.825 and r=0.854 for peak and trough levels, respectively . The correlation coefficients obtained by MLRA were r=0 . 037 and r=0.276 for peak and trough levels, respectively . These results indicate that ANN shows better performance in prediction of aminoglycoside plasma levels from patients' physiological measurements than MLRA . CONCLUSIONS: Prediction of plasma levels of antibiotic in patients with severe illness by ANN was superior to the standard statistical method . Standardization of input data was found to be important for better prediction . ANN has some advantages over standard statistical methods, as it can recognize complex relationships in the data.

Int Dent J, 2000 Apr, 50(2), 73 - 7
Grievances in cases using antibiotics due to orodental problems and assessment of the need for antibiotics; Kandemir S et al.; OBJECTIVE: To assess the complaints of patients who were prescribed antibiotics following orodental problems and the need for antibiotics prescribed for this purpose . SETTING: Examinations were carried out in the Department of Oral Diagnosis and Radiology, Ege University, Turkey . PARTICIPANTS: A total of 203 patients (129 females and 74 males) between 8-70 years of age (mean age 37.7 +/- 13.9) . INTERVENTION: Examination and report . MAIN OUTCOME MEASURES: Frequency of unnecessary antibiotic use . RESULTS: Antibiotic therapy was not necessary for 151 (74.4 per cent) cases . Antibiotics were unnecessarily prescribed in 45 cases of acute irreversible pulpitis, 10 chronic apical abscess, 6 acute apical paradontitis, 7 gingivitis, 10 periodontitis, 4 epulis, 2 TMJ (temporomandibular junction) dysfunction, 2 sharp ridge of alveolar bone, 1 burning mouth syndrome and 1 recurrent aphthous stomatitis . In 108 (53.2 per cent) of the cases, the prescribed antibiotics were found to be penicillins, 102 of which were broad-spectrum . It was also determined that only 6 (7.7 per cent) of the 78 cases diagnosed as acute apical abscess were given drainage as local therapy . CONCLUSIONS: Principles for treating dental infections suggest that an antibiotic should only be used to supplement and not substitute for conventional surgical methods . Therefore, in cases with acute apical abscess, mechanical treatment (drainage) should be the first step . Inappropriate antibiotic use is quite widespread in dentistry . Dentists should avoid inappropriate use of antibiotics . To prevent inappropriate administration, necessary precautions need to be taken against dispensing antibiotics without prescription.

J Biotechnol, 2000 Mar, 74(1), 39 - 60
Structure, recognition and discrimination in RNA aptamer complexes with cofactors, amino acids, drugs and aminoglycoside antibiotics; Patel DJ et al.; Through the use of in vitro selection techniques, a number of RNA aptamers have been selected for their ability to bind ligands with high affinity and specificity . The three-dimensional solution structures of a number of these complexes have been solved within the last 4 years . This review focuses on the structural characterization of the RNA aptamers bound to the cofactors FMN and AMP, the amino acids arginine and citrulline, the drug theophylline and the aminoglycoside antibiotic tobramycin in solution . Analysis of the structural features of these complexes allows the identification of molecular themes in RNA aptamer structure, recognition and discrimination.

Biomaterials, 2000 Oct, 21(19), 1981 - 7
Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release; van de Belt H et al.; In this study, the release of gentamicin as a function of time was measured for six different gentamicin-loaded bone cements and related with the surface roughness, porosity and wettability of the cements . Initial release rates varied little between the six bone cements (CMW1, CMW3, CMW Endurance, CMW 2000, Palacos, and Palamed) and ranged from 8.6 to 14.1 microg/cm2/h . The total amounts of gentamicin released after 1 week varied between 4.0 and 5.3% of the total amount of antibiotic incorporated for the CMW cements and was 8.4% for Palacos . Palamed released after 1 week significantly more of the gentamicin incorporated (17.0%) . The wettability of all cements was similar (water contact angles between 70 and 80 degrees), but the surface roughness and the porosity of the cements varied markedly . Initial release rates increased with surface roughness, although the correlation coefficient was low (0.64), while total amounts released increased linearly (correlation coefficient 0.97) with the bulk porosity of the cements . Consequently, it can be concluded that the release kinetics of gentamicin from bone cements is controlled by a combination of surface roughness and porosity.

J Am Vet Med Assoc, 2000 Aug 1, 217(3), 369 - 71
Antibiotic residues in milk following bulbar subconjunctival injection of procaine penicillin G in dairy cows; Liljebjelke KA et al.; OBJECTIVE: To determine whether, and at what time, penicillin enters milk at a concentration that is detectable following bulbar subconjunctival injection in lactating dairy cows . DESIGN: Randomized clinical trial . ANIMALS: 66 Holstein cows that were at least 2 weeks past calving and had not been treated with antibiotics in the preceding 30 days . PROCEDURE: Cows were randomly assigned to receive a treatment of 1 ml (300,000 units) procaine penicillin G by bulbar subconjunctival injection or remain untreated . Composite milk samples were collected immediately before treatment and 4, 10, 16, 22, 28, and 40 hours after treatment . Milk samples were tested by use of a commercial test for beta-lactam antibiotics . RESULTS: Among penicillin-treated cows, the first positive test results were observed 4 hours after treatment, and the last positive result was observed 22 hours after treatment . The percentages of positive test results before treatment and at 4, 10, 16, 22, 28, and 40 hours after treatment were 0, 9, 87, 42, 8, 0, and 0%, respectively . None of the untreated cows had positive test results for beta-lactam antibiotics at any sampling time . CONCLUSIONS AND CLINICAL RELEVANCE: Penicillin was detected in milk for up to 22 hours after a single subconjunctival injection of procaine penicillin G in cows . This result should be considered when recommending milk withholding periods following the administration of penicillin by this route in lactating dairy cows.

Iowa Orthop J, 2000, 20, 31 - 5
Antibiotic bead production; Cunningham A et al.; We are reporting a practical technique for the production of antibiotic beads for use in combating musculoskeletal infections . The technique utilizes bead molds with tobramycin powder mixed with polymethylmethacrylate on twisted wire strands to produce strands of 25 beads of various sizes . These beads are gas sterilized and available for use "off the shelf" in a manner that is much more efficient than traditional production by hand on the back table in the operating room . Our technique was also utilized at a second institution to demonstrate its efficacy at another site.

J Pharm Biomed Anal, 2000 Aug 15, 23(2-3), 353 - 62
Rapid liquid chromatographic method for simultaneous determination of tetracyclines antibiotics and 6-epi-doxycycline in pharmaceutical products using porous graphitic carbon column; Monser L et al.; A rapid and selective high performance liquid chromatographic (HPLC) method has been developed for the separation and determination of five commercially used tetracyclines . The chromatography was performed on a porous graphitic carbon (PGC) column, using 0.05 M potassium phosphate buffer (pH 2.0)--acetonitrile (40 + 60) as the mobile phase and ultraviolet detection at 268 nm . The method permits the simultaneous determination of oxytetracycline, metacycline, chlortetracycline and doxycycline as well as the separation of one of their common impurities (6-Epi-doxycycline) in bulk powder and pharmaceutical preparations with detection limits of 0.5-2 microg ml(-1) and recoveries of 98.9-100.5% . Correlation coefficients for calibration curves in the range of 5-50 microg ml(-1) were greater than 0.999 for all tetracyclines . The within- and between-day precision was determined for both retention times and peak area . It is suggested that the proposed HPLC-PGC method should be used for routine quality control and dosage form assay of tetracyclines in pharmaceutical preparations . The chromatographic behaviour of the five tetracyclines was examined under variable mobile phase compositions, the results revealed that elution order and selectivity were dependent on the buffer agent used . Comparison between retentions obtained with PGC and with silica-based stationary phase (ODS), showed similar variations of the capacity factors with the mobile phase composition, but with a different elution order.

J Am Pharm Assoc (Wash), 2000 Jul-Aug, 40(4), 509 - 14
Compatibility and stability of linezolid injection admixed with three cephalosporin antibiotics; Xu QA et al.; OBJECTIVE: To evaluate the physical compatibility and chemical stability of linezolid (Zyvox-Pharmacia) 200 mg/100 mL admixed with cefazolin sodium 1 gram, ceftazidime 2 grams, and ceftriaxone sodium 1 gram for 7 days at 4 degrees C and 23 degrees C . DESIGN: Controlled experimental trial . SETTING: Laboratory . INTERVENTIONS: The test samples were prepared by adding the required amount of the cephalosporin antibiotic to bags of linezolid injection 200 mg/100 mL . MAIN OUTCOME MEASURES: Physical stability and chemical stability based on drug concentrations initially and after 1, 3, 5, and 7 days of storage at 4 degrees C and 23 degrees C protected from light . RESULTS: All of the linezolid admixtures with cephalosporins were clear when viewed in normal fluorescent room light and with a Tyndall beam . Measured turbidity and particulate content were low and exhibited little change . The cefazolin sodium-containing samples were colorless throughout the study . The admixtures with ceftazidime and ceftriaxone sodium had a slight yellow tinge initially, and the room temperature samples became a frank yellow color after 5 days . The refrigerated samples did not change color . High-performance liquid chromatography analysis found little or no loss of linezolid in any sample stored at either temperature throughout the study . Cefazolin sodium and ceftazidime in the linezolid admixtures at 4 degrees C remained stable for 7 days, but at 23 degrees C cefazolin sodium was stable for 3 days and ceftazidime for only 24 hours before cephalosporin decomposition exceeded 10% . Ceftriaxone sodium was less stable in the admixtures; 10% loss occurred in 3 days at 4 degrees C and more than 20% loss occurred in 24 hours at 23 degrees C . CONCLUSION: Admixtures of linezolid 200 mg/100 mL with cefazolin sodium 1 gram and ceftazidime 2 grams were physically compatible and chemically stable for at least 7 days stored at 4 degrees C protected from light and for 3 days and 1 day, respectively, at 23 degrees C protected from light . Admixtures of linezolid with ceftriaxone sodium 1 gram exhibited a rapid rate of cephalosporin loss at 23 degrees C, which precludes admixture of the two drugs.

Cornea, 2000 Jul, 19(4), 459 - 63
Comparison of antibiotic drops placed in the conjunctival cul-de-sac to antibiotic ointment applied to the lid margin in reduction of bacterial colonization on the lid margin; Hashemi K et al.; PURPOSE: To compare the efficacy of antibiotic drops placed in the conjunctival cul-de-sac to antibiotic ointment applied to the lid margin in reduction of bacterial colonization on the lid margin . METHODS: A randomized, prospective, single-masked study was conducted on 19 patients with culture-proven colonization of bacteria on the lid margins . Ophthalmic eligibility criteria included the presence of > or =50 colony-forming units/mL (CFU/mL) of bacteria on both right and left lids . Each patient received one drop of ofloxacin in one eye every night for one week, followed by one drop once a week for one month . In the same manner, each patient received bacitracin ointment (erythromycin or gentamicin ointment if lid margin bacteria were resistant to bacitracin) to the lid margin of the fellow eye . Quantitative lid cultures were taken at initial visit, one week, one month, and two months . Fifteen volunteers (30 lids) served as controls . Lid cultures were taken at initial visit, one week, and one month . RESULTS: Both antibiotic drop and ointment reduced average bacterial CFU/mL at one week and one month . Average bacterial CFU/mL reestablished to baseline values at two months . There was no statistically significant difference between antibiotic drop and ointment in reducing bacterial colonization on the lid margin . CONCLUSION: Antibiotic drops placed in the conjunctival cul-de-sac appear to be as effective as ointment applied to the lid margins in reducing bacterial colonization in patients with > or =50 CFU/mL of bacteria on the lid margins.

Biochemistry, 2000 Aug 8, 39(31), 9502 - 7
Quinoxaline antibiotics enhance peptide nucleic acid binding to double-stranded DNA; Mollegaard NE et al.; The effects of a wide range of DNA binding drugs on peptide nucleic acid (PNA) binding to double-stranded DNA by strand displacement have been investigated using a gel retardation assay . The bis-PNA {H-(Lys)-TTJTTJTTTT-(eg)(3)-TTTTCTTCTT-Lys-NH(2)} was used together with a 248 bp DNA fragment containing an appropriate target for the PNA . Most of the ligands that were studied, including DNA minor groove binders as well as intercalators and bis-intercalators, either have no effect or strongly inhibit PNA binding to DNA . By contrast, quinoxaline antibiotics facilitate PNA-DNA complex formation . The "PNA-helper" effect of echinomycin was studied in more detail using time and temperature dependence experiments to elucidate the mechanism . PNA binding to DNA follows pseudo-first-order kinetics, but the initial rate of binding is accelerated more than 10-fold in the presence of 10 microM echinomycin . The activation energy for PNA binding to dsDNA is lowered 2-fold by the antibiotic (45 vs 90 kJ/mol in the control) . The reasons why quinoxalines promote the binding of PNA to DNA are not entirely clear but may well include distortions (opening) of the double helix that facilitate PNA invasion . This study establishes that the efficacy of DNA-targeted PNA antigene molecules could potentially be enhanced by judiciously adding certain DNA-interactive ligands.

RNA, 2000 Jul, 6(7), 1044 - 55
Aminoglycoside antibiotics mediate context-dependent suppression of termination codons in a mammalian translation system; Manuvakhova M et al.; The translation machinery recognizes codons that enter the ribosomal A site with remarkable accuracy to ensure that polypeptide synthesis proceeds with a minimum of errors . When a termination codon enters the A site of a eukaryotic ribosome, it is recognized by the release factor eRF1 . It has been suggested that the recognition of translation termination signals in these organisms is not limited to a simple trinucleotide codon, but is instead recognized by an extended tetranucleotide termination signal comprised of the stop codon and the first nucleotide that follows . Interestingly, pharmacological agents such as aminoglycoside antibiotics can reduce the efficiency of translation termination by a mechanism that alters this ribosomal proofreading process . This leads to the misincorporation of an amino acid through the pairing of a near-cognate aminoacyl tRNA with the stop codon . To determine whether the sequence context surrounding a stop codon can influence aminoglycoside-mediated suppression of translation termination signals, we developed a series of readthrough constructs that contained different tetranucleotide termination signals, as well as differences in the three bases upstream and downstream of the stop codon . Our results demonstrate that the sequences surrounding a stop codon can play an important role in determining its susceptibility to suppression by aminoglycosides . Furthermore, these distal sequences were found to influence the level of suppression in remarkably distinct ways . These results suggest that the mRNA context influences the suppression of stop codons in response to subtle differences in the conformation of the ribosomal decoding site that result from aminoglycoside binding.

Eur Arch Otorhinolaryngol, 2000, 257(5), 256 - 9
Intranasal budesonide spray as an adjunct to oral antibiotic therapy for acute sinusitis in children; Yilmaz G et al.; We investigated the clinical value of intranasal budesonide in acute sinusitis in 52 children with acute maxillary sinusitis . We randomly divided them into two groups: group 1 received oral pseudoephedrine (2 x 30 mg) and cefaclor (40 mg/kg) for 10 days, and group 2 received intranasal budesonide (2 x 100 microg) and cefaclor (40 mg/kg) for 10 days . Symptoms of headache, cough, and nasal stuffiness and signs of nasal discharge were graded before and after treatment . The patients whose symptoms and signs completely normalized after treatment were considered to have recovered, and those with persisting symptoms and signs after treatment as having not recovered . The results of the two treatment groups were compared . The recovery rate of the children in group 2 were significantly higher than those in group 1 (P < 0.05) . No adverse drug effects were determined during the study period . These findings suggest that topical steroids may be a useful adjunctive agent in the treatment of acute sinusitis of children without apparent side effects and can possibly hasten the resolution of symptoms.

FEBS Lett, 2000 Jul 28, 478(1-2), 137 - 40
Solution NMR structures of the polyene macrolide antibiotic filipin III; Volpon L et al.; The solution structure of filipin III, an antifungal polyene macrolide biosynthesized by Streptomyces filipinensis and widely used for the detection and the quantitation of cholesterol in biomembranes, has been calculated with a set of geometrical restraints derived from 1H NMR in DMSO-d(6) at 25 degrees C . Filipin III appears as a rod-shaped molecule of 18 A length . Its amphiphilic structure is made of an all-syn 1,3-polyol motif, stabilized by intramolecular hydrogen bonds on one side, and a conjugated pentaene moiety on the other side of the molecule . The overall shape is comparable to cholesterol, and the molecular structure of filipin III affords a first molecular basis to the comprehensive understanding of the interactions possible in the filipin III-cholesterol complex which is still unknown at the atomic resolution.

Rev Esp Quimioter, 2000 Jun, 13(2), 193 - 8
{Cost of antibiotic therapy in neutropenic patients undergoing peripheral blood stem cell transplantation for breast cancer}; Palau J et al.; The increase in pharmaceutical costs, especially for expensive procedures such as bone marrow transplants, has led to the study of the economic impact of febrile neutropenia in peripheral blood stem cell transplantation (PBSCT) . We analyzed 89 consecutive patients with breast cancer who underwent PBSCT . All patients developed febrile neutropenia and were administered an empirical intravenous regimen based on the combination of piperacillin-tazobactam and amikacin . We analyzed the direct costs of this treatment and grouped them into drug acquisition cost, administration costs (cost of the additional material), and preparation costs (time employed for the preparation and administration of the drug) . We found that the overall cost was $1,110, 65% of which corresponded to the initial therapy and the rest (35%) to the use of additional antibiotics . This higher cost was especially related to the use of vancomycin or teicoplanin (50%) . The acquisition costs accounted for 90% of the overall treatment costs . Thirty-six patients (40%) did not need additional antibiotics and the cost in this group was less ($663) . We concluded that knowledge of the costs of pharmacological therapy for infection in PBSCT is indispensable for the appropriate development of treatment units, especially in terms of optimizing resources and comparing different therapeutic or prophylactic approaches.

Am J Kidney Dis, 2000 Aug, 36(2), 238 - 49
Polyene antibiotics: relative degrees of in vitro cytotoxicity and potential effects on tubule phospholipid and ceramide content; Zager RA; Polyene antibiotic administration is limited by dose-dependent nephrotoxicity . The latter is believed to be mediated by polyene anchoring to plasma membrane cholesterol, resulting in pore formation, abnormal ion/solute flux, adenosine triphosphate (ATP) declines, and, ultimately, a loss of tubule viability . The relative nephrotoxicity of these agents and their liposomal preparations has remained poorly defined . Thus, freshly isolated mouse proximal tubules or cultured human proximal tubule (HK-2) cells were exposed to either nystatin, amphotericin B, or three different polyene liposomal preparations (Nyotran, AmBisome, or Abelcet; 4 to 64 microg/mL) . The impact of these agents on (1) plasma membrane injury (sodium-driven ATP consumption, assessed by ATP-adenosine diphosphate {ADP} ratios); (2) cellular susceptibility to superimposed injury (chemical hypoxia or ferrous ammonium sulfate-mediated oxidative stress; assessed by lactate dehydrogenase release); and (3) membrane cholesterol, phospholipid, and ceramide expression was assessed . Amphotericin B was more cytotoxic than nystatin (approximately 25% to 50% greater ATP-ADP ratio declines) . Most of this toxicity could be eliminated by polyene liposomal formulation . Nevertheless, the liposomal polyenes still fully sensitized tubule cells to superimposed chemical hypoxic (antimycin/deoxyglucose), but not oxidant, attack . Nystatin and amphotericin B caused acute increments in tubule sphingomyelin-phosphatidylcholine ratios and ceramide content (indicating an impact on the plasma membrane extending beyond the classic view of pore formation with ion flux) . In conclusion, (1) nystatin is seemingly less cytotoxic than amphotericin B (in contrast to the prevailing clinical view); (2) liposomal formulation markedly decreases this cytotoxicity; (3) despite this reduced toxicity, liposomal polyenes are still able to render tubule cells more vulnerable to selected forms of superimposed injury; and (4) acute alterations in plasma membrane phospholipid and ceramide expression are previously unrecognized consequences and potential mediators of polyene-mediated tubular cell attack.

Adv Ther, 2000 Jan-Feb, 17(1), 32 - 44
Antibiotic consumption patterns and drug leftovers in 6000 Brazilian households; Marliere GL et al.; Worldwide data indicate that antibiotics are frequently used indiscriminately . The present study used a questionnaire in an attempt to quantify and qualify outpatient antibiotic consumption habits, including when the drug was used, who recommended it, and to what extent treatment was completed, and to question householders on the presence of antibiotics in their homes, including leftovers from previous treatments . The questionnaire was distributed to residents of 6000 households that made up a representative sample of the Brazilian population and was completed by designated respondents from 4932 residences (82.2%) with or without field interviewer supervision . Each household reported an average of 3.7 treatments in the previous year, with amoxicillin the most frequently used antibiotic in this survey (18%), regardless of socioeconomic class . Most treatments were recommended through medical prescription, and this source of antibiotic was associated with the highest rate of completed therapy (80.4%) . Azithromycin and ciprofloxacin produced the highest rates of completed treatment and the lowest rates of antibiotic leftovers . Storing antibiotics at home increases the cost of each treatment event, reduces efficacy, and may encourage the emergence of resistant organisms in the community . Educational efforts must be redoubled to promote the rational and effective use of drugs, especially antibiotics.

Biochim Biophys Acta, 2000 Jul 26, 1475(3), 329 - 36
Identification of a plausible biosynthetic enzyme for the IM-2-type autoregulator in Streptomyces antibioticus; Shikura N et al.; Virginiae butanolides (VBs) and IM-2 are members of Streptomyces hormones called 'butyrolactone autoregulators' which regulate the antibiotic production in Streptomyces species at nanomolar concentrations . Cell-free extract of a VB-A overproducer, Streptomyces antibioticus NF-18, is capable of catalyzing the final step of the autoregulator biosynthesis, namely, the NADPH-dependent reduction of 6-dehydroVB-A . However, physico-chemical analyses of the purified enzymatic products revealed that, in addition to the VB-type isomer {(2R,3R,6S)-enantiomer}, IM-2-type isomers {(2R,3R, 6R)- and (2S,3S,6S)-enantiomers} were also produced from (+/-)-6-dehydroVB-A, suggesting the existence of several 6-dehydroVB-A reductases with respective stereoselectivities . The reductase activity of the crude extracts was separated into two activity peaks, peak I (major) and peak II (minor), by DEAE-5PW HPLC . Chiral HPLC analyses demonstrated that peak I enzyme and peak II enzyme catalyzed the production of (2R,3R,6S), (2R,3R,6R) and (2S,3S, 6S) isomers at ratios of 46:1:3.2 and 4.9:1:1.5, respectively, indicating clearly that S . antibioticus NF-18 possesses at least two 6-dehydroVB-A reductases: one much favored toward VB-A biosynthesis, the other with relaxed stereoselectivity capable of synthesizing both VB-type and IM-2-type autoregulators.

FEBS Lett, 2000 Jul 7, 476(3), 186 - 9
Inversion of the anomeric configuration of the transferred sugar during inactivation of the macrolide antibiotic oleandomycin catalyzed by a macrolide glycosyltransferase; Quiros LM et al.; Macrolides are a group of antibiotics structurally characterized by a macrocyclic lactone to which one or several deoxy-sugar moieties are attached . The sugar moieties are transferred to the different aglycones by glycosyltransferases (GTF) . The OleI GTF of an oleandomycin producer, Streptomyces antibioticus, catalyzes the inactivation of this macrolide by glycosylation . The product of this reaction was isolated and its structure elucidated . The donor substrate of the reaction was UDP-alpha-D-glucose, but the reaction product showed a beta-glycosidic linkage . The inversion of the anomeric configuration of the transferred sugar and other data about the kinetics of the reaction and primary structure analysis of several GTFs are compatible with a reaction mechanism involving a single nucleophilic substitution at the sugar anomeric carbon in the catalytic center of the enzyme.

Arch Fam Med, 2000 Jul, 9(7), 589 - 95
Characteristics and experiences of parents and adults who want antibiotics for cold symptoms; Braun BL et al.; OBJECTIVE: To characterize people who want antibiotics for cold symptoms and to suggest reasons for antibiotic expectations . DESIGN: Cross-sectional telephone survey in the spring of 1997 (March 10 to May 16) . SETTING: Three primary care clinics in metropolitan Minneapolis, Minn . PARTICIPANTS: Two hundred forty-nine parents of symptomatic children and 256 symptomatic adults contacting their medical provider (primary care physician, nurse practitioner, or physician assistant) for care of cold symptoms . MAIN DEPENDENT MEASURE: Wanting an antibiotic prescription for cold symptoms . RESULTS: Thirty percent of parents and 50% of symptomatic adults wanted an antibiotic prescription . Factors associated with desire for antibiotics differed between groups . Parents who wanted antibiotics for their children were more likely than other parents to report severe symptoms (odds ratio {OR}, 2.11; 95% confidence interval {CI}, 1.16-3.85), to want relief for their child (OR, 2.63; 95% CI, 1.34-5.46), and to believe that antibiotic therapy helps cold symptoms (OR, 1.95; 95% CI, 1.08-3.55) . Symptomatic adults who wanted antibiotics were more likely than other symptomatic adults to report severe cold symptoms (OR, 2.10; 95% CI, 1.22-3.67) that have lasted too long (OR, 2.40; 95% CI, 1.31-4.49), to previously have recovered faster with antibiotic therapy (OR, 2.82; 95% CI, 1.65-4.89), and to be confident that they know how to treat the cold (OR, 1.79; 95% CI, 1.03-3.16) . They were less likely to believe that too many people take antibiotics for a cold (OR, 0.57; 95% CI, 0.33-0.98) . CONCLUSIONS: Parents may be amenable to clinical messages that other treatments may be more effective than antibiotics in managing cold symptoms . Experiences of symptomatic adults may conflict with this message . Previous cold-related medical management and drug resistance might need to be discussed with adult patients.

Folia Med Cracov, 1999, 40(3-4), 17 - 25
{Effects of antibiotic therapy on endoscopic examination of the upper gastrointestinal tract in children with Helicobacter pylori infections}; Banach T et al.; The aim of the study was defining the antibiotic influence for endoscopic picture of the upper segment of gastrointestinal tract in Helicobacter pylori infection . We remained retrospectively analysis of 790 endoscopies . In 62 of the analysed patients we found Helicobacter pylori infection . We divided these children into two groups . The first group, contained 15 children, who received antibiotics for the previous year, for any reasons . The second, comparative group was made up of 47 children, who didn't receive antibiotics . We compared 18 characteristics of endoscopic picture in the oesophagus, stomach and duodenum mucosa . As a result of this study we conclude, that: 1) the most frequently the endoscopic changes were found in the stomach, as an erythema, an oedema and a nodularity of mucosa; 2) the inflammatory changes were in oesophagus and duodenum, as well; 3) we didn't observe the clear influence of antibiotics on the development of endoscopic changes in Helicobacter pylori infection; 4) in children, who didn't receive antibiotics, we observed polypus in the oesophagus, erosions in the stomach and ulcer in the duodenum . This may suggest the preventive role of antibiotics on intensity of gastrointestinal changes in Helicobacter pylori infected children.

J Am Vet Med Assoc, 2000 Jul 1, 217(1), 68 - 73
Risk of adverse effects in pneumonic foals treated with erythromycin versus other antibiotics: 143 cases (1986-1996); Stratton-Phelps M et al.; OBJECTIVE: To determine whether foals with pneumonia that were treated with erythromycin, alone or in combination with rifampin or gentamicin, had a higher risk of developing adverse effects, compared with foals treated with trimethoprim-sulfamethoxazole (TMS), penicillin G procaine (PGP), or a combination of TMS and PGP (control foals) . DESIGN: Retrospective study . ANIMALS: 143 foals < 240 days old . PROCEDURE: Information on age, sex, breed, primary drug treatment, total days of treatment with the primary drug, and whether the foal developed diarrhea, hyperthermia, or respiratory distress was obtained from the medical records . Relative risk (RR) and attributable risk (AR) were calculated to compare risk of adverse reactions between foals treated with erythromycin and control foals . RESULTS: Only 3 (4.3%) control foals developed diarrhea; none developed hyperthermia or respiratory distress . Foals treated with erythromycin had an 8-fold risk (RR, 8.3) of developing diarrhea, compared with control foals, and increased risks of hyperthermia (AR, 25%) and respiratory distress (AR, 15%) . CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of erythromycin to treat foals with pneumonia was associated with an increased risk of diarrhea, hyperthermia, and respiratory distress, compared with use of TMS or PGP.

J Antibiot (Tokyo), 2000 May, 53(5), 502 - 8
Cloning, characterization and heterologous expression of a polyketide synthase and P-450 oxidase involved in the biosynthesis of the antibiotic oleandomycin; Shah S et al.; The gene cluster encoding the deoxyoleandolide polyketide synthase (OlePKS) was isolated from the oleandomycin producing strain Streptomnyces antibioticus . Sequencing of the first two genes encoding OlePKS, together with the previously identified third gene revealed an overall genetic and protein architecture similar to that of the erythromycin gene cluster encoding the 6-deoxyerythronolide B synthase (DEBS) from Saccharopolyspora erythraea . When the entire OlePKS (10,487 amino acids) was expressed in the heterologous host Streptomyces lividans, it produced 8,8a-deoxyoleandolide, an aglycone precursor of oleandomycin . The role of the P-450 monooxygenase, OleP, in oleandomycin biosynthesis was also examined in vivo by co-expression with DEBS in S . lividans . The production of 8,8a-dihydroxy-6-deoxyerythronolide B and other derivatives indicates that OleP is involved in the epoxidation pathway of oleandomycin biosynthesis . Since there are currently no genetic systems available for manipulation of the natural oleandomycin producing strain, the heterologous expression system reported here provides a useful tool for studying this important macrolide antibiotic.

Pol Merkuriusz Lek, 1997 Jan, 2(9), 161 - 4
{Antibiotics in treatment of respiratory tract infection}; Plusa T; Antibiotics are discussed in sequential therapy of respiratory tract infection . Penetration into bronchial tissue and bronchial resistance are presented as a main therapeutical problem.

Rev Neurol, 2000 Jun 1-15, 30(11), 1022 - 6
{Aminoglycoside antibiotics neomycin and kanamycin inhibit the increase of of pyroglutamyl aminopeptidase activity by depolarizing synaptosomes of the frontal cortex of the rate}; Ramirez-Exposito MJ et al.; INTRODUCTION: Thyrotrophin releasing hormone (TRH) has emerging in the last few years as a neuropeptide with important functions, not only as neurohormone into the hypothalamus-pituitary axis, but as neurotransmitter in several areas of the nervous system . Although little is known about its extra-endocrine functions, TRH has been related with several types of psychiatric disorders . Pyroglutamyl aminopeptidase (pGluAP) is the enzyme involved in the degradation of TRH . OBJECTIVES: The present research studies the levels of pGluAP activity under basal (resting) and KCl-stimulated (depolarized) conditions . The role of intracellular free calcium homeostasis, by means of the aminoglycoside antibiotics neomycin and kanamycin as voltage-dependent calcium channels blockers, is also studied . MATERIAL AND METHODS: Both pGluAP activity and intracellular free calcium concentration were analyzed in synaptosomes obtained from the frontal cortex of rats . Synaptosomes were incubated in artificial cerebrospinal fluid, under basal (resting) or KCl-stimulated (depolarized) conditions, with of without neomycin or kanamycin at different concentrations . RESULTS: Depolarization increases significantly pGluAP activity, which is completely abolished by neomycin and kanamycin at the lower concentrations used . On the contrary, aminoglycoside antibiotics do not block completely the increase on intracellular free calcium concentration induced by depolarization . Under basal conditions, no changes were found on pGluAP activity nor intracellular free calcium . CONCLUSIONS: pGluAP activity could regulate the neurotransmitter/neuromodulatory functions of TRH trough intracellular free calcium movements through aminoglycoside-sensitive voltage-dependent calcium channels . A role for inositol 4,5-bisphosphate breakdown products is also suggested.

Biopolymers, 1997 Dec, 42(7), 759 - 69
Structure, dynamics, and topological orientation of the polyether, ionophore antibiotic monensin, in a micellar environment; Mercurio E et al.; The structure and dynamics of the ionophoric antibiotic monensin in the presence of micelles have been determined . The conformation of monensin was derived from 50 nuclear Overhauser enhancement (NOE) derived distance restraints and metric-matrix based distance geometry calculations . The conformation was further refined with extensive NOE restrained molecular dynamics simulations carried out in a biphasic simulation cell . From the addition of doxylstearate and monitoring of the induced relaxation of the nmr signals, the relative topological orientation of the molecule within the micelle was ascertained . The results indicate two dihedral angles that act as hinge regions allowing the molecule to adopt a wide range of conformations . Considering the biological activity of monensin, i.e., the capture and transport of cations across cell membranes, an open and closed form of monensin have been postulated . The identification of these hinge regions, which are only observed in the membrane-like environment of the detergent micelles, provides insight into the mechanism of action and can serve as targets for modification to alter the biological profile of monensin.

Clin Exp Pharmacol Physiol, 2000 Aug, 27(8), 587 - 93
Reversal of anticancer drug resistance by macrolide antibiotics in vitro and in vivo; Wang L et al.; 1 . The combined effects of the macrolide antibiotics erythromycin, josamycin, clarithromycin and YM17K (3,4'-dideoxy mycaminosyl tylonolide hydrochloride) on in vitro intracellular accumulation of vinblastine or cyclosporine (Cs)A and on the in vivo antitumour activity of vinblastine were investigated using mouse leukaemia P388 cells (P388/S) and anticancer drug-resistant (P388/ADR) cells . These effects were compared with those of a calcium antagonist (verapamil) or immunosuppressants (FK506 and CsA) . 2 . All tested macrolide antibiotics increased the accumulation of both vinblastine and CsA in P388/ADR cells in a dose-dependent manner, but their potency was lower than that of verapamil, CsA or FK506 . 3 . When vinblastine (200 microg/kg) was administered intraperitoneally with each of the macrolide antibiotics (10 or 100 mg/kg) or with verapamil (25 mg/kg) once a day for 10 days in P388/ADR-bearing mice, combined effects of vinblastine with the macrolide antibiotics (erythromycin, clarithromycin and YM17K) or verapamil were observed . 4 . The present study suggests that macrolide antibiotics may overcome anticancer drug resistance by inhibiting the binding of vinblastine or CsA to P-glycoprotein in P388/ADR cells . 5 . We believe that these results are encouraging for combination chemotherapy to overcome P-glycoprotein-dependent anticancer drug-resistant tumours in clinical practice.

Brain Res, 2000 Jul 21, 871(2), 319 - 32
Cytoskeletal protein mRNA expression in the chick utricle after treatment in vitro with aminoglycoside antibiotics: effects of insulin, iron chelators and cyclic nucleotides; Stacey DJ et al.; In birds, spontaneous recovery of the hair cells of the inner ear can occur after damage induced by aminoglycoside antibiotics . The factors that influence this recovery and the process of hair cell regeneration itself have until recently been investigated largely by morphological and histological methods . The aim of this work was to use a molecular biological approach to the analysis of hair cell regeneration by measuring the changes that occur in expression of mRNA for hair cell-specific cytoskeletal proteins fimbrin and class III beta-tubulin, along with that for beta-actin, in the utricle of chicks after hair cell damage both in vitro and in vivo . Utricles were removed from 1-day-old chicks and incubated with the aminoglycoside antibiotics gentamicin or neomycin (both 1 mM), or chicks were injected intraperitoneally with 100 mg/kg gentamicin or neomycin for 4 consecutive days . At the end of the treatment periods, total RNA was extracted from single utricles, reverse transcribed to cDNA and the cDNA amplified by PCR with primers for beta-actin, fimbrin and class III beta-tubulin . Co-amplification allowed quantitative comparison of mRNA between fimbrin, or class III beta-tubulin and beta-actin from the same utricle . Both aminoglycosides, either after 48 h in vitro or immediately after treatment in vivo, caused a significant decrease in the expression of fimbrin mRNA and class III beta-tubulin mRNA, relative to beta-actin mRNA, which itself increased . Light and electron microscopy confirmed that this corresponded to loss of, and damage to, hair cells . The relative expression of fimbrin and class III beta-tubulin mRNAs was partly restored almost to control levels 4 days after cessation of treatment in vivo and fully normalised by 4 weeks, by which time hair cells appeared normal . However, their relative expression remained depressed 4 days after removal of antibiotic in vitro . The iron chelator desferrioxamine (100 microM) in vitro prevented the aminoglycoside-induced reduction in relative expression of mRNA for both fimbrin and class III beta-tubulin . Neither insulin (5 microM) nor a combination of dibutyryl cyclic AMP (5 mM) and the phosphodiesterase inhibitor IBMX (0.5 mM) prevented the decrease in relative expression of the mRNAs for the hair cell-specific proteins, but both treatments allowed their partial recovery in vitro during the 4-day-period after removal of aminoglycoside . It is concluded that the cells of the sensory epithelium of the chick utricle subjected to aminoglycoside-induced damage undergo a process in which mRNA expression is switched away from the production of functional proteins and towards proteins necessary for structural re-organisation . The restoration of mRNA expression to a normal pattern is promoted by the growth factor insulin and by cyclic AMP.

Theriogenology, 2000 Apr 15, 53(7), 1489 - 99
Flow cytometric evaluation of antibiotic effects on viability and mitochondrial function of refrigerated spermatozoa of Nile tilapia; Segovia M et al.; Improved techniques for storage and evaluation of fish sperm would enhance breeding programs around the world . The goal of this study was to test the effect of antibiotics on refrigerated sperm from Nile tilapia (Oreochromis niloticus) by use of flow cytometry with 2 dual-staining protocols for objective assessment of sperm quality . Concentrations of 1 x 10(9) . sperm/mL were suspended in Ringer's buffer at 318 mOsmol/kg (pH 8.0) . The fluorescent stains Sybr 14 (10 microM), propidium iodide (2.4 mM), and rhodamine 123 (0.13 microM) were used to assess cell viability and mitochondrial function . Three concentrations of ampicillin, gentamicin, and an antibiotic/antimycotic solution were added to fresh spermatozoa . Motility estimates and flow cytometry measurements were made daily during 7 d of refrigerated storage (4 degrees C) . The highest concentrations of gentamicin and antibiotic/antimycotic and all 3 concentrations of ampicillin significantly reduced sperm viability . The highest of each of the 3 antibiotic concentrations significantly reduced mitochondrial function . This study demonstrates that objective sperm quality assessments can be made using flow cytometry and that addition of antibiotics at appropriate concentrations can lengthen refrigerated storage time for tilapia spermatozoa . With minor modifications, these protocols can be adapted for use with sperm from other species and with other tissue types.

Eur J Clin Microbiol Infect Dis, 2000 May, 19(5), 332 - 5
Management of brain abscesses with sequential intravenous/oral antibiotic therapy; Skoutelis AT et al.; Eight patients with brain abscesses who refused prolonged hospitalisation were treated with a short course (6-12 days) of intravenous antibiotics followed by prolonged treatment (15-19 weeks) with an oral antibiotic regimen consisting of metronidazole, ciprofloxacin and amoxicillin . All patients responded favourably as shown clinically and in imaging studies . No severe adverse events or sequelae were noted . On admission all patients had a normal or mildly impaired mental status, abscesses less than 3 cm in diameter and no serious predisposing factors . Although combined surgical/medical treatment remains the standard approach in management of these patients, the findings suggest that oral antibiotic therapy only subsequent to a short course of intravenous antibiotics may be an acceptable alternative in selected cases.

J Chromatogr A, 2000 Jun 16, 882(1-2), 109 - 33
Chromatographic analysis of tetracycline antibiotics in foods; Oka H et al.; Tetracycline antibiotics (TCs), such as oxytetracycline, tetracycline, chlortetracycline, and doxycycline, have for decades continued to play an important role in veterinary medicine and feed additives because of the broad spectrum antibiotics and their economical advantages . Many analysis methods of TCs, therefore, have been reported to monitor their residues in foods . We review the recent developments in chromatographic analysis methods for TCs in foods . This review involves the following techniques: thin layer chromatography, capillary electrophoresis, high-performance liquid chromatography, and sample preparation including extraction and clean up procedures.

Dermatology, 2000, 200(4), 342 - 5
Three cases of cutaneous sarcoidosis: search for bacterial agent by the 16S RNA gene analysis and treatment with antibiotics; Toutous-Trellu L et al.; BACKGROUND: The aetiology of sarcoidosis remains controversial . An infectious origin is often discussed, but only anti-inflammatory or immunosuppressive treatment is recommended . OBJECTIVES: To investigate the hypothesis of bacterial origin by treating cutaneous sarcoidosis with antibiotics . METHODS: Patients with chronic cutaneous sarcoidosis, unresponsive to the usual treatment and not requiring systemic corticotherapy, were given combined antibiotherapy for 6 months . Search for bacterial DNA by amplification and sequencing of the 16S ribosomal RNA gene in skin biopsies of lesions before and after antibiotherapy was done . RESULTS: Three patients received a combined treatment with clarithromycin 1 g/day and ciprofloxacin 1 g/day . No clinical changes occurred in 2 cases and transient worsening in 1 . Amplification for bacterial DNA was positive in all skin biopsies . The sequencing of this DNA could not identify a unique bacterial species . CONCLUSION: No evident bacterial origin could be demonstrated; however, this approach should be extended to more patients .

Respir Care, 2000 Jun, 45(6), 667 - 75
Aerosolized antibiotics: current and future; Smaldone GC et al.; Aerosolized antibiotic therapy appears to have potential for targeted therapy to the airways and deep lung to prevent VAP in patients at high risk for this disease . The definition of that high-risk population is important if this model is to be successful . We are attempting to define susceptible patients by measuring the volume of airway secretions, which mirrors the inflammation milieu of the central airways . Elevated sputum volume is marked by heavy growth of pathogenic organisms and high levels of inflammatory cytokines . Large-scale clinical trials are necessary to define the usefulness of these surrogates in defining a targeted population and for assessing the potential of aerosolized antibiotic prophylactic therapy for preventing pneumonia and mortality . If successful, the aerosol approach may avoid systemic therapy and its associated complications.

Gastroenterol Clin Biol, 2000 May, 24(5), 495 - 500
{Treatment of Helicobacter pylori infection with lansoprazole 30 mg or 60 mg combined with two antibiotics for duodenal ulcers}; Lamouliatte H et al.; OBJECTIVE: The primary objective of the present study was to evaluate the efficacy of 30 and 60 mg of lansoprazole administered in combination with two antibiotics for 7 or 10 days in eradicating Helicobacter pylori in duodenal ulcer patients . METHODS: This multicenter double-blind study randomized for the lansoprazole dose was carried out by 325 gastroenterologists . The H . pylori-positive diagnosis was based on three antral biopsies (one for a rapid urease test and two for histological examination) . Eradication was checked by a (13) C-urea breath test . Patients were given 30 or 60 mg of lansoprazole with 2 g of amoxicillin and 1 g of clarithromycin for 10 days or 7 days, followed by 30 mg of lansoprazole daily for 18 or 21 days, i.e . the total duration of antisecretory therapy was 28 days . RESULTS: Out of the 665 patients included, 620 were analyzed on the intent-to-treat basis and 567 on the per protocol basis . The eradication rates were significantly higher in the group receiving 60 mg of lansoprazole than in the 30 mg group in both the intent-to-treat analysis (P=0.003) and the per protocol analysis (P=0.006) . In the intent-to-treat analysis 60 mg group, the rates (95% confidence intervals) in the 7-day and 10-day sub-groups were 82.5 (CI: 75.2 - 89.8) and 86.8% (CI: 82.2 - 91.4), respectively, and in the per protocol analysis 84.2 (CI: 76.9 - 91.5) and 91.5% (CI: 87.6 - 95.4), respectively . With either lansoprazole dose, the eradication rates seemed higher when therapy was administered for 10 days . CONCLUSION: The double dose of lansoprazole optimizes H . pylori eradication rates . The highest eradication rates were obtained after 10 days of therapy . Additional studies should be carried out to determine the optimal duration of triple therapy for eradicating H . pylori.

Arch Dermatol, 2000 Jul, 136(7), 849 - 54
Antibiotic rashes in children: a survey in a private practice setting; Ibia EO et al.; OBJECTIVE: To document the frequency and severity of various types of rashes seen with commonly used oral antibiotics in the pediatric outpatient setting . DESIGN: A retrospective review of 5923 patient records at a pediatric office . SETTING: A private group pediatric practice in northern Virginia with about 12,000 registered active patients . PATIENTS AND METHODS: Approximately 50% of the clinic medical records were reviewed . All children (defined as those aged 0-18 years in this study) identified on their medical records as having developed a rash following treatment with 1 or more of the commonly used oral antibiotics were included in the study . For further validation, a questionnaire about parental recollection of description of rash, other associated symptoms, physician verification, and outcome was mailed to families with children designated as being allergic to an antibiotic . RESULTS: On a prescription basis, significantly more rashes were documented for cefaclor (4.79%) compared with penicillins (2.72%), sulfonamides (3 . 46%), and other cephalosporins (1.04%) . Based on the number of patients for whom each group of antibiotic was prescribed, the documented frequencies of rashes were 12.3%, 7.4%, 8.5%, and 2.6% for cefaclor, penicillins, sulfonamides, and other cephalosporins, respectively . None of the children had rashes severe enough to require hospitalization . CONCLUSIONS: In a review of almost 6000 records in a private pediatric primary care setting, rashes occurred in 7.3% of children who were given the commonly used oral antibiotics . Significantly more rashes were documented with cefaclor use than with use of any of the other oral antibiotics.

Br Poult Sci, 2000 May, 41(2), 174 - 7
Food safety implication: certain antibiotics may rapidly contaminate egg albumen during the process of its formation; Donoghue DJ et al.; 1 . Egg white formation occurs in 3 phases: synthesis and storage of albumen proteins prior to ovulation, secretion of proteins during passage of the ovum down the reproductive tract (preplumping) and addition of water (plumping phase) . 2 . This study was to determine if oxytetracycline would transfer into egg albumen during the latter 2 phases of albumen formation . 3 . In 2 experiments 48 hens were injected with either 400 mg/kg oxytetracycline or physiological saline . Hens were dosed at 0.5 h (preplumping phase) or 5.5 h (plumping phase) after oviposition . 4 . Five hours following injections, hens were euthanised and albumen was collected from the reproductive tract . 5 . Oxytetracycline transferred into albumen during both phases of albumen formation . Concentrations (ppm) were greater in the preplump vs plump phase (3.2 vs 1.8 in experiment 1; or 2.8 vs 1.6 in experiment 2 . However, when differences in albumen weights were accounted for, total microg transfer did not differ between the 2 phases . 6 . Drugs may transfer into egg whites during the latter phases of formation prior to oviposition . Therefore, poultry producers or veterinary practitioners dosing laying hens must consider that egg whites contained in the 1st egg laid after dosing may contain drug residues.

Drug Deliv, 2000 Apr-Jun, 7(2), 69 - 75
Polyacrylamide-chitosan hydrogels: in vitro biocompatibility and sustained antibiotic release studies; Risbud MV et al.; Controlled drug delivery is gaining importance over the conventional methods of drug administration because of its inherent benefits . Self-regulated release from the delivery vehicle may enhance drug potency with a sustained action . The present study describes a novel hydrogel blend of polyacrylamide with chitosan for controlled delivery of antibiotics . Hydrogel was synthesized by cross-linking acrylamide-chitosan mixture (8:2 v/v) with N,N' methylene bisacrylamide . Hydrogel was characterized for surface morphology, hydrophilicity, pH-dependent swelling properties, cytotoxicity, and control release properties . Scanning electron microscopy (SEM) revealed the macroporous surface morphology of the matrix with average pore size at 104 +/- 7.61 mu . Hydrogel was found to be highly hydrophilic as assessed by octane contact angle (154.5 + 0.572) measurement . Hydrogel showed no cytotoxic effects on NIH3T3 and HeLa cells up to 40% of extract concentrations as determined by MTT and neutral red assay . This showed hydrogel biocompatibility and thus absence of deleterious effects of the hydrogel on cell viability and functionality . Hydrogels did not show any pH-dependent swelling profile, and they swelled considerably to achieve a swelling ratio of approximately 16.0 at the end of 24 hr . Amoxicillin was incorporated in the hydrogel matrix as a candidate antibiotic for release studies . In vitro release studies of amoxicillin revealed the sustained nature of delivery and matrix released 56.47 + 1.12% and 77.096 + 1.72% of amoxicillin at the end of 24 and 75 hr, respectively . Although in vivo studies are awaited, the present study provides enough documentation to consider polyacrylamide-chiotsan hydrogel as a possible candidate for controlled delivery of antibiotics.

J Agric Food Chem, 2000 Jun, 48(6), 2244 - 8
Determination of tetracycline antibiotics in beef and pork tissues using ion-paired liquid chromatography; Moats WA; A simplified procedure was developed for determination of tetracycline antibiotics in tissues which improved stability of these compounds in sample extracts and eliminated the need for troublesome cleanup procedures . Tissues were homogenized in water . Acetonitrile (16 mL) and then 1 mL of 0.1 M H(3)PO(4) were added to 4 mL of homogenate and the clear supernatant was filtered . The filtrate was mixed with hexane and dichloromethane and the resulting water layer was collected, evaporated to 1-2 mL, and filtered into autosampler vials . Ion-pairing liquid chromatography was used to separate tetracyclines from interferences in sample extracts, eliminating the need for further cleanup . Analysis was isocratic using a Phenomonex Prodigy ODS(3) column with a mobile phase of 4 mM oxalic acid, 4 mM sodium oxalate, 10 mM sodium decanesulfonate-acetonitrile (70 + 30 for oxytetracycline and tetracycline; 66 + 34 for chlortetracycline) . Recoveries were generally in the 90-100% range with limits of quantitation of 0 . 05-0.1 ppm . The procedure was evaluated with beef and pork muscle, liver, and kidney.

Hosp Pract (Off Ed), 1999 Oct 15, 34(11), 117 - 22, 126
Oral antibiotics: are the old still gold?
Joshi N.
Most common infections in ambulatory care can be treated effectively and safely with conventional antibiotics . A rational approach using such antibiotics as primary choices and reserving newer antibiotics for selected, more difficult-to-treat infections will result in substantial cost savings and may help to prevent the rapid development of drug resistance.

J Control Release, 2000 Jul 31, 68(1), 23 - 30
pH-sensitive freeze-dried chitosan-polyvinyl pyrrolidone hydrogels as controlled release system for antibiotic delivery; Risbud MV et al.; The aim of this study was to develop a pH-sensitive chitosan/polyvinyl pyrrolidone (PVP) based controlled drug release system for antibiotic delivery . The hydrogels were synthesised by crosslinking chitosan and PVP blend with glutaraldehyde to form a semi-interpenetrating polymer network (semi-IPN) . The semi-IPN formation was confirmed by Fourier transform infrared spectroscopic (FTIR) analysis . Semi-IPNs, viz, air-dried and freeze-dried, were compared for their surface morphology, wettability, swelling properties and pH-dependent swelling . Air- and freeze-dried membranes were also incorporated with amoxicillin and antibiotic release was studied . Porous freeze-dried hydrogels (pore diameter, 39.20+/-2.66 microm) exhibited superior pH-dependent swelling properties over non-porous air-dried hydrogels . A high octane contact angle (144.20+/-0.580) of hydrogel was indicative of its hydrophilic nature . Increased swelling of hydrogels, under acidic conditions, was due to the protonation of a primary amino group on chitosan, as confirmed by FTIR analysis . Freeze-dried membranes released around 73% of the amoxicillin (33% by air-dried) in 3 h at pH 1.0 and, thus, had superior drug-release properties to air-dried hydrogels . Freeze-dried membranes could serve as potent candidates for antibiotic delivery in an acidic environment.

J Biomed Mater Res, 2000 Sep 5, 51(3), 424 - 9
In vitro bioactivity and gentamicin release from glass-polymer-antibiotic composites; Ragel CV et al.; Composite materials have been prepared from bioactive glass powders in the SiO(2)-CaO-P(2)O(5) system, a biodegradable polymer {poly(L-lactic acid) (PLA)}, a biostable polymer {polymethylmethacrylate (PMMA)}, and an antibiotic {gentamicin} . The purpose of such composites is to obtain implantable materials that are able to lead to bone growth and also can, at the most critical inflammation-infection step, release an antibiotic . X-ray diffraction, scanning electron microscopy, X-ray energy dispersive spectroscopy, and FTIR analyses after different soaking periods in SBF demonstrated the growth of an apatite-like layer on the composite surface . Therefore the bioactive glass-polymer-antibiotic combination used in this work does not inhibit the glass bioactivity . The release of gentamicin after a soaking of the materials in SBF was followed by UV-visible spectroscopy . A fast initial release during the first 10 h of soaking, followed by a controlled release of the drug was observed .

Cutis, 2000 Jun, 65(6), 401 - 4
A newly formulated topical triple-antibiotic ointment minimizes scarring; Berger RS et al.; A randomized study of polymyxin B sulfate-bacitracin zinc-neomycin sulfate versus simple gauze-type dressings in dermabrasion wounds assessed the effects that each treatment had on scarring . Each of three uniform dermabrasion wounds created on the upper backs of 70 subjects was treated concurrently with a triple-antibiotic ointment (polymyxin B-bacitracin-neomycin), a double antibiotic (polymyxin B-bacitracin), or a simple, non-occlusive, gauze-type dressing, twice daily for up to 14 days . Pigmentary changes and textural changes (scarring) appearing after healing at the skin surface test sites were compared to adjacent normal skin at 45 and 90 days post-dermabrasion . These changes were graded visually utilizing fluorescent light, long-wave ultraviolet light, and by clinical color photography . The triple-antibiotic ointment was superior to simple gauze-type dressing alone in minimizing the scarring observed in dermabrasion wounds . The benefit of this new ointment was more pronounced in its effect on pigmentary changes.

Mediators Inflamm, 2000, 9(1), 39 - 43
Suppressive activity of a macrolide antibiotic, roxithromycin on co-stimulatory molecule expression on mouse splenocytes in vivo; Kawazu K et al.; The influence of roxithromycin (RXM) on the expression of co-stimulatory molecules, CD40, CD80 and CD86, was examined in vivo . When BALB/c mice were immunized intraperitoneally with two doses of dinitrophenylated ovalbumin (DNP-OVA) at 1 week intervals, intraperitoneal administration of RXM at 250 microg/kg once a day for 14 days strongly suppressed IgE contents in sera obtained from mice 22 days after the first immunization . In addition, RXM treatment of mice suppressed endogenous IL-4 contents in aqueous spleen extracts, which were enhanced by DNP-OVA immunization . We next examined the influence of RXM on co-stimulatory molecule expression on splenic lymphocytes . RXM treatment of the immunized mice caused suppression of CD40 expression, but this treatment did not affect CD80 and CD86 expression.

Yi Chuan Xue Bao, 1999, 26(6), 721 - 30
{Over-expression of a polyketide synthase (PKS) module of a giant polyene antibiotic gene cluster in E . coli by double induction}; Tao MF et al.; A 2,671 bp DNA carrying a type I PKS module with KS and AT domains from Streptomyces sp . FR-008 was cloned in-frame into the BamHI site immediately downstream of the PT7 promoter of the E . coli expression vector pET-15b, no considerable expression under IPTG induction was detected . The same PKS gene cloned downstream of the tandem PRPL promoters of pBV220 also yielded no over-expression under 42 degrees C induction . This gene was, however, over-expressed when it was cloned downstream of the tandem PRPT7 or PRPLPT7 promoters . In the case of the tandem PRPLPT7 promoters, the over-expression was dependent on the 42 degrees C plus IPTG double induction . While in the case of the tandem PRPT7 promoters, over-expression could be achieved when the gene was induced by IPTG or 42 degrees C individually or by IPTG and 42 degrees C double induction . Based on these experiences an expression vector pHZ330 containing the tandem PRPT7 promoters was constructed . In addition, the PKS protein expressed in E . coli was injected into rabbits to generate PKS-specific antibodies . Western blotting experiment indicated that these antibodies were PKS-specific which could be used either for the study of the PKS gene cluster or for the detection of the heterologous expression of Streptomyces sp . FR-008 PKS genes.

Pediatrics . 2000 Jul;106(1):E10.
How much antibiotic suspension is enough?
Dusdieker LB, Murph JR, Milavetz G.
OBJECTIVES: Pilot data suggest that inadequate antibiotic volumes are often dispensed . Study goals were to determine the frequency of inadequate antibiotic volumes dispensed by local pharmacies, develop prescription-writing guidelines to ensure that adequate antibiotic suspension volumes are dispensed, and document the adequacy of verbal/written counseling pharmacists provide . METHODS: Sixty-one local pharmacies filled prescriptions for penicillin potassium (PCN; 250 mg/5 mL {5 mL orally 3 times daily for 10 days}) and Bactrim (trimethoprim-sulfamethoxazole {TMP-SMX} 5 mL orally twice daily for 10 days) . The prescriptions noted only to "dispense a 10-day supply . " Volumes were measured first as total amount dispensed and then into total doses dispensed . Written/verbal instructions were documented . RESULTS: The volume of PCN dispensed was 195 +/- 25 mL (range: 105-222 mL) for an average of 29.4 doses, where 30 doses were needed . TMP-SMX dispensed had a volume of 107 +/- 5 mL (range: 98-120 mL) resulting in an average of 16.5 doses, where 20 doses were needed . Twenty pharmacies (33%) did not dispense a measuring device . Verbal counseling by the pharmacist and written instructions were not uniformly given . CONCLUSIONS: We suggest calculating the actual volume needed plus an additional 10% to 30% of volume (depending on the viscosity) . The prescription should also request a medication-measuring/administering device . Patient counseling and instruction should be expanded.

Am J Med Sci, 2000 Jun, 319(6), 360 - 5
Antibiotics and return visits for respiratory illness: a comparison of pooled versus hierarchical statistical methods; Pan Q et al.; BACKGROUND: Antibiotic prescribing for respiratory illness has been associated with small reductions in return visits in an analysis of a large practice-based network . In this study, we apply hierarchical analytical methods that account for the clustering of patients by practices to identify whether antibiotic prescribing by primary care physicians reduces subsequent visits for 6 acute respiratory illnesses-upper respiratory infection, pharyngitis, bronchitis, otitis media, sinusitis, and cough . METHODS: The study data came from 318 family physicians and internists in 45 practices in the Practice Partner Research Network from January 1995 through December 1996, with 255,564 active patients . Patients treated with antibiotics were compared with those who were not on the frequency of revisit within the next 14 days . A simple pooling model and 3 hierarchical statistical models (fixed-effects, random-effects, and Bayesian) were used to compare the odds-ratios for return visits . RESULTS: Statistically significant results were found only for bronchitis and sinusitis by the hierarchical models, but the simple pooling model produced statistically significant results for all study conditions . CONCLUSION: We conclude that antibiotics may reduce return visits for patients with bronchitis and sinusitis, but not for patients with other respiratory illness (upper respiratory infection, pharyngitis, otitis media, or cough) . Studies of large clinical databases should use methods of analysis that account for the grouping of patients by practice to avoid false positive associations (type I errors.)

Ann Fr Anesth Reanim, 2000 May, 19(5), 418 - 23
{Ecological consequences of preventive antibiotic prescriptions}; Korinek AM; Assessing the ecological impact of preventive antibiotherapy in hospital practice is an important piece in the strategies aiming at circumventing the development of bacterial resistance . In the present review of the literature, two situations will be taken into account: surgical antibioprophylaxis and selective digestive decontamination . Only the consequences of these on bacterial flora will be considered . Despite some discrepancies, only partially attributable to methodological differences, data as a whole are consistent . For antibioprophylaxis, they confirm the importance of a strict observance of the right therapeutic regimen, especially the duration of treatment . Selective digestive decontamination unquestionably encounters hazards of selecting a resistant flora . Monitoring the intestinal flora under treatment is mandatory . The indications must remain strictly limited.

Ann Fr Anesth Reanim, 2000 May, 19(5), 409 - 17
{Antibiotic use and bacterial resistance}; Monnet DL; The relationships between antibiotic use and bacterial resistance are not so easy to demonstrate . However, the evidence is abundant and mostly consistent . In this review, we will consider and discuss the different levels of evidence models: biological, consistent associations, dose-effect relationship, and concomitant variations . Decision-making is dependent of the local conditions . In the hospital, establishing an epidemiological diagnosis is a prerequisite to any decision, including restriction of antibiotic use.

Ann Fr Anesth Reanim, 2000 May, 19(5), 403 - 8
{Regulation of the use of antibiotics: objectives, means and perspectives}; Schlemmer B; Antibiotics account for an important fraction of hospital pharmaceutical expense, especially in intensive care units . Moreover, they represent a permanent threat for bacterial ecology . Induced resistance tends, in turn, to inflate the costs . In that way, economical point of view and concerns for quality and safety of care become convergent . Restrictive and(or) educational actions to regulate the prescriptions have therefore been settled in many centres . In the present review, based on published studies, we describe some examples of the results achieved from these actions . Computer-based networks and expert systems offer promising possibilities of improvement for the near future.

Chem Biol, 2000 Jun, 7(6), 395 - 403
Biosynthesis of the polyene antifungal antibiotic nystatin in Streptomyces noursei ATCC 11455: analysis of the gene cluster and deduction of the biosynthetic pathway; Brautaset T et al.; BACKGROUND: The polyene macrolide antibiotic nystatin produced by Streptomyces noursei ATCC 11455 is an important antifungal agent . The nystatin molecule contains a polyketide moiety represented by a 38-membered macrolactone ring to which the deoxysugar mycosamine is attached . Molecular cloning and characterization of the genes governing the nystatin biosynthesis is of considerable interest because this information can be used for the generation of new antifungal antibiotics . RESULTS: A DNA region of 123,580 base pairs from the S . noursei ATCC 11455 genome was isolated, sequenced and shown by gene disruption to be involved in nystatin biosynthesis . Analysis of the DNA sequence resulted in identification of six genes encoding a modular polyketide synthase (PKS), genes for thioesterase, deoxysugar biosynthesis, modification, transport and regulatory proteins . One of the PKS-encoding genes, nysC, was found to encode the largest (11,096 amino acids long) modular PKS described to date . Analysis of the deduced gene products allowed us to propose a model for the nystatin biosynthetic pathway in S . noursei . CONCLUSIONS: A complete set of genes responsible for the biosynthesis of the antifungal polyene antibiotic nystatin in S . noursei ATCC 11455 has been cloned and analyzed . This represents the first example of the complete DNA sequence analysis of a polyene antibiotic biosynthetic gene cluster . Manipulation of the genes identified within the cluster may potentially lead to the generation of novel polyketides and yield improvements in the production strains.

Br Dent J, 2000 May 27, 2000(10), 554 - 8
A study of therapeutic antibiotic prescribing in National Health Service general dental practice in England; Palmer NA et al.; OBJECTIVE: To study the therapeutic prescribing of antibiotics by general dental practitioners . DESIGN: A postal questionnaire of National Health Service general dental practitioners in ten English Health Authorities . SUBJECTS: General dental practitioners (1,544) contracted to provide NHS treatment in the Health Authorities of Liverpool, Wirral, Oxfordshire, Buckinghamshire, Nottingham, North Nottinghamshire, Sheffield, Newcastle, Northumberland and North Tyneside . MAIN OUTCOME MEASURES: The questionnaires were analysed and the responses to each question expressed as absolute frequencies . RESULTS: Responses to the questionnaire were received from 929 (60.1%) practitioners . More than 95% of practitioners recognised the need for prescribing antibiotics where there was evidence of spreading infection . Some practitioners (12.5%) prescribed antibiotics for acute pulpitis and (3.3%) for chronic marginal gingivitis . Antibiotics were prescribed by practitioners before drainage of acute abscesses (69%) and by 23% after drainage . Practitioners were generally not influenced by patient's expectations of receiving antibiotics (92%), but would prescribe when under pressure of time (30.3%), if they were unable to make a definitive diagnosis (47.3%), or if treatment had to be delayed (72.5%) . Amoxicillin was the most frequently prescribed antibiotic used for most clinical conditions apart from pericoronitis, acute ulcerative gingivitis and dry sockets where metronidazole was the drug of choice . There was a wide variety of dosage, frequency and duration for all the antibiotics used in the treatment of acute dental infections . CONCLUSIONS: The results obtained from this questionnaire support the conclusion that the therapeutic prescribing of antibiotics in general dental practice varies widely and is suboptimal . There is a clear need for the development of prescribing guidelines and educational initiatives to encourage the rational and appropriate use of the antibiotics in National Health Service general dental practice.

Aust N Z J Med, 1999 Aug, 29(4), 512 - 6
Helicobacter pylori treatment and antibiotic susceptibility: results of a five-year audit; Fraser AG et al.; BACKGROUND: Helicobacter pylori eradication treatment has been a rapidly evolving field . Audit of treatment results provides reassurance that trial data can be translated into routine clinical practice . METHODS: Data were collected prospectively over five years . Patients were given four different treatment regimens over the audit period 'standard' triple therapy, two types of clarithromycin-based treatment or ranitidine, amoxycillin and metronidazole . Eradication was proven by a urea breath test at least four weeks after completing treatment . RESULTS: Eradication treatment for H . pylori was given to 665 patients; 89% had follow-up data . H . pylori eradication was significantly associated with treatment type (p<0.0001) and smoking (p=0.04) by univariate analysis, but was not associated with sex, age, alcohol consumption, endoscopic diagnosis, recent treatment with anti-secretory drugs or NSAIDs . By logistic regression analysis, only treatment type was significant (p=0.0001) . H . pylori culture and sensitivities were available for 255 patients . Metronidazole resistance was shown for 84 isolates (32%) and clarithromycin resistance for 18 isolates (6.8%) . Metronidazole resistance was significantly associated with younger age (p=0.02), ethnicity (p=0.02), female sex (p=0.02), and year of endoscopy (p=0.04), but was not associated with clarithromycin resistance . Clarithromycin resistance was not associated with age, sex, or ethnicity . Metronidazole resistance significantly affected H . pylori eradication for regimens containing metronidazole without clarithromycin . Eradication with metronidazole without clarithromycin was achieved in 90% of sensitive strains but only 55% of resistant strains (p<0.001) . Metronidazole resistance was not significantly associated with treatment failure when metronidazole was combined with clarithromycin . Eradication with metronidazole and clarithromycin was achieved in 86% of sensitive strains and 78% of resistant strains (p=0.42) . CONCLUSION: Treatment type and antibiotic susceptibility are the most important determinants of treatment success.

Prikl Biokhim Mikrobiol, 2000 May-Jun, 36(3), 307 - 11
{Transposon mutagenesis in preparing mutants of a strain--a producer of a new antibiotic batumin}; Smirnov VV et al.; Various plasmids carrying transposon Tn5 were used to generate insertion mutants synthesizing batumin, a unique antibiotic with a selective antistaphylococcal effect . One of the plasmids used provided a sufficient yield of the clones in question . An analysis of over 7000 clones allowed us to select the mutant clones with increased and decreased levels of batumin synthesis and the mutants that lost the ability to synthesize this antibiotic.

J Org Chem, 2000 Jun 16, 65(12), 3738 - 53
Total synthesis of the ansamycin antibiotic (+)-thiazinotrienomycin E; Smith AB 3rd et al.; The first total synthesis of (+)-thiazinotrienomycin E (1), member of a novel class of cytotoxic ansamycin antibiotics, has been achieved . Key features of the synthetic strategy include (a) the efficient construction of sulfone 7 incorporating TBS protection of the aniline, (b) an improved synthesis of allyl chloride (-)-6, the advanced intermediate employed in our trienomycins A and F total syntheses, (c) application of the Kocienski modified Julia protocol to elaborate the E,E,E-triene subunit in a stereo-controlled fashion, (d) an efficient union of sulfone 7 with advanced iodide 62, and (e) Mukaiyama macrolactamization to access the thiazinotrienomycin macrocyclic ring.

Antibiot Khimioter, 2000, 45(5), 6 - 8
{The action of its own antibiotic on the producer of imbricin growing on an agarized medium}; Gorbunova NA et al.; The action of imbricin on its own producer Streptomyces imbricatus grown on an agarized medium was studied . Comparatively low concentrations of the antibiotic were shown to have a high lethal action on the streptomycete . The morphological and cultural features of S . imbricatus did not change under the action of imbricin while the variation with respect to the antibiotic production property markedly increased . After the strain exposure to 200 micrograms/ml of imbricin, a stable variant with the antibiotic potency 20 per cent higher than that of the initial organism was isolated.

Brain Res, 2000 Jun 23, 868(2), 222 - 9
Vinpocetine protects from aminoglycoside antibiotic-induced hearing loss in guinea pig in vivo; Nekrassov V et al.; The principal objective of this study is to explore the hypothesis that a blockade of Na(+) channels can prevent some of the mechanisms involved in ototoxicity . For this purpose, the potential action of the voltage sensitive Na(+) channel antagonist, vinpocetine, on the ototoxicity induced by the representative aminoglycoside antibiotic, amikacin, in guinea pigs was tested for almost half a year . Amikacin (450 mg/kg) administered daily (i.m.) for 5 days increases the thresholds of the auditory brainstem response (ABR) to the two frequencies tested (4 and 8 kHz) . These threshold increases are permanent or at least long-lived, as after 40 days they are already established and are maintained until the end of the experiment (160 days after the antibiotic administration) . Amikacin decreases the amplitude of ABR waves, particularly P1, and after 160 days increases the latency of ABR waves, particularly at the higher frequency tested (8 kHz) . When the above amikacin regimen is followed by a daily (i.p.) vinpocetine (2 mg/kg) administration for 13 days the increase in ABR threshold and latency caused by amikacin alone is prevented . Moreover, the animals treated with amikacin alone show a decreased weight gain and a remarkable increased mortality in comparison with the group of animals post-treated with vinpocetine . We hope that the multiple beneficial effects exerted by the Na(+) channel blocker, vinpocetine, against aminoglycoside antibiotics-induced side effects could help to solve the serious limitations of the use of this type of antibiotic.

Antibiot Khimioter, 2000, 45(4), 10 - 3
{The effect of protoplast formation on the antibiotic activity and composition of the actinomycin complex in a strain of Streptomyces galbus (F) subsp . achromogenes 695 and in its active variants}; Iocheva LD et al.; Protoplasting and regeneration promoted variation by the antibiotic production property in Streptomyces galbus (F) subsp . achromogenes 695 and its active variants 695-3-2 and 695-3-2-206 . Variant 695-P24 with the potency 2 times higher than that of the initial strain 695 revertants was selected . No variants lacking the capacity for biosynthesis of the main components of antibiotic A-695 were detected among the revertants still, protoplasting of strains 695-3-2-206 and 695-P24 resulted in formation of variants synthesizing new components of the actinomycin complex.

Antibiot Khimioter, 2000, 45(4), 6 - 9
{The hypolipidemic action of antibiotic 86/88 (enniatin B) in a hepatoblastoma G2 cell culture}; Trenin AS et al.; A cyclodepsipeptide antibiotic 86/88 (enniatin B) with strong hypolipidemic action was isolated from the culture liquid of the fungus INA F-86/88 identified as Fusarium lateritium Nees var . stilboides (Wr.) Bilai . In the Hep G2 cell culture the antibiotic suppressed 14C-acetate incorporation into cholesterol (IC50 1.75 microM), cholesterol ethers (IC50 1 microM), triglycerides (IC50 1.3 microM) and free fatty acids (IC50 2.2 microM) . The most pronounced effect of the drugs, i.e . the suppression of the cholesterol ethers synthesis is likely due not only to the ACAT inhibition but also to the inhibition of the triglyceride synthesis and the diminishing of the free fatty acids pool in the cells.

Chemistry, 2000 May 15, 6(10), 1731 - 7
On the electrostatics of cell-membrane recognition: from natural antibiotics to rigid push-pull rods; Sakai N et al.; The question why pore-forming, alpha-helical natural antibiotics are not toxic is discussed within the general context of the interaction of electrostatically asymmetric "nanorods" with neutral, anionic, and polarized bilayer membranes . We suggest that simplification of the structural complexity of natural systems will be necessary to ultimately define the involved subtle balance between constructive and destructive electrostatic interactions.

BJOG, 2000 Jun, 107(6), 770 - 5
The transplacental transfer of the macrolide antibiotics erythromycin, roxithromycin and azithromycin; Heikkinen T et al.; OBJECTIVE: To investigate the transplacental transfer of the macrolide antibiotics erythromycin, roxithromycin and azithromycin . METHODS: Twenty-one term placentas were obtained with maternal consent immediately after delivery and a two-hour nonrecirculating perfusion of a single placental cotyledon was performed . Erythromycin (2 microg/mL), roxithromycin (2 microg/mL) and azithromycin (0.3 microg/mL) were infused to the maternal inflow at a constant rate, with antipyrine as a reference compound, and their appearance in the fetal circulation was followed . Drug concentrations were measured by high performance liquid chromatography for 120 min . RESULTS: The mean transplacental transfers (TPT(SS)) for erythromycin, roxithromycin and azithromycin were 3.0%, 4.3% and 2.6%, respectively, calculated as the ratio between the steady state concentrations in fetal venous and maternal arterial sides . Similar results were obtained when the TPT was calculated as the absolute amount of drug transferred across the placenta during 2-hour perfusion (TPT(A)) . No significant differences were found among the three macrolides in TPT(SS) (P = 0.39) or TPT(A) (P = 0.35) . The TPT(SS) of erythromycin, roxithromycin and azithromycin were 41%, 35% and 32% of the freely diffusable reference compound antipyrine, respectively . Steady state was reached in 60 minutes in each perfusion indicating sufficient perfusion time . CONCLUSION: The limited transplacental transfer of erythromycin, roxithromycin and azithromycin suggests compromised efficacy in the treatment of fetal infections . On the other hand, the placenta seems to produce an effective barrier reducing the fetal exposure when these three macrolides are used to treat maternal infections.

J Fr Ophtalmol, 2000 May, 23(5), 510 - 3; quiz 523
{Bioavailability of antibiotics}; Robert PY et al.; To be effective, an antibiotic must achieve therapeutic concentrations at the site of infection . This article is a review on the bioavailability of local and systemic antibiotics . Amongst topical antibiotics, fluoroquinolones and fusidic acid have the best intra-corneal and intra-cameral penetration . Chloramphenicol penetrates the anterior chamber but not always at therepeutic levels . Serum levels are low from topical administration, and haematological toxicity of chloramphenicol eyedrops is still not proven . Amongst systemic antibiotics, the molecules capable of penetrating the eye at therapeutic levels are fosfomycin, imipenem, some of third generation cephalosporins, fluoroquinolones and ureidopenicillins . Intra-ocular penetration of antibiotics is increased by infection, corneal epithelium abrasion, increasing dose frequency or delivery using a biomaterial reservoir (soft contact lenses or collagen schields) . Antibiotic-antiinflammatory associations can make infected sites more accessible to antibiotics . The choice of a treatment must take in consideration molecules, dosing and route, and be adapted to the germ to kill and the infected site to treat.

J Infect Dis, 2000 Jun, 181 Suppl 3, S558 - 62
Antibiotics in the prevention and treatment of coronary heart disease; Meier CR; Seroepidemiology, pathology, and animal studies provide evidence for a possible association between Chlamydia pneumoniae infections and atherosclerosis, coronary heart disease, and myocardial infarction . If this association exists, then exposure to certain antibiotics may positively affect the clinical course after an acute ischemic cardiac event (secondary prevention) and affect the risk of developing a first-time myocardial infarction (primary prevention) . Preliminary evidence from clinical trials suggests that treatment with new macrolide antibiotics may improve outcome after ischemic events, and evidence from a large case-control analysis indicates that exposure to tetracyclines or quinolones may reduce the risk of developing a first-time myocardial infarction . However, antibiotics for the treatment or prevention of ischemic heart disease must not be recommended yet . This review of published studies briefly summarizes the currently available literature on the effects of antibiotics on the risk of developing coronary heart disease and myocardial infarction.

FEBS Lett, 2000 Jun 2, 474(2-3), 228 - 32
EPR study of the dinuclear active copper site of tyrosinase from Streptomyces antibioticus; van Gastel M et al.; The {Cu(I)-Cu(II)} half-met form of the dinuclear copper site of tyrosinase has been probed by continuous wave electron paramagnetic resonance (EPR) and hyperfine sublevel correlation (HYSCORE) spectroscopy in the presence and absence of inhibitors . In all cases the EPR spectrum is indicative of a d(x(2)-y(2)) ground state for the unpaired electron . From the cross-peaks observed in the HYSCORE spectra, proton hyperfine coupling constants were obtained that are compatible with a hydroxide ion in an equatorial coordination position of the paramagnetic copper . After changing the water solvent to D(2)O or after addition of the inhibitors p-nitrophenol or L-mimosine, the proton signals disappear . The relevance of these findings for understanding the catalytic cycle is discussed.

J Fam Pract, 2000 May, 49(5), 407 - 14
Predictors of antibiotic prescribing for nonspecific upper respiratory infections, acute bronchitis, and acute sinusitis . An UPRNet study . Upper Peninsula Research Network; Dosh SA et al.; BACKGROUND: Antibiotics are often prescribed for viral respiratory infections . The goal of our study was to determine the factors associated with antibiotic prescribing for acute respiratory infections in primary care . METHODS: We performed an observational study in 15 primary care practices in Michigan using patient and physician surveys distributed during visits for acute respiratory infections . We included patients 4 years or older presenting with symptoms of an acute respiratory infection (n=482) . The main outcome measures were prescriptions of antibiotics, signs and symptoms associated with antibiotic prescribing, and clinician-reported reasons for prescribing an antibiotic . RESULTS: We found that patients who were older than 18 years, sick for more than 14 days, and seen in urgent care clinics were more likely to receive antibiotics . Patients expected antibiotics if they perceived that the drug had helped with similar symptoms in the past . In an adjusted model, the variables significantly associated with antibiotic prescribing were physical findings of sinus tenderness (odds ratio {OR}=20.0; 95% confidence interval {CI}, 8.3-43.2), rales/rhonchi (OR=19.9; 95% CI, 9.2-43.2), discolored nasal discharge (OR=11.7; 95% CI, 4.3-31.7), and postnasal drainage (OR=3.1; 95% CI, 1.6-6.0) . The presence of clear nasal discharge on examination was negatively associated (OR=0.3; 95% CI, 0.2-0.5) . CONCLUSIONS: Several physical signs play an important role in clinicians' decisions to prescribe antibiotics for respiratory infections . This information will be useful in designing interventions to decrease inappropriate antibiotic prescribing for upper respiratory infections.

Eur J Gastroenterol Hepatol, 2000 May, 12(5), 489 - 95
One-week therapy with pantoprazole versus ranitidine bismuth citrate plus two antibiotics for Helicobacter pylori eradication; Gisbert JP et al.; AIM: A combination of omeprazole plus amoxycillin (Amo) and clarithromycin (CIa) for 7 days has been studied extensively . However, the role of other proton pump inhibitors, such as pantoprazole (Pan), in this therapy is not well known . On the other hand, ranitidine bismuth citrate (RBC) also seems to be effective when combined with Amo and CIa . Our aim was to evaluate and to compare these two novel short-term triple therapies (Pan+Amo+Cla and RBC+Amo+Cla) for treatment of Helicobacter pylori . METHODS: In a randomized clinical trial 150 consecutive patients (38 with duodenal ulcer, 112 with non-ulcer dyspepsia) infected by H . pylori were studied prospectively . Exclusion criteria were: previous H . pylori eradication therapy, gastroerosive drug use, gastric surgery, and associated diseases . One of two regimens was given for 7 days: Pan (40 mg b.i.d.), Amo (1 g b.i.d.), Cla (500 mg b.i.d.) (group Pan+Amo+Cla, n = 75); or RBC (400 mg b.i.d.), Amo (1 g b.i.d.), Cla (500 mg b.i.d.) (group RBC+Amo+Cla, n = 75) . All drugs were administered together after meals . Compliance was evaluated by return tablet count . Data were analysed by univariate (chi2) and multivariate (multiple logistic regression) analysis . Eradication was defined as a negative 13C-urea breath test 1 month after completing therapy . RESULTS: The distribution of studied variables (age, gender, smoking, duodenal ulcer/non-ulcer dyspepsia) was similar in both therapy groups . Per-protocol eradication was achieved in 48/71 (68%) in group Pan+Amo+Cla, and in 61/70 (87%) in group RBC+Amo+Cla (P= 0.01) . Intention-to-treat (ITT) eradication was achieved in, respectively, 48/ 75 (64%) and in 61/75 (81%) (P= 0.03) . The RBC+ Amo+Cla regimen was more effective than Pan+Amo+Cla in non-ulcer dyspepsia patients (ITT, 84% vs 58%; P = 0.005), but statistically significant differences were not demonstrated in duodenal ulcer patients (72% vs 80%) . In the multivariate analysis the odds ratio for the effect of the type of therapy on H . pylori eradication in patients with non-ulcer dyspepsia was 3.8 (95% Cl, 1.6-9.3; P = 0.003) . No relevant adverse effects were reported with any regimen . CONCLUSION: A RBC+Amo+Cla regimen for only 1 week is a promising therapy for H . pylori infection, due to its high efficacy, simple posology, and excellent tolerability . Combination of Pan with Amo and Cla, although effective in duodenal ulcer patients, but in non-ulcer dyspepsia has not achieved the favourable results previously reported with other proton pump inhibitors.

Indian J Pediatr, 1995 May-Jun, 62(3), 327 - 31
Do neonates with meconium aspiration syndrome require antibiotics?
Shankar V, Paul VK, Deorari AK, Singh M.
A randomized clinical trial was conducted to evaluate the utility of antibiotics in the routine management of Meconium Aspiration Syndrome (MAS) . Neonates diagnosed to have MAS were randomly allocated to either the antibiotic group (n = 20) receiving gentamicin for 7 days, or the control group (n = 20), receiving no antibiotic . All infants were given identical supportive care . The two groups were comparable with respect to birth weight, gestation, sex distribution, mode of delivery, Apgar scores, and initial clinical and radiological severity of the illness . Results showed that the mean duration and the severity of respiratory distress at 24 hours and 48 hours were similar in the two groups . No secondary infection was documented in either group . A single death occurred in the antibiotic group . It is concluded that empirical use of antibiotics in the routine management of meconium aspiration syndrome is of no benefit.

Biophys J, 2000 Jun, 78(6), 3026 - 35
Asymmetrical ion-channel model inferred from two-dimensional crystallization of a peptide antibiotic; Ionov R et al.; The structural organization of ion channels formed in lipid membranes by amphiphilic alpha-helical peptides is deduced by applying direct structural methods to different lipid/alamethicin systems . Alamethicin represents a hydrophobic alpha-helical peptide antibiotic forming voltage-gated ion channels in lipid membranes . Here the first direct evidence for the existence of large-scale two-dimensional crystalline domains of alamethicin helices, oriented parallel to the air/water interface, is presented using synchrotron x-ray diffraction, fluorescence microscopy, and surface pressure/area isotherms . Proofs are obtained that the antibiotic peptide injected into the aqueous phase under phospholipid monolayers penetrates these monolayers, phase separates, and forms domains within the lipid environment, keeping the same, parallel orientation of the alpha-helices with respect to the phospholipid/water interface . A new asymmetrical, "lipid-covered ring" model of the voltage-gated ion channel of alamethicin is inferred from the structural results presented, and the mechanism of ion-channel formation is discussed.

Electrophoresis, 2000 Apr, 21(7), 1349 - 53
Separation and determination of the macrolide antibiotics (erythromycin, spiramycin and oleandomycin) by capillary electrophoresis coupled with fast reductive voltammetric detection; Zhou J et al.; Separation and determination of erythromycin, spiramycin and oleandomycin by capillary zone electrophoresis coupled with fast reductive voltammetric detection using an Hg-film electrode was investigated in a simple aqueous phosphate buffer system . The influence of pH, concentration of phosphate, applied voltage, capillary length and dimension on the separation was examined and optimized . The entire separation of erythromycin, spiramycin, and oleandomycin was achieved in a 0.2 mol/L phosphate buffer system without organic modifiers . The electrochemical detection parameters, such as electrode material, applied waveform, scan rate, preconcentration potentials and preconcentration times, were investigated and discussed . This approach provides high separation efficiency and high sensitivity for all compounds, with detection limits (3 x peak-to-peak baseline noise) of 7.5 x 10(-8) mol/L for spiramycin, and 3 x 10(-7) mol/ L for erythromycin and oleandomycin . The calibration plot of peak areas for each separated peak vs . concentration of analyte was found to be linear over three orders of magnitude.

Clin Infect Dis, 1999 Apr, 28(4), 750 - 2
Antibiotic use in the elderly: issues and nonissues; McCue JD; Despite the well-recognized increase in mortality and morbidity due to infections in the elderly, antibiotics may, in most cases, be used in a manner similar to that in younger patients . The decreased lean body weight and reduced renal function typical of elderly patients, however, require consideration of reduced doses and longer dosing intervals, especially for renally excreted antibiotics . Length of therapy should be conservative because underlying anatomic or functional predispositions to infections tend to complicate treatment . Oral antibiotics are equally well absorbed in the elderly and younger patients and may be used for the same indications as for younger patients . A notable, important difference in the choice of antibiotics for serious infections in older versus younger patients is that empirical therapy should be broader in spectrum for elderly patients, and especially for elderly long-term residents, since the variety of infecting bacteria tends to be greater and polymicrobial infections tend to be common.

Proc Natl Acad Sci U S A, 2000 Jun 6, 97(12), 6345 - 9
Structural basis for the interaction of the fluorescence probe 8-anilino-1-naphthalene sulfonate (ANS) with the antibiotic target MurA; Schonbrunn E et al.; The extrinsic fluorescence dye 8-anilino-1-naphthalene sulfonate (ANS) is widely used for probing conformational changes in proteins, yet no detailed structure of ANS bound to any protein has been reported so far . ANS has been successfully used to monitor the induced-fit mechanism of MurA {UDPGlcNAc enolpyruvyltransferase (EC )}, an essential enzyme for bacterial cell wall biosynthesis . We have solved the crystal structure of the ANS small middle dotMurA complex at 1.7-A resolution . ANS binds at an originally solvent-exposed region near Pro-112 and induces a major restructuring of the loop Pro-112-Pro-121, such that a specific binding site emerges . The fluorescence probe is sandwiched between the strictly conserved residues Arg-91, Pro-112, and Gly-113 . Substrate binding to MurA is accompanied by large movements especially of the loop and Arg-91, which explains why ANS is an excellent sensor of conformational changes during catalysis of this pharmaceutically important enzyme.

J Virol, 2000 Jun, 74(12), 5432 - 40
Opposite effects of dextran sulfate 500, the polyene antibiotic MS-8209, and Congo red on accumulation of the protease-resistant isoform of PrP in the spleens of mice inoculated intraperitoneally with the scrapie agent; Beringue V et al.; The mode and the site of action of the major antiscrapie drugs have been studied by investigating their effects on the abnormal protease-resistant isoform of PrP (PrPres) and on its accumulation in mouse spleen . Day-by-day PrPres accumulation in the spleen and in other peripheral organs was first monitored to describe the early steps of scrapie pathogenesis . Three phases were identified: the detection of scrapie inoculum on the day of scrapie infection, a clearance phase, and then the peripheral accumulation of PrPres . In a second step, the effects of the polyene antibiotic MS-8209, the polyanion dextran sulfate 500 (DS500), and Congo red were assessed on these phases, after the drugs were coincubated with scrapie inoculum . Highly different mechanisms and sites of action were apparent . MS-8209 had a weak effect on the accumulation of PrPres in spleen, suggesting another site of intervention for this drug . DS500 delayed the beginning of the clearance phase but then blocked PrPres synthesis for a long period of time, probably because of its immunological effects on the spleen . Surprisingly, Congo red suppressed the clearance phase of scrapie inoculum and then increased transiently accumulation of PrPres in spleen . We showed in vitro that this effect was related to a direct enhancement of the protease resistance of PrPres by the drug.

Can J Clin Pharmacol, 2000 Spring, 7(1), 38 - 41
Multiple antibiotic sensitivity syndrome in children; Park J et al.; BACKGROUND: Multiple antibiotic sensitivity syndrome with adverse drug reactions to multiple classes of antibiotics has been described in adults but is not well characterized in children . PATIENTS AND METHODS: Charts of children referred to the adverse drug reaction clinic at the Children's Hospital of Western Ontario, London, Ontario, with adverse drug reactions to multiple antibiotics were reviewed to determine the number of patients with adverse drug reactions to multiple classes of antibiotics and the clinical characteristics of the adverse events . RESULTS: The records of 97 children who were selected as possible candidates for multiple antibiotic sensitivity were studied . These records constituted 11% of referrals to a highly specialized adverse drug reaction clinic, suggesting that in usual clinical practice, this entity, if it does indeed constitute a distinct clinical entity, is quite uncommon . Age at time of the first adverse drug reaction was 26.1+/-26.3 (mean +/- SD) months . Among the 97 children, adverse reactions to five classes of antibiotic were noted in 3.1%, to four in 10.3%, to three in 47 . 4% and to two in 39.2% . Most children (85.6%) experienced an adverse reaction to a penicillin, while 71.1% reacted to a cephalosporin, 80 . 4% to a sulphonamide and 35.1% to a macrolide . Clinical presentations of the adverse reactions included urticaria or pruritus, other rash, serum sickness-like reaction, angioedema or anaphylaxis, erythema multiforme or Stevens-Johnson syndrome . CONCLUSIONS: There are children who have what appears to be immunologically mediated adverse drug reactions to antibiotics of multiple classes . These reactions, which most commonly manifest as urticaria or other rashes, follow drug use patterns . It remains to be defined whether this is a distinct clinical syndrome or a manifestation of a more fundamental problem in dealing with xenobiotics in the setting of infection . Further work on the immunological and/or biochemical determinants of the multiple antibiotic sensitivity syndrome (MASS) is needed to understand the pathophysiology and determinants of MASS and whether MASS constitutes a distinct clinical entity.

J Clin Immunol, 2000 Mar, 20(2), 107 - 16
Il-4 and IFN-gamma mRNA induction in human peripheral lymphocytes specific for beta-lactam antibiotics in immediate or delayed hypersensitivity reactions; Gaspard I et al.; Beta-lactam antibiotics elicit CD4+ and CD8+ T-cell-mediated immune responses that play a central role in allergic reactions . However, the involvement of a type 1- (Th1 or Tc1) or a type 2-like (Th2 or Tc2) differentiation in drug allergy remains unclear . We investigated the expression of interleukin 4 (IL-4) and interferon gamma (IFN-gamma) mRNA by quantitative reverse transcription and polymerase chain reaction (RT-PCR) in patient-derived peripheral blood lymphocytes following specific in vitro stimulation . Samples were collected from a total of 19 patients who had developed immediate or delayed clinical manifestations of hypersensitivity to beta-lactam and from 11 control subjects . Peripheral blood mononuclear cells (PBMCs) were stimulated with either free antibiotics or antibiotic-human serum albumin (HSA) conjugates . Specific induction of IFN-gamma mRNA expression was observed in 11 of 11 allergic patients with immediate reactions, in 6 of 8 patients with delayed reactions, and in 4 of 11 control subjects . IL-4 mRNA expression was induced in 5 of 11 allergic individuals with immediate reactions but in none of the 8 patients with delayed responses and none of the 11 control subjects . IL-4 mRNA expression was only induced following activation with free drugs, while IFN-gamma mRNA expression was predominantly induced in CD4+ T cells following stimulation with HSA-conjugated drugs . Immediate-type hypersensitivity to beta-lactams was not associated with a pure type 2-like response when PBMCs were specifically stimulated in vitro: Some patients with well-documented history of beta-lactam-induced immediate allergic reaction showed a high IFN-gamma response . Contact dermatitis involved Tc1 and Th1 cells and other delayed hypersensitivity reactions to beta-lactams were restricted to Th1 responses.

Pediatr Infect Dis J, 2000 May, 19(5), 458 - 63
Five vs . ten days of antibiotic therapy for acute otitis media in young children; Cohen R et al.; BACKGROUND: Many publications in recent years have argued in favor of shortened therapy for acute otitis media . However, doubt persists regarding children younger than 2 years, and some authors therefore restrict short course therapy to children older than 2 years . METHODS: In a prospective, comparative, double blind, randomized, multicenter trial we compared cefpodoxime-proxetil, 8 mg/kg/day in two divided doses for 10 days, with an identical 5-day regimen followed by a 5-day placebo period . RESULTS: Between October, 1996, and April, 1997, 450 children (mean age, 14.3 months) were enrolled, 227 in the 5-day group and 223 in the 10-day group . In the per protocol analysis clinical success was obtained on Days 12 to 14 after the beginning of treatment (main analysis) in 175 (84.1%) of the 208 children receiving the 5-day regimen and 194 (92.4%) of the 210 children receiving the 10-day regimen (P = 0.009) . The superiority of the standard regimen was more marked among children cared for outside their homes (92.5% vs . 81.5%) . Clinical success persisted on Days 28 to 42 among 134 (85.4%) of the 157 assessable patients in the 5-day group and 144 (83.7%) of the 172 assessable patients in the 10-day group (P = 0.68) . CONCLUSIONS: The 10-day regimen resulted in a higher success rate at the conclusion of therapy, but there were no differences between the two study groups 4 to 6 weeks after enrollment in the study protocol.

J Antibiot (Tokyo), 2000 Mar, 53(3), 233 - 40
Arisostatins A and B, new members of tetrocarcin class of antibiotics from Micromonospora sp . TP-A0316 . II . Structure determination; Igarashi Y et al.; Structures of arisostatins A and B were determined by spectroscopic analyses . Arisostatins were found to be new analogs of tetrocarcin A and possess an iso-butanoyldigitoxose unit instead of the acetyldigitoxose one . NMR analyses of arisostatins and tetrocarcin A led to the revision of the anomeric configurations in the tetrasaccharide moiety of tetrocarcin A.

Br Dent J, 2000 Apr 8, 188(7), 398 - 400
Antibiotic prescribing for dental conditions: general medical practitioners and dentists compared; Anderson R et al.; OBJECTIVE: To compare the level of prescribing and types of antibiotics prescribed for dental problems by general medical practitioners and dentists . DESIGN: Secondary analysis of standard consultation data and prescription records from four different settings . SETTING: 30 participating general practices in the General Practice Morbidity Database for Wales in 1996 . SUBJECTS: 1,185 attendances for tooth-related problems, at 30 participating practices in the General Practice Morbidity Database for Wales in 1996 . Standard consultation records from a GDP emergency dental rota, and two weekend emergency dental clinics: one in a health centre, the other in a dental hospital . RESULTS: More than two thirds (68%) of attendances at general medical practices for tooth-related problems resulted in a prescription for antibiotics . In contrast less than a third (28%) of patients seen by a GDP rota, about half (52%) of patients at a weekend emergency clinic in a health centre, and just more than a third (38%) of patients attending the dental hospital clinic received antibiotics . General medical practitioners were also more likely to prescribe broad-spectrum antibiotics than dentists . CONCLUSION: For acute dental problems general medical practitioners are more likely to prescribe antibiotics than dentists . There also appear to be inter-professional differences in the tendency to prescribe broad spectrum antibiotics . Initiatives to rationalise prescribing for dental conditions may need to target doctors as well as dentists.

J Org Chem, 2000 Feb 25, 65(4), 1102 - 7
Design and synthesis of novel thiazole-containing cross-linked polyamides related to the antiviral antibiotic distamycin; Sharma SK et al.; A family of naturally occurring oligopeptides includes netropsin, distamycin, anthelvencin, kikumycin B, amidinomycin, and norformycin . Netropsin (I) and distamycin (II) express their biological activities by targeting specific sequences of chemical functionalities in the minor groove of DNA . Both netropsin and distamycin can be regarded as polyamide chains in which each alpha-carbon has been replaced by a five-membered pyrrole ring . The repeat distance in such an augmented polyamide chain is almost the same as the distance from one base pair to the next along the floor of a minor groove within beta-DNA . In this paper we report the synthesis of 16-21 cross-linked polyamides containing a thiazole heterocyclic ring bearing the active functionalites NH(2), NHCHO, or H . 16 and 17 were synthesized by DCC and HOBt catalyzed reaction of 5 with 14 and 15, while the formylation products 18 and 19 were obtained by coupling the formylated 4-methyl-thiazolated acid 6 with 14 and 15 . The deaminated compounds 20 and 21 were obtained by the coupling of 5-trichloroacetyl-4-methylthiazole 7 synthesized from 4-methylthiazole . All the six cross-linked polyamides 16-21 were tested for their DNA gyrase inhibition . The studies have shown these polyamides have better sequence recognition and a greater percentage of inhibition than the corresponding monomers . The compound 17 shows complete inhibition of gyrase at 0.5 microM concentration as compared to the naturally occurring distamycin at 1.0 microM.

J Org Chem, 2000 Feb 11, 65(3), 640 - 4
Synthesis of two naphthoquinone antibiotics, dehydroherbarin and 6-deoxybostrycoidin; Kesteleyn B et al.; The synthesis of two naphthoquinone antibiotics, dehydroherbarin (7) and 6-deoxybostrycoidin (5), was accomplished by reaction of 3-acetonyl-2-bromomethyl-6,8-dimethoxy-1,4-naphthoquinone (23) with either triethylamine or ammonia, respectively . This is the first report on their synthesis.

J Pept Sci, 2000 Apr, 6(4), 149 - 67
New sequences and new fungal producers of peptaibol antibiotics antiamoebins; Jaworski A et al.; Mixtures of the microheterogeneous 16-mer peptaibol antibiotics called antiamoebins (AAM) have been isolated from the culture broths of strains of the filamentous fungi Stilbella erythrocephala ATCC 28144, Stilbella fimetaria CBS 548.84 and Gliocladium catenulatum CBS 511.66 . Sequences were determined using on-line HPLC together with positive- and negative-ion electrospray ionization mass spectrometry . Some characteristic features are recognized in the mass spectrometric fragmentation pattern of AAM . From a sample originally used for sequencing AAM (from Hindustan Antibiotics, Ltd., Pimpri, Poona-411018, India), and a sample of AAM commercially available (from Sigma Chemicals, St . Louis, MO, USA) HPLC elution profiles and sequences were assigned . Further, sequences of AAM previously isolated from Emericellopsis synnematicola CBS 176.60 and Emericellopsis salmosynnemata CBS 382.62 were determined . The peptide designated AAM I was the most abundant in all isolates and its structure could be confirmed . AAM II was detectable as a minor component (1.9%) only in the original sample of AAM, but not in the other isolates . The structures of AAM III, IV and V, which had previously been partly assigned, were definitely established, and the new sequences AAM VI-XVI were elucidated . AAM showing Phe1/Leu1 or Phe1/Val1 exchange, respectively, are produced in amounts only by S . erythrocephala . Sequences, HPLC elution profiles ('fingerprints') and relative amounts of peptides of all isolates were correlated.

Pneumonol Alergol Pol, 1999, 67(9-10), 398 - 408
{Drug compliance in patients treated with antibiotics in an ambulatory setting for respiratory tract infections}; Kardas P; Patient non-compliance is a phenomenon which leads to less effective and more expensive therapy, particularly in general practice conditions . One of the most common problem of out-patients care are respiratory infections . The aim of this study was to evaluate the extent of patient non-compliance among out-patients treated with short-time antibiotic for respiratory tract infections and to find factors associated with patient adherence . Two methods of compliance measurement were used: the questionnaire method and pill count . The study group consisted of 154 out-patients with respiratory infections . The pill count method revealed that 46.8% of patients did not take their antibiotics as prescribed, and only 9.7% stated that in inquiry . Patient compliance was associated with such factors as being married, subjective estimation of health state as lower then peers, present chronic diseases, present ischemic heart disease, subjective estimation of disease as "serious", localisation of infection in lower respiratory tract, dosage schedule, the number of drugs taken at examination > 2, the number of drugs doses taken at examination > 6 and the number of drugs taken longer then a week > 2 . Age, gender, education and professional activity did not influence the level of compliance . The study points out usefulness of both inquiry and pill count method in revealing patient non-compliance in conditions of general practice.

Bone Marrow Transplant, 2000 Apr, 25(8), 907 - 8
Cross-sensitivity reaction between tacrolimus and macrolide antibiotics; Riley L et al.; A patient with an allergy to a macrolide antibiotic was given tacrolimus and developed a sudden cutaneous reaction.

Chest, 2000 May, 117(5), 1345 - 52
Antibiotics are associated with lower relapse rates in outpatients with acute exacerbations of COPD; Adams SG et al.; BACKGROUND: COPD is a complex disease with exacerbations characterized by worsening of symptoms resulting in deteriorating lung function . STUDY OBJECTIVE: To assess predictive factors of relapse for patients with acute exacerbations of COPD (AECB) . DESIGN: Retrospective cohort analysis of visits for AECB . SETTING: Veterans Affairs Medical Center . PATIENTS: Three hundred sixty-two visits (173 patients) with documented COPD treated as outpatients for AECB . MEASUREMENTS: Severity of underlying COPD, severity of AECB, comorbid conditions, therapy, and relapse rates (return visit within 14 days with persistent or worsening symptoms) . RESULTS: Each visit was analyzed individually (referred to as a patient-visit) . One group received antibiotics (270 patient-visits), and the second group (92 patient-visits) did not . Both groups had similar demographics and severity of underlying COPD . The overall relapse rate was 22% . The majority of patient-visits (95%) with severe symptoms at presentation were prescribed antibiotics vs only 40% of those with mild symptoms . Twenty-nine of 92 patient-visits (32%) were followed by relapse in the group that was not given antibiotics, whereas only 50 of 270 (19%) treated with antibiotics relapsed (p < 0.001) . Those treated with amoxicillin had an even higher relapse rate (20 of 37 patient-visits, or 54%) than those who did not receive antibiotics (p = 0.006) . CONCLUSIONS: Relapse from AECB was not related to the severity of underlying disease or to the severity of the acute exacerbation . Patients treated with antibiotics had significantly lower relapse rates than those who did not receive antibiotics . However, the specific choice of antibiotic is important because those treated with amoxicillin had the highest relapse rates of all groups.

Rinsho Byori, 2000 Jan, Suppl 111, 150 - 8
{The present status of susceptibility tests for detection of antibiotic-resistant bacteria in Japan}; Kanno H; Recently, NCCLS Susceptibility tests have been widely used in Japan . NCCLS Susceptibility tests are one of the most excellent systems in the world . However, there are some differences in the type of antibiotic-resistant bacteria and systems of chemotherapy between Japan and the USA . To use NCCLS methods more effectively in Japan, it is necessary to make a partial amendment concerning with the choice of antibiotics and break points of resistance.

J Reprod Med, 2000 Apr, 45(4), 323 - 6
Continuous low-dose antibiotics and cerclage for recurrent second-trimester pregnancy loss; Shiffman RL; OBJECTIVE: To evaluate the role of continuous low-dose antibiotics in the prolongation of pregnancy in women at risk for recurrent second-trimester loss . METHODS: Only patients with a history of previous recurrent second-trimester losses associated with failed cervical cerclages were prospectively included in the study . Patients received low-dose antibiotics until delivery . Cerclage was performed at 14-24 weeks' gestation on the basis of transvaginal sonographic findings of cervical funneling . Outcome was evaluated by weeks of pregnancy gained in the current pregnancy as compared to the previous pregnancy . RESULTS: Ten patients were eligible for study after exclusions . All 10 achieved fetal viability . Pregnancy was prolonged by a mean of 13.4 +/- 4.2 weeks beyond the previous pregnancy . This was highly statistically significant (P < .001) . CONCLUSION: Continuous low-dose antibiotics prolonged pregnancy in patients with recurrent second-trimester pregnancy losses and prior failed cerclage . Randomized clinical trials are needed to confirm the role of antibiotics in these high-risk pregnancies.

J Biomol Struct Dyn, 2000 Apr, 17(5), 779 - 85
Computational analysis of the first biheterocyclization site of the antibiotic microcin B17; Donnelly MA et al.; Microcin B 17 (MccB17) undergoes an enzyme catalyzed posttranslational modification to form four oxazole and four thiazole rings . Four of these rings form 4,2 - connected biheterocyclic functionalities . In this study, the hexapeptide sequence surrounding the first biheterocyclization site of microcin B17 was examined using computational calculations and database analysis to see if it was preorganized for cyclization in a manner similar to that found in the autocatalytic posttranslational cyclization of Green Fluorescent Protein (GFP) . Attention was focused on the intermolecular distances between the sulfur and oxygen atoms of the cysteine and serine residues and the carbonyl carbons which they attack in the ring formation . Conformational searches located some low energy conformations that contained relatively short oxygen to carbonyl carbon distances, which indicated that the oxazole forming fragment in microcin B17 is preorganized for cyclization . However, the lack of any clear patterns for the sulfur to carbon distances show that the side-chain of cysteine does not adopt any low energy conformations that are geometrically preorganized for cyclization . The MccB17 synthetase enzyme complex which catalyzes the cyclization process therefore has both steric and electronic functions . The data obtained in this investigation is in agreement with empirical data which shows that biheterocyclization will only occur if the thiazole forms before the oxazole.

J Chromatogr B Biomed Sci Appl, 2000 Mar 31, 740(1), 71 - 80
Determination of the cephalosporin antibiotic cephradine in human plasma by high-performance liquid chromatography with ultraviolet detection; Johnson VM et al.; A simple and sensitive high-performance liquid chromatographic method, for the determination of cephradine in human plasma samples has been developed and validated . Cephradine and cephaloridine (internal standard) were extracted from human plasma by perchloric acid protein precipitation followed by centrifugation . Aliquots of the extracts were analysed by reversed-phase high-performance liquid chromatography (HPLC) utilising a polymeric reversed-phase PLRP-S column, followed by ultraviolet detection at 260 nm . The method has a working dynamic range from 0.2 to 30.0 microg/ml from 200 microl human plasma . The precision of the method at 0.2 microg/ml was 4.9% (intra-assay) and negligible (inter-assay) as calculated by one-way analysis of variance and the accuracy of the method at 0.2 microg/ml was -4.1% in terms of percentage bias . This method has been successfully applied to clinical studies including an oral bioequivalence study comparing the pharmacokinetics of 500 mg tablets of Kefdrin with 500 mg tablets of Velosef in healthy human volunteers.

Pharmazie, 2000 Apr, 55(4), 303 - 6
Charge-transfer chromatographic study of the interaction of antibiotics with cetyltrimethylammonium bromide; Cserhati T et al.; The interaction of 20 antibiotics with the cationic surfactant cetyltrimethylammonium bromide (CTAB) was studied by charge-transfer reversed-phase chromatography carried out on impregnated alumina layers using water-methanol mixtures as eluents . The lipophilicity and specific hydrophobic surface area of antibiotics and the relative strength of their interaction with CTAB was calculated . CTAB interacted with 10 antibiotics the antibiotic--CTAB complex generally being more hydrophilic than the uncomplexed molecule . The relative strength of interaction depended considerably on the molecular structure of the antibiotics . Significant linear correlation was found between the lipophilicity of antibiotics and their capacity to interact with CTAB indicating the involvement of hydrophobic forces in the interaction.

Acta Physiol Pharmacol Ther Latinoam, 1999, 49(4), 242 - 50
Sites and mechanisms of antibiotic-induced neuromuscular block: a pharmacological analysis using quantal content, voltage clamped end-plate currents and single channel analysis; Fiekers JF; Since the original observation of Vital Brazil and Corrado (1957) concerning the antibiotic induced neuromuscular block produced by streptomycin, there has been considerable interest in the mechanisms responsible for not only neuromuscular block but also the effects of antibiotics on different systems . We used the voltage clamped end-plate of transacted skeletal muscle to examine the concentration-dependent actions of several groups of antibiotics . The aminoglycoside antibiotics, neomycin and streptomycin, were both more effective at reducing quantal release of acetylcholine (ACh) than interacting with the postjunctional ACh receptor-channel complex . Neomycin was approximately 10 X more potent prejunctionally than streptomycin and the prejunctional effects of each antibiotic were reversed competitively by raising extracellular calcium . Both neomycin and streptomycin also had postjunctional actions at higher concentrations . Neomycin interacted with the open state of the ACh receptor ion channel complex while streptomycin blocks the ACh receptor . The lincosamide antibiotics, lincomycin and clindamycin produced their neuromuscular block postjunctionally by interacting with the open state of the ACh-receptor channel complex . Clindamycin is approximately 20 X more effective at blocking the open channel than was lincomycin . Using cell attached patch clamp recordings in cultured rat myotubes, we demonstrated a lincosamide-induced block of open ion channels with clindamycin having a much slower unblocking rate than lincomycin . Using epimers of the lincosamides, we demonstrated that lipophilicity of the molecule, rather than stereochemical considerations, is important for open channel blockade affecting primarily the "off" rate of channel blocking . This mechanism appears important for not only the lincosamide antibiotics but also for the postjunctional actions of the aminoglycoside antibiotics, particularly neomycin.

Cochrane Database Syst Rev . 2000;(2):CD001306.
Antibiotics for treating leptospirosis; Guidugli F et al.; BACKGROUND: Leptospirosis is a parasitic disease transmitted by animals . Severe leptospirosis may result in hospitalisation and about five per cent of the patients die . In clinical practice, penicillin is widely used for treating leptospirosis . OBJECTIVES: To evaluate the effectiveness and safety of antibiotics versus placebo or other antibiotic regimens in treating leptospirosis . We addressed the following clinical questions: a) Are treatment regimens with antibiotics more efficient than placebo for leptospirosis? b) Are treatment regimens with antibiotics safe when compared to placebo for leptospirosis? c) Which antibiotic regimen is the most efficient and safest in treating leptospirosis? SEARCH STRATEGY: Electronic searches and searches of the identified articles were combined . SELECTION CRITERIA: STUDIES: Randomised clinical trials in which antibiotics were used as treatment for leptospirosis . Language, date, or other restrictions were not applied . PARTICIPANTS: Patients with clinical manifestations of leptospirosis . INTERVENTIONS: Any antibiotic regimen compared with a control group (placebo or another antibiotic regimen) . DATA COLLECTION AND ANALYSIS: Data and methodological quality of each trial were independently extracted and assessed by two reviewers . The random effects model was used irrespective of significant statistical heterogeneity . MAIN RESULTS: Three trials met inclusion criteria . Allocation concealment and double blind methods were not clearly described in two . Of the patients enrolled, 75 were treated with placebo and 75 with antibiotics: 61 (81.3%) penicillin and 14 (18.6%) doxycycline . The patients assigned to antibiotics compared to placebo showed: a) Mortality: 1% (1/75) versus 4% (3/75); risk difference -2%, 95% confidence interval -8% to 4% . b) Duration of hospital stay (days): weighted mean difference 0.30, 95% confidence interval -1.26 to 1.86 . c) Prolonged hospital stay (> seven days): 30% (7/23) versus 74% (14/19); risk difference -43%, 95% confidence interval -70% to -16% . Number needed-to-treat 3, 95% confidence interval 2 to 7 . d) Period of disappearance of fever (days): weighted mean difference -4.04, 95% confidence interval -8.65 to 0.58 . e) Leptospiruria: 5% (4/75) versus 40% (30/75); risk difference -46%, 95% confidence interval -88% to -3% . Number needed-to-treat 2, 95% confidence interval 1 to 33 . REVIEWER'S CONCLUSIONS: Antibiotic regimens for treatment of leptospirosis is a form of care for which the evidence is insufficient to provide clear guidelines for practice . The randomised trials suggest that antibiotics could be a useful treatment for leptospirosis . Because of the questionable quality of two of the three trials, the indication for general use of antibiotics is uncertain . However, the evidence suggest that penicillin may cause more good than harm.

Biochem Pharmacol, 1999 May 1, 57(9), 981 - 7
Membrane interaction of an antitumor antibiotic, mithramycin, with anionic phospholipid vesicles; Majee S et al.; Small unilamellar vesicles (SUV) composed of zwitterionic phosphatidylcholine and two different anionic phospholipids, phosphatidic acid and phosphatidylserine, in different compositions, were employed to study the membrane interaction of an antitumor antibiotic, mithramycin (MTR) . Binding of MTR to dimyristoylphosphatidylcholine (DMPC) liposomes containing the anionic phospholipid dimyristoylphosphatidic acid (DMPA) was estimated by measuring the increase in intensity of the intrinsic fluorescence of MTR with increasing concentrations of phospholipids . Membrane perturbations were observed in acidic SUV of DMPC/DMPA and DMPC/bovine brain phosphatidylserine by MTR and its magnesium complex as studied by monitoring the leakage of the entrapped fluorescent marker carboxyfluorescein and by electron microscopic measurements of the size of the liposomes . These results indicated a possible role of anionic phospholipids in mediating binding of MTR and its magnesium complex to the cell surface membranes before reaching the target DNA.

East Mediterr Health J, 1999 Mar, 5(2), 328 - 32
{Antibiotic therapy in general medicine in Monastir, Tunisia}; Belghith Z et al.; In order to determine the cost and frequency of antibiotic prescription by general practitioners, we studied 563 outpatients from health centres in Monastir (Tunisia) . All patients had acute diseases . Antibiotics were prescribed to 50.4% . Single antibiotics were generally prescribed, but 52.8% of these patients did not have any laboratory tests . The more frequently used antibiotics were penicillin G and A . Antibiotics cost represented 34.7% of medicinal cost borne by patients and 49.7% of the cost borne by the public sector . Rationalization of medicinal prescription would have a positive impact on household and state budgets.

Am J Vet Res, 1999 Oct, 60(10), 1312 - 6
Evaluation of certification in the Milk and Dairy Beef Quality Assurance Program and associated factors on the risk of having violative antibiotic residues in milk from dairy farms in Michigan; Gibbons-Burgener SN et al.; OBJECTIVE: To determine whether certification in a Milk and Dairy Beef Quality Assurance Program (MDBQAP) was associated with a reduced risk of having antibiotic residues in milk and to define specific management factors that may have predisposed dairy farms to having violative antibiotic residues in milk . SAMPLE POPULATION: 124 dairy farms in Michigan that had > 1 violative residue in milk during 1993 and 248 randomly selected control farms in Michigan that did not have violative residues in milk during 1993 . PROCEDURE: A pretested structured questionnaire was mailed to case and control farms . A conditional multivariate logistic regression model was developed to determine risk factors associated with having a violative antibiotic residue in milk . RESULTS: Certification in the MDBQAP did not significantly reduce the risk of having a violative antibiotic residue . Annual treatment of > 10% of a herd for metritis was associated with a reduced risk of having a violative residue . Evidence suggested that a routine request for a milk processor to perform residue testing was associated with a decreased risk of having had a violative antibiotic residue, but routine on-farm residue testing was associated with an increased risk of having had a residue . CONCLUSIONS AND CLINICAL RELEVANCE: MDBQAP certification was associated, although not significantly, with a reduced risk of having violative antibiotic residues in milk . Risk factors significantly associated with violative antibiotic residues are addressed by various critical control points in the MDBQAP and may be indicators for strengths and weaknesses of MDBQAP.

Can Fam Physician, 2000 Apr, 46(4), 851 - 9
Pilot study for appropriate anti-infective community therapy . Effect of a guideline-based strategy to optimize use of antibiotics; Stewart J et al.; OBJECTIVE: To determine whether a community-wide, multi-intervention educational strategy (CoMPLI model) could enhance adoption of clinical guidelines and improve the use of antibiotics . DESIGN: Before-after trial using baseline and study periods with a control group . SETTING: A small community in central Ontario . PARTICIPANTS: Health professionals, the general public, and the pharmaceutical industry . INTERVENTIONS: The educational strategy (CoMPLI), carried out during 6 winter months, consisted of continuing medical education sessions for health professionals and pharmaceutical representatives and a parallel public education campaign that included town hall meetings and pamphlets distributed by local pharmacists . The two main messages were: do not use antibiotics for viral respiratory infections, and use drugs recommended in the publication, Anti-infective Guidelines for Community-Acquired Infections . MAIN OUTCOME MEASURES: Total number of antibiotic claims and adjusted odds ratios (OR) were used to measure the likelihood of physicians prescribing first- or second-line agents compared with the previous year and compared with control physicians . RESULTS: Claims in the study community decreased by nearly 10% during the 6-month study period compared with the baseline period from the previous year . Study physicians were 29% less likely (OR-1 = 0.71, range 0.67 to 0.76) to prescribe second-line antibiotics during the study period than physicians in the rest of the province . CONCLUSIONS: Physicians participating in the pilot study were more likely to follow drug recommendations outlined in published guidelines.

Anal Biochem, 2000 May 1, 280(2), 264 - 71
Measuring dissociation constants of RNA and aminoglycoside antibiotics by electrospray ionization mass spectrometry; Sannes-Lowery KA et al.; Electrospray ionization mass spectrometry (ESI-MS) has been used to determine the dissociation constants (K(D)s) and binding stoichiometry for tobramycin and paromomycin with a 27-nucleotide RNA construct representing the A-site of the 16S ribosomal RNA . K(D) values determined by holding the ligand concentration fixed are compared with K(D) values derived by holding the RNA target concentration fixed . Additionally, the effect of solution conditions such as the amount of organic solvent present and the amount of salt present in the solution on the K(D) measurement is investigated . It is shown that the preferred method for determining dissociation constants using ESI-MS is holding the RNA target concentration fixed below the expected K(D) and titrating the ligand . K(D) measurements should also be carried out at as high as possible salt concentration to minimize nonspecific binding due primarily to electrostatic interactions . For tobramycin, two nonequivalent binding sites were found with K(D1) = 352 nM and K(D2) = 9 microM . For paromomycin, there is only one binding site with K(D) = 52 nM .

J Foot Ankle Surg, 2000 Mar-Apr, 39(2), 124 - 30
Antibiotic beads in the treatment of diabetic pedal osteomyelitis; Roeder B et al.; Antibiotic-impregnated polymethylmethacrylate (PMMA) beads have improved the outcome of osteomyelitis treatment in both experimental models and clinical trials . The primary benefit of antibiotic-impregnated PMMA beads is that they provide high local concentrations of antibiotic while systemic levels of antibiotic remain low . Little has been written about the specific use of antibiotic-impregnated PMMA beads in the treatment of diabetic pedal osteomyelitis . The authors review antibiotic-impregnated PMMA beads and provide examples of their use in the treatment of diabetic pedal osteomyelitis.

J Trauma, 2000 Apr, 48(4), 753 - 7
Practice Management Guidelines for Prophylactic Antibiotic Use in Tube Thoracostomy for Traumatic Hemopneumothorax: the EAST Practice Management Guidelines Work Group . Eastern Association for Trauma; Luchette FA et al.; Multiple factors contribute to the development of posttraumatic empyema . These factors include the conditions under which the tube is inserted (emergent or urgent), the mechanism of injury, retained hemothorax, and ventilator care . The incidence of empyema in placebo groups ranges between 0 and 18% . The administration of antibiotics for longer than 24 hours did not seem to significantly reduce this risk compared with a shorter duration, although the numbers in each series were small . Most reports found a significant reduction in pneumonitis when patients received prolonged prophylactic antibiotics . This use of antibiotics might possibly be better described as presumptive therapy rather than prophylactic.

Nucleic Acids Symp Ser, 1999, (42), 21 - 2
The first synthesis of herbicidin B, a tricyclic-sugar adenine nucleoside antibiotic, using samarium diiodide-promoted aldol-type C-glycosidation reaction as a key-step; Shuto S et al.; A first total synthesis of the nucleoside antibiotic herbicidin B (1) was achieved in which a novel aldol-type C-glycosidation reaction promoted by samarium diiodide (SmI2) was used as a key step . Construction of the desired stereochemistry of the tricyclic-sugar moiety was successfully achieved by conformational restriction strategy based on repulsion between adjacent bulky protecting groups on the pyranose ring.

Nucleic Acids Symp Ser, 1999, (42), 15 - 6
Synthesis of nucleotide antibiotics having N-acyl phosphoramidate linkages; Moriguchi T et al.; This paper reports the synthesis of nucleotide antibiotics having N-acyl phosphoramidate linkages . The key reaction, the construction of the N-acyl phosphoramidate linkage was achieved by the reaction of nucleoside 5'-phosphoramidite derivatives with carboxamide derivatives in the presence of 5-(3,5-dinitrophenyl)-1H-tetrazole as a very effective activator . By use of this activator, Phosmidosine was synthesized by condensation of an appropriately protected 8-oxoadenosine 5'-O-phosphoramidite derivative with an N-protected prolinamide derivative . In the case of Agrocin 84, the two P-N bonds were constructed progressively . The N-acyl phosphoramidate linkage at the 5'-position of the ribose moiety was similarly synthesized . After phosphorylation of the amino group of the adenine moiety, a fully protected Agrocin 84 derivative, which would be converted to Agrocin 84, was successfully synthesized.

Biofizika, 2000 Mar-Apr, 45(2), 197 - 206
{1H-NMR analysis of heteroassociation of caffeine with antibiotic actinomycin D in the aqueous solution}; Veselkov DA et al.; The molecular basis of the action of caffeine as a complex forming agent, an interceptor of aromatic drugs intercalating into DNA was studied by the example of the an anticancer antibiotic actinomycin D examined . The hetero-association of caffeine and actionomycin D was studied by one- and two-dimensional 1H-NMR spectroscopy (500 MHz) . Concentration and temperature dependences of the proton chemical shifts of molecules in aqueous solution were measured . The equilibrium reaction constant of hetero-association of caffeine with actinomycin D (K = 246 +/- 48 M-1), the limiting chemical shifts of caffeine protons in complexes were determined . The most favourable structure of the 1:1 caffeine-actinomycin D hetero-complex in aqueous solution was constructed using the calculated values of the induced proton chemical shifts of molecules and the quantum-mechanical iso-shielding curves for caffeine and actinomycin D . The thermo-dynamical parameters of the hetero-complex formation between caffeine and actinomycin D were also determined . The structural and thermo-dynamical analysis showed that dispersive forces and hydrophobic interactions play the major role in hetero-association of caffeine and actinomycin D in aqueous-salt solution . The relative content of different complexes in mixed solutions containing caffeine and actinomycin D was calculated and distinctive features of the dynamic equilibrium of caffeine-actinomycin D hetero-associates were revealed as a function of concentration and temperature . It is concluded that hetero-association of caffeine and actinomycin D molecules a lowers the effective concentration of the drug in solution and hence the pharmacological activity of actinomycin D.

Pharmacotherapy, 2000 Apr, 20(4), 394 - 9
Antibiotic-heparin lock: in vitro antibiotic stability combined with heparin in a central venous catheter; Vercaigne LM et al.; Long-term hemodialysis frequently requires vascular access through central venous catheters (CVCs) . Infection related to these catheters is a significant complication . The use of an antibiotic-heparin lock could decrease the risks associated with infected permanent catheters . As an initial step in developing an antibiotic-heparin lock, we investigated the in vitro stability of antibiotic-heparin combinations in CVCs . Initially, cefazolin, vancomycin, ceftazidime, ciprofloxacin 10 mg/ml each, and gentamicin 5 mg/ml were incubated separately in glass test tubes in the dark at 37 degrees C for 72 hours . Samples were analyzed spectrophotometrically for stability at 24-hour intervals . The procedure was repeated with the addition of heparin (final concentration 5000 U/ml in glass test tubes), and the combination was also examined in CVCs . High-performance liquid chromatography analysis was conducted on the antibiotic-heparin combinations at 72 hours to confirm the spectrophotometric results . Ciprofloxacin produced an immediate precipitate with the addition of heparin and was not analyzed further . Absorbance values decreased for all antibiotics, with the greatest decreases at 72 hours for cefazolin (27.4%), vancomycin (29.7%), ceftazidime (40.2%), and gentamicin (8%) when combined with heparin . These decreases were postulated to be secondary to adsorption of the antibiotics to the luminal surface of the catheters because submitting the catheters to ultrasound with 1% sodium bicarbonate and analyzing the resulting solution for absorbance revealed that some of the drug was recovered . Although free antibiotic in CVC solution was reduced, the concentration should be sufficient (approximately 5 mg/ml) to decrease the frequency of infections associated with CVCs . We conclude that the concentrations of vancomycin, ceftazidime, cefazolin, or gentamicin used in our study should be sufficient for an antibiotic-heparin lock.

Antimicrob Agents Chemother, 2000 May, 44(5), 1322 - 7
Actinomycin production persists in a strain of Streptomyces antibioticus lacking phenoxazinone synthase; Jones GH; Truncated fragments of the phenoxazinone synthase gene, phsA, were prepared by the PCR . The resulting fragments were cloned into conjugative plasmid pKC1132 and transferred to Streptomyces antibioticus by conjugation from Escherichia coli . Two of the resulting constructs were integrated into the S . antibioticus chromosome by homologous recombination, and each of the resulting strains, designated 3720/pJSE173 and 3720/pJSE174, contained a disrupted phsA gene . Strain 3720/pJSE173 grew poorly, and Southern blotting suggested that genetic changes other than the disruption of the phsA gene might have occurred during the construction of that strain . Strain 3720/pJSE174 sporulated well and grew normally on the medium used to prepare inocula for antibiotic production . Strain 3720/pJSE174 also grew as well as the wild-type strain on antibiotic production medium containing either 1 or 5.7 mM phosphate . Strain 3720/pJSE174 was shown to be devoid of phenoxazinone synthase (PHS) activity, and PHS protein was undetectable in this strain by Western blotting . Despite the absence of detectable PHS activity, strain 3720/pJSE174 produced slightly more actinomycin than did the wild-type parent strain in medium containing 1 or 5.7 mM phosphate . The observation that strain 3720/pJSE174, lacking detectable PHS protein or enzyme activity, retained the ability to produce actinomycin supports the conclusion that PHS is not required for actinomycin biosynthesis in S . antibioticus.

Antimicrob Agents Chemother, 2000 May, 44(5), 1266 - 75
Identification and expression of genes involved in biosynthesis of L-oleandrose and its intermediate L-olivose in the oleandomycin producer Streptomyces antibioticus; Aguirrezabalaga I et al.; A 9.8-kb DNA region from the oleandomycin gene cluster in Streptomyces antibioticus was cloned . Sequence analysis revealed the presence of 8 open reading frames encoding different enzyme activities involved in the biosynthesis of one of the two 2, 6-deoxysugars attached to the oleandomycin aglycone: L-oleandrose (the oleW, oleV, oleL, and oleU genes) and D-desosamine (the oleNI and oleT genes), or of both (the oleS and oleE genes) . A Streptomyces albus strain harboring the oleG2 glycosyltransferase gene integrated into the chromosome was constructed . This strain was transformed with two different plasmid constructs (pOLV and pOLE) containing a set of genes proposed to be required for the biosynthesis of dTDP-L-olivose and dTDP-L-oleandrose, respectively . Incubation of these recombinant strains with the erythromycin aglycon (erythronolide B) gave rise to two new glycosylated compounds, identified as L-3-O-olivosyl- and L-3-O-oleandrosyl-erythronolide B, indicating that pOLV and pOLE encode all enzyme activities required for the biosynthesis of these two 2,6-dideoxysugars . A pathway is proposed for the biosynthesis of these two deoxysugars in S . antibioticus.

Clin Infect Dis, 2000 Apr, 30(4), 639 - 42 Epub 2000 Apr 04.
Financial impact of a home intravenous antibiotic program on a medicare managed care program; Dalovisio JR et al.; This study quantitates cost savings achieved by a home intravenous antibiotic (HIVA) program in a Medicare managed health care program . In 1998, 66 treatment courses of HIVA therapy were administered for a total of 1542 patient-days of therapy . The calculated cost of HIVA therapy included the actual costs of drugs, supplies, nursing and therapists' salaries, and laboratory studies . Savings were calculated based on the average daily direct variable cost (DDVC) for hospital acute unit or skilled nursing facility (SNF) care associated with the patient's discharge diagnosis-related-group . The number of days on HIVA therapy was assumed to equal the number of days in the hospital acute unit or hospital-based SNF . The average cost per day of HIVA therapy was $122, whereas average DDVC of hospital acute unit care was $798, and the average DDVC of SNF care was $541 . In 1 year, the HIVA program saved our health care system $646,000-$834,000, which demonstrates that HIVA programs are powerful tools to reduce costs in Medicare managed health care programs.

J Chemother, 2000 Feb, 12(1), 72 - 8
Differential costs and outcomes among pediatric oral antibiotic formulations identified from a large prescription database; Bowman L et al.; Differential performance of oral antibiotics continues to be a difficult characteristic to measure . As payers make efforts to identify selected antibiotics to place on their formularies or to reimburse, the challenge to these decision-makers is to determine which agent will work best in their population . Given the differences from one clinical trial to another, identifying performance characteristics that might impact effectiveness in clinical practice is quite challenging . This study's aim was to determine which beta-lactam and macrolide antibiotic provided the best clinical and economic outcome when used in difficult pediatric infections that previously experienced amoxicillin or cotrimoxazole failure . The findings demonstrated that cefaclor, azithromycin, and amoxicillin/clavulanate were associated with a decreased need for subsequent antibiotic therapy . Total drug treatment costs for beta-lactams and macrolides were lowest for cefaclor and azithromycin, respectively . These results are consistent with previous published literature and seem plausible given potential compliance advantages of these products as reported in studies of product tolerability and taste.

J Biol Chem, 2000 Apr 21, 275(16), 11713 - 20
Glycosylation of macrolide antibiotics . Purification and kinetic studies of a macrolide glycosyltransferase from Streptomyces antibioticus; Quiros LM et al.; The oleD gene has been identified in the oleandomycin producer Streptomyces antibioticus and it codes a macrolide glycosyltransferase that is able to transfer a glucose moiety from UDP-glucose (UDP-Glc) to many macrolides . The glycosyltransferase coded by the oleD gene has been purified 371-fold from a Streptomyces lividans clone expressing this protein . The reaction product was isolated, and its structure determined by NMR spectroscopy . The kinetic mechanism of the reaction was analyzed using the macrolide antibiotic lankamycin (LK) as substrate . The reaction operates via a compulsory order mechanism . This has been shown by steady-state kinetic studies and by isotopic exchange reactions at equilibrium . LK binds first to the enzyme, followed by UDP-glucose . A ternary complex is thus formed prior to transfer of glucose . UDP is then released, followed by the glycosylated lankamycin (GS-LK) . A pH study of the reaction was performed to determine values for the molecular pK values, suggesting possible amino acid residues involved in the catalytic process.

Clin Exp Obstet Gynecol, 2000, 27(1), 27 - 8
The role of antibiotics after dilatation and curettage in women with metrorrhagia in the prevention of pelvic inflammatory disease; Makris N et al.; A follow-up study was carried out in 67 healthy women with negative vaginal-cervical cultures after an endometrial curettage for metrorrhagia . The women were separated into two treatment groups and clinically followed for one month after the operation . The first group included 33 women (aged 23-67, mean 43) who received doxycycline 200 mg daily for a period of one week after the procedure . The second group included 34 women (aged 28-70, mean 43.5) who did not receive any antibiotic regimen after the dilatation and curettage . Four and three women from the 1st and 2nd group, respectively, developed PID during follow-up; a difference not statistically significant.

Int, J . Angiol. . 2000 Mar, 9(2), 78 - 81
Internal Mammary Artery Harvesting and Antibiotic Concentrations in Sternal Bone During Coronary Artery Bypass; Vuorisalo S et al.; The concentrations of two antibiotics (vancomycin and cefuroxime) in sternal bone during coronary artery bypass surgery were analyzed to examine whether antibiotic penetration is impaired after dissection and harvesting of the left internal mammary artery for grafting . Bone samples (250 mg of cancellous sternal bone from both halves of the dissected manubrium) were obtained at the time of sternal opening and closure . Twenty patients undergoing primary coronary artery bypass grafting with the left internal mammary artery were randomized so that ten received 1.5 g of vancomycin over 180 minutes and ten 3 g of cefuroxime over 30 minutes beginning at the time of induction of anesthesia . Serum samples were collected at the same time as the bone samples and 12 h after the start of the infusions . There was a slight difference in vancomycin concentration between two sternal halves after IMA dissection at the time of sternal closure (median difference, 0.2 microg/g, and 95% confidence interval, -0.55 to 0.1) . This difference was not statistically significant at the P = 0.05 level (P = 0.15, Wilcoxon matched-pair test) . The cefuroxime concentration of the bone was below the detection limit (7.6 to 9.2 microg/g) in all ten patients at the time of sternal closure . Harvesting the internal mammary artery for coronary artery bypass grafting may influence the concentration of vancomycin in the manubrium of the sternum.

Br J Gen Pract, 1999 Sep, 49(446), 735 - 6
Age- and sex-specific antibiotic prescribing patterns in general practice in England and Wales in 1996; Majeed A et al.; Using data from 288 general practices in England and Wales contributing data to the General Practice Research Database in 1996, we derived age-sex specific antibiotic prescribing and exposure rates . The overall antibiotic prescribing rate was 607 per 1000 in males and 852 per 1000 in females . In both males and females, prescribing rates were highest in children aged 0-4 years and in the elderly . Prescribing rates in young and middle-aged women were substantially higher than in men of the same age . Overall, 29% of males and 39% of females were prescribed antibiotics in 1996 . Children under five years of age were most likely to receive a prescription for an antibiotic . Antibiotic prescribing rates for the 288 practices in the study varied nearly five-fold, from 333 to 1616 per 1000 . Reducing this variation and overall antibiotic prescribing rates will be major challenges for general practitioners.

Probl Tuberk, 2000, (1), 23 - 4
{Use of antibiotics in chronic bronchitis}; Guseinov KhIu; Whether it is advisable to use tarivide, a wide-spectrum acting antibiotic, in 193 patients aged 23 to 50 years who had chronic catarrhal bronchitis . The experimental group included 43 and 57 patients with chronic nonobstructive and obstructive bronchitis, respectively . For comparison, a matched group receiving penicillin comprised 40 and 53 patients, respectively . Tarivide eliminated most strains of pathogens and improves cellular immunity . Cure and improvement were achieved in 147 (77%) and 13 (12%) patients, respectively . The favourable pharmacokinetics of tarivide, its easy-to-use regimen make it the drug of choice for oral treatment.

Semin Respir Infect, 2000 Mar, 15(1), 59 - 70
Antibiotic therapy of exacerbations of chronic bronchitis; Niederman MS; The role of antibiotics in acute exacerbations of chronic bronchitis (AECB) remains controversial because patients commonly harbor the same bacteria in their sputum at times of stability and at times of acute illness . However, prospective randomized controlled trials do show a benefit for the use of antibiotics, compared with placebo, in AECB, particularly if patients have at least 2 of the following 3 symptoms: increased dyspnea, increased sputum volume, increased sputum purulence . In this setting, antibiotics have value, leading to a more rapid resolution of symptoms and a more rapid return of peak flow rate, compared with placebo . In addition, antibiotics may prevent some patients from developing secondary pneumonia and may prolong the time between exacerbations . When antibiotics are used, a variety of factors must be considered in choosing an agent . These include the likelihood of antibiotic-resistant bacteria, a factor that relates to defining subsets of patients . Patients can fall into 1 of 3 categories, each with a different suggested therapy . These categories include simple AECB, complicated AECB, and AECB at risk for infection with P . aeruginosa . In addition, an antibiotic should be chosen with pharmacokinetics and pharmacodynamic behavior in mind . In the future, research will need to confirm that careful selection of specific agents for specific patients can lead to improved patient outcomes, but already some preliminary data are supporting this concept.

Allergy Asthma Proc, 2000 Jan-Feb, 21(1), 39 - 44
Approach to the patient with multiple antibiotic sensitivities; Gruchalla RS; Allergists sometimes are asked to evaluate patients who have experienced multiple adverse drug reactions . By the time the patient reaches the allergist, the referring physician, as well as the patient, often are frustrated . Each seeks a quick and simple answer regarding the particular drugs the patient may safely receive . Unfortunately, however, in most instances, simple answers cannot be given . Currently we have limited knowledge of the mechanisms and of the clinically-relevant drug metabolites responsible for many of the reactions demonstrated and, for these reasons, we have few valid diagnostic tests that are able to provide clear-cut answers for our patients who present with multiple drug "allergies." Despite these limitations, using accurate and complete historical information along with limited diagnostic testing, logical and practical management approaches can be devised . In addition, due to new exciting data that are being generated from basic research studies in drug allergy, the mechanisms underlying the immunopathology of many drug reactions are becoming more clear . Through the acquisition of scientific information of this type, it is hoped that valid diagnostic tools soon will be developed so that definitive answers, desired by both the patient and the referring physician, can be provided.

Chemistry, 2000 Feb 4, 6(3), 504 - 9
The formation of heterodimers by vancomycin group antibiotics; Staroske T et al.; The formation of heterodimers in mixtures of glycopeptide antibiotics has been detected by electrospray ionization mass spectrometry (ESI-MS), and dimerization constants have been determined . By using NMR spectroscopy, it has been shown that these heterodimers indeed exist in aqueous solution . The dimerization constants obtained by NMR spectroscopy are in good agreement with those determined by ESI-MS . Structural information on the heterodimer interface of some of the heterodimers is obtained by using two-dimensional NMR techniques and reveals that these heterodimers are similar in structure to the homodimers.

Cornea, 2000 Mar, 19(2), 204 - 6
Effect of fortified antibiotic solutions on corneal epithelial wound healing; Lin CP et al.; PURPOSE: To evaluate the influence of fortified antibiotic eyedrops on corneal epithelial wound healing . METHODS: We developed an in vitro epithelial wound-healing model to evaluate the toxicity of antibiotics . An excimer laser was used to create an epithelial defect 1.5 mm in diameter, 70 microm in depth on the central area of porcine cornea . The intact animal globes were maintained in the incubator by a perfusion system . Fortified antibiotics: 10% piperacillin, 5% cefazolin, 0.5% chloramphenicol, 5% vancomycin, 1% amikacin, 2% gentamicin, and 0.1% amphotericin B were applied to the wound in three applications . The wounds were evaluated 24 h after setup with fluorescein stain and a scoring system . RESULTS: The 0.1% amphotericin B and 2% gentamicin disturbed the corneal epithelial healing rate significantly . The remaining antibiotics did not interfere with the epithelial healing rate in our study design . CONCLUSION: Fortified antibiotic eyedrops demonstrated varied degrees of influence on corneal epithelial wound healing . When antibiotic eyedrops are used, both the efficacy and toxicity of the antibiotics should be the major concern . If efficacy is equivalent, less-toxic agents should be given preference.

Acta Orthop Scand, 2000 Feb, 71(1), 80 - 4
Cancellous bone as an antibiotic carrier; Witso E et al.; We compared the release characteristics of antibiotics from in vivo and in vitro processed morselized cancellous bone . The bone was impregnated with 7 antibiotics and compressed into a wire-mesh cylinder . In vitro, the bone was processed by daily transfer of the cylinder with its contents into test tubes with broth . The amount of antibiotic eluted from the bone was measured after 1, 3 and 7 days . In vivo, the cylinder was implanted intramuscularly in the interscapular region in rats . After 1, 3 and 7 days, the cylinder was removed and the amount of antibiotic eluted in broth was measured . The results showed that morselized cancellous bone can act as a carrier of antibiotics in vitro and in vivo . The elution profiles of netilmicin-, vancomycin-, clindamycin- and rifampicin-impregnated cancellous bone processed in vitro and in vivo were similar.

Soc Sci Med, 2000 May, 50(10), 1445 - 50
Family self-medication and antibiotics abuse for children and juveniles in a Chinese city; Bi P et al.; To identify the determinants of self-medication and antibiotics abuse by parents treating their children aged between 2 and 18 over the previous year, an investigation was conducted in Hefei City, China in April, 1995 . A total of 1596 students from a kindergarten, a primary school and a high school were included in the study, and 1459 completed questionnaires were collected (the response rate: 91.4%) . The results showed the rate of parental self-medication for their children in the sample was 59.4% . It increased with children's age; about 51% of children had received parental self-medication on six or more occasions during the 1-year period and 32.8% on four to five occasions; there were associations between parental self-prescribers and sources of medicine and severity of disease . The rate of antibiotics abuse was 35.7% . Logistic regression analysis showed that there were significant associations between self-medication and payment of the mother's medical fees by employers, severity of diseases as well as the mother's educational level.

Clin Orthop, 2000 Mar, (372), 254 - 61
Comparison of antibiotic beads and intravenous antibiotics in open fractures; Moehring HD et al.; This study compared the efficacy of antibiotic impregnated beads with conventional intravenous antibiotics in the treatment of open fractures . A randomized prospective study was designed and conducted during a 29-month period . Sixty-seven patients with 75 open fractures were treated similarly, with the exception of the method of antibiotic administration, and were followed up for at least 1 year after injury . Infection occurred in two of 24 (8.3%) fractures treated with antibiotic beads alone and in two of 38 (5.3%) fractures treated with conventional intravenous antibiotics . In an unanticipated nonrandomized third cohort group, patients received antibiotic beads and intravenous antibiotics administered for nonorthopaedic reasons or limb threatening injury, or both . Two of 13 (15.4%) fractures in this high risk group became infected . Infection ultimately resolved in all fractures treated with antibiotic beads alone or antibiotic beads in conjunction with conventional intravenous antibiotics . This study was unable to achieve statistical significance; however, the data suggest antibiotic beads may be useful in preventing infection in open fractures . Thus, a larger multicenter randomized prospective study of isolated open fractures, eliminating other variables, is justified.

Aliment Pharmacol Ther, 2000 Mar, 14(3), 325 - 30
Seven-day triple therapy with ranitidine bismuth citrate or omeprazole and two antibiotics for eradication of Helicobacter pylori in duodenal ulcer: a multicentre, randomized, single-blind study; Spinzi GC et al.; AIM: To investigate the efficacy of a 1-week triple therapy with amoxycillin, clarithromycin, and omeprazole or ranitidine bismuth citrate (RBC) in curing Helicobacter pylori infection and healing duodenal ulcers . METHODS: One hundred and ninety-two consecutive out-patients with duodenal ulcer, in whom H . pylori infection was confirmed by histology and a urease biopsy test, were randomly assigned to a 1-week treatment with either 400 mg b.d . ranitidine bismuth citrate (RAC group) or 20 mg omeprazole b.d . (OAC group) in combination with 1 g amoxycillin b.d . and 500 mg clarithromycin b.d . RESULTS: Eradication of H . pylori was successful in 77% (per protocol) and 61% (intention-to-treat) of the patients in the RAC group and in 79% (per protocol) and 70% (intention-to-treat) of those in the OAC group . The difference was not significant . Per protocol analysis showed ulcers were healed in 97% of patients in the RAC group and 96% in the OAC group . Adverse effects were seen in four patients in each group: they caused discontinuation of the therapy in one patient of the OAC group . CONCLUSIONS: Eradication rates obtained in this study were lower than those expected on the basis of previously reported studies . The two 1-week treatment regimens were equally effective in healing H . pylori associated duodenal ulcer disease.

Photochem Photobiol, 2000 Mar, 71(3), 281 - 93
Spectroscopic properties of fluoroquinolone antibiotics and nanosecond solvation dynamics in aerosol-OT reverse micelles; Park HR et al.; Among fluoroquinolone antibiotics, ofloxacin (OFL) and norfloxacin (NOR) have piperazinyl groups but flumequine (FLU) does not have this substitutent . The emission spectra of OFL and NOR are strong, broad structureless bands with large Stokes' shifts in water but the emission intensities are very weak in organic solvents . Thus we find that these compounds exist as different chemical species in various solvents . A continuous red shift in the emission bands for OFL and NOR is observed as the water concentration within the aerosol-OT (AOT; sodium 1,4-bis{2-ethylhexyl}sulfosuccinate) micelle increases or temperature of this solution rises . From the fluorescence anisotropy measurements of OFL and NOR, we assume the intramolecular charge transfer after excitation from the nitrogen of the piperazinyl group to the keto oxygen . Theoretical calculations further support this observation . Multifrequency phase and modulation experiments and time-resolved emission spectra clearly show the occurrence of intramolecular charge transfer and the subsequent nanosecond water reorganization around OFL or NOR in the AOT micelle . Upon increasing the water concentration within the AOT micelle, the relaxation rate increases because of the large amount of free water . The emission spectra of FLU do not exhibit any significant response to the physical properties of their environment.

Obes Surg, 1995 Aug, 5(3), 293 - 297
Local vs Systemic Antibiotics to Decrease Wound Complications following Vertical Banded Gastroplasty: Results of a Prospective Randomized Trial; Miller K et al.; BACKGROUND: Obesity is generally regarded as one factor predisposing to wound infection . Most reports of infection rates range from I to 16% for similar procedures . In our department the wound infection rate for morbidly obese patients was 12% without perioperative antibiotics . METHODS: In a prospective randomized study we compared local gentamicin-collagen fleece application in the subcutaneous layer with patients receiving a perioperative single I.V . dose of amoxicillin-clavulanic acid 2.2 g . We examined the results of different perioperative management of antibiotics on 50 morbidly obese patients who underwent vertical banded gastroplasty from March 1993 to August 1994 . The fascial, subcutaneous and skin closure technique were identical in the two groups . For both groups we used a closed-suction system to drain the bottom of the deep subcutaneous layer . On the third postoperative day, the subcutaneous drains were removed . Patients stayed in hospital an average of 10 days . They had follow-up visits after 1, 3 and 6 months, and then yearly . RESULTS: None of the 50 patients developed a wound infection, hematoma, or seroma in the hospital . During the follow-up (median 6 months), no patient developed a wound abscess . CONCLUSIONS: We believe that perioperative antibiotic management is an important factor in obtaining a low infection rate.

Br J Ophthalmol, 2000 Apr, 84(4), 378 - 84
Fluoroquinolone and fortified antibiotics for treating bacterial corneal ulcers; Gangopadhyay N et al.; AIM: To compare the clinical efficacy of commercially available fluoroquinolone drops with the use of combined fortified antibiotics (tobramycin 1.3%-cefazolin 5%) in treatment of bacterial corneal ulcer . METHODS: The medical records of 140 patients with a diagnosis of bacterial corneal ulcer who were admitted to the Royal Victorian Eye and Ear Hospital, Melbourne, Australia between January 1993 and December 1997 were reviewed retrospectively . Final outcome and results of 138 ulcer episodes were compared between those treated initially with fluoroquinolone and those who received fortified antibiotics . Two patients had been treated with chloramphenicol . RESULTS: No significant treatment difference was found between fluoroquinolone and fortified therapy in terms of final visual outcome . However, serious complications such as corneal perforation, evisceration, or enucleation of the affected eye were more common with fluoroquinolone therapy (16.7%) compared with the fortified therapy (2.4%, p= 0.02) . The duration of intensive therapy was less with fluoroquinolone especially in those over 60 years of age (4 days v 6 days, p=0.01) . Hospital stay was also less in the fluoroquinolone group compared with the fortified group for all patients and was significantly less with fluoroquinolone treatment (7 days v 10 days, p=0.02) in patients in the age group over 60 years old . CONCLUSIONS: Monotherapy with fluoroquinolone eye drops for the treatment of bacterial corneal ulcers led to shorter duration of intensive therapy and shorter hospital stay compared with combined fortified therapy (tobramycin-cefazolin) . This finding may have resulted from quicker clinical response of healing as a result of less toxicity found in the patients treated with fluoroquinolone . However, as some serious complications were encountered more commonly in the fluoroquinolone group, caution should be exercised in using fluoroquinolones in large, deep ulcers in the elderly.

Theriogenology, 1999 Mar, 51(4), 689 - 97
Failure of antibiotics gentamycin, tylosin, lincomycin and spectinomycin to eliminate Mycoplasma bovis in artificially infected frozen bovine semen; Visser IJ et al.; To study the effect of antibiotics upon Mycoplasma bovis in fresh bovine semen just before freezing, specimens of bovine semen were artificially infected with 1 of 9 different strains of M . bovis . Inocula of each strain were prepared to contain 10(5) to 10(6)/mL colony-forming units of M . bovis at 3 different stages of the growth phase . The infected semen was diluted with a Tris extender by a 3-step procedure using an antibiotic mixture of gentamicin, tylosin, lincomycin and spectinomycin (GTLS) . This semen-antibiotic mixture was placed into French straws that were stored at -196 degrees C . The control semen specimens contained no antibiotics Mycoplasmas were counted after 8 d of storage in 3 decimal dilutions of the frozen semen . No evident effect was noticed upon the 9 tested strains of mycoplasmas in the semen frozen with the antibiotics, compared with that of the untreated control samples . It was further shown that this lack of effect was irrespective of the stage of the growth phase of the mycoplasmas . It was concluded that the antibiotic mixture (GTLS) in semen specimens is not capable of total elimination of mycoplasmas in frozen bovine semen.

Biochim Biophys Acta, 2000 Apr 5, 1464(2), 309 - 21
Oligonucleotide delivery by a cationic derivative of the polyene antibiotic amphotericin B . II: study of the interactions of the oligonucleotide/cationic vector complexes with lipid monolayers and lipid unilamellar vesicles; Blanc I et al.; We report a study of the behavior of oligodeoxyribonucleotide (ODN)/amphotericin B3-(N'-dimethylamino)propylamide (AMA) complexes, in the presence of lipid monolayers and large unilamellar vesicles . This study follows the recent discovery of the capacity of AMA, as a new cationic vector, to enhance ODN cellular uptake and efficacy . It aims at investigating the internalization mode of a nucleic acid by AMA . A first study at the air-water interface of AMA and AMA/ODN by surface pressure measurement shows that only free AMA would adsorb at the air-water interface . Second, in the presence of zwitterionic phospholipid- and sterol-containing mixture, ODN-AMA interactions in solution would be higher than lipid-AMA interactions at the interface . In monolayer or with large unilamellar vesicles, AMA monomers adsorb mainly at the phospholipid interface . These results favor a crossing mechanism through AMA channel formation, despite the size of ODN.

Biochim Biophys Acta, 2000 Apr 5, 1464(2), 299 - 308
Oligonucleotide delivery by a cationic derivative of the polyene antibiotic amphotericin B . I: interaction oligonucleotide/vector as studied by optical spectroscopy and electron microscopy; Blanc I et al.; Antisense strategy requires efficient systems for the delivery of oligodeoxyribonucleotides (ODN) into target cells . Cationic amphiphiles have shown good efficiency in vitro and a lot of attention is currently paid to their interaction with nucleic acids . In the present study, this interaction was, for the first time, analysed at the molecular level, taking advantage of the spectroscopic properties of the positively charged chiral polyene molecule amphotericin B 3-dimethylaminopropyl amide (AMA), the efficiency of which, as delivery system, has been demonstrated {Garcia et al., Pharmacol . Ther . (2000), in press} . By UV-visible absorption and circular dichroism (CD) we studied its self-association properties in pure water, saline and RPMI medium . Drastic changes were observed upon ODN addition, stronger in pure water than in media of high ionic strength . At low AMA concentration (<10(-6) M), the strong increase of the CD signal, characteristic of self-association, indicated condensation of AMA on the ODN molecules . At a higher concentration (10(-4) M), and for a nucleic acid negative charge/AMA positive charge ratio higher than 1, spectra were interpreted as a reorganisation of free self-associated AMA species into smaller ones 'decorating' the nucleic acid molecule . Electron microscopy data were interpreted according to this scheme.

Int J STD AIDS, 2000 Mar, 11(3), 168 - 9
Is it evidence-based practice? Prophylactic antibiotics for termination of pregnancy to minimize post-abortion pelvic infection?
Uthayakumar S, Tenuwara W, Maiti H.
Sexually transmitted infections (STIs) causing upper genital tract problems after termination of pregnancy (TOP) is well recognized . We undertook this study to assess the local prevalence of Chlamydia trachomatis infection and to estimate the potential benefits of introducing screening . The prevalence rate of C . trachomatis was 6% . Nine sexual contacts of the index cases were identified . They were symptom free, but all had non-specific urethritis (NSU) . Four of them were positive for C . trachomatis . We conclude that screening for chlamydial infection is essential and routine prophylactic antibiotic cover may not be beneficial.

J Antibiot (Tokyo), 1999 Sep, 52(9), 787 - 96
Decatromicins A and B, new antibiotics produced by Actinomadura sp . MK73-NF4 . II . Structure determination; Momose I et al.; The structures of decatromicins A and B that strongly inhibit the growth of MRSA were elucidated by the analysis of various NMR experiments . The planar structure was determined by 1H, 13C, COSY, HMQC and HMBC NMR spectra . The relative configuration of aglycone was elucidated by NOESY experiments and the absolute structure was determined by application of the modified Mosher's method . The absolute structure of glycosyl moiety was determined by X-ray analysis of the O-(p-bromobenzoyl) derivative.

Stud Health Technol Inform, 1999, 68, 690 - 5
A probabilistic approach to improved antibiotic therapy; de Bruijn N et al.; PTA is a decision-theoretic expert system that aims to assist clinicians in diagnosing and treating patients with pneumonia in the intensive care unit . Its underlying probabilistic network model includes knowledge for diagnosing pneumonia on the basis of the likelihood of tracheobronchial-tree colonisation by pathogens, and symptoms and signs actually present in the patient . Optimal antibiotic therapy is selected by balancing the expected efficacy of treatment, which is related to the likelihood of pathogen-specific pneumonias, against costs and side effects of treatment . In this article, the model underlying the system and results of a preliminary evaluation are described.

J Antibiot (Tokyo), 2000 Jan, 53(1), 38 - 44
PF1163A and B, new antifungal antibiotics produced by Penicillium sp . II . Physico-chemical properties and structure elucidation; Sasaki T et al.; The structures of new antifungal antibiotics, PF1163A and B, were elucidated by spectroscopic analyses of the degradation products and by X-ray crystallography of the de-2-hydroxyethyl derivative of PF1163B . Both antibiotics consist of a 13-membered macrocyclic structure containing a derivative of N-methyl tyrosine and a hydroxy fatty acid . PF1163A differs from PF 1163B by having an additional hydroxyl group on the side chain.

Int J Antimicrob Agents, 2000 Mar, 14(2), 91 - 8
Antibiotic efficacy in vivo predicted by in vitro activity; Mattie H; A brief overview of arguments found in the literature is presented to apply the E(max) concept to experimental studies of antibiotics as well as to their clinical application . It may turn out to be more flexible than schedules based on arbitrary parameters that have the disadvantage that they have to be proven in each individual situation.

Acta Otorhinolaryngol Belg, 2000, 54(1), 23 - 8
Short term effects of antibiotics (Zinnat) after endoscopic sinus surgery; Annys E et al.; The effects of antibiotics after endoscopic sinus surgery (ESS) were investigated in a prospective, randomized, double blind, placebo controlled study in 202 patients . Hundred and one patients received cefuroxime axetil (Zinnat, 2 x 250 mg/d) . The other half received placebo . Patients received no nasal packing and were treated with nasal washes and steroids . Ten subjective symptoms (headache, maxillary pressure, nasal obstruction, nasal secretions, blood, post nasal drip, sneezing, cough, smell disturbances and illness) were recorded daily and at weekly postoperative visits (including suction cleaning when indicated) seven endoscopic parameters were evaluated . There were no statistical differences in the total and individual symptom and endoscopic scores . There was no significant difference in the incidence of postoperative infections between both groups . In conclusion, antibiotics do not influence the immediate postoperative clinical evolution after ESS.

Presse Med, 2000 Feb 19, 29(6), 321 - 6
{Allergy to macrolide antibiotics . Review of the literature}; Demoly P et al.; MACROLIDE CLASSES: Macrolides are characterized by their basic structure made up of a lactonic cycle with 2 osidic chains . They are classified according to the number of carbon atoms in the cycle: 14-membered macrolides (erythromycin, troleandomycin, roxithromycin, dirithromycin, clarithromycin), 15-membered macrolides (azithromycin) and 16-membered macrolides (spiramycin, josamycin, midecamycin) . MACROLIDE ALLERGY: Allergy to macrolides is extremely rare (0.4% to 3% of treatments) . The little information available in the literature is insufficient to establish the usefulness of diagnostic tests . An immediate IgE-dependent hypersensitivity has been shown with erythromycin in some cases but the mechanism remains unknown and skin tests are quite often negative . Clinical manifestations are the same as those encountered with beta-lactams . It would appear that macrolide allergies are unlikely to be class allergies . This is important as eviction advice could be limited to the single causal macrolide.

Proc Natl Acad Sci U S A, 2000 Mar 28, 97(7), 3112 - 7
Heterologous expression in Escherichia coli of the first module of the nonribosomal peptide synthetase for chloroeremomycin, a vancomycin-type glycopeptide antibiotic; Trauger JW et al.; The gene cluster from Amycolotopsis orientalis responsible for biosynthesis of the vancomycin-type glycopeptide antibiotic chloroeremomycin was recently sequenced, indicating that this antibiotic derives from a seven-residue peptide synthesized by a three-subunit (CepA, CepB, and CepC) modular nonribosomal peptide synthetase . Expression of all or parts of the peptide synthetase in Escherichia coli would facilitate biochemical characterization of its substrate specificity, an important step toward the development of more potent glycopeptides by combinatorial biosynthesis . To determine whether CepA, a three-module 3,158-residue peptide synthetase expected to assemble the first three residues of the heptapeptide precursor, could be heterologously expressed in E . coli and converted to active, holo form by posttranslational priming with a phosphopantetheinyltransferase, we expressed two CepA fragments (CepA1-575 and CepA1-1596) as well as full-length CepA (CepA1-3158) . All three constructs were expressed in soluble form . We find that the CepA1-575 fragment, containing adenylation and peptidyl carrier protein domains (A1-PCP1), specifically adenylates l-leucine and d-leucine in a 6:1 ratio, and it can be converted to holo form by the phosphopantetheinyltransferase Sfp; also, we find that holo-CepA1-575 can be covalently aminoacylated with l-leucine on the peptidyl carrier protein 1 domain . However, no amino acid-dependent adenylation or aminoacylation activity was detected for the larger CepA constructs with l-leucine or other expected amino acid substrates, suggesting severe folding problems in the multidomain proteins.

Pharmacol Res, 2000 Jan, 41(1), 107 - 111
EFFECTS OF SOME ANTIBIOTICS ON ENZYME ACTIVITY OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE FROM HUMAN ERYTHROCYTES; Ciftci M et al.; Inhibitory effects of some antibiotics on glucose-6-phosphate dehydrogenase from the erythrocytes of human have been investigated . For this purpose, at the beginning, erythrocyte glucose-6-phosphate dehydrogenase was purified 13.654 times in a yield of 28% by using ammonium sulphate precipitation and 2',5'-ADP Sepharose 4B affinity gel . Temperature of +4 degrees C was maintained during the purification process . Enzyme activity was determined with the Beutler method by using a spectrophotometer at 340 nm . This method was utilized for all kinetic studies . Sodium ceftizoxime, sodium ampicillin, sodium cefuroxime, sodium cefazolin, sodium cefoperazone, streptomycin sulphate, gentamicin sulphate, and netilmicin sulphate were used as antibiotics . All the antibiotics indicated the inhibitory effects on the enzyme . K(i)constants for glucose-6-phosphate dehydrogenase were found by means of Lineweaver-Burk graphs . While sodium cefoperazone, gentamicin sulphate, and netilmicin sulphate showed competitive inhibition, the others displayed non-competitive inhibition . In addition, I(50)values of the antibiotics were determined by plotting activity percent vs {I} . In addition, in vivo studies were done for sodium sefuroxime in Sprague-Dawley type rats . It was found that G6PD in erythrocyte was more inhibited by the drug in 2.5 h . 2000 Academic Press@p$hr

Eur J Biochem, 2000 Mar, 267(6), 1698 - 706
Molecular characterization of two genes from Streptomyces tendae Tü901 required for the formation of the 4-formyl-4-imidazolin-2-one-containing nucleoside moiety of the peptidyl nucleoside antibiotic nikkomycin; Lauer B et al.; The genes nikQ and nikR were identified by sequencing DNA of the nikkomycin biosynthetic gene cluster from Streptomyces tendae Tu901/8c . The nikQ gene encodes a P450 cytochrome, and the predicted NikR gene product shows 48-56% sequence identity with uracil phosphoribosyltransferases from eukaryotic organisms . The nikQ and nikR genes were inactivated separately by insertion of a kanamycin-resistance cassette . Inactivation of the nikQ gene abolished synthesis of nikkomycins containing 4-formyl-4-imidazolin-2-one as the base (nikkomycins X and I), whereas production of nikkomycins containing uracil (nikkomycins Z and J) was not affected . Nikkomycin X and I production could be restored by feeding 4-formyl-4-imidazolin-2-one to the nikQ mutants, indicating that NikQ is responsible for its formation from L-histidine . Disruption of the nikR gene resulted in formation of decreased amounts of nikkomycins X and I, whereas nikkomycins Z and J were synthesized at wild-type levels . A fluorouracil-resistant nikR mutant lacking uracil phosphoribosyltransferase (UPRTase) activity did not synthesize nikkomycins X and I and accumulated 4-formyl-4-imidazolin-2-one in its culture filtrate, whereas formation of nikkomycins Z and J was unimpaired . The mutant was complemented to nikkomycin X and I production by nikR expressed from the mel promoter of plasmid pIJ702 . The nikR gene expressed in Escherichia coli led to the production of UPRTase activity . Our results indicate that NikR converts 4-formyl-4-imidazolin-2-one to yield 5'-phosphoribosyl-4-formyl-4-imidazolin-2-one, the precursor of nikkomycins containing this base.

Biochim Biophys Acta, 2000 Mar 7, 1477(1-2), 35 - 50
Bacterial proteinases as targets for the development of second-generation antibiotics; Travis J et al.; The emergence of bacterial pathogen resistance to common antibiotics strongly supports the necessity to develop alternative mechanisms for combating drug-resistant forms of these infective organisms . Currently, few pharmaceutical companies have attempted to investigate the possibility of interrupting metabolic pathways other than those that are known to be involved in cell wall biosynthesis . In this review, we describe multiple, novel roles for bacterial proteinases during infection using, as a specific example, the enzymes from the organism Porphyromonas gingivalis, a periodontopathogen, which is known to be involved in the development and progression of periodontal disease . In this manner, we are able to justify the concept of developing synthetic inhibitors against members of this class of enzymes as potential second-generation antibiotics . Such compounds could not only prove valuable in retarding the growth and proliferation of bacterial pathogens but also lead to the use of this class of inhibitors against invasion by other infective organisms.

Antibiot Khimioter, 2000, 45(2), 15 - 21
{The immunological aspects of predicting antibiotic therapy efficacy in peritonitis patients}; Briskin BS et al.; The analysis of the impact of various group antibiotics on the mechanisms of development and correction of pathogenetically heterogeneous immune deficiency in 235 patients at age of 17 to 85 years with local (80 patients) and general (155 patients) peritonitis is presented . Cephalosporins and fluoroquinolones promoted restoration of the immune and interleukin (IL-1 and IL-2 of donors, IL-1r and IL-2r of patients) status and lowered the immunodepressive effect of glucocorticoids (GC) at the organism (cortisol, ACTH and cortisol-binding globulin) and cellular (GC receptors III) levels . Aminoglycosides and penicillins had no significant action on the immune and interleukin status but lowered the EG effect at the organism (aminoglycosides) and cellular (penicillins) levels . It is recommended that the antibiotics be used with an account of their involvement in the systemic reactions of the host.

Antibiot Khimioter, 2000, 45(2), 10 - 4
{Calcium ions and the differentiation of Streptomyces hygroscopicus 155, a producer of an antibiotic complex}; Moncheva PA et al.; The effect of Ca2+ on differentiation of Streptomyces hygroscopicus 155 and its inactive variant 155-0 was studied . Addition of Ca2+ to the medium induced formation of the aerial mycelium in the inactive variant and accelerated formation of the aerial mycelium in the parent strain . The inhibitory effect of EGTA, verapamil, nifedipin, chlorpromazine and dilthiazeme on the aerial mycelium formation demonstrated the physiological role of Ca2+ in the process . Addition of pandavir (nigericin) and azalomycin B, the antibiotics produced by the streptomycete, induced formation of the aerial mycelium in the inactive variant . The effect was higher in the presence of Ca2+ . Streptomyces hygroscopicus 155 and its inactive variant synthesized a proteolytic complex containing metalloproteases and trypsin-like proteases . The total proteolytic activity of the inactive variant was lower than that of the parent strain . Addition of Ca2+ to the medium stimulated their proteolytic activity . The inducing action of the antibiotics produced by the parent strain on differentiation of S.hygroscopicus 155-0 and the increase of their action in the presence of Ca2+ suggested that they controlled the differentiation and that such a function of the antibiotics expressed itself through the Ca2+ signal system.

Chemosphere, 2000 Apr, 40(7), 751 - 7
Effects of the antibiotics oxytetracycline and tylosin on soil fauna; Baguer AJ et al.; Antibiotics may enter the terrestrial environment when amending soils with manure . A Note of Guidance on ecological risk assessment of veterinary medicines was issued in January 1998 . Hardly any information about ecotoxicological effects of already existing substances are available . This study has tested the effects of two widely used antibiotics, tylosin and oxytetracycline, on three species of soil fauna: Earthworms, springtails and enchytraeids . Neither of the substances had any effect at environmentally relevant concentrations . The lowest observed effect concentration was 3000 mg kg-1 and in many cases no effect was seen even at the highest test concentration of 5000 mg kg-1.

Chemosphere, 2000 Apr, 40(7), 723 - 30
Acute and chronic toxicity of veterinary antibiotics to Daphnia magna; Wollenberger L et al.; The acute and chronic toxicity of nine antibiotics used both therapeutically and as growth promoters in intensive farming was investigated on the freshwater crustacean Daphnia magna . The effect of the antibiotics metronidazole (M), olaquindox (OL), oxolinic acid (OA), oxytetracycline (OTC), streptomycin (ST), sulfadiazine (SU), tetracycline (TC), tiamulin (TI) and tylosin (TY) was tested in accordance to the ISO (1989) and OECD (1996) standard procedures . The acute toxicities (48-h EC50 value, mg/l) in decreasing order were OA (4.6), TI (40), SU (221), ST (487), TY (680) and OTC (approximately 1000) . NOECs were 340 mg/l for TC and 1000 mg/l for M and OL . Toxic effect on reproduction occurred generally at concentrations, which were one order of magnitude below the acute toxic levels . The chronic toxicity (EC50 values, mg/l) in the D . magna reproduction test in decreasing order were TI (5.4), SU (13.7), TC (44.8) and OTC (46.2) . The NOECs (mg/l) obtained in the reproduction test with OA, ST, TY and M were 0.38 for OA, 32 for ST, 45 for TY and 250 for M . The observed toxicity of OA to D . magna indicates that this substance, which is a commonly used feed additive in fish farms, has a potential to cause adverse effects on the aquatic environment.

Chem Pharm Bull (Tokyo), 2000 Jan, 48(1), 126 - 30
A short-step synthesis of orally active carbapenem antibiotic CS-834; Mori M et al.; An orally bioavailable carbapenem CS-834, which is a pivaloyloxymethyl (POM) ester-type prodrug and has (R)-5-oxopyrrolidin-3-ylthio moiety at the C-2 position of the 1 beta-methylcarbapenem skeleton, is currently under clinical trial . We accomplished a short-step synthesis of CS-834 by using phosphorus ylide from the intramolecular Wittig-type reaction in the key step for cyclization to the bicyclic carbapenem system . The POM ester group was found to be suitable for the cyclization conditions.

J Pharm Biomed Anal, 1999 Aug, 20(4), 643 - 53
Selective spectrofluorimetric determination of phenolic beta-lactam antibiotics through the formation of their coumarin derivatives; El Walily AF et al.; A simple, sensitive and selective spectrofluorimetric procedure was developed for the determination of amoxycillin, cefadroxil and cefoperazone . The method is based on the reaction between these drugs and ethyl acetoacetate, in acidic medium, to give yellow fluorescent products with excitation wavelengths ranging from 401 to 467 nm and emission wavelengths ranging from 465 to 503 nm . The reaction conditions were studied and optimized . The reaction obeyed Beer's law over the range of 10.0-20.0, 1.5-1.0 and 50.0-100.0 microg ml(-1) for amoxycillin, cefadroxil and cefoperazone, respectively . Interference's from other antibiotics, drugs and dosage forms additives, in capsules and vials dosage forms, were investigated . The proposed method was applied to the analysis of pharmaceutical formulations (capsules and vials) containing the above antibiotics, either alone or in combination with other antibiotics or drugs . The validity of the method was tested by the recovery studies of standard addition which were found to be satisfactory . The results of the proposed method demonstrated that the method is equally accurate, precise and reproducible as the official methods (USP XXIII) and those published for the non-official binary mixtures.

Mediators Inflamm, 1999, 8(4-5), 199 - 204
Suppressive activity of a macrolide antibiotic, roxithromycin, on pro-inflammatory cytokine production in vitro and in vivo; Suzaki H et al.; This study was designed to examine the influence of a macrolide antibiotic, roxithromycin (RXM), on the production of pro-inflammatory cytokines, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha . In the first experiments, we examined the effect of RXM on in vitro cytokine production from lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes . The monocytes were cultured in the presence of various doses of the agent . After 24 h, the culture supernatants were obtained and assayed for IL-1beta and TNF-alpha contents by enzyme-linked immunosorbent assay . RXM suppressed the in vitro production of IL-1beta and TNF-alpha in response to LPS stimulation . This was dose dependent and first noted at a concentration of as little as 0.05 microg/ml, which is much lower than therapeutic blood levels . In the second part of the experiments, we examined the influence of RXM on the appearance of IL-1beta and TNF-alpha in mouse lung extract induced by LPS inhalation . RXM was administered orally into BALB/c mice at a single dose of 2.5 mg/kg once a day for 5-12 weeks . These mice were then instilled with LPS into the trachea and examined for the presence of cytokines in aqueous lung extracts . Pretreatment of mice with RXM for 5 weeks did not influence of the appearance of both IL-1beta and TNF-alpha in aqueous lung extracts . However, pretreatment for more than 7 weeks dramatically suppressed the cytokine appearance in the extracts.

Gen Physiol Biophys, 1999 Oct, 18 Spec No, 126 - 39
Adverse drug reactions to antibiotics and major antibiotic drug interactions; Novotny J et al.; Adverse drug reaction and drug interactions represent negative consequences of pharmacotherapy . A thorough knowledge of how the adverse reactions and drug interactions occur will aid in our ability to provide the best patient care possible . Adverse drug reactions and drug interactions are defined and mechanisms of their occurrence are discussed; ways to identify, assess, manage, and report these reactions are presented . The importance of postmarketing surveillance is highlighted . A thorough understanding of the mechanism of adverse drug reactions and drug interaction is essential for the health care practitioner . Improved patient care can be achieved by applying this knowledge to the individual patient . When drugs are administered to patients, many things can go wrong . The magnitude of this problem warrants spending sufficient resources to establish programs to identify, assess, and manage these reactions . Having effective reporting programs will help prevent many reactions and will provide earlier detection of adverse reactions to new drugs.

J Antimicrob Chemother, 2000 Mar, 45(3), 383 - 6
Once-daily versus multiple-daily gentamicin in empirical antibiotic therapy of febrile neutropenia following intensive chemotherapy; Bakri FE et al.; The clinical efficacy and toxicity of once-daily compared with multiple-daily gentamicin dosing, in combination with azlocillin, were studied retrospectively in febrile neutropenic episodes following intensive chemotherapy . Fifty-two episodes were studied in 28 patients with acute myeloid leukaemia . Reasons for initiation of antibiotic therapy, dose, duration of treatment, organism isolation rates, response, cost comparison and toxicity were studied in the two treatment groups . The main indication for initiation of antibiotic therapy was neutropenic fever without a documented infection (80.8% of episodes) . The response rate to once-daily gentamicin dosing and azlocillin was three times higher than to multiple-daily gentamicin dosing and azlocillin (P = 0.0112) . The incidence of toxicity was low overall and was slightly but not significantly higher in the once-daily group . In this clinical context once-daily gentamicin at a dose of 7 mg/kg/day is more effective than a multiple-daily dosing regimen but may be more toxic.

Angiology, 2000 Feb, 51(2), 173 - 7
Internal jugular vein thrombosis, Lemierre's syndrome; oropharyngeal infection with antibiotic and anticoagulation therapy--a case report; Nakamura S et al.; The authors present a case of Lemierre's syndrome that is an uncommon septic thrombophlebitis of the internal jugular vein . A 31-year-old man developed pharyngeal pain one month before hospital admission when he suffered from a severe headache and painful swelling of the left side of his neck . He was diagnosed with tonsillitis . Contrast-enhanced computed tomography and magnetic resonance imaging of the neck revealed the presence of an occlusive thrombosis of the left internal jugular vein and an inflamed mesopharynx . His symptoms and the jugular vein thrombus showed remarkable improvement after administration of antibiotic and anticoagulation therapy . No pulmonary embolism or other metastatic infection were observed . It was suggested that accurate diagnosis during early treatment is essential to obtain a successful prognosis for Lemierre's syndrome.

Chem Phys Lipids, 1999 Dec, 103(1-2), 57 - 65
A differential scanning calorimetry study of the interaction of lasalocid antibiotic with phospholipid bilayers; Tahir A et al.; Interaction of lasalocid sodium salt (Las-Na) with dipalmitoylphosphatidylcholine (DPPC) as a membrane model was investigated by highly-sensitive differential scanning calorimetry (DSC) . The insertion properties of the antibiotic were studied both in multilamellar suspensions and unilamellar vesicles, for Las-Na/DPPC molar ratios (r) ranging from 0.005 to 0.1 . The effect of the antibiotic on the lipid thermotropic behavior is concentration dependent and drastically changes at a critical r of 0.04 in both model membranes . Below this ratio, Las-Na molecules interact with DPPC bilayers without disrupting the global organization of the membrane . In the multilamellar systems only the transition cooperativity is affected whereas for the mixed vesicles, a decrease in the enthalpy change suggests a different mode of insertion . Above this ratio, implantation of the antibiotic give rise to lateral phase separation in multilamellar systems . These structural modifications have repercussions on the formation of mixed LAS-Na/DPPC vesicles which seems limited to an r value of 0.04.

J Pharm Biomed Anal, 1999 Feb, 19(1-2), 239 - 52
Pulsed electrochemical detection of sulfur-containing antibiotics following high performance liquid chromatography; LaCourse WR et al.; Pulsed electrochemical detection (PED) following reversed-phase chromatography has been applied to the direct detection of sulfur-containing antibiotics, specifically, penicillins, cephalosporins, and lincomycin . The compounds are detected sensitively and selectively without the need for derivatization . Integrated pulsed amperometric detection (IPAD) yields limits of detection lower than UV detection for these compounds . Detection limits using an optimized IPAD waveform are typically 10 ppb or less . The high selectivity of PED for thiocompounds reduces sample preparation . This work is applied to the determination of penicillin and related analogues in various pharmaceutical formulations/preparations, including a chicken feed.

J Pharm Biomed Anal, 1999 Feb, 19(1-2), 183 - 92
Transport studies of beta-lactam antibiotics and their degradation products across electrified water/oil interface; Basaez L et al.; An electrochemical method for quantifying beta-lactam antibiotics (cephalexin and ampicillin) and their hydrolysis products is described . Cyclic voltammetry at the water/nitrobenzene interface in a four-electrode system was used . The zwitterionic compounds were ionized to the necessary electrochemical form by pH adjustment . The pH change, however, resulted also in hydrolysis of the antibiotics . Hydrolysis products were characterized across UV-vis spectrum . The various hydrolysis products as well as the ionized antibiotics were studied in voltammetric transfer from water to nitrobenzene using the method of the interface between two immiscible electrolyte solutions (ITIES) . It was concluded that this electrochemical method is suitable for the quantification of beta-lactam antibiotics and their hydrolysis products.

J Am Soc Mass Spectrom, 2000 Mar, 11(3), 200 - 9
Collisionally activated dissociations of aminocyclitol-aminoglycoside antibiotics and their application in the identification of a new compound in tobramycin samples; Hu P et al.; Several aminocyclitol-aminoglycoside antibiotics have been studied by tandem mass spectrometry . Glycosidic bond cleavages were the major reactions in the low energy collisionally activated decomposition (CAD) of the protonated antibiotics . Only the glycoside residing on the C6-O of the 2-deoxystreptamine was observed to undergo significant decomposition at the C2-C3 and O-C1 bonds . The comprehension of the CAD of known aminoglycosides aided in the identification of an unknown impurity in tobramycin . The unknown compound was initially detected by reverse phase high-performance liquid chromatography following dinitrofluorobenzene derivatization of the amino groups . The molecular weight of the dinitrobenzene derivative measured by LC mass spectrometry (MS) led to the detection of two isomeric impurities in tobramycin by LC-MS using an amino column . Their CAD spectra were subsequently acquired by LC-MS/MS . One of the two compounds was determined to be a known compound, 6"-O-carbamyltobramycin with the carbamyl group substituted on the glycoside residing on the C6-O of 2-deoxystreptamine . The fragmentation pattern of the other compound was interpreted as that the unknown was also a carbamyltobramycin . The carbamyl group was, however, substituted on 2-deoxystreptamine . It was speculated that the carbamyl group was substituted at the C1 amino group . This compound, to our knowledge, has not been reported before.

Rocz Akad Med Bialymst, 1999, 44, 111 - 8
Enzymuria in antibiotic therapy of acute infections; Sawicka E et al.; Activities of N-acetyl-beta-D-glucosaminidase (NAG), its isoenzyme NAG-B, alanylaminopeptidase (AAP), elastase and trypsin inhibitor (alpha 1 PI) were evaluated as markers of nephrotoxicity and inflammation in acute infections treated with various antibiotics (vancomycin, netilmicin, pefloxacine, cefoperazone and imipenem).

J Trauma, 2000 Feb, 48(2), 246 - 55
Antibiotic-impregnated autogenic cancellous bone grafting is an effective and safe method for the management of small infected tibial defects: a comparison study; Chan YS et al.; OBJECTIVE: Bone grafting plays an important role in reconstructing infected tibial nonunions . The effects of antibiotic-impregnated bone grafting in infection elimination and bone incorporation was reported in this retrospective study . METHODS: Ninety-six patients treated for infected tibial nonunions were evaluated . These patients were managed with local antibiotic bead therapy and staged antibiotic-impregnated autogenous cancellous bone graft or pure autogenous cancellous bone graft . Patients were randomized to antibiotic-impregnated bone grafting or bone grafting-only groups on the basis of whether the admission date was odd or even . Patients were divided into two groups (antibiotic-impregnated bone grafting group and pure cancellous bone grafting group), according to the procedure used in preparing the bone grafts . The antibiotic-impregnated bone grafting group included 37 men and 9 women whose average age was 36 years (range, 17 to 72 years) . The average follow-up period was 4.8 years . By using the Cierny-Mader staging classification of chronic osteomyelitis, 32 of 46 patients (70%) were stage 4A, and 14 of 36 patients (30%) were stage 4B . The pure cancellous bone grafting group included 39 men and 11 women whose average age was 37 years (range, 18 to 72 years) . The average follow-up period was 4.5 years (range, 4 to 6 years) . Thirty-nine of 50 patients (78%) were stage 4A, and 11 of 50 patients (22%) were stage 4B . The bone defects in both groups ranged from 2 to 4 cm . RESULTS: Wound healing and bony union were achieved in the antibiotic-impregnated bone grafting group . Only two patients had recurrent infections . The infection arrest rate was 95.6% . However, 9 of 50 patients in the pure cancellous bone grafting group had recurrent infections . The infection arrest rate was 82% . The antibiotic-impregnated bone grafting group had significantly superior results (95.6% vs . 82% chi2 test, p < 0.05) in infection elimination than the pure cancellous bone grafting group . CONCLUSION: After 4 to 6 years of follow-up, our results suggest that the use of impregnating antibiotics have no adverse effects on autogenic cancellous bone graft incorporation and could help to eliminate infection effectively.

Soc Sci Med, 2000 Mar, 50(6), 891 - 903
Social factors influencing the acquisition of antibiotics without prescription in Kerala State, south India; Saradamma RD et al.; We investigated the magnitude of self-medication with antibiotics in a peri-urban area of Southern Kerala State, India and factors influencing this practice . First, a random sample of 400 households was surveyed in one primary health centre area near Trivandrum . We found 69.3% (95% CI = 64.8-73.8) of households had at least one person using a pharmaceutical product during the two-week recall period; antibiotics formed almost 11% of the medicines consumed . Next, pharmacy based interview and observation data were collected from 405 antibiotic purchasers sampled from 11 out of the 12 private pharmacies in the area . Seventy-three of these 405 customers purchased antibiotics without a prescription (18%; 95% CI = 14.3-21.7) . By combining the household survey and pharmacy observations, we estimate that almost half of 1% (0.41%; 95% CI = 0.24-1.16) of the population, or four people per 1000, is engaged in self-medication using antibiotics in Kerala in any two-week period . Our data show that people least likely to follow this practice are from higher income families, having more education and higher status occupations and receiving the benefits of medical insurance . Conversely, logistic regression analysis indicated that risk of buying antibiotics without a script was associated with education at secondary level or below, the perception that it is expensive to consult a doctor and low satisfaction with medical practitioners . Keralites' self-medication patterns are interpreted broadly using social, cultural, historical and economic perspectives . Solutions to the problem of antibiotic misuse are suggested, proceeding on several fronts: among practitioners, suppliers and marketeers of medicines, and among the population of pharmaceutical consumers themselves.

J Pharm Sci, 2000 Feb, 89(2), 232 - 40
Physico-chemical characterization of a novel tricyclic beta-lactam antibiotic; Marini A et al.; GV118819X, a novel tricyclic beta-lactam antibiotic of GlaxoWellcome, is a racemic mixture of two diastereoisomers, A and B . Of the two diastereoisomers, only A is available as a pure compound . By analyzing mixtures of GV118819X and A, a partial phase diagram is constructed, which indicates the presence of a eutectic when the A fraction is approximately 39% . Moreover, the melting enthalpies of the eutectic mixture and of diastereoisomer B can be estimated . With the exception of the pure A form, all mixtures undergo important modifications in morphology and microstructure as a consequence of thermal treatments, which induce melting/amorphization of the eutectic, and crystallization of the A form . Analyses of the sieved fractions of GV118819X demonstrate that it consists of acicular crystals of different composition, with the larger crystals having a larger A fraction than the smaller ones . Grinding causes melting/amorphization of the eutectic and, following hours-long treatments, the formation of a substantial fraction of submicron particles with unusually low melting temperatures .

Pediatr Med Chir, 1999 May-Jun, 21(3), 119 - 23
Study on 480 hospitalized febrile children: evaluation of the septic risk and results of the antibiotic and corticosteroid combined therapy; Memmini G et al.; The febrile child, previously healthy, represents a frequent diagnosis and management problem for pediatricians who work in private offices and those in hospital emergency departments . We are specifically interested in the identification, for the febrile child with septic risk, of severity parameters permitting to assess the likelihood of a serious bacterial infection . In the retrospective study we present, carried out on children admitted for febrile illness, two factors were mainly evaluated: 1 . identification of the septic risk on the basis of some laboratory and clinical parameters; 2 . effectiveness of an early antibiotic plus corticosteroid treatment in a sub-group of children with septic risk . The parameters we considered have been the degree of temperature upon admission, the clinical appearance and the C-reactive protein (C-RP) values . A significant correlation resulted for levels of temperature over 39 degrees C, toxic-appearing child and very positive C-RP values . We have defined this condition as a "threatening" fever requiring an immediate hospitalization in order to administer appropriate blood tests and cultures, and also, according to our rationale, to start an early antibiotic plus corticosteroid therapy (within 6-12 hours from the disease onset).

Thromb Res, 2000 Feb 1, 97(3), 143 - 51
Platelet aggregation during abdominal surgery in an experimental pig model: the effects of presurgical antibiotic protocols and volume replacement with hydroxyethyl starch; Frese A et al.; The effect of presurgical antibiotic protocols in combination with hemodilution on platelet aggregation was studied . Thirty pigs were randomly assigned to three groups . Group 1 received amoxicillin/clavulanic acid, group 2 metronidazole+cefuroxime, and group 3, as a control, sodium chloride . They underwent laparotomy, massive blood loss, and volume replacement with hydroxyethyl starch 200, followed by an anaphylactoid reaction . Platelet aggregation was measured by the turbidometric method . Neither antibiotic protocols had any effect on platelet aggregation as compared with the control group . In all three groups, aggregation to ADP and collagen was significantly reduced after volume replacement with hydroxyethyl starch . In contrast, the sensitivity to the aggregating effects of collagen was increased as assessed by a higher frequency of responses to low concentrations of collagen and a shortened latency of the aggregation response after collagen addition . Further in vitro studies revealed that dilution of plasma with hydroxyethyl starch specifically induced the changes seen after in vivo volume replacement . The results suggest that the plasma substitute hydroxyethyl starch 200 increases the sensitivity to low doses of collagen, an effect never described before and considered of clinical relevance.

Antimicrob Agents Chemother, 2000 Mar, 44(3), 763 - 6
Iron-chelating activity of tetracyclines and its impact on the susceptibility of Actinobacillus actinomycetemcomitans to these antibiotics; Grenier D et al.; Three tetracyclines (tetracycline, doxycycline, and minocycline) were found to possess iron-chelating activity in a colorimetric siderophore assay . Determination of MICs indicated that the activity of doxycycline against the periodontopathogen Actinobacillus actinomycetemcomitans was only slightly influenced by the presence of an excess of iron that likely saturates the antibiotic . On the other hand, the MICs of doxycycline and minocycline were significantly lower for A . actinomycetemcomitans cultivated under iron-poor conditions than under iron-rich conditions.

Arch Intern Med, 1999 Nov 8, 159(20), 2449 - 54
Early switch from intravenous to oral antibiotics and early hospital discharge: a prospective observational study of 200 consecutive patients with community-acquired pneumonia; Ramirez JA et al.; To determine the proportion of patients who can be treated with early switch to oral antibiotics and early discharge, to evaluate clinical outcome and patient satisfaction for patients treated with early switch and early discharge, and to define the factors that interfere with early discharge for some of the patients who underwent early switch to oral antibiotic therapy . Design: Prospective study . Participants: Two hundred consecutive hospitalized patients with community-acquired pneumonia . Main Outcome Measures: Number of days needed to switch to oral therapy and length of hospital stay . Clinical outcome and satisfaction with care were evaluated for those patients treated with early switch and early discharge . Results: Early switch to oral antibiotics (within the first 3 days of hospitalization) was performed in 133 patients (67%) . Clinical failure was documented in 1 patient . Early switch and early discharge was performed in 88 patients (44%) . The mean length of hospital stay for this group was 3.4 days . The most common reason for prolonged hospitalization after the switch to oral antibiotics was the need for diagnostic workup . More than 95% of patients were satisfied with the care they had received . Conclusions: Using simple clinical and laboratory criteria, a significant proportion of hospitalized patients with community-acquired pneumonia (44%) can be treated with early switch and early discharge . This model did not affect patient outcome, decreased the length of hospitalization, and was associated with a high level of patient satisfaction.

Arch Pediatr Adolesc Med, 2000 Feb, 154(2), 180 - 3
Child care center staff contribute to physician visits and pressure for antibiotic prescription; Skull SA et al.; OBJECTIVE: To determine whether child care center (CCC) providers contribute to unnecessary physician referrals and antibiotic prescriptions in young children with upper respiratory tract infections . DESIGN: A survey using a structured telephone questionnaire between May 3, 1998, and July 27, 1998 . PARTICIPANTS: Child care center providers from randomly selected licensed Ontario CCCs accepting diapered children . MAIN OUTCOME MEASURES: Knowledge, attitudes, and practices concerning physician referral; exclusion; and antibiotic use for children with upper respiratory tract infections . Indications for exclusion were compared with published Canadian guidelines . RESULTS: Contact was made with 42 eligible CCCs to obtain the requisite number of 36 participants (participation rate, 86%) . Of the 36 centers, staff reported advising that children visit a physician for colored nasal discharge in 28 (78%), for productive cough in 23 (64%), and for unusual behavior in 9 (25%) . Also of the 36 centers, staff reported excluding children for colored nasal discharge in 20 (56%), for productive cough in 16 (44%), and for unusual behavior in 15 (42%) . Antibiotics were thought useful for nonspecific upper respiratory tract infections to prevent the spread of infection in 9 (26%), to speed up recovery in 7 (21%), and to prevent bacterial infection in 13 (38%) of 34 centers . In the previous 6 months, 25 (69%) of 36 staff members reported making an exception to exclusion because a child had an antibiotic prescription . CONCLUSIONS: Many children are referred by CCC staff to physicians contrary to established guidelines . As staff must act on behalf of parents, a low threshold for referral is not unreasonable . However, this survey confirms that CCC staff recommend children to receive antibiotics and exclude children inappropriately . These practices are based on incomplete knowledge . Research on appropriate management of upper respiratory tract infections by CCC staff is needed . Education to correct specific knowledge deficits should be initiated.

J Antimicrob Chemother, 2000 Feb, 45(2), 251 - 6
Antibiotic use in Dutch hospitals 1991-1996; Janknegt R et al.; The use of antibiotics in Dutch hospitals between 1991 and 1996 was investigated . A total of 54 hospitals responded to the enquiry, representing over 70% of all hospital beds in The Netherlands . The use of antibiotics in Dutch hospitals, expressed as defined daily doses (DDD) per hundred bed days, gradually increased from 37.2 DDD per 100 bed days in 1991 to 42.5 DDD per 100 bed days in 1996 . The antibiotic that showed the largest increase in use was co-amoxiclav . Its use increased more than three-fold from 3.93 DDD per 100 bed days in 1991 to 12.5 DDD per 100 bed days in 1996 . The increase in use of co-amoxiclav exceeded the increase in total antibiotic consumption . The use of cephalosporins remained fairly constant during the study period, but there were changes in the relative use of the different cephalosporin groups . The use of earlier cephalosporins gradually decreased, whereas the use of the more recently developed cephalosporins increased between 1991 and 1996 . Ciprofloxacin and norfloxacin were the most commonly used fluoroquinolones throughout the study period . The use of ofloxacin increased significantly between 1991 and 1996, approaching the levels of use of ciprofloxacin and norfloxacin . There may be complex reasons for the increases, which need further analysis, but they mirror those few data available from elsewhere in the world . Possible explanations include more intensive treatment to expedite patient discharges, sicker patients with more serious infections and more resistant organisms.

Semin Thorac Cardiovasc Surg, 1999 Oct, 11(4 Suppl 1), 28 - 34
Twenty-year follow-up of aortic valve replacement with antibiotic sterilized homografts in 200 patients; Langley SM et al.; The aim of this study was to determine long-term results from one unit of subcoronary homograft aortic valve replacement (AVR) using the same sterilization and preservation techniques in each case . Between 1973 and 1983, 200 patients underwent AVR using an unstented homograft previously sterilized in antibiotics and preserved at 4 degrees C . Surviving patients were monitored for a minimum of 15 years to the end of 1998 . Mean age was 50.0+/-14 (1 standard deviation) years; 121 patients were men (60.5%) . Mean patient follow-up time was 15.6+/-6.7 years, with a total follow-up time of 3,115 patient years . Follow-up was 95.6% complete . There were three early deaths (1.5%) . At autopsy, the homograft was anatomically normal and in a satisfactory position . Kaplan-Meier survival, including early death, was 81.2%+/-2.8% (1 standard error) at 10 years, 68.1%+/-3.4% at 15 years, and 58.0%+/-3.7% at 20 years . Repeat AVR was undertaken in 74 patients, giving a freedom from reoperation for any reason of 86.5%+/-2.6%, 69.6%+/-3.8%, and 38.8%+/-5.3% at 10, 15, and 20 years, respectively . Freedom from structural valve degeneration at 10, 15, and 20 years was 81.1%+/-2.9%, 61.7%+/-3.9%, and 31.2%+/-4.7%, respectively . Freedom from endocarditis at 10, 15, and 20 years was 98.7%+/-0.9%, 96.0%+/-1.8%, and 94.6%,+/-2.3%, respectively . Homograft AVR with an antibiotic-sterilized valve stored at 4 degrees C and implanted in the subcoronary position offers low operative mortality and good long-term outcome for patients.

Mol Gen Genet, 2000 Jan, 262(6), 957 - 64
Cloning of the gene encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase from terpenoid antibiotic-producing Streptomyces strains; Dairi T et al.; We have isolated a mutant lacking 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity from a terpenoid antibiotic (terpentecin) producer, Streptomyces griseolosporeus MF730-N6, which uses both the mevalonate and nonmevalonate pathways for the formation of isopentenyl diphosphate, by screening terpentecin non-producing mutants . Terpentecin is known to be synthesized via the mevalonate pathway . The gene encoding HMG-CoA reductase (hmgg) was cloned and identified by complementation of the mutant, using a self-cloning system developed in this study for strain MF730-N6 . The corresponding hmgs gene for HMG-CoA reductase was also cloned from Streptomyces sp . KO-3988, which produces the terpenoid antibiotic furaquinocin . Sequence analysis of hmgg and hmgs showed that both genes encode polypeptides of 353 amino acids which are 84% identical to each other . A search of protein sequence databases revealed that both gene products were also similar to HMG-CoA reductases from a variety of other organisms, including Streptomyces sp . CL190 (hmgg is 89% and hmgs 85% identical to its CL190 homolog), sea urchin (40.3 and 40.5%), German cockroach (37.6 and 38.4%), and Camptotheca acuminata (39.7 and 40.8%).

J Hosp Infect, 1999 Dec, 43 Suppl, S265 - 8
How do you measure the impact of an antibiotic policy?
Nathwani D.
The principle aim of antibiotic policies is to bring about a change in prescribing which will lead to decreased cost, reduction of resistance and improved quality (judicious, safe and appropriate) of antibiotic prescribing . Before embarking upon developing, disseminating and subsequently implementing an antibiotic policy clinicians and key decision makers need to make explicit at the onset of policy development, how they plan to evaluate its impact . Quality indicators of the process of implementing policies and their impact on various outcomes need to be identified . These number and complexity of these indicators is dependent on local resource but they must be specific to the organisation, simple, measurable and meaningful . This information needs to be shared and acted upon.

Microbiology, 2000 Jan, 146 ( Pt 1), 147 - 54
Two new tailoring enzymes, a glycosyltransferase and an oxygenase, involved in biosynthesis of the angucycline antibiotic urdamycin A in Streptomyces fradiae Tü2717; Faust B et al.; Urdamycin A, the principal product of Streptomyces fradiae Tu2717, is an angucycline-type antibiotic and anticancer agent containing C-glycosidically linked D-olivose . To extend knowledge of the biosynthesis of urdamycin A the authors have cloned further parts of the urdamycin biosynthetic gene cluster . Three new ORFs (urdK, urdJ and urdO) were identified on a 3.35 kb fragment, and seven new ORFs (urdL, urdM, urdJ2, urdZl, urdGT2, urdG and urdH) on an 8.05 kb fragment . The deduced products of these genes show similarities to transporters (urdJ and urdJ2), regulatory genes (urdK), reductases (urdO), cyclases (urdL) and deoxysugar biosynthetic genes (urdG, urdH and urdZ1) . The product of urdM shows striking sequence similarity to oxygenases (N-terminal sequence) as well as reductases (C-terminal sequence), and the deduced amino acid sequence of urdGT2 resembles those of glycosyltransferases . To determine the function of urdM and urdGT2, targeted gene inactivation experiments were performed . The resulting urdM deletion mutant strains accumulated predominantly rabelomycin, indicating that UrdM is involved in oxygenation at position 12b of urdamycin A . A mutant in which urdGT2 had been deleted produced urdamycin I, urdamycin J and urdamycin K instead of urdamycin A . Urdamycins I, J and K are tetracyclic angucyclinones lacking a C-C connected deoxysugar moiety . Therefore UrdGT2 must catalyse the earliest glycosyltransfer step in the urdamycin biosynthetic pathway, the C-glycosyltransfer of one NDP-D-olivose.

Bioorg Med Chem, 1999 Dec, 7(12), 2671 - 82
Towards the development of novel antibiotics: synthesis and evaluation of a mechanism-based inhibitor of Kdo8P synthase; Du S et al.; The design and two synthetic pathways to aminophosphonate 4 which mimics the ionic and steric properties of putative oxocarbenium intermediate 3 in the Kdo8P synthase-catalyzed reaction are reported . It was found that 4 is a slow-binding, most potent inhibitor of the enzyme yet tested, with a Ki value of 0.4 microM.

Carcinogenesis, 2000 Feb, 21(2), 251 - 6
Inhibitory effects of combined administration of antibiotics and anti-inflammatory drugs on lung tumor development initiated by N-nitrosobis(2-hydroxypropyl)amine in rats; Tsutsumi M et al.; The effects of antibiotics and anti-inflammatory drugs on the promotion stage of lung carcinogenesis initiated with N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats were investigated in two experiments with a similar protocol . In experiment 1, rats received tap water containing 2000 p.p.m . BHP for 12 weeks followed by basal diet or basal diet containing 0.02% erythromycin (EM), 0 . 04% ampicillin (ABPC), 1.5% sho-saiko-to, 0.02% EM plus 1.5% sho-saiko-to or 0.04% ABPC plus 1.5% sho-saiko-to for 8 weeks after BHP administration . The development of adenocarcinomas (AC), squamous cell carcinomas (SqC) and adenosquamous carcinomas (ASqC) was completely inhibited in rats given ABPC plus sho-saiko-to and the numbers of lung lesions including alveolar hyperplasias, adenomas and carcinomas were decreased in rats given EM plus sho-saiko-to or ABPC plus sho-saiko-to . Neutrophil and macrophage infiltration into alveolar spaces of the lung were also markedly suppressed . In experiment 2, rats received BHP in the same manner as in experiment 1 and basal diet or basal diet containing 0.04% ABPC, 0.006% piroxicam, 0.04% ABPC plus 0.006% piroxicam and 0.04% ABPC plus 0.75% ougon for 8 weeks . The incidence and number of carcinomas, including ACs, SqCs and ASqCs were decreased in rats given ABPC plus piroxicam or ABPC plus ougon . Bacteria, mainly Escherichia coli, were detected in broncho-alveolar lavage of rats receiving BHP . The results suggest that chronic inflammation might be involved in the progression of lung carcinogenesis by BHP in rats and its suppression may therefore be useful as a chemopreventive strategy in lung cancer clinics.

Pflugers Arch, 2000, 439(3 Suppl), R87 - 9
The use of molecular biology to reprogram Streptomyces to make polyketide antibiotics more efficiently, and create novel secondary metabolites; Petkovic H et al.; Recent advances in the molecular genetics of Streptomyces have increased our understanding of polyketide antibiotic biosynthesis, to the point where recombinant DNA approaches to generate novel structures are possible . Our understanding of how antibiotic pathways are regulated and integrated into central metabolism also provides the opportunity for strain manipulation to enhance productivity.

N Engl J Med, 2000 Jan 27, 342(4), 225 - 31
The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children; Neuzil KM et al.; BACKGROUND: Despite high annual rates of influenza in children, influenza vaccines are given to children infrequently . We measured the disease burden of influenza in a large cohort of healthy children in the Tennessee Medicaid program who were younger than 15 years of age . METHODS: We determined the rates of hospitalization for acute cardiopulmonary conditions, outpatient visits, and courses of antibiotics over a period of 19 consecutive years . Using the differences in the rates of these events when influenzavirus was circulating and the rates from November through April when there was no influenza in the community, we calculated morbidity attributable to influenza . There was a total of 2,035,143 person-years of observation . RESULTS: During periods when influenzavirus was circulating, the average number of hospitalizations for cardiopulmonary conditions in excess of the expected number was 104 per 10,000 children per year for children younger than 6 months of age, 50 per 10,000 per year for those 6 months to less than 12 months, 19 per 10,000 per year for those 1 year to less than 3 years, 9 per 10,000 per year for those 3 years to less than 5 years, and 4 per 10,000 per year for those 5 years to less than 15 years . For every 100 children, an annual average of 6 to 15 outpatient visits and 3 to 9 courses of antibiotics were attributable to influenza . In winter, 10 to 30 percent of the excess number of courses of antibiotics occurred during periods when influenzavirus was circulating . CONCLUSIONS: Healthy children younger than one year of age are hospitalized for illness attributable to influenza at rates similar to those for adults at high risk for influenza . The rate of hospitalization decreases markedly with age . Influenza accounts for a substantial number of outpatient visits and courses of antibiotics in children of all ages.

Angew Chem Int Ed Engl, 1999 Dec 16, 38(24), 3703 - 3707
Membrane Anchoring and Intervesicle Transfer of a Derivative of the Antibiotic Moenomycin A; Anikin A et al.; The anchoring of moenomycin A (1) to the bacterial cell cytoplasmic membrane is essential for its biological activity . The first details of the strength of this interaction and the kinetics of the diffusion-mediated intervesicle transfer have been obtained by means of fluorescence spectroscopic methods using a coumarin-labeled moenomycin A derivative.

Eur J Cardiothorac Surg, 1999 Dec, 16(6), 660 - 2
The fate of antibiotic sterilized aortic allografts in Fontan circulation: results of the long-term follow-up; Kiraly L et al.; OBJECTIVE: Between 1977 and 1988, 27 patients, mean age 8.9 (range 4-22) received an antibiotic sterilised aortic allograft in the setting of the Fontan procedure . This study describes the long-term follow-up of these patients . METHODS: Fifteen patients had tricuspid atresia, nine double inlet ventricles and three others . The connection with the allograft was made to the pulmonary artery on the right side of the aorta in ten and to a left-sided main pulmonary artery in eight . In nine patients the allograft was anastomosed between the right atrium and the right ventricle . RESULTS: There were five early and five late deaths . One late death may have been allograft related . Survival was 81, 74 and 68% at 5, 10 and 15 years, respectively . Conduit calcification was universal . Twelve patients underwent reoperation, freedom from reoperation was 100, 88 and 54% at 5, 10 and 15 years following the initial Fontan procedure . At reoperation the gradient across the allograft was never more than 3 mmHg . The allograft was explanted with conversion to atriopulmonary or cavopulmonary connection in nine and a second allograft was inserted between the right atrium and right ventricle in two . No mortality occurred at reoperation . 41.1% of survivors still have their original allograft . CONCLUSIONS: Although there is a significant attrition rate allograft inclusion in the Fontan circulation does not change survival, but results in an increased reoperation rate . Inclusion of a valved conduit between the right atrium and ventricle does not usually enhance the growth potential of the rudimentary ventricle . All patients are in a good functional class which may represent the strict original selection criteria . The inclusion of a valve in the Fontan circulation is not recommended.

Mutagenesis, 2000 Jan, 15(1), 45 - 55
Carboxylesterases, a key factor in evaluating potential genotoxicity of Trinem antibiotics; Oliver J et al.; Sanfetrinem cilexetil, a hexetil ester of a Trinem antibiotic, does not induce micronuclei in rat bone marrow cells or induce DNA repair synthesis in rat hepatocytes following oral dosing . However, in vitro chromosome damage and mutations are induced in mammalian cells lacking carboxylesterase activity (human lymphocytes and mouse lymphoma L5178Y cells) . In cells possessing carboxylesterase activity (CHL cells), chromosome damage induced by Sanfetrinem cilexetil is not observed . Similarly, if induced rat liver preparations or non-induced preparations from rat or human intestinal cells are present during exposure, genotoxic activity is lost, even in those cells lacking carboxylesterase enzymes . Thus the lack of demonstrable genotoxicity in vivo, in the assays used, is likely to be due to hydrolysis of the parent molecule by non-specific carboxylesterases present within the intestinal epithelium . In turn this data indicates that a genotoxic hazard to humans under therapeutic conditions is unlikely.

Antimicrob Agents Chemother, 2000 Feb, 44(2), 418 - 20
Role of the PDR gene network in yeast susceptibility to the antifungal antibiotic mucidin; Michalkova-Papajova D et al.; Yeast strains disrupted in the PDR1, PDR3, or PDR5 gene, but not in SNQ2, exhibited higher sensitivity to mucidin (strobilurin A) than did the isogenic wild-type strains . Different gain-of-function mutations in the PDR1 and PDR3 genes rendered yeast mutants resistant to this antibiotic . Mucidin induced PDR5 expression, but the changes in the expression of SNQ2 were only barely detectable . The results indicate that PDR5 provides the link between transcriptional regulation by PDR1 and PDR3 and mucidin resistance of yeast.

Antimicrob Agents Chemother, 2000 Feb, 44(2), 382 - 92
Genes for production of the enediyne antitumor antibiotic C-1027 in Streptomyces globisporus are clustered with the cagA gene that encodes the C-1027 apoprotein; Liu W et al.; C-1027, the most potent member of the enediyne antitumor antibiotic family, is produced by Streptomyces globisporus C-1027 and consists of an apoprotein (encoded by the cagA gene) and a nonpeptidic chromophore . The C-1027 chromophore could be viewed as being derived biosynthetically from a benzoxazolinate, a deoxyamino hexose, a beta-amino acid, and an enediyne core . By adopting a strategy for cloning of the C-1027 biosynthesis gene cluster by mapping a putative dNDP-glucose 4,6-dehydratase (NGDH) gene to cagA, we have localized 75 kb of contiguous DNA from S . globisporus . DNA sequence analysis of two regions of the cloned gene cluster revealed two genes, sgcA and sgcB, that encode an NGDH enzyme and a transmembrane efflux protein, respectively, and confirmed that the cagA gene resides approximately 14 kb upstream of the sgcAB locus . The involvement of the cloned gene cluster in C-1027 biosynthesis was demonstrated by disrupting the sgcA gene to generate C-1027-nonproducing mutants and by complementing the sgcA mutants in vivo to restore C-1027 production . These results represent the first cloning of a gene cluster for enediyne antitumor antibiotic biosynthesis and provide a starting point for future genetic and biochemical investigations of C-1027 biosynthesis.

Nucleic Acids Res, 2000 Feb 1, 28(3), 710 - 9
Structural basis for recognition of the RNA major groove in the tau exon 10 splicing regulatory element by aminoglycoside antibiotics; Varani L et al.; Drug-like molecules that bind RNA with sequence selectivity would provide valuable tools to elucidate gene expression pathways and new avenues to the treatment of degenerative and chronic conditions . Efforts at discovering such agents have been hampered, until recently, by the limited knowledge of RNA recognition principles . Several recent structures of aminoglycoside-RNA complexes have begun to reveal the structural basis for RNA-drug recognition . However, the absence of suitable chemical scaffolds known to bind the RNA major groove, where specificity could be provided by the diversity of functional groups exposed on the RNA bases, has represented a major obstacle . Here we report an investigation of the structural basis for recognition of an RNA stem-loop by neomycin, a naturally occurring aminoglycoside antibiotic . We found that neomycin binds the RNA stem-loop that regulates alternative splicing of exon 10 within the gene coding for human tau protein . Mutations within this splicing regulatory element destabilise the RNA structure and cause frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17), an autosomal dominant condition leading to neurodegeneration and death . The three-dimensional structure of the RNA-neomycin complex shows interaction of the drug in the major groove of the short RNA duplex, where familial mutations cluster . Analysis of the structure shows how aminoglycosides and related drugs bind to the RNA major groove, adding to our understanding of the principles of drug-RNA recognition.

J Biol Chem, 2000 Jan 21, 275(3), 1699 - 707
beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter; Ganapathy ME et al.; Therapeutic use of cephaloridine, a beta-lactam antibiotic, in humans is associated with carnitine deficiency . A potential mechanism for the development of carnitine deficiency is competition between cephaloridine and carnitine for the renal reabsorptive process . OCTN2 is an organic cation/carnitine transporter that is responsible for Na(+)-coupled transport of carnitine in the kidney and other tissues . We investigated the interaction of several beta-lactam antibiotics with OCTN2 using human cell lines that express the transporter constitutively as well as using cloned human and rat OCTN2s expressed heterologously in human cell lines . The beta-lactam antibiotics cephaloridine, cefoselis, cefepime, and cefluprenam were found to inhibit OCTN2-mediated carnitine transport . These antibiotics possess a quaternary nitrogen as does carnitine . Several other beta-lactam antibiotics that do not possess this structural feature did not interact with OCTN2 . The interaction of cephaloridine with OCTN2 is competitive with respect to carnitine . Interestingly, many of the beta-lactam antibiotics that were not recognized by OCTN2 were good substrates for the H(+)-coupled peptide transporters PEPT1 and PEPT2 . In contrast, cephaloridine, cefoselis, cefepime, and cefluprenam, which were recognized by OCTN2, did not interact with PEPT1 and PEPT2 . The interaction of cephaloridine with OCTN2 was Na(+)-dependent, whereas the interaction of cefoselis and cefepime with OCTN2 was largely Na(+)-independent . Furthermore, the Na(+)-dependent, OCTN2-mediated cellular uptake of cephaloridine could be demonstrated by direct uptake measurements . These studies show that OCTN2 plays a crucial role in the pharmacokinetics and therapeutic efficacy of certain beta-lactam antibiotics such as cephaloridine and that cephaloridine-induced carnitine deficiency is likely to be due to inhibition of carnitine reabsorption in the kidney.

J Med Chem, 2000 Jan 13, 43(1), 128 - 32
A light-inactivated antibiotic; Lee W et al.; Sodium 7beta-{(R)-2-(N(b)()-o-nitrobenzyloxycarbonyl)hydrazino-3-pheny lpropa namido}cephalosporanate (1) is described as a new type of beta-lactam antibiotic, which undergoes light-induced destruction of its beta-lactam moiety and hence becomes biologically inactive . This type of antibiotic holds the promise of self-destruction over a number of hours of exposure to light, so that it would not allow selection of resistance in the environment.

Nurs Stand, 1999 Jul 28-Aug 3, 13(45), 49 - 54; quiz 55
Antibiotic therapy; Jordan S et al.; The nurse's role in the administration of antibiotics involves more than just giving medication to patients . Sue Jordan and Mike Tait describe how antibiotics work, their side effects, and the important aspects of nursing care for patients on these powerful drugs.

J Gen Intern Med, 1999 Dec, 14(12), 756 - 8
Physicians' perceptions about managed care restrictions on antibiotic prescribing; Hasty M et al.; The purpose of this study was to compare physicians' perceptions about managed care restrictions on drug prescribing with objective measures of the restrictions' effects . When asked a general question, 17 emergency medicine physicians in one urban, university hospital answered that they had to prescribe an antibiotic that was not their first choice because of managed care restrictions 32% of the time . The actual frequency of prescribing other than first-choice antibiotics, which was determined by asking the same physicians about the prescription of specific antibiotics for specific patients seen recently in the emergency department, was 6% ( p <.0001) . We conclude that emergency medicine physicians treating patients in one managed care system significantly overestimated the restrictions imposed by managed care formularies on their antibiotic prescribing practices . Additional studies are warranted to measure the extent of this bias.

J Chemother, 1999 Oct, 11(5), 323 - 30
Classification of betalactam antibiotics according to their pharmacodynamics; Periti P et al.; Considerable information on the pharmacodynamics of betalactams has accumulated throughout the past 20 years demonstrating a time-dependent killing and some pharmacodynamic differences in the type of activity in-vitro and in animal models that should have clinical significance . Unfortunately few clinical studies have directly examined the effects of different dosages that might be predicted to result in failure or success of the outcome, particularly in serious sepsis . Thus on the basis of a long preclinical and clinical experience we propose a pharmacodynamic classification of betalactam antibiotics . Three classes are delineated by the extent of PBP pattern saturation, biomass increase, PAE length and initial killing power.

J Chromatogr B Biomed Sci Appl, 1999 Nov 26, 735(1), 121 - 6
Protein-binding patterns of the antitumor antibiotic cryptophycin 52 as measured with a two-phase partitioning system; Kessel D; Exposure of murine leukemia L1210 cells to the antitumor antibiotic cryptophycin 52 (C52) resulted in a rapid and dose-dependent increase in cell-surface hydrophobicity, as measured with a two-phase partitioning system . This effect was not observed with inactive drug analogs that lacked an epoxy residue . While the C52 has distinctly hydrophobic properties, the drug does not uniformly bind to all proteins . Affinity for human high- and low-density lipoprotein and albumin was demonstrated, but the drug binds only to the albumin fraction of mouse plasma, in spite of the high HDL level in the latter species.

J Chromatogr A, 1999 Dec 9, 864(1), 69 - 76
Application of centrifugal counter-current chromatography to the separation of macrolide antibiotic analogues . I . Selection of solvent systems based on solubility and partition coefficient investigations; Wang-Fan W et al.; As the first part of our studies on counter-current chromatography, the methodology for selecting suitable solvent systems was established based on detailed investigations of solubility and partition coefficients (log K) of macrolide antibiotic analogues . The solubility of two important macrolides, ascomycin and FK-506, was measured in a series of common solvents, where their polarities were ranked with dielectric constants . The partition coefficients of the two macrolides were compared in various binary, ternary, quaternary solvent systems . Hexane-tert.-butyl methyl ether-methanol-water system was selected based on suitable log K of solutes and hydrogen-bonding properties of solvents . In the further optimisation of composition proportions in the multicomponent solvent system, hexane-tert.-butyl methyl ether-methanol-water (1:3:6:5) showed the best solvent selectivity by giving the most prominent difference of partition coefficient (delta log K) between ascomycin and FK-506 . With this solvent system, a baseline preparative separation of these two very closely related 23-membered macrolide antibiotics was successfully achieved by employing the newly introduced Quattro counter-current chromatograph.

Emerg Med Clin North Am, 2000 Nov, 18(4), 671 - 708
The new antibiotics; Birnbaumer D et al.; It is easy to become overwhelmed by the amount of information available on the new antibiotics and difficult to keep abreast of the appropriate indications for each of them . For most patients with community-acquired infections, the first-line agent is usually not one of the newer agents, but a standard regimen, or at times, no antibiotic at all . The development of resistance is likely to parallel the extent to which these agents are prescribed . They should be used only when standard treatment fails, when compliance with treatment is a real and serious issue, or when the patient has a real allergic reaction to the standard regimen.

J Fam Pract, 1999 Dec, 48(12), 993 - 6
Antibiotic use for the treatment of upper respiratory infections in a diverse community; McKee MD et al.; BACKGROUND: Previous studies have not addressed whether cultural factors influence beliefs and practices related to the treatment of upper respiratory infections (URIs) . The purpose of our project was to assess beliefs, care-seeking behavior, use of antibiotics, and means of obtaining antibiotics for the treatment of URIs among different ethnic groups in an urban community . METHODS: A total of 192 adults completed a self-administered questionnaire indicating their likelihood of seeking care, the perceived effectiveness of treatment methods, and their usual use of treatment regimens for 2 scenarios consistent with uncomplicated URIs . Respondents were also asked about their use of antibiotics not prescribed by a physician for a URI . RESULTS: A majority of subjects reported a belief in the effectiveness of antibiotics for URIs and indicated they are likely to seek care for URIs . Many (26%) had obtained antibiotics from sources other than a physician's prescription (e.g., directly from pharmacists or a supplier outside the United States) . Many (31%) believed that antibiotics should be available over the counter . Individuals who reported using antibiotics for a URI were more likely than those who did not to obtain them without a prescription (35% vs . 11%, P = .001) . Subjects with a cultural background from countries where antibiotics are available over the counter are more likely to use antibiotics not prescribed by a physician than those from countries with variably enforced regulations or the United States (40%, 30%, and 20%, respectively, P = .049) . CONCLUSIONS: Members of an ethnically diverse community believe antibiotics are effective for colds, are very likely to seek care for colds, and often obtain antibiotics without a prescription . The ease of antibiotic access worldwide may influence their use in some communities in the United States.

Gastrointest Endosc, 2000 Jan, 51(1), 55 - 9
Non-surgical treatment of biliary liver abscesses: efficacy of endoscopic drainage and local antibiotic lavage with nasobiliary catheter; Dull JS et al.; BACKGROUND: It is universally recognized that the most frequent cause of hepatic abscess is biliary disease . The aim of this study was to determine the efficacy of endoscopic drainage and local antibiotic lavage via nasobiliary catheter in the treatment of liver abscesses of biliary origin . METHOD: From January 1994 to December 1995, twenty-two cases of pyogenic liver abscess were treated . Diagnosis was established with ultrasound, computed tomography, endoscopic retrograde cholangiography, and laboratory tests . All patients were assigned prospectively to endoscopic or other non-surgical forms of therapy, depending on the etiology of the pyogenic process . Patients in whom this treatment failed underwent surgical drainage . Twenty patients had hepatic abscesses of biliary origin . In this subgroup, a nasobiliary catheter was placed into the biliary tree for continuous antibiotic lavage (infusion technique: 1 to 1.5 mL/min for 8 to 10 days) after endoscopic sphincterotomy . Two patients had hepatic abscesses of hematogenous and amebic origin, respectively . They were treated only with the appropriate systemic antibiotics . RESULTS: Nineteen patients of the biliary subgroup (95%) and the two patients with non-biliary disease (100%) had complete resolution of the abscesses . "Salvage" surgical drainage was required in only one patient (4.5%) . There was no treatment related mortality . CONCLUSION: Endoscopic sphincterotomy and local antibiotic lavage via an endoscopically placed nasobiliary catheter is a safe and effective treatment for biliary liver abscesses . It should be considered as first-line treatment in this subgroup of patients with liver abscesses . Percutaneous or surgical drainage modalities should be reserved for patients in whom endoscopic treatment fails.

Eur J Oral Sci, 1999 Dec, 107(6), 437 - 41
Antibiotic therapy in impacted third molar surgery; Monaco G et al.; The use of routine antibiotic therapy in patients undergoing surgical third molar extraction is controversial . The efficacy of antibiotic therapy in preventing postoperative complications following surgical third molar extractions was evaluated in 141 patients . In the test group (66 patients), the protocol utilized a regimen of 2 g of amoxicillin orally daily for 5 d postoperatively, starting at the completion of surgery . In the control group (75 patients), no antibiotic therapy was given . No significant difference was found between the test group and the control group in the incidence of postoperative sequelae, i.e . fever, pain, swelling and alveolar osteitis . A statistically significant association between smoking, habitual drinking and increased postoperative pain and fever was found . Patient age > or = 18 yr was positively correlated with an increased incidence of alveolar osteitis . Swelling was found to be gender-related, in that female patients experienced more swelling than male patients . No correlation was found between the time required for surgery or difficulty of extraction and post-operative pain . In conclusion, no difference was found between patients receiving postoperative amoxicillin and the control group in the incidence of postoperative sequelae.

J Bone Joint Surg Br, 1999 Nov, 81(6), 1046 - 50
A comparison of short- and long-term intravenous antibiotic therapy in the postoperative management of adult osteomyelitis; Swiontkowski MF et al.; The current standard recommendation for antibiotic therapy in the management of chronic osteomyelitis is intravenous treatment for six weeks . We have compared this regime with short-term intravenous therapy followed by oral dosage . A total of 93 patients, with chronic osteomyelitis, underwent single-stage, aggressive surgical debridement and appropriate soft-tissue coverage . Culture-specific intravenous antibiotics were given for five to seven days, followed by oral therapy for six weeks . During surgery, the scar, including the sinus track, was excised en bloc . We used a high-speed, saline-cooled burr to remove necrotic bone, and osseous laser Doppler flowmetry to ensure that the remaining bone was viable . Infected nonunions (Cierny stage-IV osteomyelitis) were stabilised by internal fixation . In 38 patients management of dead space required antibiotic-impregnated polymethylmethacrylate beads, which were exchanged for an autogenous bone graft at six weeks . Free-tissue transfer often facilitated soft-tissue coverage . These 93 patients were compared with 22 consecutive patients treated previously who had the same surgical management, but received culture-specific intravenous antibiotics for six weeks . Of the 93 patients, 80 healed without further intervention . Of the 31 Cierny-IV lesions, 27 healed without another operation, and four fractures required additional bone grafts . No more wound drainage was needed . Treatment was successful in 91% of patients, regardless of the organism involved . There was no difference in outcome in terms of these variables when the series were compared . We conclude that the long-term administration of intravenous antibiotics is not necessary to achieve a high rate of clinical resolution of wound drainage for adult patients with chronic osteomyelitis.

Rev Esc Enferm USP, 1998 Dec, 32(4), 369 - 76
{Adverse effects of drugs in intensive care units: analysis of the administration of electrolyte solutions and antibiotics}; Manenti S et al.; The aims of this study were: 1) to verify the incidence of adverse occurrences (AOs) with medication related to the time of electrolyte solutions infusion and the frequency of doses of antibiotics prescribed and administered to the patients; 2) to characterize the nature of those occurrences . The study was developed in two ICUs of a general hospital of Sao Paulo City . The population was composed by 51 patients that were in the ICUs in August of 1996 . Sixty percent of the patients were older than 60 years, 58.8% were women, 49.1% remained in ICU from 1 to 4 days and 41.2% went to the Intermediate Care Units after ICU . Regarding the incidence of AOs related to the time of administration of the electrolyte solutions and the frequency of doses of antibiotics the non execution of the patient's medical prescriptions was verified in 76.3% and 38.8% respectively . The largest frequency of irregularities with the electrolyte solutions (60.2%) was the infusion faster than the prescribed time followed by the reduction of the number of doses of antibiotics administered . Taking these into consideration we have to invest in preventive measures to reduce those occurrences.

Eur J Clin Microbiol Infect Dis, 1999 Nov, 18(11), 827 - 9
In vitro anticryptosporidial activity of ranalexin alone and in combination with other peptides and with hydrophobic antibiotics; Giacometti A et al.; The in vitro activity of ranalexin alone and in combination with other cationic peptides, macrolides, rifampin, and rifabutin was investigated against a clinical isolate of Cryptosporidium parvum . Susceptibility tests were performed by inoculation of the isolate onto cell monolayers and determining the parasite count after 48 h of incubation at 37 degrees C . Antibiotic-free cultures were used as controls in the study . Ranalexin showed low anticryptosporidial activity: it suppressed the growth of parasites by > or = 40% at 50 microM . Ranalexin showed enhanced activity when it was combined with noninhibitory concentrations of other compounds: a 74.4-94.1% reduction in the number of parasites was observed when ranalexin 50 microM was combined with magainin II 50 microM, indolicidin 50 microM, clarithromycin 8 mg/l, azithromycin 8 mg/l, rifampin 8 mg/l, and rifabutin 8 mg/l . The results suggest that ranalexin may be effective in inhibiting Cryptosporidium parvum growth in vitro upon combination with other peptides and hydrophobic antibiotics.

Leuk Lymphoma, 1999 Dec, 36(1-2), 195 - 7
MALT lymphoma of nasal mucosa treated with antibiotics; Gupte S et al.; Mucosa associated lymphoid tissue (MALT) lymphomas occur in sites other than the gastrointestinal tract and in the early stages respond to treatment with antibiotics . We report a rare case of nasal mucosal MALT lymphoma which responded to treatment with antibiotics and has since then remained in remission.

J Mol Recognit, 1999 Nov-Dec, 12(6), 346 - 54
Characterization of the sequential non-covalent and covalent interactions of the antitumour antibiotic hedamycin with double stranded DNA by NMR spectroscopy; Pavlopoulos S et al.; Hedamycin, a member of the pluramycin class of antitumour antibiotics, consists of a planar anthrapyrantrione chromophore to which is attached two aminosugar rings at one end and a bisepoxide-containing sidechain at the other end . Binding to double-stranded DNA is known to involve both reversible and non-reversible modes of interaction . As a part of studies directed towards elucidating the structural basis for the observed 5'-pyGT-3' sequence selectivity of hedamycin, we conducted one-dimensional NMR titration experiments at low temperature using the hexadeoxyribonucleotide duplexes d(CACGTG)(2) and d(CGTACG)(2) . Spectral changes which occurred during these titrations are consistent with hedamycin initially forming a reversible complex in slow exchange on the NMR timescale and binding through intercalation of the chromophore . Monitoring of this reversible complex over a period of hours revealed a second type of spectral change which corresponds with formation of a non-reversible complex .

Biomed Chromatogr, 1999 Dec, 13(8), 520 - 4
Quantitative determination of clenbuterol enantiomers in human plasma by high-performance liquid chromatography using the macrocyclic antibiotic chiral stationary phase teicoplanin; Aboul-Enein HY et al.; We report a method for the high-performance liquid chromatographic (HPLC) chiral separation of racemic clenbuterol in human plasma . Human plasma was spiked with stock solutions of clenbuterol hydrochloride and practolol as the internal standard . Following a liquid-liquid extraction procedure with 10% (+/-)-2-butanol/isopropyl ether under alkaline conditions, the dried samples were reconstituted in methanol and chromatographed using a macrocyclic antibiotic chiral stationary phase (CSP) known as Chirobiotic T(trade mark) (teicoplanin) . The mobile phase composition was methanol:acetonitrile (70:30, v/v), containing 0.3% (v/v) acetic acid and 0.2% (v/v) triethylamine . The resulting chromatogram achieved baseline separation for the clenbuterol enantiomers . Calibration curves (peak area ratio vs plasma concentration, n = 10) were constructed for the (-)-R-and (+)-S-clenbuterol enantiomers with a plasma concentration range of 0 . 25-10 microM . The correlation coefficient (r) range was 0.99988-0 . 99999 (mean = 0.99999) . The lowest concentration measured was 0.25 microM . Inter- and intra-assay variation was determined for the lowest, medium and highest plasma concentration (0.25, 2 and 10 microM) by calculating the analytical recoveries with a range of 96-104% . The percentage recoveries for the clenbuterol enantiomers were 88.4-102% over the concentration range used . Detailed methodology is presented .

J Infect, 1999 Sep, 39(2), 129 - 33
Feasibility of an outpatient and home parenteral antibiotic therapy (OHPAT) programme in Tayside, Scotland; Seaton RA et al.; Outpatient and home parenteral antibiotic therapy (OHPAT) is under-utilized in the U.K . We performed a feasibility study over a 5-month period in a regional U.K . infection unit . After exclusions, 183 antibiotic treated patients were evaluated . Ninety-five received intravenous (i.v.) therapy, of whom 32 received at least 4 days . Prolonged i.v . therapy was most frequent in soft tissue infections . In these patients, length of stay and duration of i.v . treatment were correlated (r = 0.74, 0.51-0.87) . Eighty-three (86%) of patients who received IV therapy judged OHPAT to be an acceptable alternative to hospitalization . Those who did not were older (mean age 64 vs . 46 years, P<0.001) and were less likely to have a carer willing to administer the antibiotic at home (8/28 vs . 117/151, P<0.001) . Twenty-five of 32 (79%) patients treated with prolonged parenteral therapy and 27/95 (28%) treated with any length of parenteral therapy met criteria for OHPAT . Thirteen of these were safely and successfully managed as outpatients by ward staff, OHPAT is an acceptable alternative to inpatient therapy in Tayside and may reduce the duration of hospitalization or prevent admission in certain patients.

J Infect Dis, 2000 Jan, 181(1), 216 - 29
Major related sets of antibiotic-resistant Pneumococci in the United States as determined by pulsed-field gel electrophoresis and pbp1a-pbp2b-pbp2x-dhf restriction profiles; Gherardi G et al.; To assess the genetic diversity of pneumococci causing serious disease within the United States, restriction profiles of 3 penicillin-binding protein (PBP)-gene amplicons and the dhf amplicon were examined in 241 recent sterile-site isolates from 7 population centers . This analysis provided markers useful for epidemiologic studies and was generally predictive of resistances to beta-lactam antibiotics and trimethoprim-sulfamethoxazole . Eight pulsed-field gel electrophoresis (PFGE) types, each representing 3-40 isolates, accounted for 134 of the 144 beta-lactam-resistant pneumococci (MICs >/=1 microgram/mL for penicillin, cefotaxime, or both) . Five of these PFGE types contained subtypes highly related to subtypes of previously characterized pneumococcal clones . Within 4 of these PFGE types, the major composite PBP gene-dhf profile was highly related to the composite profile from the previously characterized related clone . Eight capsular serotypes were found among the 144 beta-lactam-resistant pneumococci . Divergent capsular types among isolates with identical PBP gene-dhf profiles and related PFGE types indicated several instances of capsular serotype switching.

Lakartidningen, 1999 Nov 24, 96(47), 5239 - 43
{Reduced utilization of antibiotics in Swedish hospitals . Considerable variations between hospitals concerning choice and use of preparations}; Linder CH et al.; Defined daily dose (DDD) consumption of antibiotics in 26 Swedish hospitals decreased by an average of 25% from 1990 to 1998, according to statistics from Apoteket AB . In one hospital, the decrease was 61% . Average consumption of tetracyclines and penicillins, expressed as percentage of total antibiotics consumption, decreased by 5% and 7% respectively, while quinolones and cephalosporins increased by 4% and 7% respectively . Consumption of tetracyclines and quinolones varied between individual hospitals by a factor of four.

Eur J Biochem, 2000 Jan, 267(1), 269 - 75
Differences in the skin peptides of the male and female Australian tree frog Litoria splendida . The discovery of the aquatic male sex pheromone splendipherin, together with phe8 caerulein and a new antibiotic peptide caerin 1.10; Wabnitz PA et al.; The skin secretions of female and male Litoria splendida have been monitored monthly over a three-year period using HPLC and electrospray mass spectrometry . Two minor peptides are present only in the skin secretion of the male . The first of these is the female-attracting aquatic male sex pheromone that we have named splendipherin, a 25 amino acid peptide (GLVSSIGKALGGLLADVVKSKGQPA-OH) . This pheromone constitutes about 1% of the total skin peptides during the breeding season (January to March), dropping to about 0.1% during the period June to November . Splendipherin attracts the female in water at a concentration of 10-11-10-9 M, and is species specific . The second peptide is a wide-spectrum antibiotic of the caerin 1 group, a 25 residue peptide (GLLSVLGSVAKHVLPHVVPVIAEKL-NH2) named caerin 1.10 . The neuropeptides of L . splendida are also seasonally variable, the change identical for both the female and male . During the period October to March, the sole neuropeptide present in skin secretions is caerulein {pEQDY(SO3)TGWMDF-NH2}; this is active on smooth muscle and is also an analgaesic . During the southern winter (June to September), more than half of the caerulein is hydrolysed to {pEQDYTGWMDF-NH2}, a peptide that shows no smooth muscle activity . In place of caerulein, a new peptide, Phe8 caerulein {pEQDY(SO3)TGWFDF-NH2}, becomes a major component of the skin secretion . Perhaps this seasonal change is involved in thermoregulation, that is, with the initiation and maintenance of the inactive (hibernation) phase of the animal.

Can J Clin Pharmacol, 1999 Winter, 6(4), 203 - 11
{Accuracy of a self-administered questionnaire on the use of antibiotics}; Tremblay E et al.; BACKGROUND: To document the ambulatory use of drugs and the indications for that use, investigators often rely on self-administered questionnaires of questionable accuracy . The present study assessed the accuracy of a French Canadian self-administered questionnaire with regard to documenting current antibiotic drug use . METHODS: The information independently obtained from physicians and pharmacists was compared with the information reported by 340 patients . Patients were asked to participate in the study by their pharmacist at the time that their prescribed antibiotic was dispensed . The proportion of agreement between the data sources was calculated with regard to antibiotic regimen characteristics and indications for use and the nature of the treated infection . RESULTS: Self-reported information demonstrated a high level of agreement with data provided by physicians (k = 0.87) and pharmacists (k = 0.94), with regard to antibiotic names . Regarding the nature of the treated infection, the agreement between self-reported information and data obtained from physicians was substantial (k = 0.63) . A total of 242 patients completed the questionnaire twice at two-week intervals . Test-retest reliability was high regarding both the antibiotic name (k = 0.72) and the nature of the treated infection (k = 0.86) . CONCLUSIONS: The self-administered questionnaire assessed in this study can reliably and accurately document the name of antibiotics used and the nature of the treated infections . Further work is needed to improve the accuracy of the questionnaire with regard to other components of antibiotics use.

Pharmacol Res, 2000 Jan, 41(1), 109 - 13
Effects of some antibiotics on enzyme activity of glucose-6-phosphate dehydrogenase from human erythrocytes; Ciftci M et al.; Inhibitory effects of some antibiotics on glucose-6-phosphate dehydrogenase from the erythrocytes of human have been investigated . For this purpose, at the beginning, erythrocyte glucose-6-phosphate dehydrogenase was purified 13.654 times in a yield of 28% by using ammonium sulphate precipitation and 2',5'-ADP Sepharose 4B affinity gel . Temperature of +4 degrees C was maintained during the purification process . Enzyme activity was determined with the Beutler method by using a spectrophotometer at 340 nm . This method was utilized for all kinetic studies . Sodium ceftizoxime, sodium ampicillin, sodium cefuroxime, sodium cefazolin, sodium cefoperazone, streptomycin sulphate, gentamicin sulphate, and netilmicin sulphate were used as antibiotics . All the antibiotics indicated the inhibitory effects on the enzyme . K(i) constants for glucose-6-phosphate dehydrogenase were found by means of Lineweaver-Burk graphs . While sodium cefoperazone, gentamicin sulphate, and netilmicin sulphate showed competitive inhibition, the others displayed non-competitive inhibition . In addition, I(50) values of the antibiotics were determined by plotting activity percent vs {I} . In addition, in vivo studies were done for sodium sefuroxime in Sprague-Dawley type rats . It was found that G6PD in erythrocyte was more inhibited by the drug in 2.5 h .

Electrophoresis, 1999 Oct, 20(15-16), 3269 - 79
Analysis of antibiotics by capillary electrophoresis; Flurer CL; The broad category of antibiotics encompasses some of the most widely prescribed pharmaceuticals in the world . As is the case with any pharmaceutical, an antibiotic must be characterized in terms of its potency and the presence and quantity of impurities . Additionally, any residue or metabolite that may be present as a result of its use must be monitored . Many capillary electrophoretic techniques have been utilized in the analysis of antibiotics, addressing the various aspects of quantifying, profiling, and monitoring . Some of the more recent applications are summarized in this review article.

J Chromatogr A, 1999 Nov 12, 862(2), 179 - 89
Detection of new sequences of peptaibol antibiotics trichotoxins A-40 by on-line liquid chromatography-electrospray ionization mass spectrometry; Jaworski A et al.; Using high-performance liquid chromatography (HPLC) coupled to electrospray ionization mass spectrometry (ESI-MS) the sequences of the microheterogeneous peptide mixture of the 18-residue "peptaibol" antibiotics trichotoxins A-40, isolated from the mold Trichoderma viride strain NRRL 5242, were reinvestigated . The structures of two major and one minor component {J . Chromatogr., 296 (1984) 236} could be confirmed and hitherto not known sequences of a further major and two minor peptides could be determined . It is demonstrated that ESI-MS in the positive ionization mode is advantageously completed by applying negative ionization . The methods used make possible the sequence determination of components of peptaibols without previous isolation and allow, in certain cases, sequencing of peptides which are incompletely or not resolved by HPLC.

Int J Pediatr Otorhinolaryngol, 1999 Oct 15, 50(1), 45 - 50
How easily do topical antibiotics pass through tympanostomy tubes?--an in vitro study; Saunders MW et al.; BACKGROUND: Despite potential ototoxicity, eardrops containing aminoglycosides remain in widespread use in the presence of indwelling tympanostomy tubes (grommets) . It is unclear how readily they pass into the middle ear during administration, nor whether this is affected by middle ear secretions . MATERIALS AND METHODS: The trans-tympanic pressure required to force antibiotic solutions through a tympanostomy tube in an artificial middle ear model was investigated with six ototopical preparations and two sizes of tube . To assess the effect of middle ear secretions, tympanostomy tubes removed from patients ears were investigated in addition to new tubes . The intra-canal pressure generated during tragal massage was also measured . RESULTS: Pressures required for leakage of solutions differed significantly between solutions (P=0.001) and tube sizes, smaller lumen tubes requiring higher trans-tympanic pressure for leakage to occur . The presence of middle ear secretions reduced the pressure required for leakage of solution . Tragal massage generated pressures of over 20 cm of H20 which would be enough to force solution into the middle ear in all tube/solution combinations . DISCUSSION: Some antibiotic solution is likely to leak into the middle ear during most applications of antibiotic solution . Although the risk is small, this suggests the possibility of ototoxicity, previously demonstrated in animal experiments . The relatively low incidence of this occurrence in clinical practice is thought to be related to inter-species anatomical variations.

J Agric Food Chem, 1999 Sep, 47(9), 3723 - 6
Determination of the antibiotic fungicide validamycin A in formulated products by micellar electrokinetic chromatography; Hsiao YM et al.; A micellar electrokinetic capillary chromatographic method (MEKC) was used to determine validamycin A content in commercial products . The results indicated that this method was capable of analyzing the validamycin A content in formulated products with an instrument detection limit of 0.94 microg/mL and a method detection limit of 1 . 70 microg/mL . Relative standard deviation (RSD) values of MEKC determination of validamycin A in formulated products ranged from 0 . 61 to 2.09% . Recoveries of validamycin A in formulated products were in the region of 99.5-105.1% . All commercial products collected from markets contained validamycin A . The high percentage of recovery, the low detection limit, and the low RSD values confirmed that the MEKC technique is a senstivie and selective method.

J Agric Food Chem, 1999 Aug, 47(8), 3372 - 80
Isolation, antifungal activity, and structure elucidation of the glutarimide antibiotic, streptimidone, produced by Micromonospora coerulea; Kim BS et al.; The antibiotic Ao58A,which showed strong antifungal activity against some plant pathogenic fungi, was purified from the culture broth and mycelial mats of Micromonospora coerulea strain Ao58 using various chromatographic procedures . The molecular formula of the antibiotic Ao58A was deduced to be C(16)H(23)NO(4) (M + H, m/z 294.1707) by high-resolution FAB mass spectroscopy . Analyses of (1)H NMR, (13)C NMR, and 2D NMR spectral data revealed that the antibiotic Ao58A is the glutarimide antibiotic streptimidone, 4-(2-hydroxy-5, 7-dimethyl-4-oxo-6,8-nonadienyl)-2,6-piperidinedione . The antibiotic Ao58A was very effective in inhibiting growth of Phytophthora capsici,Didymella bryoniae, Magnaporthe grisea, and Botrytis cinerea in the range approximately 3-10 microg mL(-)(1) of MICs . In vivo evaluation of the antibiotic Ao58A under greenhouse condition showed strong control efficacies against the development of P . capsici, B . cinerea, and M . grisea on pepper, cucumber, and rice plants, respectively . The antibiotic Ao58A was equally as effective as metalaxyl, vinclozolin, and tricyclazole in the control of these plant diseases . However, it did not show any phytotoxicity on the plants even when treated with 500 microg mL(-)(1).

J Antimicrob Chemother, 1999 Nov, 44(5), 693 - 5
In-vitro activity of antibiotics against Legionella pneumophila isolates from water systems; Tsakris A et al.; The activity of five antibiotics was tested against 82 isolates of Legionella pneumophila obtained from water systems in nine European countries . All isolates were susceptible to clarithromycin (MICs 0 . 03-0.5 mg/L), erythromycin (MICs 0.125-2.0 mg/L), ciprofloxacin (MICs 0.06-0.25 mg/L), pefloxacin (MICs 0.06-0.5 mg/L) and rifampicin (MICs < or = 0.007-0.015 mg/L) . It seems that antibiotics used for legionellosis continue to exhibit good activity against L . pneumophila isolates from environmental sources in European countries.

Mol Microbiol, 1999 Dec, 34(5), 1039 - 48
Interspecies complementation in Saccharopolyspora erythraea : elucidation of the function of oleP1, oleG1 and oleG2 from the oleandomycin biosynthetic gene cluster of Streptomyces antibioticus and generation of new erythromycin derivatives; Doumith M et al.; Two glycosyltransferase genes, oleG1 and oleG2, and a putative isomerase gene, oleP1, have previously been identified in the oleandomycin biosynthetic gene cluster of Streptomyces antibioticus . In order to identify which of these two glycosyltransferases encodes the desosaminyltransferase and which the oleandrosyltransferase, interspecies complementation has been carried out, using two mutant strains of Saccharopolyspora erythraea, one strain carrying an internal deletion in the eryCIII (desosaminyltransferase) gene and the other an internal deletion in the eryBV (mycarosyltransferase) gene . Expression of the oleG1 gene in the eryCIII deletion mutant restored the production of erythromycin A (although at a low level), demonstrating that oleG1 encodes the desosaminyltransferase required for the biosynthesis of oleandomycin and indicating that, as in erythromycin biosynthesis, the neutral sugar is transferred before the aminosugar onto the macrocyclic ring . Significantly, when an intact oleG2 gene (presumed to encode the oleandrosyltransferase) was expressed in the eryBV deletion mutant, antibiotic activity was also restored and, in addition to erythromycin A, new bioactive compounds were produced with a good yield . The neutral sugar residue present in these compounds was identified as L-rhamnose attached at position C-3 of an erythronolide B or a 6-deoxyerythronolide B lactone ring, thus indicating a relaxed specificity of the oleandrosyltransferase, OleG2, for both the activated sugar and the macrolactone substrate . The oleP1 gene located immediately upstream of oleG1 was likewise introduced into an eryCII deletion mutant of Sac . erythraea, and production of erythromycin A was again restored, demonstrating that the function of OleP1 is identical to that of EryCII in the biosynthesis of dTDP-D-desosamine, which we have previously proposed to be a dTDP-4-keto-6-deoxy-D-glucose 3, 4-isomerase.

J Antimicrob Chemother, 1999 Dec, 44(6), 839 - 42
Multiple prescriptions of antibiotics for children aged 0 to 5 years in relation to type of antibiotic; Thrane N et al.; The risk of receiving more than one prescription within an antibiotic course was examined for all children aged 0 to 5 years in a Danish county during 1997 . We identified 29,307 prescriptions of systemic antibiotics for 16,245 children in a prescription database . Ten per cent of the prescriptions were followed by a new prescription within 10 days . In children who received two prescriptions (n = 3993), 19% redeemed the prescriptions within the same course . When the child was prescribed penicillin V, compared with broad-spectrum penicillin, the odds ratio of receiving a repeat prescription within 1-2 days was 2.9 (95% CI 2.5-3.4) and within 3-10 days 1.3 (95% CI 1.2-1.5).

Ned Tijdschr Geneeskd, 1999 Nov 20, 143(47), 2364 - 9
{Early change from intravenous to oral antibiotics: 'switch therapy'}; Sevinc F et al.; There has been growing interest in recent years in early switch therapy: antibiotics are administered intravenously during the early phase of the infection, and then continued orally . A large number of recent prospective and randomized studies justify the application of an early switch . There is consensus in the literature about the circumstances in which an early switch is justified: (a) the patient must show clinical improvement; (b) the oral therapy should result in sufficiently high levels at the infection site; (c) the patient must be capable of taking oral medication, there must be no signs of malabsorption and interactions with food or with other drugs should be taken into account; (d) if these rules are observed, switch to oral therapy as a rule is justified after 2 to 3 days' intravenous administration . An early switch is more comfortable to the patient, eases the load on the nursing staff and considerably reduces expenses.

Aten Primaria, 1999 Sep 30, 24(5), 274 - 80
{The factors that influence the use of antibiotics in primary care}; Torralba Guirao M et al.; OBJECTIVE: To identify factors influencing volume, quality and power of antibiotic prescription in primary care . DESIGN: Descriptive, crossover study . SETTING: Sanitary Region Coast of Ponent, 1992 . PARTICIPANTS: They were studied 468 practitioners of primary care attention . 68 practitioners were excluded by various reasons . MEASUREMENTS AND MAIN RESULTS: The factors studied were: factors coming from the practitioner, the centre, and the assisted population . The following parameters were analysed: amount of prescribed antibiotics in DDDs, election level ("antibiotic power") and percentage of DDDs of low intrinsic value . It was used for the comparison of means, Student-Fisher t test and the confidence intervals of the difference . Also it was used the step-wise multiple regression analysis . Greater use of antibiotics . The variability can be explained through regression in a 45.7% in function of the doctors factors, not integrated in a team, older, doctor who works in a rural centre, of young population and of smaller revenue . Greater antibiotic power . It's explained in a 5.09% by the medical factors like man, that works in a not educational centre and of greater population revenue . Greater percentage of DDDs of low intrinsic value . It's greater in doctors not specialized in family care, permanent job, of greater age, men, not reformed professional and not of an educational centre . CONCLUSIONS: The volume of prescription of antibiotics and in minor extent its quality of prescription are in some part justified by variables coming from the practitioner, the centre and the assisted population . The antibiotic power mainly doesn't.

Microbiology, 1999 Nov, 145 ( Pt 11), 3059 - 67
Genetic and functional analysis of genes required for the post-modification of the polyketide antibiotic TA of Myxococcus xanthus; Paitan Y et al.; The antibiotic TA of Myxococcus xanthus is a complex macrocyclic polyketide, produced through successive condensations of acetate by a type I PKS (polyketide synthase) mechanism . The genes encoding TA biosynthesis are clustered on a 36 kb DNA fragment, which has been cloned and analysed . The chemical structure of TA and the mechanism by which it is synthesized indicate the need for several post-modification steps, which are introduced into the carbon chain of the polyketide to form the final bioactive molecule . These include the addition of several carbon atoms originating from acetate carbonyl, three C-methylations, O-methylation and a specific hydroxylation . This paper reports the analysis of five genes which are involved in the post-modification of TA . Their functional analysis, by specific gene disruption, suggests that they may be essential for the production of the active antibiotic . The characteristics and organization of the genes suggest that they may be involved in the addition of the carbon atoms which arise from acetate.

J Pediatr, 1999 Dec, 135(6), 768 - 9
Failure of pre-diarrheal antibiotics to prevent hemolytic uremic syndrome in serologically proven Escherichia coli O157:H7 gastrointestinal infection; Igarashi T et al.; A girl had hemolytic uremic syndrome after Escherichia coli O157:H7 infection, despite pre-diarrheal administration of an antibiotic that prevented detectable intestinal colonization . This report casts doubt on the advisability of antibiotic therapy for E coli O157:H7 infections and has implications for our understanding of the mechanism of this disorder.

Complement Ther Med, 1999 Sep, 7(3), 156 - 63
Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing genotoxic effects produced by arsenic trioxide in mice: II . Comparative efficacy of an antibiotic, actinomycin D alone and in combination with either of two microdoses; Datta S et al.; OBJECTIVE: To determine whether actinomycin-D (AMD), an antibiotic, alters the reported efficacy of a potentized homoeopathic drug, Arsenicum Album, in reducing genotoxic effects produced in arsenic-trioxide-injected mice . DESIGN: Mice were separately injected with AMD, As2O3, and conjointly with AMD plus As2O3, AMD plus homoeopathic drug, AMD plus As2O3 plus homoepathic drug, and As2O3 plus homoeopathic drug in separate sets . METHODS: Several standard cytogenetical endpoints were assessed at different fixation intervals by adopting conventional techniques . RESULTS: Both Ars Alb-30 and Ars Alb-200 showed protective ability against AMD and As2O3 when injected individually, but this ability was reduced considerably in mice injected with AMD and As2O3 together . AMD itself had genotoxic effects, but also apparently reduced genotoxic effects of arsenic to some extent . CONCLUSION: AMD reduced the protective efficacy of the homoeopathic drug against arsenic . This result suggests a mechanism of action for homoeopathy, as AMD is a known transcription-blocker.

J Antibiot (Tokyo), 1999 Aug, 52(8), 748 - 53
UK-2A,B,C and D, novel antifungal antibiotics from Streptomyces sp.517.02 . V . Inhibition mechanism of bovine heart mitochondrial cytochrome bc1 by the novel antibiotic UK-2A; Machida K et al.; UK-2A is a potent antifungal antibiotic isolated from Streptomyces sp . 517-02 and its structure is highly similar to that of antimycin A . We investigated the inhibition mechanism of bovine heart mitochondrial cytochrome bc1 complex by the UK-2A using antimycin A and myxothiazol as the reference inhibitors of ubiquinol oxidation (Qo) and ubiquinone reduction (Qi) sites, respectively . The inhibitory potency of UK-2A was about 3-fold less than antimycin A . On the basis of the effects of UK-2A on the reduction kinetics of b and c1 hemes, this compound appeared to be an inhibitor of the Qi site . However, since spectral changes of dithionite-reduced cytochrome b induced by UK-2A binding differed from that of antimycin A, the precise binding manner of UK-2A to the enzyme is not identical to that of antimycin A . It could be concluded that antimycin A binding to cytochrome b is primarily decided by structural specificity of the salicylic acid moiety.

Toxicology, 1999 Nov 5, 138(2), 59 - 67
Low convulsive activity of a new carbapenem antibiotic, DK-35C, as compared with existing congeners; Jin C et al.; Since carbapenems and cephalosporins have been suggested to induce convulsive side effects through an inhibitory action on the central gamma-aminobutyric acid (GABA)-mediated inhibitory transmission, the present study evaluated the convulsive activity of a new carbapenem antibiotic (1R,5S,6S)-6{(R)-1-hydroxyethyl}-2-{(3S,5S)-5(S-methyl-4thiomorpholin ylcarbonyl)pyrrolidin-3-thio}-l-methylcarbapen-2-em-3- carboxylic acid (DK-35C) in in vitro and in vivo experiments, in comparison with cefazolin, imipenem and meropenem . In in vitro experiments, their abilities to inhibit {3H}muscimol (5 nM) binding to GABA(A) receptors were measured using crude synaptic membranes prepared from the rat cerebral cortex . The concentrations (mM) of the antibiotics which inhibit 50% of the specific binding, were 0.6 for imipenem, 1.8 for cefazolin, 15.4 for DK-35C and 27.6 for meropenem . In in vivo experiments, intracerebroventricular (i.c.v.) injections of cefazolin, imipenem and DK-35C induced convulsions in a dose-dependent manner in rats . The doses (nmol/rat) of the antibiotics which induce convulsions in 50% of rats, were 57 for imipenem, 96 for cefazolin, 377 for DK-35C and >3000 for meropenem . In the mouse pentylenetetrazole (PTZ) convulsive model, intravenous pretreatment with cefazolin (800 mg/kg) or imipenem (200 mg/kg) shifted the dose-response curve of PTZ (i.p.) to the left, indicating enhancement of the convulsive activity of PTZ . However, pretreatment with cefazolin, meropenem or DK-35C at a dose of 400 mg/kg did not produce any marked effects on the convulsive activity of PTZ compared with the saline vehicle-pretreated control . The results clearly demonstrate a good correlation between in vitro GABA(A) receptor binding assay and in vivo i.c.v . convulsive model using rats, and suggest that DK-35C may possess a relatively weak convulsive activity mediated through an interaction with GABA(A) receptors.

Radiats Biol Radioecol, 1999 Sep-Oct, 39(5), 568 - 71
{Treatment of infectious complications of experimental acute radiation injury with combined antibiotic sulacillin}; Chertkov KS et al.; An anti-infectious effect of sulacillin (ampicillin/sulbactam) is higher than that of ampicillin in treatment of irradiated mice infected with a beta-lactamaseproducing strain of Kl . pneumoniae . Involving of sulacillin as a principal antibiotic into the therapeutic scheme for acute radiation sickness results in 67% dogs survival at LD90/45.

Chem Biol, 1999 Nov, 6(11), 789 - 99
Expressed protein ligation to probe regiospecificity of heterocyclization in the peptide antibiotic microcin B17; Roy RS et al.; BACKGROUND: The Escherichia coli peptide antibiotic microcin B17 (MccB17) contains thiazole and oxazole heterocycles derived from a distributive yet directional cyclization of cysteines and serines in the McbA precursor catalyzed by MccB17 synthetase . Whether the formation of upstream rings potentiates downstream heterocyclization has not been previously determined . RESULTS: McbA fragments (46-61 residues) containing glycine substitutions or homocysteine at select upstream cysteine or serine sites were assembled using expressed protein ligation (EPL) . Most of these substrates were only partially cyclized by MccB17 synthetase, in contrast to the efficient processing of wild-type McbA(1-61) . Homocysteine was not processed to the six-membered heterocycle . CONCLUSIONS: The formation of upstream rings in McbA potentiates the cyclization of carboxy-terminal cysteines and serines, probably by selecting against unfavorable substrate conformations . EPL allows structure-function analysis including unnatural amino acid placements to probe the regiospecificity and chemoselectivity of post-translational heterocyclization during antibiotic maturation.

J Ark Med Soc, 1999 Nov, 96(6), 216 - 20
A call for the judicious use of antibiotics; Merchant RJ et al.; In the United States alone, more than one-fifth of antibiotic prescriptions written are for viral illnesses . Due to the increasing resistance rates among commonly encountered bacteria, it is imperative that physicians re-examine their prescription writing habits . Physician and patient re-education, better use of diagnostic testing, the use of narrow spectrum antibiotic agents and shorter course therapy are essential for this to occur . The future health of Arkansas residents is dependent upon changes being implemented before it is too late.

Rheum Dis Clin North Am, 1999 Nov, 25(4), 861 - 81, viii
Antibiotics for the treatment of rheumatologic syndromes; Sigal LH; Design of rational therapy depends on knowledge of the causes of the disease, which is knowledge often lacking in rheumatology . There have been theories of infectious causes of many rheumatologic diseases but no proof . The seductive possibility of an infectious etiology has led to the use of antibiotics for treating these diseases . This article reviews the effectiveness of antibiotics against rheumatologic syndromes, including rheumatoid arthritis and Lyme disease.

J Gen Intern Med, 1999 Nov, 14(11), 658 - 62
Public beliefs and use of antibiotics for acute respiratory illness; Wilson AA et al.; OBJECTIVE: To better understand public beliefs and use of antibiotics for acute respiratory illnesses . DESIGN: Cross-sectional telephone survey . PARTICIPANTS: Three hundred eighty-six adult members (aged 18 years or older) of a group-model HMO in the Denver metropolitan area . MEASUREMENTS AND MAIN RESULTS: Two hundred seventy-three (70%) of the respondents reported that antibiotics were beneficial for bacterial respiratory illnesses, 211 (55%) reported that antibiotics were beneficial for viral respiratory illnesses, and 82 (21%) reported that antibiotics were beneficial for bacterial but not for viral illness . Multivariate regression analysis identified consulting an advice nurse (odds ratio {OR} 2.9; 95% confidence interval {CI} 1.7, 5.3), ever being told by a provider that antibiotics were not needed for a respiratory illness episode (OR 2.0; 95% CI 1.2, 3.6), having a chronic medical condition (OR 2.0; 95% CI 1.0, 3.9), and believing antibiotics to be helpful for viral (OR 2.5; 95% CI 1.3, 4.7) or bacterial (OR 2.6; 95% CI 1.2, 6.7) respiratory illnesses to be independently associated with antibiotic use for respiratory illnesses during the previous year . There was a trend toward lower previous antibiotic use among those believing antibiotics to be helpful for bacterial illness but not for viral illness . CONCLUSIONS: A lack of understanding about antibiotic effectiveness exists in the community . Increased previous antibiotic use among those believing antibiotics to be effective for viral illnesses suggests that improvements are needed in communications to patients and the public about antibiotic appropriateness.

Appl Microbiol Biotechnol, 1999 Oct, 52(4), 484 - 8
Stimulatory effect of growth in the presence of alcohols on biotransformation of penicillin G into cephalosporin-type antibiotics by resting cells of Streptomyces clavuligerus NP1; Fernandez MJ et al.; Growth of Streptomyces clavuligerus NP1 in the presence of methanol or ethanol resulted in a marked increase in production of cephalosporin(s) from penicillin G by resting cells . The mycelium produced in alcohol-supplemented medium was fragmented and dispersed as compared with growth in control medium . HPLC analysis showed that at least two products were present in the biotransformation supernatant fluid after 1 h incubation . One of them has been identified as deacetoxycephalosporin G (DAOG).

Biochemistry, 1999 Nov 23, 38(47), 15623 - 30
Posttranslational heterocyclization of cysteine and serine residues in the antibiotic microcin B17: distributivity and directionality; Kelleher NL et al.; To produce the antibiotic Microcin B17, four Cys and four Ser residues are converted into four thiazoles and four oxazoles by the three subunit Microcin B17 synthetase . High-resolution mass spectrometry (MS) was used to monitor the kinetics of posttranslational heterocyclic ring formation (-20 Da per ring) and demonstrated the accumulation of all intermediates, from one to seven rings, indicating distributive processing . All of the intermediates could be converted by the enzyme to the eight ring product . Enzymatic chemoselectivity (Cys vs Ser cyclization rates) was assessed using iodoacetamido-salicylate to alkylate unreacted cysteines (+193 Da) in the 8 kDa biosynthetic intermediates; three of the first four rings formed were thiazoles, and by the five ring stage, all four of the cysteines had been heterocyclized while three of the original four serines remained uncyclized . Finally, tandem MS using a 9.4 T Fourier transform instrument with electrospray ionization was used to elaborate the major processing pathway: the first two rings formed are at the most amino proximal sites (Cys(41) then Ser(40)) followed by the remaining three cysteines at positions 48, 51, and 55 . The cyclization of serines at positions 56, 62, and 65 then follows, with Ser(62) and Ser(65) the last to heterocyclize and the first of these at a slower rate . Thus, despite free dissociation of intermediates after each of seven ring-forming catalytic cycles, there is an overall directionality of ring formation from N-terminal to C-terminal sites . This remarkable regioselectivity is determined more by the substrate than the enzyme, due to a combination of (1) initial high-affinity binding of the posttranslational catalyst to the N-terminal propeptide of substrate 88mer, and (2) a chemoselectivity for thiazole over oxazole formation . This mechanism is consistent with antibiotic biosynthesis in vivo, yielding microcin with six, seven, and eight rings, all with bioactivity.

Proc AMIA Symp . 1999;:440-4.
Modeling empiric antibiotic therapy evaluation of QID; Warner H Jr et al.; At AMIA 1997, we reported on the design and development of a new computer-based tool, called QID, for empiric antibiotic decision support . QID was designed to help physicians identify the antibiotic regimens with the highest probability of covering the pathogens that are most likely to be present in individual patients . QID creates a list of antibiotics, ordered by potential benefit in treatment, for a patient with a suspected infection before culture results are available . Since our initial publication, a "before and after" study has been done using 20 internal medicine residents and the same number of internal medicine attendings . In order to test the hypothesis that physician's would make more appropriate empiric antibiotic choices with the aid of QID, we chose University of Utah physicians and had each evaluate four infectious disease cases that were abstracted from medical record infectious disease cases . Immediately following their initial review and determination of antibiotic therapy for each case, the study participants were presented with QID's antibiotic recommendations on the same case to see if this information would change their initial drug regimen . The tool was shown to have a greater impact on the most difficult cases but statistically improved scores overall (p < .001) . Details of our study design and results are presented.

Kansenshogaku Zasshi, 1999 Oct, 73(10), 1048 - 53
{Combination effect of teicoplanin and various antibiotics against hetero-VRSA and VRSA}; Hanaki H et al.; Eleven clinical strains of MRSA which were detected as heterogeneously-resistant to vancomycin (hetero-VRSA) on Mu3-medium (a newly devised hetero-VRSA detecting medium) were subjected to a study to explore the therapeutic possibility of combination therapy . Combination effects of teicoplanin with six different beta-lactam antibiotics (imipenem, panipenem, meropenem, flomoxef, sulbactam/ampicillin, cefoselis), arbekacin, and minocycline were evaluated on the strains of Mu3, Mu50 and the above 11 strains . Combination of teicoplanin with five beta-lactam antibiotics individually (except for cefoselis) showed a synergistic effect, while that with cefoselis showed synergistic or additive effect . Neither indifference nor antagonism effect was observed in combination of seicoplanin with beta-lactam antibiotics on these MRSA strains . The degree of synergistic effect in combination with teicoplanin was the strongest in imipenem, followed by panipenem > meropenem > flomoxef > sulbactam/ampicillin > cefoselis in this order . The average FIC index of the beta-lactam antibiotics against these strains was 0.113, 0.124, 0.163, 0.230, 0.264 and 0.388, respectively . Arbekacin and minocycline showed variable of effects in combination with teicoplanine . In the case of arbekacin, the ratio of synergy, addition, indifference, and antagonism were 30.8, 30.8, 0 and 38.4%, respectively, and in the case of minocycline, they were 15.4 . 7.7, 0 and 76.9%, respectively . Vancomycin activity against hetero-VRSA and VRSA is antagonized with beta-lactam antibiotics, while teicoplanin activity is synergistic or additive . It is known that MRSA is relatively easy to emerge resistance to teicoplanin . Therefore, teicoplanin is not desirable for a monotherapy . However, in a combination with beta-lactam antibiotics, teicoplanin appeared to be a promising agent for the treatment of MRSA infection.

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