Antibiotics

Perit Dial Int, 2003 Jul-Aug, 23(4), 331 - 8
Antibiotic administration in an animal model of chronic peritoneal dialysate exposure; Mortier S et al.; OBJECTIVES: The high incidence of intraperitoneal infection remains an important problem in animal models of chronic dialysate exposure . Prophylactic antibiotic administration can be used to resolve this problem, but the isolated effects of antibiotics on peritoneal membrane function and structure are unknown . The present study examined the effects of prophylactic antibiotics on infection rate and peritoneal membrane function and structure in a rat model of chronic dialysate exposure . DESIGN: A first group of rats (A; n = 12) received 10 mL 3.86% glucose dialysate twice daily through a heparin-coated catheter . In a second group of animals (B; n = 12), oxacillin 2.5 mg/day and gentamicin 0.04 mg/day were added to the dialysate . Group C (n = 12) was injected twice daily with an identical dose of antibiotics dissolved in 1 mL of buffer solution . Group D (n = 12) was left untreated . Dialysate cultures were obtained regularly . After 8 weeks of exposure, peritoneal transport studies were performed and samples for histology were obtained . RESULTS: Technique survival was 92% in group A and 100% in the remaining groups . Five rats in group A but none of the animals in the other groups developed peritonitis . The transport rates of small solutes were elevated and net ultrafiltration was decreased in group A compared to the controls . Fibrosis, as evaluated by quantifying Picro Sirius Red staining with image analysis, was significantly elevated in group A (3.48% +/- 1.06% vs 0.72% +/- 0.51% in group D, p < 0.05) but not in group B (0.29% +/- 0.07%) or in group C (0.52% +/- 0.28%) . Vascular density, measured by counting the number of blood vessels that stained positive for endothelial NO synthase, was increased in both groups that were exposed to dialysate: 153.0 +/- 12.9/microm2 in group A and 131.6 +/- 14.3/microm2 in group B, versus 76.76 +/- 12.37/microm2 in group C and 73.2 +/- 10.4/microm2 in group D (p < 0.01) . CONCLUSIONS: Prophylactic administration of oxacillin and gentamicin adequately prevented intraperitoneal infection in an animal model of chronic dialysate exposure . In addition, fibrosis was absent, suggesting intraperitoneal infection rather than dialysate exposure is a causative factor.

J Chromatogr A, 2003 Aug 8, 1008(2), 145 - 55
Trace enrichment of (fluoro)quinolone antibiotics in surface waters by solid-phase extraction and their determination by liquid chromatography-ultraviolet detection; Turiel E et al.; A new and simple analytical methodology for the simultaneous analysis of acidic and zwitterionic (fluoro)quinolones in surface waters at trace concentration level is presented . The method is based on the preconcentration of these analytes by a solid-phase extraction procedure and their subsequent quantification by liquid chromatography using ultraviolet detection . The breakthrough volumes of the selected (fluoro)quinolones in four different sorbents--C18, styrenedivinylbenzene (SDB), C18-cation-exchange and SDB-cation-exchange--have been evaluated and varied between 25 and 150 ml depending on the antibiotic and the sorbent used . An exhaustive study of the influence of sample pH on the preconcentration step has been carried out in order to find a suitable procedure for extraction of acidic and zwitterionic FQs in one single step . Under optimum conditions, it was possible to percolate up to 250 ml of water solution onto both C18 and SDB-cation-exchange cartridges with quantitative recoveries for all the analytes tested . However, matrix components of the surface water samples analysed negatively affected the recoveries of the analytes in the SDB-cation-exchange cartridge and thus, C18 cartridges were finally selected for the analysis of the (fluoro)quinolones in lake and river water . The limits of detection achieved with this procedure varied between 8 and 20 ng l(-1) proving its suitability for the determination of the (fluoro)quinolones in water samples at a realistic environmental concentration level.

Farm Hosp, 2003 Jul-Aug, 27(4), 258 - 63
{Pharmacokinetic interaction between valproic acid and carbapenem-like antibiotics: a discussion of three cases}; Llinares Tello F et al.; A number of literature references suggest that carbapenem-like antibiotics decrease plasma concentrations of valproic acid in epileptic patients . This interaction may result in a recurrence of epileptic seizures in these patients . To clarify the possible mechanism of such carbapenem-valproic acid interaction several experimental studies have been carried out in animals . However, the mechanism of this drug-drug interaction is as yet uncertain . in this article we report three new cases that were observed in our hospital within three months . One of these patients developed seizures . We also review the different mechanisms proposed, as well as cases published to this day . All these data demonstrate that care should be taken in using these potent antibiotics in patients receiving valproic acid.

Spectrochim Acta A Mol Biomol Spectrosc, 2003 Sep, 59(11), 2541 - 6
Flow-injection chemiluminescence study of Ce(IV)-Na2SO3-Tb(III)-fluoquinolone antibiotic system with DNA; Yi L et al.; A novel flow injection chemiluminescence (CL) system is developed to determine DNA . According to the fact that DNA linearly quenches the CL intensity of Ce(IV)-Na(2)SO(3)-Tb(III)-fluoquinolone antibiotic (FLUQ) system, DNA concentration is determined . The calibration graphs are linear in the range of 0.04-10 microg/ml (for both natural and denatured DNA), and the 3sigma limits of detection are 7.8 ng/ml (natural DNA) and 9.5 ng/ml (denatured DNA) . According to fluorescence spectrum and CL spectrum, and through studying the reaction of Ce(IV)-Na(2)SO(3)-Tb(III)-FLUQ with nucleotides and bases, we conclude that DNA counteracts the energy transfer from FLUQ to Tb(III), and this function is related to both bases and phosphate groups in DNA.

Eksp Klin Farmakol, 2003 Mar-Apr, 66(2), 42 - 5
{Effects of aminoglycoside antibiotics on various structures of the acoustic analyzer}; Fisenko VP; Aminoglycoside antibiotics decrease the microphone potential amplitude and the auditory nerve potential in response to acoustic stimulation . These drugs suppress the bioelectrical activity of medulla, cerebral cortex, and olivo-cochlear efferent system . The experiments on freely moving cats showed that cortical response to electric stimulation of thalamocortical fibers originating from medial geniculate body are more sensitive to aminoglycoside antibiotics than the microphone potential and the auditory nerve potential.

J Leukoc Biol, 2003 Nov, 74(5), 908 - 15 Epub 2003 Aug 01.
Antibiotic cyclic AMP signaling by "primed" leukocytes confers anti-inflammatory cytoprotection; Abeyama K et al.; The mechanism underlying anti-inflammatory effects of macrolide antibiotics remains uncertain . In this study, we first show the evidences concerning the possible link between leukocytic cyclic adenosine monophosphate (cAMP) signaling and the mechanism of anti-inflammatory, cytoprotective actions of macrolides . The clinical range of macrolides (i.e., erythromycin, roxithromycin, and clarithromycin) preferentially inhibited nuclear factor-kappaB activation mediated by reactive oxygen intermediates, inducing cAMP-dependent signaling {i.e., cAMP and cAMP-responsive element-binding protein (CREB)} by "primed" but not "resting" leukocytes . In this context, cAMP/CREB inhibition with adenosine 3':5'-cyclic monophosphothioate, rp-isomer (rp-cAMPs) and CREB decoy oligonucleotides reduced the anti-inflammatory actions of macrolides . These results thus indicate that macrolide-induced cAMP/CREB signaling, selectively by primed leukocytes, plays a major role in the mechanism of anti-inflammatory actions of macrolides.

Anal Bioanal Chem, 2003 Nov, 377(5), 909 - 21 Epub 2003 Aug 30.
Hyphenation of liquid chromatography to ion trap mass spectrometry to identify minor components in polypeptide antibiotics; Govaerts C et al.; The application of liquid chromatography-ion trap mass spectrometry for the characterization of linear and cyclic polypeptide antibiotics was investigated . The aim was on-line identification of impurities in those antibiotic complexes without recourse to time-consuming isolation and purification procedures . Hyphenated techniques, such as liquid chromatography coupled to mass spectrometry, are ideally suited for this purpose . Characterization was performed with an ion trap mass spectrometer offering MS(n) capability; this enables more structural information to be obtained . Liquid chromatography in combination with ion trap mass spectrometry was successfully applied for the characterization of impurities in gramicidin, polymyxin B, polymyxin E, and bacitracin and the study of the degradation products of polymyxins B and E.

J Am Chem Soc, 2003 Sep 10, 125(36), 10899 - 905
Synthesis of the antifungal macrolide antibiotic (+)-roxaticin; Evans DA et al.; The total synthesis of the antifungal macrolide antibiotic roxaticin has been accomplished . The synthesis relies principally on aldol and directed reduction steps to construct the extended 1,3-polyol array present in the natural product . Three principal nonpolyene containing fragments were assembled and then coupled using Julia olefination and methyl ketone aldol addition reactions . A series of functionalization reactions incorporated the sensitive polyene and provided the protected roxaticin seco-acid, which was lactonized in good yield . Acidic deprotection completed this convergent synthesis of roxaticin.

Immunobiology, 2003, 207(4), 237 - 45
Macrophage L-type Ca2+ channel antagonists alter Chlamydia pneumoniae MOMP and HSP-60 mRNA gene expression, and improve antibiotic susceptibility; Azenabor AA et al.; Recent data have shown a unique relationship between Ca2+ signaling in macrophages through L-type channels and the outcome of C . pneumoniae infection of such cells . The present investigation seeks to provide insights into the manner in which macrophage L-type Ca2+ channel operation affects major outer membrane protein (MOMP) and heat shock protein-60 (HSP-60) mRNA gene expression (factors associated with Chlamydia chronicity), and the possible effect of this on antibiotic susceptibility . Intracellular calcium ({Ca2+}i) chelation using varying doses of 1,2-bis (o-aminophenoxy) ethane-N,N,N'N'--tetra acetic acid (acetoxymethyl) ester (BAPTA-AM) induced an increase in MOMP and a decrease in HSP-60 mRNA gene expression . L-type Ca2+ channel antagonists produced an identical but enhanced effect . Since these findings associate specialized Ca2+ channels to Chlamydia chronicity, it was important to determine Ca2+ channel effect on the usual antibiotic refractory form of C . pneumoniae in macrophages . Inhibition of macrophage L-type Ca2+ channel operation improved C . pneumoniae antibiotic susceptibility assessed by decreased inclusion counts or down-regulated MOMP and HSP-60 mRNA gene expression . These findings provide molecular insights into how specialized Ca2+ channels influence Chlamydia chronic course in macrophages and demonstrates a role for L-type Ca2+ channel inhibitors in enhanced C . pneumoniae susceptibility to antibiotic therapy.

J Antimicrob Chemother, 2003 Oct, 52(4), 675 - 8 Epub 2003 Sep 01.
Outpatient antibiotic prescriptions from 1992 to 2001 in the Netherlands; Kuyvenhoven MM et al.; OBJECTIVES: Although Dutch outpatient antibiotic prescription rates are low compared with other European countries, continuing to scrutinize trends in outpatient antibiotic use is important in order to identify possible increases in antibiotic use or inappropriate increases in the use of particular classes of antibiotics . METHODS: We assessed the volume of Dutch outpatient antibiotic prescriptions from 1992 to 2001 by calculating the mean number of outpatient antibiotic prescriptions (indicating the number of times physicians decide to prescribe an antibiotic agent) per 1000 patients insured by the Dutch Sickness Fund per year, according to subgroups (narrow-spectrum penicillins, broad-spectrum penicillins, tetracyclines, macrolides, sulphonamides and trimethoprim, and quinolones) . Data were obtained from the Dutch Drug Information Project/Health Care Insurance Board . RESULTS: The total volume of outpatient antibiotic prescriptions in 2001 was 394 prescriptions per 1000 patients insured by the Dutch Sickness Fund . Overall, the rates were stable between 1992 and 2001, with small variations across years, but with marked differences in volumes within antibiotic groups across these years: a decrease in prescribing of narrow-spectrum penicillins (-29%), amoxicillin (-23%), tetracycline (-24%), doxycycline (-19%) and trimethoprim and derivatives (-45%) was accompanied by an increase in prescribing of co-amoxiclav (+85%), macrolides (+110%) and quinolones (+86%) . CONCLUSIONS: The international trend of a decline in the use of narrow-spectrum and older penicillins and prescribing more broad-spectrum and new chemotherapeutics was shown to exist in a low prescribing country, The Netherlands . Therefore, inappropriate antibiotic prescribing should remain prominent on the research agenda in intervention studies in order to improve the appropriate selection of antibiotic class and to reduce the prescription of antibiotics.

Eur J Biochem, 2003 Sep, 270(18), 3675 - 83
Kinetics of enzyme acylation and deacylation in the penicillin acylase-catalyzed synthesis of beta-lactam antibiotics; Alkema WB et al.; Penicillin acylase catalyses the hydrolysis and synthesis of semisynthetic beta-lactam antibiotics via formation of a covalent acyl-enzyme intermediate . The kinetic and mechanistic aspects of these reactions were studied . Stopped-flow experiments with the penicillin and ampicillin analogues 2-nitro-5-phenylacetoxy-benzoic acid (NIPAOB) and d-2-nitro-5-{(phenylglycyl)amino}-benzoic acid (NIPGB) showed that the rate-limiting step in the conversion of penicillin G and ampicillin is the formation of the acyl-enzyme . The phenylacetyl- and phenylglycyl-enzymes are hydrolysed with rate constants of at least 1000 s-1 and 75 s-1, respectively . A normal solvent deuterium kinetic isotope effect (KIE) of 2 on the hydrolysis of 2-nitro-5-{(phenylacetyl)amino}-benzoic acid (NIPAB), NIPGB and NIPAOB indicated that the formation of the acyl-enzyme proceeds via a general acid-base mechanism . In agreement with such a mechanism, the proton inventory of the kcat for NIPAB showed that one proton, with a fractionation factor of 0.5, is transferred in the transition state of the rate-limiting step . The overall KIE of 2 for the kcat of NIPAOB resulted from an inverse isotope effect at low concentrations of D2O, which is overridden by a large normal isotope effect at large molar fractions of D2O . Rate measurements in the presence of glycerol indicated that the inverse isotope effect originated from the higher viscosity of D2O compared to H2O . Deacylation of the acyl-enzyme was studied by nucleophile competition and inhibition experiments . The beta-lactam compound 7-aminodesacetoxycephalosporanic acid (7-ADCA) was a better nucleophile than 6-aminopenicillanic acid, caused by a higher affinity of the enzyme for 7-ADCA and complete suppression of hydrolysis of the acyl-enzyme upon binding of 7-ADCA . By combining the results of the steady-state, presteady state and nucleophile binding experiments, values for the relevant kinetic constants for the synthesis and hydrolysis of beta-lactam antibiotics were obtained.

Pediatrics, 2003 Sep, 112(3 Pt 1), 527 - 31
Treatment of otitis media with observation and a safety-net antibiotic prescription; Siegel RM et al.; OBJECTIVE: Several studies have demonstrated that acute otitis media (AOM) in children can be managed without antibiotics . Because children with AOM have traditionally been treated with antibiotics in the United States, there are concerns that parents may not be comfortable with their children being treated with pain control alone . Recently, Cates in England showed that antibiotic usage for AOM could be decreased by prescribing a safety-net antibiotic prescription (SNAP) to be filled if symptoms do not resolve with observation after 48 hours . It is not clear whether a SNAP will be acceptable to parents in other settings such as the United States . The objective of our study was to determine whether parents in the United States find a SNAP for AOM acceptable and whether antibiotic usage could be decreased by its use . METHODS: A pediatric practice-based research network in a midwestern community of 1.8 million was the setting for this study . The Cincinnati Pediatric Research Group (CPRG) includes practices in Ohio, Kentucky, and Indiana . Children who were between 1 and 12 years of age and presented to the offices of the CPRG with uncomplicated AOM were eligible for the study . Children were excluded when they had temperature >101.5 degrees F, had an ear infection in the past 3 months, showed signs of another bacterial infection, or were toxic appearing . Families were given acetaminophen, ibuprofen, or topical otic anesthetic drops for pain control . They were also given a prescription for an antibiotic and instructed not to fill it unless symptoms either increased or did not resolve after 48 hours . The data were entered directly by investigators via an Internet site . RESULTS: A total of 194 children were enrolled in 11 offices over 12 months; 175 (90%) completed the follow-up interview . The average child's age was 5.0 years . Only 55 (31%) of the 175 who were contacted for follow-up had filled their antibiotic prescription . Compared with their previous experience, parents were overwhelmingly willing to treat AOM with pain medication alone (chi(2) = 111) . Seventy-eight percent (95% confidence interval: 71%-84%) of parents reported that the pain medication was effective . Sixty-three percent (95% confidence interval: 55%-70%) of parents reported that they would be willing to treat future AOM episodes without antibiotics and with pain medication alone . CONCLUSIONS: A subset of parents find a safety-net prescription and pain control acceptable in the treatment of AOM, and antibiotic usage can be lowered with this strategy.

Anal Chem, 2003 Jun 1, 75(11), 2730 - 9
FTMS structure elucidation of natural products: application to muraymycin antibiotics using ESI multi-CHEF SORI-CID FTMS(n), the top-down/bottom-up approach, and HPLC ESI capillary-skimmer CID FTMS; McDonald LA et al.; The molecular formulas for the structures and substructures of muraymycin antibiotics A1 (C52H90N14O19, MW 1214) and B1 (C49H83N11O18, MW 1113) were determined using electrospray ionization (ESI) Fourier transform mass spectrometry (FTMS) . The muraymycin A1 and B1 structures were elucidated by utilizing capillary-skimmer fragmentation with up to five stages of mass spectrometry (MS5) . Multi-CHEF, a multiple ion isolation method, was used at each stage of MS(n) to isolate a parent ion and up to four reference ions, for exact-mass calibration . The parent ions were fragmented by SORI-CID and the product ions internally calibrated with average absolute mass errors less than 1 ppm at each stage in the fragmentation processes . Using the top-down/bottom-up approach, the molecular formulas for the antibiotics were determined by summing the elemental formulas of the neutral losses, obtained by measuring the mass differences (<500 Da) between the genetically related sequential parent ion masses in the MS(n) spectra, with the unique elemental formula of the lowest parent ion mass (<500 Da) . The structures of 12 additional compounds in the muraymycin complex were elucidated using HPLC ESI capillary-skimmer CID FTMS by correlating their fragmentation patterns with those of muraymycins A1 and B1 . Sequential neutral losses of an aminosugar, a valine, a uridine, and an ester fatty acid from the muraymycin parent ions provided diagnostic fragments for characterization.

Anal Chem, 2003 Jun 1, 75(11), 2640 - 6
Interference-free analysis using three-way fluorescence data and the parallel factor model . Determination of fluoroquinolone antibiotics in human serum; Munoz de la Pena A et al.; Three-way fluorescence data and multivariate calibration based on parallel factor analysis (PARAFAC) are combined for the simultaneous quantitation of three fluoroquinolone anitibiotics (norfloxacin, enoxacin, and ofloxacin) in human serum samples . The three analytes can be adequately determined with limits of detection of 0.2, 3.0, and 0.5 microg L(-1), respectively, with minimum experimental effort . The selected analytical methodology fully exploits the so-called second-order advantage of the employed three-way data, allowing obtaining individual concentrations of calibrated analytes in the presence of any number of uncalibrated (serum) components . In contrast to PARAFAC, less satisfactory results were obtained with a multidimensional partial least-squares (nPLS) model trained with the same calibration set.

Drug Deliv, 2003 Jul-Sep, 10(3), 201 - 7
Incorporation of antibiotics in liposomes designed for tuberculosis therapy by inhalation; Justo OR et al.; Liposomal encapsulation of tuberculostatic drugs can potentially increase their therapeutic index . The incorporation of isoniazid, pyrazinamide, rifampicin, ethionamide, and streptomycin in extruded distearoylphosphatidylcholine/cholesterol liposomes designed for administration through inhalation was evaluated . Ethionamide and rifampicin were incorporated during lipid film formation, whereas solutions of the remaining drugs were used to hydrate preformed lipid bilayers . Final drug to lipid ratios around 0.3 were achieved for isoniazid and pyrazinamide, and mean vesicle diameters varied from 286 to 329 nm . No expressive drug leakage or mean vesicle diameter changes occurred during 3 weeks . No significant incorporation was achieved for streptomycin, ethionamide, and rifampicin.

Org Lett, 2003 Sep 4, 5(18), 3233 - 6
Synthesis of proposed oxidation-cyclization-methylation intermediates of the coumarin antibiotic biosynthetic pathway; Tao J et al.; {structure: see text} A chemoenzymatic synthesis was described to prepare proposed oxidation-cyclization-methylation intermediates of the coumarin antibiotic biosynthetic pathway . The successful synthesis of these fragile molecules relies heavily on mild enzymatic deprotection and efficient enzymatic kinetic resolution to minimize epimerization, decomposition, multiple orthogonal protections, and retro aldol reactions often encountered in their chemical synthesis.

Comput Methods Programs Biomed, 2003 Oct, 72(2), 139 - 54
Methods, architecture, evaluation and usability of a case-based antibiotics advisor; Gierl L et al.; In this paper, we discuss the usability of an antibiotics therapy adviser, with a broad, complex spectrum of functions which we have developed within the ICONS project . We present the architecture of the system, case-based reasoning methods used, steps and results of medical evaluations, which are concerning the quality of the recommended therapies, the user friendliness of the system and the interpretation of laboratory results . Furthermore, we discuss problems of transferability of such a system from one site to another as well as problems of local susceptibility patterns and individual dose regimens.

Mol Microbiol, 2003 Sep, 49(5), 1179 - 90
Analysis of the biosynthetic gene cluster for the polyether antibiotic monensin in Streptomyces cinnamonensis and evidence for the role of monB and monC genes in oxidative cyclization; Oliynyk M et al.; The analysis of a candidate biosynthetic gene cluster (97 kbp) for the polyether ionophore monensin from Streptomyces cinnamonensis has revealed a modular polyketide synthase composed of eight separate multienzyme subunits housing a total of 12 extension modules, and flanked by numerous other genes for which a plausible function in monensin biosynthesis can be ascribed . Deletion of essentially all these clustered genes specifically abolished monensin production, while overexpression in S . cinnamonensis of the putative pathway-specific regulatory gene monR led to a fivefold increase in monensin production . Experimental support is presented for a recently-proposed mechanism, for oxidative cyclization of a linear polyketide intermediate, involving four enzymes, the products of monBI, monBII, monCI and monCII . In frame deletion of either of the individual genes monCII (encoding a putative cyclase) or monBII (encoding a putative novel isomerase) specifically abolished monensin production . Also, heterologous expression of monCI, encoding a flavin-linked epoxidase, in S . coelicolor was shown to significantly increase the ability of S . coelicolor to epoxidize linalool, a model substrate for the presumed linear polyketide intermediate in monensin biosynthesis.

J Environ Sci Health A Tox Hazard Subst Environ Eng, 2003 Sep, 38(9), 1971 - 9
Treatment of spent broth from an antibiotic manufacturing unit using anaerobic fixed film fixed bed reactor; Satyanarayan S et al.; Studies on bench scale reactor were undertaken to determine its performance at various organic loading rate (OLR) and hydraulic retention time (HRT) . The results indicated BOD and COD removals in the range of 67.2-77.4% and 57.8-69.1% respectively at the OLRs between 0.84 and 2.5 kgCOD/m3 d and HRT of 10 days . Daily gas production was measured by gas flow meter . Daily gas production varied between 0.268 and 0.326 m3/kgCOD added at the different OLRs . Studies were also carried out at lower HRT of 5 days . But BOD/COD removals reduced and correspondingly gas production also reduced . Gas composition remained constant at both the HRT and the Methane content was around 65-68% while the CO2 was around 32-35% . This paper discusses in detail the feasibility of upflow anaerobic fixed film fixed bed (UAFFFB) reactor system in treating the strong spent broth from the antibiotic industry.

J Chromatogr A, 2003 Jul 18, 1006(1-2), 121 - 6
Optimization of experimental conditions for the preparative displacement chromatography of antitumor anthracycline antibiotics on carboxylic sorbents; Toshchevikova AY et al.; The physico-chemical conditions and the limits of the rates of mobile phases are determined when effective regimes of preparative chromatography in the conditions of sharpening the boundaries of chromatographic zones of anthracycline antibiotics are realized . The influence of pH on the equilibrium, kinetics and dynamics of sorption of anthracycline antibiotics (rubomycin, doxorubicin and carminomycin) on the carboxylic sorbents has been studied.

Guang Pu Xue Yu Guang Pu Fen Xi, 2002 Oct, 22(5), 825 - 7
{Study on two kinds of antibiotics by the fluorescence thin-layer chromatograph}; Huang SP et al.; Carbostyril medicine is a kind of important chemically synthesized antibiotics, used extensively in the clinic . Ofloxacin (OFXL) and ciprofloxacin (CPLX), being similar in structures, were separated by micellar thin layer chromatography . The 0.0015 mol.L-1 Cetyl trimethyl ammonium bromide (CTAB) and 1% sodium dodecyl sulfate (SDS) (1:1) mixture containing ammonia liquor (1%) and polyamide plates were selected, respectively, as mobile and stationary phases . Various factors affecting the Rf values of drugs on the plates such as the concentration of CTAB, SDS and ammonia liquor, were investigated . Under the appropriate condition, the corresponding Rf is 0.87 and 0.76 . The fluorescence determination was carried out at the 280 nm excitation wave-length . Moreover, the stability and the sensibility were measured . The first analytical application of micellar as a mobile phase for the separation of OFLX and CPLX was developed.

J Chromatogr Sci, 2003 Jul, 41(6), 311 - 6
A chromatographic approach to analyze dansyl amino acid-HP-beta-CD association using macrocyclic antibiotic as the stationary phase; Andre C et al.; The retention mechanism for a series of D,L-dansyl amino acids in high-performance liquid chromatography is investigated using a teicoplanin stationary phase and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as the mobile phase additive (0-16mM) . A theoretical treatment is developed to determine the HP-beta-CD influence on the equilibrium between the teicoplanin phase and the aqueous medium, respectively . From the experimental data, the association constants of the D,L-dansyl amino acids-HP-beta-CD inclusion complexes are determined and discussed in relation to the enantiomer structure . A thermodynamic study confirms that both the retention and complexation mechanisms are independent of the dansyl amino acid molecular structure and its absolute carbon configuration.

Kansenshogaku Zasshi, 2003 Jul, 77(7), 499 - 504
{Epidemiological investigation of "beta-lactam antibiotic induced vancomycin-resistant MRSA (BIVR)"}; Hanaki H et al.; Mu3 strain with heterogeneous intermediated-resistance to vancomycin (hetero-VISA) reported in 1997, also have possessed a character of an antagonistic effect of beta-lactam antibiotics and vancomycin . Mu3 is only strain which satisfies the definition of hetero-VISA in Japan . But, MRSA with antagonistic effects of beta-lactam antibiotics and vancomycin, was reported by many institutions . To separate hetero-VISA, we called "beta-lactam antibiotic induced vancomycin-resistant MRSA (BIVR)" . But the detection rate of clinical isolated BIVR in Japan is unknown, we reported on the detection method and the epidemiological investigation for BIVR . Mu 3 agar containing 4 micrograms/mL of vancomycin is used to detect BIVR . Mu3 strains were spread on the agar, BIVR can grow around the paper disc impregnated with ceftizoxime or grow on the whole surface on Mu 3 agar after incubation . The detection rate of BIVR was 45 in 717 (6.3%) clinical isolated strains . In detected strains as BIVR, the number of strains with grown on the whole surface of Mu3 agar showing a high resistance to vancomycin were 10 strains (1.4%) . Besides, from 106 strains of blood isolates MRSA, BIVR were detected 16 strains (15.1%), from 611 strains of non-blood isolates MRSA, BIVR were detected 29 strains (4.7%) (P < 0.0001) . In BIVR strains grown on the whole surface of Mu3 agar, the number of BIVR strains isolated from blood were 8 in 106 (7.5%), from non-blood were 2 in 611 (0.3%) (P < 0.0001) . On one side, hetero-VISA were not detected from all of BIVR growing on the whole surface of Mu3 agar . As a result, detection method and the definition of BIVR were quite different from those of hetero-VISA . An existence of BIVR in Japan was confirmed, we thought that the high detection rate of BIVR isolated from blood compared with that of non-blood showed the pathogenecity of BIVR which contribute to MRSA infections.

Nucleic Acids Res, 2003 Sep 1, 31(17), 5074 - 83
Effect of polyamines on the inhibition of peptidyltransferase by antibiotics: revisiting the mechanism of chloramphenicol action; Xaplanteri MA et al.; Chloramphenicol is thought to interfere competitively with the binding of the aminoacyl-tRNA 3'-terminus to ribosomal A-site . However, noncompetitive or mixed-noncompetitive inhibition, often observed to be dependent on chloramphenicol concentration and ionic conditions, leaves some doubt about the precise mode of action . Here, we examine further the inhibition effect of chloramphenicol, using a model system derived from Escherichia coli in which a peptide bond is formed between puromycin and AcPhe-tRNA bound at the P-site of poly(U)-programmed ribosomes, under ionic conditions (6 mM Mg2+, 100 mM NH4+, 100 microM spermine) more closely resembling the physiological status . Kinetics reveal that chloramphenicol (I) reacts rapidly with AcPhe-tRNA.poly(U).70S ribosomal complex (C) to form the encounter complex CI which is then isomerized slowly to a more tight complex, C*I . A similar inhibition pattern is observed, if complex C modified by a photoreactive analogue of spermine, reacts in buffer free of spermine . Spermine, either reversibly interacting with or covalently attached to ribosomes, enhances the peptidyltransferase activity and increases the chloramphenicol potency, without affecting the isomerization step . As indicated by photoaffinity labeling, the peptidyltransferase center at which chloramphenicol binds, is one of the preferred cross-linking sites for polyamines . This fact may explain the effect of spermine on chloramphenicol binding to ribosomes.

J Food Prot, 2003 Aug, 66(8), 1499 - 502
Comparative study of a semisynthetic derivative of natamycin and the parent antibiotic on the spoilage of shredded cheddar cheese; Suloff EC et al.; A water-soluble N-alkyl semisynthetic derivative of natamycin was synthesized by the Michael addition reaction of the parent with an N-substituted malemide . A comparative study was carried out to investigate the effectiveness of the semisynthetic derivative and the parent antibiotic in suppressing mold growth on shredded Cheddar cheese stored in modified atmosphere packaging (MAP) . The effects of 0-, 10-, and 20-ppm antimycotic treatments were examined . A 20-ppm natamycin treatment effectively suppressed visible mold growth (< 10(4) CFU/g) in MAP samples for up to 30 days after packages were opened . The performance of the 20-ppm semisynthetic derivative was similar to that of the 10-ppm natamycin treatment . For these treatments, visible mold growth did not occur in MAP samples until 20 days after packages were opened . These results indicate that the semisynthetic derivative of natamycin is less effective than the parent compound in suppressing mold growth on shredded Cheddar cheese.

Org Biomol Chem, 2003 Jan 7, 1(1), 60 - 6
DNA recognition by the anthracycline antibiotic respinomycin D: NMR structure of the intercalation complex with d(AGACGTCT)2; Searle MS et al.; Respinomycin D is a member of the anthracycline family of antitumour antibiotics that interact with double stranded DNA through intercalation . The clinical agents daunomycin and doxorubicin are the most well-studied of this class but have a relatively simple molecular architecture in which the pendant daunosamine sugar resides in the DNA minor groove . Respinomycin D, which belongs to the nogalamycin group of anthracyclines, possesses additional sugar residues at either end of the aglycone chromophore that modulate the biological activity but whose role in molecular recognition is unknown . We report the NMR structure of the respinomycin D-d(AGACGTCT)2 complex in solution derived from NOE restraints and molecular dynamics simulations . We show that the drug threads through the DNA double helix forming stabilising interactions in both the major and minor groove, the latter through a different binding geometry to that previously reported . The bicycloaminoglucose sugar resides in the major groove and makes specific contacts with guanine at the 5'-CpG intercalation site, however, the disaccharide attached at the C4 position plays little part in drug binding and DNA recognition and is largely solvent exposed.

Graefes Arch Clin Exp Ophthalmol, 2003 Sep, 241(9), 730 - 3 Epub 2003 Aug 20.
Risk factors for antibiotic-resistant conjunctival bacterial flora in patients undergoing intraocular surgery; Mino de Kaspar H et al.; BACKGROUND: The purpose of this study was to determine if patients with certain risk factors are more likely to harbor conjunctival bacterial flora resistant to multiple antibiotics . METHODS: In this prospective study, detailed medical history and slit-lamp examination were performed on all patients prior to intraocular surgery . Patients with local risk factors were defined as those with chronic blepharitis, conjunctivitis or discharge . Those with systemic risk factors were patients with diabetes, autoimmune, immunodeficient or skin disorders, asthma and those taking immunosuppressant medications . Conjunctival cultures were obtained prior to preoperative antibiotics and povidone-iodine . Bacteria isolated were identified and antibiotic susceptibility was determined . Bacteria resistant to five or more antibiotics were defined as multi-resistant (MR) . RESULTS: Among the 207 patients enrolled in the study, 73 patients had local risk factors . Of these patients, 32 patients (44%) carried MR organisms, compared to 32 of the 134 patients (24%) without local risk factors (P=0.0049) . Thirty-two of 71 patients (45%) with systemic risk factors harbored MR organisms, compared to 32 of 136 patients (24%) without systemic risk factors (P=0.0025) . Seventeen of 93 patients (18%) who had neither local nor systemic risk factors had MR organisms on their conjunctiva . In contrast, 17 of the 30 patients (57%) with both local and systemic risk factors (57%) carried MR bacteria (P=0.0001) . CONCLUSION: Patients with local and/or systemic risk factors are more likely to harbor MR organisms . This may be one mechanism for the reported increased risk of postoperative endophthalmitis in this group of patients.

Biopolymers, 2003 Sep, 70(1), 42 - 57
Molecular recognition of aminoglycoside antibiotics by ribosomal RNA and resistance enzymes: an analysis of x-ray crystal structures; Vicens Q et al.; The potential of RNA molecules to be used as therapeutic targets by small inhibitors is now well established . In this fascinating wide-open field, aminoglycoside antibiotics constitute the most studied family of RNA binding drugs . Within the last three years, several x-ray crystal structures were solved for aminoglycosides complexed to one of their main natural targets in the bacterial cell, the decoding aminoacyl-tRNA site (A site) . Other crystallographic structures have revealed the binding modes of aminoglycosides to the three existing types of resistance-associated enzymes . The present review summarizes the various aspects of the molecular recognition of aminoglycosides by these natural RNA or protein receptors . The analysis and the comparisons of the detailed interactions offer insights that are helpful in designing new generations of antibiotics .

Int J Cancer, 2003 Oct 20, 107(1), 99 - 105
History of antibiotic use and risk of non-Hodgkin's lymphoma (NHL); Kato I et al.; A population-based, incidence case-control study was conducted among women in upstate New York to determine whether histories of certain infections and antibiotic use are associated with risk of non-Hodgkin's lymphoma (NHL) . Our study involved 376 cases of NHL identified through the New York State Cancer Registry and 463 controls selected from the Medicare beneficiary files and state driver's license records . Information about use of common medications including antibiotics, history of selected infectious diseases and potential confounding variables was obtained by telephone interview . Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using an unconditional logistic regression model . There was a progressive increase in risk of NHL with increasing frequency and duration of systemic antibiotic use, as assessed over the period of 2-20 years before the interview . The ORs for the highest exposure categories, >/=36 episodes and >/=366 days of use, were 2.56 (95% CI 1.33-4.94) and 2.66 (95% CI 1.35-5.27), respectively . These associations were primarily due to antibiotic use against respiratory infections and dental conditions . Moreover, the association with frequency of antibiotic use for respiratory infections was pronounced for marginal zone B-cell lymphoma and for respiratory tract lymphoma . Analyses by class of antibiotics did not suggest that a general cytotoxic effect of antibiotics was responsible for these increased risks . Although recall bias and selection bias remain potential concerns in our study, the results are generally consistent with the hypothesis that persistent infection/inflammation predisposes individuals to the development of NHL . However, a direct role of antibiotics in NHL induction has not been ruled out .

Sante, 2003 Jan-Mar, 13(1), 23 - 7
{Systematic preventive antibiotic therapy during hysterosalpingography in an African tropical environment: is this practice justified?}; N'Gbesso RD et al.; To find out whether preventive antibiotic therapy can be justified in the practice of hysterosalpingography in a tropical environment where the infectious risk is notoriatly high, the authors performed a prospective study concerning 49 females patients . The patients in genital activity period, were willing and volunteers and were aged from 20 to 44 years . They were examined by hysterosalpingography during a period of three months . Patients were distributed in two homogenous group, one group of 25 patients who had a preventive antibiotic therapy and the second group with 24 patients with no preventive antibiotic therapy . Hysterosalpingography examinations were performed with sterile and single-use equipment . All patients were clinically examined for medical record purposes: gynaecologic, obstetric, pelvic infection, oral contraception, previous hysterosalpingography . Biologic dosages were realized, including blood count and erythrocyte sedimentation, culture of vaginal sampling, C reactive protein rate . The results obtained showed no significant difference between the two groups . The authors conclude that hysterosalpingography can be also performed in a tropical environment without using systematic preventive antibiotic therapy provided that asepsisrules are strictly observed.

J Invest Dermatol, 2003 Sep, 121(3), 596 - 606
Molecular responses to photogenotoxic stress induced by the antibiotic lomefloxacin in human skin cells: from DNA damage to apoptosis; Marrot L et al.; Photo-unstable chemicals sometimes behave as phototoxins in skin, inducing untoward clinical side-effects when exposed to sunlight . Some drugs, such as psoralens or fluoroquinolones, can damage genomic DNA, thus increasing the risk of photocarcinogenesis . Here, lomefloxacin, an antibiotic from the fluoroquinolone family known to be involved in skin tumor development in photoexposed mice, was studied using normal human skin cells in culture: fibroblasts, keratinocytes, and Caucasian melanocytes . When treated cells were exposed to simulated solar ultraviolet A (320-400 nm), lomefloxacin induced damage such as strand breaks and pyrimidine dimers in genomic DNA . Lomefloxacin also triggered various stress responses: heme-oxygenase-1 expression in fibroblasts, changes in p53 status as shown by the accumulation of p53 and p21 proteins or the induction of MDM2 and GADD45 genes, and stimulation of melanogenesis by increasing the tyrosinase activity in melanocytes . Lomefloxacin could also lead to apoptosis in keratinocytes exposed to ultraviolet A: caspase-3 was activated and FAS-L gene was induced . Moreover, keratinocytes were shown to be the most sensitive cell type to lomefloxacin phototoxic effects, in spite of the well-established effectiveness of their antioxidant equipment . These data show that the phototoxicity of a given drug can be driven by different mechanisms and that its biologic impact varies according to cell type.

Int Clin Psychopharmacol, 2003 Sep, 18(5), 297 - 8
Increased use of antibiotics in clozapine-treated patients; Landry P et al.; A retrospective chart review of hospitalized patients was completed to verify whether there were differences in the prescription rate of antibiotics to patients treated with clozapine . Subjects were inpatients with a diagnosis of schizophrenia or schizoaffective disorder . Charts of all patients who received clozapine for 24 consecutive months during a period of 48 consecutive months of hospitalization were selected for the study . For each patient, we compared the number of infections treated with an antibiotic during the 24 months pre-clozapine versus the period when they were treated with clozapine . Our study suggests that the number of antibiotic prescriptions is significantly increased in patients treated with clozapine.

Boll Chim Farm, 2003 May, 142(4), 151 - 6
Pharmaco-economical analysis of the treatment with antibiotics in a surgery department; Dimitrov D; 6-Oxo-4(2-thienyl)-2-thioxo-1,3-dihydropyrimidine-5-carbonitrile (1) was synthesized and reacted with alkyl halides to give the S-alkyl compounds (2a,b), which reacted with phosphorous oxychloride to yield (3a,b) . Reaction of 3a,b with phenyl-hydrazine, hydrazine hydrate, ammonia, acid hydrazides and thiourea leads to formation of the compounds (4a,b), the dihydrazino compound derivative (5), the amino compounds (7a,b), triazolopyrimidine derivatives (9a-d), and the mercapto compounds (10a,b), respectively . Treatment of (10a) with chloroacetone gave (11a), which condensed with benzaldehyde giving the tricyclic compound (12) . Also (10b) reacted with ethyl chloroacetate followed by hydrolysis and cyclization yielded (14) . Heating of (5) gave (6), which reacted with sodium nitrite and/or carbondisulphide and give (15) and (16), respectively.

World J Gastroenterol, 2003 Aug, 9(8), 1832 - 3
Efficacy of saccharomyces boulardii with antibiotics in acute amoebiasis; Mansour-Ghanaei F et al.; AIM: To compare the efficacy of antibiotics therapy alone with antibiotics and saccharomyces boulardii in treatment of acute amebiasis . METHODS: In a double blind, random clinical trial on patients with acute intestinal amoebiasis, 57 adult patients with acute amoebiasis, diagnosed with clinical manifestations (acute mucous bloody diarrhea) and amebic trophozoites engulfing RBCs found in stool were enrolled in the study . Regimen 1 included metronidazole (750 mg Tid) and iodoquinol (630 mg Tid) for 10 days . Regimen 2 contained capsules of lyophilized saccharomyces boulardii (250 mg Tid) orally in addition to regimen 1 . Patients were re-examined at two and four weeks after the treatment, and stool examination was performed at the end of week 4 . Student's t-test, chi(2) and McNemar's tests were used for statistical analysis . RESULTS: Three patients refused to participate . The other 54 patients were randomized to receive either regimen 1 or regimen 2 (Groups 1 and 2 respectively, each with 27 patients) . The two groups were similar regarding their age, sex and clinical manifestations . In Group 1, diarrhea lasted 48.0+/-18.5 hours and in Group 2, 12.0+/-3.7 hours (P<0.0001) . In Group 1, the durations of fever and abdominal pain were 24.0+/-8.8 and 24.0+/-7.3 hours and in Group 2 they were 12.0+/-5.3 and 12.0+/-3.2 hours, respectively (P<0.001) . Duration of headache was similar in both groups . At week 4, amebic cysts were detected in 5 cases (18.5 %) of Group 1 but in none of the Group 2 (P<0.02) . CONCLUSION: Adding saccharomyces boulardii to antibiotics in the treatment of acute amebiasis seems to decrease the duration of clinical symptoms and cyst passage.

Org Lett, 2003 Aug 21, 5(17), 3119 - 21
Synthesis of the tetracyclic core of anthracycline antibiotics by an intramolecular dehydro Diels-Alder approach; Rodriguez D et al.; {reaction: see text} A conceptually new approach to the tetracyclic core of the anthracycline antibiotics is reported . With use of this approach, the 7,8,9,10-tetrahydronaphthacene-5,12-dione skeleton has been synthesized in three steps, from commercially available reagents, in yields of up to 85%.

Antibiot Khimioter, 2003, 48(3), 34 - 41
{Comparative clinical and epidemiological evaluation of beta-lactam antibiotics in the treatment of intraabdominal infections}; Beketov AS et al.; We performed a retrospective, comparative study to evaluate efficacy, safety and economic outcomes of empiric cefoperazone/sulbactam monotherapy compared with the meropenem, imipenem/cilastatine and combination of cefepime plus metroindazol in patients with intra-abdominal infection . A total of 468 patients diagnosed with intra-abdominal abscess, peritonitis, pancreatitis were included in the study (the severity of infection according to scale APACHE II was less than 15) . Patients were randomized to be treated with either 500 mg meropemen i.v . every 8 hours or 500 mg imipenem/cilastatine i.v . every 8 hours or 2 g cefepime i.v . every 12 hours plus 500 mg metronidazol twice daily or cefoperazone/sulbactam 2 g daily administered every 12 hours . Overall positive clinical responses (cure or improvement) were achieved at the end of treatment for 87.5 patients in meropenem group, 86.6% in the imipenem/cilastatin group, 85.3% in the cefepime group and 86.8% in cefoperazone/sulbactam group . Total cost of the treatment per 100 patients with intra-abdominal infections for cefoperazone/sulbactam was 1957031 roubles, for combinations of cefepime with metronidazol--2497815 roubles . For carbapenem group cost achieved for meropenem--3085291 rub., for imipenem/cilastatin--2653388 roubles . Rate "cost-effectiveness" in total: 784.47$ for cefepime, and 834.39$ for imipenem/cilastatine, 970.21$ for meropenem and 615.4$ for cefoperazone/sulbactam . The most expensive treatment was considered to be with meropenem and imipenem/cilastatine, main share is determined by initial cost of preparations . Less expensive was treatment by cefoperazone/sulbactam with cefepime and by metronidazol.

Respirology, 2003 Sep, 8(3), 359 - 64
Antibiotic desensitization in adults with cystic fibrosis; Burrows JA et al.; OBJECTIVE: Allergic reactions to antibiotics occur in up to 30% of patients with cystic fibrosis (CF) . Repeated antibiotic exposure and immune hyper-responsiveness increase the risk of allergic reactions and may limit antibiotic choice . Desensitization may allow the successful administration of an antibiotic despite previous allergy . We aimed to determine the success of antibiotic desensitization in patients with CF in an adult CF unit over a 7-year period . METHODOLOGY: A retrospective medical record review was performed on the 19 patients who had undergone antibiotic desensitization procedures . Data collected included drug allergy and intolerance profiles, nature of allergies, and the outcome of desensitization procedures . Desensitization procedures were performed in a ward setting according to published methods . RESULTS: Nineteen patients (13 females) reported 62 drug allergies with a mean of 3.3 per patient . Of the 71 desensitization procedures undergone by this group, 54 (76%) were successful . Fifteen of the 19 patients were allergic to two or more beta-lactam antibiotics . Over half of the patients were desensitized to more than one antibiotic . Nine different antibiotics were used in 31 different patient/drug combinations . A successful outcome was achieved in 18/31 (58%) combinations, with three requiring treatment for mild allergic reactions . Allergic reactions caused drug cessation in a total of 19 patient/drug combinations (three after initial successful desensitization and full courses of antibiotics) . Over 50% of these reactions occurred on day 1 . Desensitization failures were more common in patients with well-documented allergic reactions to a specific drug . CONCLUSION: This study demonstrates that multiple antibiotic allergies are common in adults with CF . Cross-reactivity between beta-lactam antibiotics may limit antibiotic choice for the treatment of pulmonary exacerbations . Antibiotic desensitization allows safe and successful treatment in the ward setting of many patients with previous allergies to an antibiotic . In many patients symptoms of allergy still occur and result in cessation of the antibiotics . Use of corticosteroids and antihistamines may improve the success rate of desensitization procedures.

Stroke, 2003 Sep, 34(9), e163 - 6 Epub 2003 Aug 07.
Antibiotics in primary prevention of stroke in the elderly; Brassard P et al.; BACKGROUND AND PURPOSE: An increasing number of reports have linked infections to atherosclerosis and thrombosis . Thus, use of antibiotics may lower the risk of developing cerebrovascular disease . We investigated whether antibiotic use is associated with the risk of stroke in elderly individuals treated for hypertension . METHODS: A cohort of 29 937 elderly subjects initiating antihypertensive therapy between 1982 and 1995 was formed from the Quebec healthcare insurance database . A nested case-control design was used in which each subject hospitalized with a primary discharge diagnosis of stroke between 1987 and 1995 was matched on calendar time to 5 randomly selected controls from the cohort . Conditional logistic regression was used to estimate odds ratios of stroke after adjustment for predisposing factors . RESULTS: We identified 1888 cases and 9440 controls . The overall adjusted odds ratio for current antibiotic use was 0.80 (95% confidence interval, 0.63 to 1.01), and that for recent use was 0.81 (95% confidence interval, 0.70 to 0.94) . Penicillin was the only individual antibiotic class that showed a protective association across different time windows . No significant association was found between stroke risk and the use of fluoroquinolones, macrolides, tetracyclines, or cephalosporins . CONCLUSIONS: Although no clear, consistent associations between overall antibiotic use and cerebrovascular disease could be found, an intriguing association between penicillin use and stroke should be explored further.

J Pharm Biomed Anal, 2003 Aug 21, 32(6), 1219 - 25
Fluorimetric determination of some antibiotics in raw material and dosage forms through ternary complex formation with terbium (Tb(3+)); Bebawy LI et al.; A highly sensitive and specific fluorimetric method was developed for the determination of cefazolin sodium I, cefoperazone sodium II, ceftriaxone sodium III, and cefixime IV . The proposed method involves the formation of ternary complex with Tb(3+) in the presence of Tris buffer . The quenching of the terbium fluorescence due to the complex formation was quantitative for the four studied drugs . The effect of pH, concentration of Tris buffer and terbium were studied . The formation of the complex was highly dependent on the pH . The optimum pH was found to be pH 8 for cefazolin sodium I, ceftriaxone sodium III, cefixime IV and pH 10 for cefoperazone sodium II . The optimum concentration for Tb(3+) was found 1 ml of 10(-4) M solution and for Tris buffer 1 ml of the prepared solution . Under the described conditions, the proposed method was applicable over the concentration range 8.79 x 10(-6)-7.91 x 10(-5), 9.7 x 10(-6)-4.49 x 10(-)5, 6.10 x 10(-6)-2.50 x 10(-5), and 4.92 x 10(-6)-2.95 x 10(-5) mol with mean percentage accuracy of 99.79+/-0.24, 98.97+/-1.25, 100.05+/-0.79, and 100.15+/-0.54 for I, II, III, and IV, respectively . The proposed method was applied successfully for the determination of studied drugs in bulk powder and in pharmaceutical formulations . The results obtained by applying the described method were statistically analyzed and compared with those obtained by applying the official method . The proposed method was used as stability indicating method for the determination of the studied drugs in the presence of their degradation products.

Prostaglandins Leukot Essent Fatty Acids, 2003 Oct, 69(4), 229 - 35
Macrolide antibiotics inhibit prostaglandin E2 synthesis and mRNA expression of prostaglandin synthetic enzymes in human leukocytes; Miyazaki M et al.; We investigated the action of macrolide antibiotics, which are considered to have anti-inflammatory activity, on lipopolysaccharide (LPS)-stimulated prostaglandin (PG) E2 synthesis and the expression of mRNAs for cytosolic phospholipase A2 (cPLA2), cyclooxygenase (COX)-1, and COX-2 in human leukocytes . The production of LPS-stimulated PGE2 was significantly increased in peripheral polymorphonuclear leukocytes (PMNLs) and in mononuclear leukocytes (MNLs) . Amounts of mRNAs for COX-2 and cPLA2, but not for COX-1, were enhanced by LPS in PMNLs and MNLs . The LPS-enhanced PGE2 synthesis and the expression of cPLA2 and COX-2 mRNAs were inhibited by clarithromycin, azithromycin and dexamethasone in PMNLs and MNLs . The mRNA expression of COX-1 in PMNLs was decreased by clarithromycin and azithromycin . Macrolide antibiotics inhibited PGE2 synthesis in human leukocytes by suppressing cPLA2, COX-1, and COX-2 mRNA expression . These data indicate one mechanism of macrolide anti-inflammatory activity.

Microbiology, 2003 Aug, 149(Pt 8), 2173 - 82
Overexpression of the polynucleotide phosphorylase gene (pnp) of Streptomyces antibioticus affects mRNA stability and poly(A) tail length but not ppGpp levels; Bralley P et al.; The pnp gene, encoding the enzyme polynucleotide phosphorylase (PNPase), was overexpressed in the actinomycin producer Streptomyces antibioticus . Integration of pIJ8600, bearing the thiostrepton-inducible tipA promoter, and its derivatives containing pnp into the S . antibioticus chromosome dramatically increased the growth rate of the resulting strains as compared with the parent strain . Thiostrepton induction of a strain containing pJSE340, bearing pnp with a 5'-flanking region containing an endogenous promoter, led to a 2.5-3 fold increase in PNPase activity levels, compared with controls . Induction of a strain containing pJSE343, with only the pnp ORF and some 3'-flanking sequence, led to lower levels of PNPase activity and a different pattern of pnp expression compared with pJSE340 . Induction of pnp from pJSE340 resulted in a decrease in the chemical half-life of bulk mRNA and a decrease in poly(A) tail length as compared to RNAs from controls . Actinomycin production decreased in strains overexpressing pnp as compared with controls but it was not possible to attribute this decrease specifically to the increase in PNPase levels . Overexpression of pnp had no effect on ppGpp levels in the relevant strains . It was observed that the 3'-tails associated with RNAs from S . antibioticus are heteropolymeric . The authors argue that those tails are synthesized by PNPase rather than by a poly(A) polymerase similar to that found in Escherichia coli and that PNPase may be the sole RNA 3'-polynucleotide polymerase in streptomycetes.

Zhonghua Jie He He Hu Xi Za Zhi, 2003 Apr, 26(4), 199 - 202
{Study on the molecular mechanism of transferable multiple-antibiotic resistance in extended-spectrum beta-lactamase-producing clinical isolates}; Lu J et al.; OBJECTIVE: To investigate the molecular mechanism of transferable multiple-antibiotic resistance in extended-spectrum beta-lactamases (ESBLs) producing isolates . METHODS: Antibiotics susceptibility was tested by E-test method, and multi-resistance plasmids were screened and isolated by extracting transformant plasmids . Inserted gene Cassettes of class 1 integron were amplified and analyzed by polymerase chain reaction (PCR) and DNA sequencing . RESULTS: Eight of the nine ESBL-producing plasmids were found to comprise class 1 integron sequence, of them 7 harbored 1 or 2 antibiotic resistant gene cassettes which encoding resistance to aminoglycosides (aacA4, aadA2 or aadA5), trimethoprim (dhfrA12 or dfrA17), rifampicin (arr-3) and chloramphenicol (cmlA6) . The function of these gene cassettes corresponded to the resistance profiles of their electro-transformants . CONCLUSION: Multi-resistance gene cassettes located on plasmids and mediated by class 1 integron may play an important role in causing the development and dissemination of multiple-antibiotic resistance in ESBL-producing clinical isolates.

J Chromatogr A, 2003 Jun 27, 1003(1-2), 21 - 8
Determination of antibiotics from soil by pressurized liquid extraction and liquid chromatography-tandem mass spectrometry; Schlusener MP et al.; A method for the analysis of several macrolide and ionophore antibiotics, as well as tiamulin, from soil was developed using pressurized liquid extraction (PLE), reversed-phase liquid chromatography and atmospheric pressure chemical ionisation (APCI) tandem mass spectrometry (LC-APCI+-MS-MS) . The analytes were extracted from soil by PLE in 30 min and the extracts were cleaned up by solid-phase extraction (SPE) on a diol SPE cartridge . Liquid chromatographic (LC) separation of the antibiotics was achieved in 35 min . Recovery experiments were performed using spiked soil and concentrations varying from 1 to 2000 microg/kg . By using a macrolide internal standard the recovery rates for the macrolides erythromycin and roxithromycin ranged from 43 to 94% (RSD 20-23%), for the ionophore salinomycin the recovery rate was 76% (RSD 29%), while the pleuromutilin tiamulin was completely recovered . The limits of detection ranged from 0.2 to 1.6 microg/kg . In soil samples a maximum concentration of 0.7 microg/kg tiamulin was found.

Can J Vet Res, 2003 Jul, 67(3), 239 - 40
Effects of aminoglycoside antibiotics on renal antioxidants, malondialdehyde levels, and some serum biochemical parameters; Yazar E et al.; Effects of amikacin, gentamicin, kanamycin, and streptomycin on renal tissue superoxide dismutase, glutathione peroxidase, glutathione and malondialdehyde, serum creatinine, potassium, sodium, total protein, glucose, uric acid, and total bilirubin levels were investigated . All aminoglycoside antibiotics decreased renal tissue glutathione levels.

Nucleic Acids Res, 2003 Aug 1, 31(15), 4410 - 6
Hydropathic analysis of the free energy differences in anthracycline antibiotic binding to DNA; Cashman DJ et al.; Molecular models of six anthracycline antibiotics and their complexes with 32 distinct DNA octamer sequences were created and analyzed using HINT (Hydropathic INTeractions) to describe binding . The averaged binding scores were then used to calculate the free energies of binding for comparison with experimentally determined values . In parsing our results based on specific functional groups of doxorubicin, our calculations predict a free energy contribution of -3.6 +/- 1.1 kcal x mol(-1) (experimental -2.5 +/- 0.5 kcal x mol(-1)) from the groove binding daunosamine sugar . The net energetic contribution of removing the hydroxyl at position C9 is -0.7 +/- 0.7 kcal x mol(-1) (-1.1 +/- 0.5 kcal x mol(-1)) . The energetic contribution of the 3' amino group in the daunosamine sugar (when replaced with a hydroxyl group) is -3.7 +/- 1.1 kcal x mol(-1) (-0.7 +/- 0.5 kcal x mol(-1)) . We propose that this large discrepancy may be due to uncertainty in the exact protonation state of the amine . The energetic contribution of the hydroxyl group at C14 is +0.4 +/- 0.6 kcal x mol(-1) (-0.9 +/- 0.5 kcal x mol(-1)), largely due to unfavorable hydrophobic interactions between the hydroxyl oxygen and the methylene groups of the phosphate backbone of the DNA . Also, there appears to be considerable conformational uncertainty in this region . This computational procedure calibrates our methodology for future analyses where experimental data are unavailable.

Ambul Pediatr, 2003 Jul-Aug, 3(4), 203 - 10
Correlates of parental antibiotic knowledge, demand, and reported use; Kuzujanakis M et al.; BACKGROUND: Clinicians cite parental misconceptions and requests for antibiotics as reasons for inappropriate prescribing . AIMS: To identify misconceptions regarding antibiotics and predictors of parental demand for antibiotics and to determine if parental knowledge and attitudes are associated with use . METHODS: Survey of parents in 16 Massachusetts communities . Domains included antibiotic-related knowledge, attitudes about antibiotics, antibiotic use during a 12-month period, demographics, and access to health information . Bivariate and multivariate analyses evaluated predictors of knowledge and proclivity to demand antibiotics . A multivariate model evaluated the associations of knowledge, demand, and demographic factors with parent-reported antibiotic use . RESULTS: A total of 1106 surveys were returned (response rates: 54% and 32% for commercially-insured and Medicaid-insured families) . Misconceptions were common regarding bronchitis (92%) and green nasal discharge (78%) . Two hundred sixty-five (24%) gave responses suggesting a proclivity to demand antibiotics . Antibiotic knowledge was associated with increased parental age and education, having more than 1 child, white race, and receipt of media information on resistance . Factors associated with a proclivity to demand antibiotics included decreased knowledge, pressure from day-care settings, lack of alternatives offered by clinicians, and lack of access to media information . Among all respondents, reported antibiotic use was associated with younger child age and day-care attendance . Among Medicaid-insured children only, less antibiotic knowledge and tendency to demand antibiotics were associated with higher rates of antibiotic use . CONCLUSIONS: Misconceptions regarding antibiotic use are widespread and potentially modifiable by clinicians and media sources . Particular attention should be paid to Medicaid-insured patients in whom such misconceptions may contribute to inappropriate prescribing.

Chem Commun (Camb), 2003 Jul 21, (14), 1692 - 3
Concerted interaction between conjugated double bond CHs and multiple OHs in polyene macrolide antibiotic chainin: weak =C-H...O interactions responsible for intrinsic molecular assembly; In Y et al.; The concerted interactions observed between five conjugated double bond CHs and four hydroxy Os in the crystal of chainin, a polyene macrolide antibiotic, clarified the existence of unprecedented, weak =C-H...O interactions, which is important for forming its intrinsic molecular assembly.

Fam Pract, 2003 Aug, 20(4), 417 - 9
Acute otitis media--a brief explanation to parents and antibiotic use; Pshetizky Y et al.; BACKGROUND: Acute otitis media (AOM) is a common self-limiting disease in children . Antibiotic use is controversial . Physicians in the USA and in Israel prescribe antibiotics almost universally, while physicians in other countries report good outcome without any treatment . Parents' expectation is an important factor influencing a physician's decision to prescribe antibiotics . OBJECTIVES: Our aim was to assess whether a brief explanation to parents regarding the self-limited nature of AOM and the controversy regarding antibiotic prescription for the disease will influence the parents' decision regarding antibiotics use . METHODS: Parents of the children participating in the study in two primary care clinics belonging to HMO-Clalit Health Services (CHS) in the southern district of Israel were randomly assigned to an intervention (44) and control (37) group . The intervention group received the brief explanation . The two groups received prescription for antibiotics . The subjects comprised 81 children aged 3 months to 4 years visiting the family practice clinics and diagnosed with AOM . The rate of antibiotics purchase, using the prescription given and the factors influencing the decision were evaluated . RESULTS: Fewer parents administered antibiotics to their children in the intervention group compared with the control group (37% versus 63%, respectively, P < 0.0001) . Mother's education level was the only factor found to be significantly lower in the group that eventually purchased antibiotics (P < 0.05) . CONCLUSIONS: In children with AOM, a brief explanation by the family physician to the child's parents about the disease and the expected spontaneous recovery could decrease antibiotic use by approximately 50%.

J Antibiot (Tokyo), 2003 May, 56(5), 454 - 8
Takanawaenes, novel antifungal antibiotics produced by Streptomyces sp . K99-5278 . II . Structure elucidation; Fukuda T et al.; The structures of takanawaenes A, B and C, novel antifungal antibiotics produced by Streptomyces sp . K99-5278, were elucidated by various spectroscopic analyses including UV and NMR, and spectrometric analyses including MS . They have the common skeleton of a 28-membered pentaene macrolide.

Salud Publica Mex, 2003 May-Jun, 45(3), 159 - 64
Use of antibiotics in upper respiratory infections on patients under 16 years old in private ambulatory medicine; Pelaez-Ballestas I et al.; OBJECTIVE: To assess antibiotic use for upper respiratory infections (URI) treatment on patients under 16 years-old who are beneficiaries of a pre-paid health care scheme . MATERIAL AND METHODS: A database containing the record of all the medical prescriptions for URI treatment, from May 1997 to April 1998 was analyzed . Patients were under 16 years old and had been diagnosed with common colds, pharyngitis, bronchitis, sinusitis, otitis, and other unspecified upper respiratory tract infections . Three hundred and fifty-one physicians of seven different specialties who attended 25,300 beneficiaries wrote such prescriptions . RESULTS: A total of 30,889 assorted medications were prescribed to 5,533 patients with the above diagnoses . Antibiotics were prescribed for 77.5% of all diagnoses, ranging from 58% for pharyngitis to 91% for laryngitis . The most frequently used antibiotics were: penicillin, cephalosporins, and macrolides . CONCLUSIONS: This study presents the information of antibiotics prescription practices for URI in a pre-paid health plan in Mexico . These findings may be used to support specific campaigns for rational use of antibiotics among children attended at private ambulatory health care practices.

Chemistry, 2003 Jul 21, 9(14), 3282 - 91
Multistep solid-phase synthesis of an antibiotic and receptor tyrosine kinase inhibitors using the traceless phenylhydrazide linker; Stieber F et al.; The hydrazide group is an oxidatively cleavable traceless linker for solid-phase chemistry . This linker technology was used to develop a multistep solid-phase synthesis of an antibiotic that is active against Mycobacterium tuberculosis . Furthermore, we describe an efficient method for the traceless synthesis of 2-aminothiazoles that display dual inhibitory activity against the receptor tyrosine kinases VEGFR-2 and Tie-2 . The synthesis method proceeds through 9 steps on the solid phase and should give access to a much larger library of 2-aminothiazoles, from which a new class of anti-angiogenesis drugs may be developed.

J Mol Biol, 2003 Jul 25, 330(5), 1061 - 75
Structures of five antibiotics bound at the peptidyl transferase center of the large ribosomal subunit; Hansen JL et al.; Structures of anisomycin, chloramphenicol, sparsomycin, blasticidin S, and virginiamycin M bound to the large ribosomal subunit of Haloarcula marismortui have been determined at 3.0A resolution . Most of these antibiotics bind to sites that overlap those of either peptidyl-tRNA or aminoacyl-tRNA, consistent with their functioning as competitive inhibitors of peptide bond formation . Two hydrophobic crevices, one at the peptidyl transferase center and the other at the entrance to the peptide exit tunnel play roles in binding these antibiotics . Midway between these crevices, nucleotide A2103 of H.marismortui (2062 Escherichia coli) varies in its conformation and thereby contacts antibiotics bound at either crevice . The aromatic ring of anisomycin binds to the active-site hydrophobic crevice, as does the aromatic ring of puromycin, while the aromatic ring of chloramphenicol binds to the exit tunnel hydrophobic crevice . Sparsomycin contacts primarily a P-site bound substrate, but also extends into the active-site hydrophobic crevice . Virginiamycin M occupies portions of both the A and P-site, and induces a conformational change in the ribosome . Blasticidin S base-pairs with the P-loop and thereby mimics C74 and C75 of a P-site bound tRNA.

J Am Acad Audiol, 2003 Apr, 14(3), 157 - 68; quiz 170-1
Audiologic monitoring for potential ototoxicity in a phase I clinical trial of a new glycopeptide antibiotic; Campbell KC et al.; This study describes audiologic methodology and results for evaluating potential ototoxicity in a phase I clinical trial of a new glycopeptide . This study was conducted under good clinical practices, which are regulated by the US Food and Drug Administration (FDA) (21 Code of Federal Regulations), and input from the FDA was sought prior to study implementation . Healthy, normal volunteers underwent extensive medical and audiologic assessments as part of this phase I dose- escalation study of dalbavancin, a new glycopeptide, to assess potential side effects . Audiologic monitoring included air-conduction thresholds in the conventional (0.25-8 kHz) and high-frequency (10-16 kHz) ranges . At baseline, subjects were also tested using word recognition, bone conduction testing if indicated, and tympanometry . Full testing was to be repeated if any subject met the American Speech-Language-Hearing Association (ASHA) 1994 criteria for ototoxic change . However, no subjects demonstrated ototoxic change after receiving dalbavancin, nor were any false-positive results obtained.

Eur J Clin Pharmacol, 2003 Aug, 59(4), 331 - 5 Epub 2003 Jul 15.
Utilisation of antibiotics in young children: opposite relationships to adult educational levels in Danish and Swedish counties; Melander E et al.; BACKGROUND: Antibiotic utilisation varies profoundly among and within countries, and the extent of antibiotic utilisation correlates with the frequency of bacterial resistance, particularly among children . Hence, it is important to assess which factors may influence prescribing . In addition to variations in morbidity, health-care organisation, drug regulatory and supply systems, prescriber's attitudes, parents' behaviour, attitudes and socio-economic positions seem important . We compared socio-economic position (educational level of adults) and antibiotic utilisation in children in the municipalities within a Danish and a Swedish county which are geographically close, have similar social and economic development, and similar drug regulatory and supply systems . METHODS: Data on antibiotic utilisation (1998), expressed in defined daily doses per 1000 inhabitants per day (DDD/TID), were obtained from the Copenhagen County Health Insurance register and from the National Corporation of Swedish Pharmacies . Data on municipal educational levels were obtained from Statistics Denmark and Statistics Sweden . RESULTS: The utilisation of antibiotics in 0- to 6-year-old children was higher in the Swedish than in the Danish county but varied between the municipalities within both the Swedish (9.6-17.7 DDD/TID) and the Danish (8.0-12.9 DDD/TID) counties . Most notably, utilisation rates correlated negatively with the education levels in the Danish (r=-0.539, P=0.021) but positively in the Swedish (r=+0.390, P=0.025) municipalities . CONCLUSION: The observed variations in antibiotic prescribing may reflect different parental and/or prescriber attitudes towards use of antibiotics and they emphasise that antibiotic prescribing is influenced by factors other than the prevalence of bacterial infections . Relationships between socio-economic position (educational level) and drug utilisation should not be generalised from one area to another.

Bioorg Med Chem Lett, 2003 Aug 4, 13(15), 2607 - 10
Synthesis and activity of novel benzoxazole derivatives of mannopeptimycin glycopeptide antibiotics; Sum PE et al.; A series of benzoxazole derivatives of the mannopeptimycin glycopeptide antibiotics was synthesized via a novel benzoxazole formation reaction by treating aminophenol of mannopeptimycin-beta with an aldehyde and DDQ in DMF . Some of these derivatives (e.g., 5b, 5d, 5m, and 7b) showed good activity against Gram-(+) bacteria when compared to the parent compound mannopeptimycin-beta.

J AOAC Int, 2003 May-Jun, 86(3), 494 - 500
Survey of residual tetracycline antibiotics and sulfa drugs in kidneys of diseased animals in the Aichi Prefecture, Japan (1995-1999); Oka H et al.; Animal kidneys were collected in order to survey the incidence of tetracycline (TC) antibiotics and sulfa (SA) drug residues in slaughtered animals that did not pass inspection for human consumption by the Japanese Food Sanitation Law and the Meat Inspection Law at the slaughterhouses in Aichi Prefecture, Japan, from April 1995 to March 2000 . The kidneys were analyzed by AOAC Official Method 995.09 for TCs and our previously reported liquid chromatographic method for SAs . Among 292 animals (94 cattle and 198 pigs), 106 (36.6%) and 41 (14.0%) contained TCs and SAs, respectively, including chlortetracycline, 59 (20.2%); oxytetracycline, 47 (16.1%); sulfamonomethoxine, 35 (12.0%); sulfadimethoxine and sulfamethoxazole, each 2 (0.7%); and sulfamerazine and sulfisoxazole, each 1 (0.3%) . A small number of animals (5 cattle and 9 pigs) contained more than one drug residue . The frequency of residue detections was significantly higher for TCs than SAs in both cattle and pig kidneys (p < 0.001).

J AOAC Int, 2003 May-Jun, 86(3), 484 - 9
Kinetic spectrophotometric determination of the macrolide antibiotic josamycin in formulations; Al-Majed AA et al.; A simple kinetic spectrophotometric method was developed for the determination of josamycin in its dosage forms . The method is based on oxidation of the drug with alkaline potassium permanganate at room temperature for a fixed time of 20 min and measuring the produced green color at 611 nm . The absorbance-concentration plot is rectilinear over the range of 2-10 microg/mL (2.4 x 10(6)-1.2 x 10(-5)M) with minimum detectability of 1.0 microg/mL (1.2 x 10(-6)M) . The determination of josamycin by fixed concentration and the rate-constant methods is also feasible with the calibration equations obtained, but the fixed-time method proved to be more applicable . The procedure was applied successfully to commercial tablets, and statistical analysis showed that the results compared favorably with those obtained by reference methods . The effect of sensitizers and surfactants on the performance of the proposed method was also studied . A proposal of the reaction pathway was presented.

Ann Transplant, 2003, 8(1), 70 - 8
Cellular viability and ultrastructure of stented, antibiotic sterilized and cryopreserved sheep biological valves implanted for one year in tricuspid position; Nozynski JK et al.; The aim of the study was an evaluation of viability and damage of biological cells sterilized with antibiotics and cryopreserved a year after the implantation . Sheep antibiotic sterilised and cryopreserved biological valves were implanted in tricuspid position in young sheeps for one-year period . After this time the valves removed and studied morphologically . The control group consisted of 7 intact valves, the comparative group, so called group of valves after the processing antibiotic sterilization and cryopreservation consisted of 7 valves after mentioned procedures . Histologic investigations were based on paraffin sections of formalin-fixed valve cusps, stained with H&E and Masson trichrome . Valve viability was assessed using intravital staining with fluoresceine diacetate, whereas damaged cells were visualized by intravital staining with neutral red . Additionally, the ultrastructural studies were performed . The viability and ultrastructural results were compared with the pathologic process in the valve . Conclusions: 1 . preliminary preparation with antibiotic sterilisation and cryopresrevation induces valve leaflet oedema and degenerative ultrastructural processes, colliquative cell necrosis and apoptotic morphology of a part of valve cells; 2 . cryopreserved and antibiotic sterilised pulmonary valve after one-year implantation behaves lining cells, but ultrastructural changes indicates many degenerative phenomena in smaller degree than after preparation, sterilization and cryopreservation . Histopathologically the degenerative changes were prevalent.

Ann Transplant, 2003, 8(1), 55 - 69
Mathematical analysis of calcifications in stented, antibiotic sterilized and cryopreserved sheep biological valves implanted for one year in tricuspid position; Nozynski JK et al.; The aim of the study was morphometric and mathematic analysis of calcification profiles present in the leaflets of a cryopreserved and alive heart valve depending on the diagnosed pathologic process . Sheep antibiotic sterilised and cryopreserved biological valves were implanted in tricuspid position in young sheeps for one-year period . After this time the valves removed and studied morphologically . The control group consisted of 7 intact valves, the comparative group, so called group of valves after the processing antibiotic sterilization and cryopreservation consisted of 7 valves after mentioned procedures . Histologic investigations were based on paraffin sections of formalin-fixed valve cusps, stained with H&E and Masson trichrome, calcium deposits were stained von Kossa technique . The measured values included: 1 . area and equivalent diameter, 2 . length, 3 . breadth, 4 . perimeter, 5 . elongation, 6 . roundness, 7 . fullness coefficient . Conclusions: 1 . A process of initial processing and cryopreservation of biological valve increases a dimension and disturbs a shape of microcalcifications . 2 . Cryopreserved biological valves explanted after one-year implantation into an animal in a tricuspid position possess microcalcifications and calcification foci . The size of microcalcifications decreases together with an intensification of degenerative processes of the connective tissue, especially in hyalinization . Hyalinization of the biological valve tissue seems to be favorable for a valve durability and as a pathological process decreasing calcification . 3 . Mathematic analysis of morphometric features defining differences in size and shape of each calcification indicate morphologic and morphometric autonomy of calcifications, characteristic for the analyzed group of valve pathologic changes.

Ann Transplant, 2003, 8(1), 45 - 54
Integrative measurements of calcifications in stented, antibiotic sterilized and cryopreserved sheep biological valves implanted for one year in tricuspid position; Nozynski JK et al.; The aim of the study was the characterization of calcification in the leaflets of a cryopreserved and alive heart valve depending on the diagnosed pathologic process . Sheep antibiotic sterilised and cryopreserved biological valves were implanted in tricuspid position in young sheeps for one year period . After this time the valves removed and studied morphologically . The control group consisted of 7 intact valves, the comparative group, so called group of valves after the processing antibiotic sterilization and cryopreservation consisted of 7 valves after mentioned procedures . Histological investigations were based on paraffin sections, calcium deposits were stained von Kossa technique . The measured values included integrative parameters as: 1 . area fraction, 2 . number of calcifications per area, 3 . anisotropy . Conclusions: 1 . A process of initial processing, sterilization and cryopreservation of biological valve increases a number of microcalcifications . 2 . Cryopreserved biological valves explanted after one-year implantation into an animal in a tricuspid position possess fine calcifications and calcification foci . A number and size of fine calcifications decreases together with an intensification of degeneration and regressive processes of the connective tissue, especially in hyalinization . Hyalinization of the biological valve tissue seems to be favorable for a valve durability and as a pathological process decreasing calcification . 3 . Mathematic analysis of morphometric features defining density and structure of calcifications indicate similarities among cryopreservation and initial processing groups, hyalinization, inflammation, whereas in a group of calcification foci, the similarity can be noticed between inflammation and hyalinization group.

J Perinatol, 2003 Jul-Aug, 23(5), 372 - 7
Pneumonia in term neonates: laboratory studies and duration of antibiotic therapy; Engle WD et al.; OBJECTIVES: To compare 2 days of antibiotic therapy (AT) to 4 days of AT in neonates with pneumonia and to assess the usefulness of neutrophil values (NV), C-reactive protein (CRP), and procalcitonin (PCT) in this population . DESIGN: The study population consisted of consecutive, eligible term neonates begun on AT for suspected pneumonia . Of 51 neonates, 26 qualified for randomization (14, 2-day group; 12, 4-day group) . NV were obtained with the initial evaluation and 12 and 24 hours later . CRP and PCT were obtained 12 and 48 hours after the initial evaluation . RESULTS: None of the 12 neonates in the 4-day group developed recurrent respiratory symptoms . Three of the 14 neonates randomized to the 2-day group had recurrence of symptoms, resulting in study termination . NV, CRP, and PCT were similar in the 2- and 4-day groups . In the three neonates who developed respiratory symptoms, all absolute total neutrophil values and five out of nine absolute total immature neutrophil values were abnormal . However, all immature:total neutrophil values were normal, and CRP was strikingly elevated in only one neonate; only one of six PCT values was abnormal . In a secondary analysis of all 51 study neonates, CRP and PCT did not provide additional benefit over NV in differentiating neonates with pneumonia . CONCLUSIONS: Four days of AT appears to be adequate for selected term neonates with pneumonia; however, 2 days of AT appears to be inadequate for this population . Relative to NV, CRP and PCT appear to have a limited role.

Can J Gastroenterol, 2003 Jun, 17 Suppl B, 49B - 52B
Helicobacter pylori resistance to antibiotics: prevalence, mechanism, detection . What's new?
Megraud F.
Helicobacter pylori resistance to antibiotics is increasingly reported and may limit the efficacy of current treatment regimens . Their resistance mechanism has been found to be point mutations for all antibiotics . Macrolide resistance is the most clinically important, but can be detected efficiently by molecular methods . Metronidazole resistance has limited clinical impact but testing methods are not reliable . Seldomly found cases of resistance, such as to amoxicillin and tetracycline, have had their mechanism recently elucidated . The existence of rapid and practical methods for the detection of macrolide resistance (eg, Fluorescence Resonance Energy Transfer assay) should improve management of H pylori-positive patients in the future, by allowing an adapted first-line therapy.

Am J Respir Crit Care Med, 2003 Nov 1, 168(9), 1060 - 7 Epub 2003 Jul 03.
Decision analysis of antibiotic and diagnostic strategies in ventilator-associated pneumonia; Ost DE et al.; The optimal strategy for ventilator-associated pneumonia remains controversial . To clarify the tradeoffs involved, we performed a decision analysis . Strategies evaluated included antibiotic therapy with and without diagnostic testing . Tests that were explored included endotracheal aspirates, bronchoscopy with protected brush or bronchoalveolar lavage, and nonbronchoscopic mini-bronchoalveolar lavage (mini-BAL) . Outcomes included dollar cost, antibiotic use, survival, cost-effectiveness, antibiotic use per survivor, and the outcome perspective of financial cost-antibiotic use per survivor . Initial coverage with three antibiotics was better than expectant management or one or two antibiotic approaches, leading to both improved survival (54% vs . 66%) and decreased cost (US dollars 55447 vs . US dollars 41483 per survivor) . Testing with mini-BAL did not improve survival but did decrease costs (US dollars 41483 vs . US dollars 39967) and antibiotic use (63 vs . 39 antibiotic days per survivor) . From the perspective of minimizing cost, minimizing antibiotic use, and maximizing survival, the best strategy was three antibiotics with mini-BAL.

Manag Care Interface, 2003 Jun, 16(6), 34 - 40, 55
Costs of broad-spectrum antibiotic use for acute sinusitis, chronic bronchitis, and pneumonia in a managed care population; Coughlin CM et al.; Respiratory infections place a heavy burden on patients, providers, employers, and health care systems . The prescribing of antibiotics is common, despite the fact that many respiratory conditions are caused by viruses . The economic effect of treating respiratory tract infections with broad-spectrum antibiotics was retrospectively analyzed by means of health care claims data from six managed care health plans affiliated with a large national insurer . A regression model was used to adjust for factors that can influence treatment costs, such as age, baseline cost, retreatment, and drug cost . The costs of treating chronic bronchitis, pneumonia, and acute sinusitis with moxifloxacin, gatifloxacin and nonfluoroquinolone broad-spectrum agents were significantly lower than the costs associated with levofloxacin treatment.

Appl Environ Microbiol, 2003 Jul, 69(7), 4256 - 9
Development of antibiotic-overproducing strains by site-directed mutagenesis of the rpsL gene in Streptomyces lividans; Okamoto-Hosoya Y et al.; Certain rpsL (which encodes the ribosomal protein S12) mutations that confer resistance to streptomycin markedly activate the production of antibiotics in Streptomyces spp . These rpsL mutations are known to be located in the two conserved regions within the S12 protein . To understand the roles of these two regions in the activation of silent genes, we used site-directed mutagenesis to generate eight novel mutations in addition to an already known (K88E) mutation that is capable of activating antibiotic production in Streptomyces lividans . Of these mutants, two (L90K and R94G) activated antibiotic production much more than the K88E mutant . Neither the L90K nor the R94G mutation conferred an increase in the level of resistance to streptomycin and paromomycin . Our results demonstrate the efficacy of the site-directed mutagenesis technique for strain improvement.

Br J Cancer, 2003 Jul 7, 89(1), 43 - 9
Oral antibiotics with early hospital discharge compared with in-patient intravenous antibiotics for low-risk febrile neutropenia in patients with cancer: a prospective randomised controlled single centre study; Innes HE et al.; Neutropenic sepsis remains a potentially life-threatening complication of anticancer chemotherapy . However, it is possible to identify patients who are at low risk for serious complications and for whom less-intensive, more-convenient treatment may be appropriate . The aim of this study was to assess the efficacy and safety of oral antibiotics in conjunction with early hospital discharge in comparison with standard in-patient intravenous antibiotics in patients with low-risk neutropenic fever . In all, 126 episodes of low-risk neutropenic fever occurred in 102 patients . Patients were randomised to receive either: an oral regimen of ciprofloxacin (750 mg 12 hourly) plus amoxicillin-clavulanate (675 mg 8 hourly) for a total of 5 days, or a standard intravenous regimen of gentamicin and tazocin (piperacillin/tazobactam) until hospital discharge . Patients randomised to oral antibiotics were eligible for discharge following 24 h of hospitalisation, if clinically stable and symptomatically improved . The efficacy of the two arms was similar: initial treatment was successful without antibiotic modification in 90% of episodes in the intravenous arm and 84.8% of episodes in the oral arm, P=0.55, absolute difference between the groups 5.2%; 95% confidence interval (CI) for the difference -7 to 17.3% . Only one episode in the oral arm was associated with significant clinical deterioration: this occurred within the initial in-patient assessment period . The median in-patient stay was 4 days in the intravenous arm (range 2-8) and 2 days in the oral arm (range 1-16 days), P&<0.0005 . The reduction in hospital stay led to significant cost-savings in the oral arm . In conclusion, this study suggests that oral antibiotics in conjunction with early hospital discharge for patients who remain stable after a 24 h period of in-patient monitoring offers a feasible and cost-effective alternative to conventional management of low-risk neutropenic fever.

J Bacteriol, 2003 Jul, 185(14), 4276 - 9
Structural insight into the antibiotic action of telithromycin against resistant mutants; Berisio R et al.; The crystal structure of the ketolide telithromycin bound to the Deinococcus radiodurans large ribosomal subunit shows that telithromycin blocks the ribosomal exit tunnel and interacts with domains II and V of the 23S RNA . Comparisons to other clinically relevant macrolides provided structural insights into its enhanced activity against macrolide-resistant strains.

Chem Biol, 2003 Jun, 10(6), 541 - 9
The gene cluster for the biosynthesis of the glycopeptide antibiotic A40926 by nonomuraea species; Sosio M et al.; The glycopeptide A40926 is the precursor of dalbavancin, a second-generation glycopeptide currently under clinical development . The dbv gene cluster, devoted to A40926 biosynthesis, was isolated and characterized from the actinomycete Nonomuraea species ATCC39727 . From sequence analysis, 37 open reading frames (ORFs) participate in A40926 biosynthesis, regulation, resistance, and export . Of these, 27 ORFs find a match in at least one of the previously characterized glycopeptide gene clusters, while 10 ORFs are, so far, unique to the dbv cluster . Putative genes could be identified responsible for some of the tailoring steps (attachment of glucosamine, sugar oxidation, and mannosylation) expected during A40926 biosynthesis . After constructing a Nonomuraea mutant by deleting dbv ORFs 8 to 10, the novel compound dechloromannosyl-A40926 aglycone was isolated.

J Am Chem Soc, 2003 Jul 9, 125(27), 8238 - 43
Total synthesis of an antitumor antibiotic, Fostriecin (CI-920); Miyashita K et al.; The total synthesis of an antitumor antibiotic, fostriecin (CI-920), via a highly convergent route is described . A characteristic feature of the present total synthesis is that the synthesis was achieved via a coupling procedure of three segments A, B, and C . The unsaturated lactone moiety of fostriecin, corresponding to segment A, was constructed from a known Horner-Emmons reagent, and the stereochemistry of the C-5 position was introduced by asymmetric reduction with (R)-BINAl-H . Segment B having a series of stereogenic centers was synthesized from (R)-malic acid and the stereogenic centers at the C-8 and C-9 positions were prepared by a combination of Wittig reaction and Sharpless asymmetric dihydroxylation reaction . The conjugated Z,Z,E-triene moiety of fostriecin, corresponding to segment C, was eventually constructed by Wittig reaction and Stille coupling reaction . The phosphate moiety, which is known to be essentially important for the antitumor activity, was introduced via two routes: (i) direct phosphorylation of the monohydroxyl derivative in which other hydroxyl groups are protected with silyl groups; (ii) cyclic phosphorylation and selective cleavage of the cyclic phosphate derivative . Although the former route is basically the same as those reported by other groups, the latter route is novel and more effective than the former one . The present total synthesis would serve as a versatile synthetic route to not only fostriecin, but also its various analogues including stereoisomers.

J Am Chem Soc, 2003 Jul 9, 125(27), 8218 - 27
Solid-phase synthesis of bleomycin group antibiotics . Construction of a 108-member deglycobleomycin library; Leitheiser CJ et al.; The bleomycins (BLMs) are structurally related glycopeptide antibiotics isolated from Streptomyces verticillus that mediate the sequence-selective oxidative damage of DNA and RNA . Deglycobleomycin, which lacks the carbohydrate moiety, cleaves DNA analogously to bleomycin itself, albeit less potently, and has been used successfully for analyzing the functional domains of bleomycin . Although structural modifications to bleomycin and deglycobleomycin have been reported, no bleomycin or deglycobleomycin analogue having enhanced DNA cleavage activity has yet been described . The successful synthesis of a deglycobleomycin on a solid support has permitted the facile solid-phase synthesis of 108 unique deglycobleomycin analogues through parallel solid-phase synthesis . Each of the deglycobleomycin analogues was synthesized efficiently; the purity of each crude product was greater than 60%, as determined by HPLC integration . The solid-phase synthesis of the deglycobleomycin library provided near-milligram to milligram quantities of each deglycobleomycin, thereby permitting characterization by (1)H NMR and high-resolution mass spectrometry . Each analogue demonstrated supercoiled plasmid DNA relaxation above background cleavage; the library included two analogues that mediated plasmid relaxation to a greater extent than the parent deglycobleomycin molecule.

J Biochem Biophys Methods, 2003 Jun 30, 56(1-3), 297 - 309
Size-exclusion high-performance liquid chromatography in the study of the autoassociating antibiotic gramicidin A in micellar milieu; Bano MC et al.; Gramicidin A (gA) is a polypeptide antibiotic which forms dimeric channels specific for monovalent cations in biological membranes . It is a polymorphic molecule that adopts several different conformations, double-stranded (ds) helical dimers (pore conformation) and single-stranded beta-helical dimers (channel conformation) . This study investigated the conformational adaptability of gramicidin A when incorporated into micelles as membrane-mimetic model system . Taking advantage of our reported, versatile, size-exclusion high-performance liquid chromatography (SE-HPLC) strategy that allows the separation of double-stranded dimers and monomers, we have quantitatively characterized the conformational transition undergone by the peptide in the micellar milieu . The importance of both hydrophobic/hydrophilic moieties of the amphipaths in the stabilization of concrete conformational species is demonstrated using detergents with different hydrocarbon chain length and/or polar head . SE-HPLC is a valuable, rapid, accurate technique for the structural characterization of hydrophobic autoassociating peptides that work in lipid environments such as biological membranes.

Anal Sci, 2003 Jun, 19(6), 927 - 32
Resonance Rayleigh scattering measurement of aminoglycoside antibiotics with Evans Blue; Liu SP et al.; In a weak acid medium, some aminoglycoside antibiotics, such as kanamycin (KANA), gentamicin (GEN), tobramycin (TOB) and neomycin (NEO), or acid bisazo dye Evans Blue (EB) can only produce very weak resonance Rayleigh scattering (RRS) signals . However, when two agents react with each other to form ion-association complexes, the RRS intensity can be greatly enhanced and a new RRS spectrum with a significant enhancement of the RRS intensity in the wavelength range from 350 nm to 600 nm can be observed . The maximum scattering peak is at 570 nm . There is a linear relationship between the RRS intensity and the antibiotic concentration in the range of 0.01-6.0 microg mL(-1) at 570 nm . This RRS method for the determination of aminoglycoside antibiotics at trace-amount levels has been developed . The detection limits (3sigma) of the four antibiotics, whose order of sensitivity from high to low ranks as KANA > NEO > TOB > GEN, are 5.2-6.9 ng mL(-1) . This method has good selectivity and has been successfully applied to the quick determination of antibiotics not only for injections and ear drops, but for clinic serum samples as well . In addition, the reaction mechanism by using a quantum chemistry method and the influencing factors of the RRS spectra and the enhancement reasons of RRS have been discussed.

FEBS Lett, 2003 Jul 10, 546(2-3), 241 - 6
Membrane topology of ABC-type macrolide antibiotic exporter MacB in Escherichia coli; Kobayashi N et al.; MacB is an ABC-type membrane protein that exports only macrolide compounds containing 14- and 15-membered lactones, cooperating with a membrane fusion protein, MacA, and a multifunctional outer membrane channel, TolC . We determined the membrane topology of MacB by means of site-specific competitive chemical modification of single cysteine mutants . As a result, it was revealed that MacB is composed of four transmembrane (TM) segments with a cytoplasmic N-terminal nucleotide binding domain of about 270 amino acid residues and a periplasmic large hydrophilic polypeptide between TM segments 1 and 2 of about 200 amino acid residues.

Expert Opin Pharmacother, 2003 Jul, 4(7), 1097 - 103
Acne: comparing hormonal approaches to antibiotics and isotretinoin; Larsen TH et al.; Acne is a common and disfiguring disease affecting a significant proportion of the general population . In milder cases topical therapy is sufficient . However, in more severe cases where papulopustular or nodulocystic acne is present, there is a need of systemic treatment . The latter include antibiotics, anti-androgens and retinoids . A systematic review of the literature was performed of systemic monotherapy using these drugs . Because of the significant methodological variability of the studies examined, it was not possible to make a meta-analysis . Instead the overall effects were assessed by calculating mean weighted effects across different reported effect variables . Isotretinoin scored 85 +/- 10% improvement compared with the baseline, whereas tetracyclines and cyproterone acetate plus ethinyloestradiol were less effective (54 +/- 3% versus 65 +/- 4% improvement compared with baseline, respectively) . Moreover, studies suggested that isotretinoin reduces the risk of acne relapse in the few studies that included a follow-up period . A number of restrictions limit the general use of these drugs as monotherapy, e.g., potential teratogenicity . There is a continued need for effective drugs for the therapy of acne, although judicious combined use of existing topical and systemic therapies offers great relief to many patients . In addition, methodological problems in previous studies prevent adequate synthesis of existing knowledge within the framework of evidence-based medicine . There is therefore a demand for future standardisation of further acne studies to enable direct comparison of different treatment efficacies.

J Chromatogr A, 2002 Mar 1, 948(1-2), 193 - 201
Preparation of monodisperse porous polymethacrylate microspheres and their application in the capillary electrochromatography of macrolide antibiotics; Zhang S et al.; Monodisperse poly(glycidyl methacrylate-divinylbenzene) microspheres were prepared by a simple one-step dispersion polymerization process . Examination of the polymeric microspheres showed that they had a mean particle diameter of 3 microm and dual pore size distribution with mean pore diameters of 300 and 800 A . The microspheres were functionalized by introducing quaternary ammonium/octadecyl groups to obtain positively charged beads in a wide pH range . The functionalized beads were packed into fused-silica capillary having 50 microm inner diameter and used to separate erythromycin derivatives by capillary electrochromatography (CEC) . These samples require gradient elution when separated by high-performance liquid chromatography (HPLC) or micro-HPLC, but with the new columns isocratic elution suffices for their separation by CEC . The column efficiency ranged from 40,000 to 50,000 theoretical plates.

Am J Respir Crit Care Med, 2003 Sep 1, 168(5), 581 - 7 Epub 2003 Jun 26.
In vivo and in vitro effects of macrolide antibiotics on mucus secretion in airway epithelial cells; Shimizu T et al.; To examine the in vivo effects of macrolide antibiotics on mucus hypersecretion, we induced hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium by intranasal instillation of ovalbumin (OVA) in OVA-sensitized rats and by intranasal LPS instillation . Oral administration of clarithromycin (CAM) (5-10 mg/kg) significantly inhibited OVA- and LPS-induced mucus production and neutrophil infiltration, whereas josamycin and ampicillin showed no effect . In vitro effects of macrolide antibiotics on airway epithelial cells were examined using NCI-H292 cells and human nasal epithelial cells cultured in air-liquid interface . Mucus secretion was evaluated by ELISA using anti-mucin monoclonal antibodies (anti-MUC5AC and HCS18) . CAM and erythromycin significantly inhibited spontaneous and tumor necrosis factor-alpha (20 ng/ml)-induced mucus secretion from NCI-H292 cells at 10-6 to 10-7 M and from human nasal epithelial cells at 10-4 to 10-5 M . MUC5AC messenger RNA expression was also significantly inhibited . These results indicate that the 14-member macrolide antibiotics, CAM and erythromycin, exert direct inhibitory effects on mucus secretion from airway epithelial cells and that they may be useful for the treatment of mucus hypersecretion caused by allergic inflammation and LPS stimulation.

Ann Emerg Med, 2003 Jul, 42(1), 117 - 23
Continuity of antibiotic therapy in patients admitted from the emergency department; Shah MN et al.; STUDY OBJECTIVE: We describe discontinuities in antibiotic therapy in patients with community-acquired pneumonia admitted from the emergency department (ED) to an inpatient unit . METHODS: We performed a retrospective cohort study of patients with community-acquired pneumonia admitted from the ED to the internal medicine service at an academic tertiary care hospital between July 1997 and June 1999 . We characterized the frequency of antibiotic delays after arrival on the inpatient unit in relation to antibiotic dosing intervals . We performed paired analysis on the patients treated both with an antibiotic dosed every 6 hours and an antibiotic dosed every 24 hours . RESULTS: Three hundred seventy-five patients were identified . The mean age was 61 years . Sixty-two percent were female . Five hundred fifty-one antibiotic doses were started in the ED and continued on the inpatient unit, with 177 ordered every 6 hours, and 351 ordered every 24 hours . Seventy-five percent of the antibiotics dosed every 6 hours and 19% of the antibiotics dosed every 24 hours were delayed more than 30 minutes (P <.001) . Analysis of the 146 patients receiving both an antibiotic dosed every 6 and 24 hours showed that the first inpatient dose of antibiotics administered every 6 hours were 10 times more likely to be delayed than antibiotics dosed every 24 hours (95% confidence interval 5.0 to 23) . The median delay for antibiotics dosed every 6 hours was 258 minutes (range 45 to 3,360 minutes), and the median delay for antibiotics dosed every 24 hours was 192 minutes (range 32 to 2,124 minutes) . CONCLUSION: Discontinuous therapy, represented through a delayed first inpatient antibiotic dose, is common in patients with community-acquired pneumonia admitted from the ED . Although the effect on outcome is unknown, theoretical concerns should lead emergency physicians to consider using longer-acting antibiotics to minimize delayed therapy.

Am J Obstet Gynecol, 2003 Jun, 188(6), 1413 - 6; discussion 1416-7
Antibiotic therapy in preterm premature rupture of membranes: Are seven days necessary? A preliminary, randomized clinical trial; Lewis DF et al.; OBJECTIVE: The purpose of this study was to determine whether 3 days of broad-spectrum antibiotic therapy, which is intended to prolong latency in patients with preterm premature rupture of membranes, is comparable to 7 days of therapy . STUDY DESIGN: Patients with preterm premature rupture of membranes at three separate study sites were asked to participate in this intent-to-treat, prospective, randomized trial . They were assigned randomly to either 3 or 7 days of ampicillin-sulbactam (3 g intravenously every 6 hours) . The primary outcome of interest was the latency period from membrane rupture to delivery . RESULTS: Forty-two individuals were enrolled in each group . No difference was noted in the latency interval between the two groups (3 days, 214 +/- 225 hours, vs 7 days, 229 +/- 218 hours) . A significantly higher number of patients in the 3-day group completed therapy (80.1% vs 47.6%, P =.003) . No other parameters were significantly different between the two groups . No adverse events or trends were noted in either group . CONCLUSION: There appears to be no difference in the latency period between 3 and 7 days of ampicillin-sulbactam antibiotic therapy . More patients are needed to exclude a type II error.

Clin Imaging, 2003 Jul-Aug, 27(4), 251 - 5
Multiloculated prostate abscess: treatment with transrectal ultrasound guided transrectal needle aspiration and lavage with the saline and antibiotic; Somuncu I et al.; Prostatic abscess is a rare but nevertheless serious disease . It should be diagnosed at an early stage by the combination of clinical examination and transrectal ultrasound, and drained . We treated a 79-year-old case with multiple prostate abscesses (PAs) by using lavage of the saline and antibiotic (cefoxitin) after transrectal ultrasound-guided transrectal puncture and aspiration . We are presenting the transrectal ultrasound images of pre- and postmedication, where we achieved complete success and no relapse was seen in follow-up of 1 year.

Soc Sci Med, 2003 Aug, 57(4), 733 - 44
Improving antibiotic use in low-income countries: an overview of evidence on determinants; Radyowijati A et al.; The inappropriate use of antibiotics has often been identified as a problem in effective health care delivery . High levels of antibiotics use, often clinically unnecessary, have led to a steady increase in drug resistance . Low-income countries, home to the majority of the world's population, are believed to have an important role in this phenomena . Effective intervention in these practices is often constrained by the paucity of information on determinants of antibiotic use.This review provides information from studies on the factors that influence the use of antibiotics by health providers, dispensers and community members in low-income countries . A proper understanding of these factors should be seen as a precondition for the development of more effective policies and programmes to address inappropriate antibiotic use.The review encompasses physicians' practices, the role of drug dispensers, and the influences on patterns of drug use across community members . Although a set of papers with useful research data was identified, probably the most important finding of the review was the scarcity of research . If interventions into antibiotic use are to be effective, future research must explore in more depth the socio-cultural rationality of antibiotic usage . The most productive approach would be to combine quantitative studies of the patterns of antibiotic use with the rich variety of qualitative methods like case simulations, focus group discussions, in-depth interviews, informal interviews, or illness diaries to explore determinants.Research programmes alone are unlikely to improve antibiotic use . Priority programme activities would include a carefully designed mix of activities by governments, health delivery systems, health training institutions, professional societies, pharmaceutical companies, consumer organisations, and international organisations . Strategies that lean too heavily on professional education are unlikely to result in large-scale or long-lasting improvement.

J Membr Biol, 2003 Apr 1, 192(3), 203 - 15
The macrolide antibiotic azithromycin interacts with lipids and affects membrane organization and fluidity: studies on Langmuir-Blodgett monolayers, liposomes and J774 macrophages; Tyteca D et al.; The macrolide antibiotic azithromycin was shown to markedly inhibit endocytosis . Here we investigate the interaction of azithromycin with biomembranes and its effects on membrane biophysics in relation to endocytosis . Equilibrium dialysis and 31P NMR revealed that azithromycin binds to lipidic model membranes and decreases the mobility of phospholipid phosphate heads . In contrast, azithromycin had no effect deeper in the bilayer, based on fluorescence polarization of TMA-DPH and DPH, compounds that, respectively, explore the interfacial and hydrophobic domains of bilayers, and it did not induce membrane fusion, a key event of vesicular trafficking . Atomic force microscopy showed that azithromycin perturbed lateral phase separation in Langmuir-Blodgett monolayers, indicating a perturbation of membrane organization in lateral domains . The consequence of azithromycin/ phospholipid interaction on membrane endocytosis was next evaluated in J774 macrophages by using three tracers with different insertion preferences inside the biological membranes and intracellular trafficking: C6-NBD-SM, TMA-DPH and N-Rh-PE . Azithromycin differentially altered their insertion into the plasma membrane, slowed down membrane trafficking towards lysosomes, as evaluated by the rate of N-Rh-PE self-quenching relief, but did not affect bulk membrane internalization of C6-NBD-SM and TMA-DPH . Azithromycin also decreased plasma membrane fluidity, as shown by TMA-DPH fluorescence polarization and confocal microscopy after labeling by fluorescent concanavalin A . We conclude that azithromycin directly interacts with phospholipids, modifies biophysical properties of membrane and affects membrane dynamics in living cells . This antibiotic may therefore help to elucidate the physico-chemical properties underlying endocytosis.

Orthopade, 2003 Jun, 32(6), 490 - 7
{Temporary articulating spacer with antibiotic-impregnated cement for an infected knee endoprosthesis}; Pietsch M et al.; Two-stage reimplantation remains the gold standard in the treatment of late infected total knee arthroplasties . The reported disadvantages include difficult exposure at the time of reimplantation and less functional outcome by using static spacers . Patients who receive an articulating spacer retain a functional joint before second-stage reimplantation . This may reduce the disadvantages of static spacers (ligament contracture, extensor lag, arthrofibrosis) . There is no difference in the success rates of eradicating infection (range: 90-96%) . In a prospective study 24 consecutive patients were treated with an articulating spacer . The articulating spacer is made by cleaning and autoclaving the removed femoral component and the tibial polyethylene insert . These are reinserted during the same operation with antibiotic-loaded cement . The average time during which the spacer was in place was 16 weeks (range: 7-28 weeks) . During an average follow-up period of 14.8 months (range: 5-33 months) one patient had a secondary reinfection . Use of an articulating spacer is economical and decreases the risk of complications in reimplantation with good functional outcome.

Anesth Analg, 2003 Jul, 97(1), 174 - 82, table of contents
A single intravenous injection of KRN5500 (antibiotic spicamycin) produces long-term decreases in multiple sensory hypersensitivities in neuropathic pain; Kobierski LA et al.; Neuropathic pain is a significant clinical problem . Currently, there are no drugs that produce complete amelioration of this type of pain . We have previously shown that KRN5500, a derivative of the antibiotic spicamycin, produces a prolonged (7-day), and significant reduction in neuropathic pain, but not nociceptive pain . Herein, we provide further evidence for the efficacy of this drug in inhibiting pain after IV injection in a spared nerve injury model of neuropathic pain . A single IV dose of the drug produces an increase in pain thresholds to punctuate mechanical stimuli and to cold stimuli over a period of 7 days, whereas IV injection of the vehicle is without any effect . No change in pain threshold was observed in the contralateral foot . In addition, a significant antiallodynic effect to mechanical stimuli was observed at 1, 2, 4, and 6 wk . The drug may be a potential candidate for cancer-related neuropathic pain as well as a marker for discovery of effective analgesics for neuropathic pain . IMPLICATIONS: We examined the effect of a novel drug (KRN5500) on nerve damage pain . After the successful effects of this drug in a single human, we have shown that the drug infused as a single application at different doses in a rat model of nerve damage pain produces pain relief in this model for many weeks.

J Antibiot (Tokyo), 2003 Apr, 56(4), 372 - 8
Biosynthetic studies on a myxobacterial antibiotic, cystothiazole A: biosynthetic precursors of the carbon skeleton; Suzuki Y et al.; Biosynthetic studies on cystothiazole A (1), a beta-methoxyacrylate-type antifungal compound from a myxobacterium, were performed by feeding the producing organism, Cystobacter fuscus, with stable-isotope-labeled compounds including {2-(13)C}acetate, {1,2-(13)C2}acetate, {1-(13)C}propionate, L-{1-(13)C}serine, L-{methyl-(13)C}methionine, and DL-valine-d8 . The polyketide moiety of 1 was found to be derived from acetate and propionate, the bithiazole moiety from L-serine, the O-methyl groups from the S-methyl group of L-methionine, and the isopropyl moiety from L-valine, which should be the metabolic precursor of isobutyryl-CoA.

Joint Bone Spine, 2003 Jun, 70(3), 169 - 74
Antibiotic-loaded bone cement in orthopedic surgery; Passuti N et al.; Acrylic cement is used to secure implants to bone . When mixed with antibiotics or anticancer agents, acrylic cement slowly releases these agents while retaining its mechanical properties, thus providing specific in situ treatment.

Cell Mol Biol Lett, 2003, 8(2), 439 - 54
A kinetics study of pig erythrocyte hemolysis induced by polyene antibiotics; Knopik-Skrocka A et al.; The kinetics of the hemolysis induced by filipin is of the damage type, indicating the formation of large nonselective perforations of erythrocyte membranes . The process is relatively independent of the ionic composition of the incubation medium, and the differences between the hemolysis induced by filipin in pig and human erythrocytes are not significant . In a sucrose medium, filipin-induced hemolysis is inhibited in humans, whereas it is stimulated in pig erythrocytes . It is suggested that low ionic strength is the reason for the different modifications of complexation of filipin in pig and human erythrocyte membranes in a sucrose medium . The kinetics of the hemolysis induced in pig erythrocytes by amphotericin B and nystatin is of the permeability type, indicating the formation of selective channels in erythrocyte membranes and colloid osmotic hemolysis . The rate of the hemolysis, which is high in a KCl medium, is decreased in all the other media tested (CaCl2, MgCl2, potassium phosphate buffer, K2SO4, sucrose), although there are no changes in the kinetics of hemolysis . The results are interpreted as the formation of highly selective channels at a low concentration of the antibiotics . At increasing concentrations, channels of decreasing selectivity occur . The resistances of pig erythrocytes to amphotericin B and nystatin are lower than those of human erythrocytes.

Extremophiles, 2003 Oct, 7(5), 401 - 7 Epub 2003 Jun 17.
Purification and biological characterization of halocin C8, a novel peptide antibiotic from Halobacterium strain AS7092; Li Y et al.; Halocins are bacteriocin-like proteins or peptides produced by many species of the family Halobacteriaceae . Halocin C8, excreted by the Halobacterium strain AS7092, is a single 6.3-kDa polypeptide with an isoelectric point of 4.4, which is sensitive to proteinase K but not to trypsin . Halocin C8 is quite stable, as it can be desalted, boiled, frozen, subjected to organic solvents, and stored in culture supernatant at 4 degrees C or in dH(2)O at -20 degrees C for more than 1 year without losing activity . The purification of this halocin was achieved by combination of tangential flow filtration (TFF), Sephadex G50 and DEAE-sepharose chromatography . The N-terminal amino acid sequence was also determined by Edman degradation . Halocin C8 appeared to have a very wide activity spectrum, including most haloarchaea and even some haloalkaliphilic rods . When a sensitive strain of Halorubrum saccharovorum was exposed to halocin C8, the treated cells swelled at the initial stage, the cell wall appeared to be nicked and the cytoplasm was then extruded out, and the whole cell was eventually completely lysed . These results indicate that halocin C8 is a novel microhalocin and its primary target might be located in the cell wall of the sensitive cells.

Biol Pharm Bull, 2003 Jun, 26(6), 832 - 9
Subacute toxicity and toxicokinetics of a new antibiotic, DW-224a, after single and 4-week repeated oral administration in dogs; Han J et al.; The subacute toxicity and toxicokinetics of a new fluoroquinolone antibiotic, DW-224a, were evaluated after single (on the 1st day) and 4-week (on the 28th day) oral administration of the drug at doses of 0 (to serve as a control), 10, 30, and 90 mg/kg/d, to male and female dogs (n=3 for male and female dogs for each dose) . During the test period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weight and histopathology were examined . The 4-week repeated oral dose of DW-224a resulted in vomiting, salivation, increased serum cholesterol level, and atrophy of thymus and testes . The target organ was determined to be the thymus and testes . The absolute toxic dose of DW-224a was 30 mg/kg and the level at which no adverse effects were observed was 10 mg/kg for both sexes . There were no significant gender differences in the pharmacokinetic parameters of DW-224a for each dose after both single and 4-week oral administration . The pharmacokinetic parameters of DW-224a were dose independent after a single oral administration; the time to reach the peak plasma concentration (T(max)) and the dose-normalized area under the plasma concentration-time curve from time zero to 24 h in plasma (AUC(0-24 h)) were not significantly different among the three doses . The accumulation of DW-224a after 4-week oral administration was not notable at the toxic dose of 90 mg/kg/d . For example, after 4-week administration, the dose-normalized AUC(0-24 h) value at 90 mg/kg/d (7.69, 7.05 microg h/ml) was not significantly greater than that at 10 mg/kg/d . After 4-week oral administration, the dose-normalized C(max) and AUC(0-24 h) at 90 mg/kg/d were not significantly higher and greater, respectively, than those after a single oral administration.

Commun Dis Intell, 2003, 27 Suppl, S117 - 20
Surveillance for antibiotic resistant Escherichia coli in food animals; Jordan D; A successful surveillance program for antibiotic resistant Escherichia coli in Australia should account for the heterogenous nature of the food-animal population . Studies that rely on measurements made on several hundred isolates can only satisfy limited objectives because they risk imprecise and biased estimation of the presence and distribution of resistance traits . Observations on a larger number of isolates are needed to ensure animal, herd and region effects are adequately represented so that findings can be extrapolated to the appropriate population of interest . An efficient methodology for measuring the resistance traits of a large number of isolates is described.

Commun Dis Intell, 2003, 27 Suppl, S32 - 8
Changing GPs' antibiotic prescribing: a randomised controlled trial; Wilson EJ et al.; A randomised controlled trial involving 54 general practitioners (GPs) was conducted in Canberra, Australian Capital Territory from September 1997 to November 1999 . In the first year of the study, 24 GPs, who constituted the active arm of the intervention group, were involved in the consideration of evidence and the development and implementation of a set of clinical guidelines for the treatment of acute respiratory infections . These guidelines were then endorsed in a meeting together with specialist colleagues . In the second year of the study the group of GPs who had been acting as controls, received a moderate intervention consisting of a brief educational event and distribution of the locally developed guidelines . We obtained data from January 1997 to December 1999 from the Health Insurance Commission on prescribing rates for 40 of the doctors in the study . The rate of prescribing was calculated as the number of antibiotic prescriptions per 100 Medicare services . The average yearly prescribing decreased significantly in the intensive intervention group and increased in the moderate intervention group, (p=0.026) . A mixed effects longitudinal time series model was fitted to the data to account for seasonal variation of antibiotic prescribing and trends over time . The intensive intervention group significantly reduced their antibiotic prescribing over time compared to the moderate intervention group, (p<0.001) . This study has shown that an intensive intervention in which general practitioners were actively engaged in development and consideration of the evidence base for the guidelines resulted in a significant fall in general antibiotic prescribing.

Cochrane Database Syst Rev . 2003;(2):CD001058.
Antibiotics for preterm rupture of membranes; Kenyon S et al.; BACKGROUND: Premature birth carries substantial neonatal morbidity and mortality . One cause, associated with preterm rupture of membranes (pROM), is often subclinical infection . Maternal antibiotic therapy might lessen infectious morbidity and delay labour, but could suppress labour without treating underlying infection . OBJECTIVES: To evaluate the immediate and long-term effects of administering antibiotics to women with pROM before 37 weeks, on maternal infectious morbidity, fetal and neonatal morbidity and mortality, and longer term childhood development . SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (January 2003) and the Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2002) . SELECTION CRITERIA: Randomised controlled trials comparing antibiotic administration with placebo that reported clinically relevant outcomes, were included . In addition, trials, in which no placebo was used, were included for the outcome of perinatal death alone . DATA COLLECTION AND ANALYSIS: Data were extracted from each report without blinding of either the results or the treatments that women received . Unpublished data were sought from a number of authors . MAIN RESULTS: Nineteen trials involving over 6000 women and their babies were included . The use of antibiotics following pROM is associated with a statistically significant reduction in chorioamnionitis (relative risk (RR) 0.57, 95% confidence interval (CI) 0.37 to 0.86) . There was a reduction in the numbers of babies born within 48 hours (RR 0.71, 95% CI 0.58 to 0.87) and seven days of randomisation (RR 0.80, 95% CI 0.71 to 0.90) . The following markers of neonatal morbidity were reduced: neonatal infection (RR 0.68, 95% CI 0.53 to 0.87), use of surfactant (RR 0.83, 95% CI 0.72 to 0.96), oxygen therapy (RR 0.88, 95% CI 0.81 to 0.96), and abnormal cerebral ultrasound scan prior to discharge from hospital (RR 0.82, 95% CI 0.68 to 0.98) . Co-amoxiclav was associated with an increased risk of neonatal necrotising enterocolitis (RR 4.60, 95% CI 1.98 to 10.72) . REVIEWER'S CONCLUSIONS: Antibiotic administration following pROM is associated with a delay in delivery and a reduction in major markers of neonatal morbidity . These data support the routine use of antibiotics in pPROM . The choice as to which antibiotic would be preferred is less clear as, by necessity, fewer data are available . Co-amoxiclav should be avoided in women at risk of preterm delivery because of the increased risk of neonatal necrotising enterocolitis . From the available evidence, erythromycin would seem a better choice.

J Laryngol Otol, 2003 May, 117(5), 382 - 5
Is the routine use of antibiotics justified in adult tonsillectomy?
O'Reilly BJ, Black S, Fernandes J, Panesar J.
Pain and secondary haemorrhage are the commonest complications of adult tonsillectomy, occurring mostly in the community . This is a randomized, double-blind, placebo-controlled, prospective trial of the effect of perioperative amoxycillin on these complications . The incidence and severity of post-operative haemorrhage was measured . For the first 10 post-operative days patients provided a linear pain score, a record of GP visits, and their use of additional antibiotics and analgesics . Of 95 patients considered: 23 suffered a secondary haemorrhage; 54 consulted their general practitioner (GP) because of pain; additional antibiotics were used by at least 31 and additional analgesics by at least 41 . No significant differences were demonstrated between the active and placebo groups for any of these measures . This study demonstrates that secondary haemorrhage is common after adult tonsillectomy . Post-operative pain remains a major problem requiring frequent GP consultations . There appears to be no justification for the routine use of perioperative antibiotics.

Zhongguo Zhong Xi Yi Jie He Za Zhi, 2003 May, 23(5), 329 - 34
{A comparative study of manchurian Dutchmanspipe and antibiotics induced acute tubular necrosis in renal cellular biological features}; Yang L et al.; OBJECTIVE: To explore the possible cell biological mechanisms of the difference in prognosis between the acute tubular necrosis (ATN) induced by Manchurian Dutchmanspipe (MD-ATN) and that by antibiotics (A-ATN), by means of comparing their renal tubular mesenchymal cell phenotype characteristics and extra-cellular stroma secretion . METHODS: The expression of proliferative cell nuclear antigen (PCNA), epithelial cell growth factor (EGF), alpha-smooth muscle actin (alpha-SMA), fibronectin (FN), collagen type III and IV, transforming growth factor beta 1 (TGF beta 1) and connective tissue growth factor in renal biopsy samples of patients with MD-ATN (4 patients) and A-ATN(5 patients) were compared with immunohistochemical SP method . The analysis of above-mentioned parameters on repairing of injury and development of fibrosis was stressed for the obvious difference in clinical prognosis between the two groups . RESULTS: (1) The PCNA positive rate of renal tubular epithelial cell (RTEC) and EGF expression in the MD-ATN group were significantly lower than those in the A-ATN group respectively (P < 0.01); (2) Renal tubular mesenchymal alpha-SMA level increased in both groups with no significant difference; (3) TGF beta 1 positive cell infiltration and obvious CTGF expression revealed in renal mesenchyma of both groups with insignificant difference; (4) FN, collagen III and IV levels were significantly higher in the MD-ATN group than that in the A-ATN group (P < 0.05) . CONCLUSION: (1) As compared with A-ATN group, the RTEC auto-repairing ability was lower in the DM-ATN group, lower expression of EGF might be one of the mechanisms of its poor repair; (2) High expression of alpha-SMA, TGF beta 1 and CTGF presented in all patients with ATN, but extra-cellular stromal deposit appeared only in the renal stroma of patients with MD-ATN, suggesting that its chronical trend might be related with the reducing of extra-cellular stromal degradation factor and/or endogenous anti-fibrosis factor.

J Clin Pharm Ther, 2003 Jun, 28(3), 197 - 201
What are the non-biomedical reasons which make family doctors over-prescribe antibiotics for upper respiratory tract infection in a mixed private/public Asian setting?
Lam TP, Lam KF.
OBJECTIVES: To examine the non-biomedical reasons which make family doctors over-prescribe antibiotics for upper respiratory tract infection (URTI) in a mixed private/public Asian setting . METHODS: The questionnaire was sent to the members of the Hong Kong College of Family Physicians between August and December 2001 . RESULTS: A total of 801 family doctors completed a postal questionnaire with an overall response rate of 65.0 . A significant number of respondents (21.8) felt they might be prescribing antibiotics too often for URTI but the majority of them felt they were using antibiotics just a bit too often . Doctors who were older, more senior or in private practice were more likely to feel that they might be prescribing antibiotics too often . More than 50 of respondents thought that to satisfy the patient or his/her carer and fear of medicolegal problem if the patient deteriorates would make them very likely or likely to over-prescribe antibiotics for patients with URTIs . Public doctors might over-prescribe in order to save time, whereas private doctors might do so in order to keep patients in their practice . CONCLUSION: The results showed that doctors with certain characteristics are more likely to over-prescribe antibiotics . Factors, other than biomedical ones, may play important roles in doctor's prescription of antibiotics for URTI.

J Gen Intern Med, 2003 May, 18(5), 326 - 34
Optimizing antibiotic prescribing for acute respiratory tract infections in an urban urgent care clinic; Harris RH et al.; OBJECTIVE: To decrease unnecessary antibiotic use for acute respiratory tract infections in adults in a point-of-service health care setting . DESIGN: Prospective, nonrandomized controlled trial . SETTING: An urban urgent care clinic associated with the major indigent care hospital in Denver, Colorado between October 2000 and April 2001 . PATIENTS/PARTICIPANTS: Adults diagnosed with acute respiratory tract infections (bronchitis, sinusitis, pharyngitis, and nonspecific upper respiratory infection) . A total of 554 adults were included in the baseline period (October to December 2000) and 964 adults were included in the study period (January to April 2001) . INTERVENTIONS: A provider educational session on recommendations for appropriate antibiotic use recently published by the Centers for Disease Control and Prevention, and placement of examination room posters were performed during the last week of December 2000 . Study period patients who completed a brief, interactive computerized education (ICE) module were classified as being exposed to the full intervention, whereas study period patients who did not complete the ICE module were classified as being exposed to the limited intervention . MEASUREMENTS AND MAIN RESULTS: The proportion of patients diagnosed with acute bronchitis who received antibiotics decreased from 58% during the baseline period to 30% and 24% among patients exposed to the limited and full intervention, respectively (P <.001 for intervention groups vs baseline) . Antibiotic prescriptions for nonspecific upper respiratory tract infections decreased from 14% to 3% and 1% in the limited- and full-intervention groups, respectively (P <.001 for intervention groups vs baseline) . CONCLUSION: Antibiotic use for adults diagnosed with acute respiratory tract infections can be reduced in a point-of-service health care setting using a combination of patient and provider educational interventions.

Ceska Slov Farm, 2003 May, 52(3), 119 - 25
{Chiral separation of drugs based on macrocyclic antibiotics using HPLC, supercritical fluid chromatography (SFC) and capillary electrochromatography (CEC)}; Dungelova J et al.; Separation of enantiomers by means of high-performance liquid chromatography (HPLC), supercritical fluid chromatography (SFC), and capillary electrochromatography (CEC) is of great importance in pharmaceutical analyses . In recent years, separation of various types of racemates employs most frequently chiral stationary phases based on macrocyclic antibiotics . This class of chiral selectors includes vancomycin, teikoplanin, ristocetin A, teikoplanin without saccharide components, avoparcin, etc . The review paper describes the properties of selected antibiotics, the effect of chromatographic conditions on enantioselectivity (effect of the composition of the mobile phase, effect of pH of the mobile phase, effect of temperature), and the study of possible mechanisms of interaction, which play an important role in the separation of enantiomers . Examples of the use of macrocyclic antibiotics in the separation of various compounds by means of the HPLC, SFC, and CEC methods follow.

Bioorg Med Chem, 2003 Jul 3, 11(13), 2965 - 81
Studies on the interaction of the antibiotic moenomycin A with the enzyme penicillin-binding protein 1b; Ruhl T et al.; The interaction of a moenomycin derivative with the enzyme penicillin binding protein 1b (PBP 1b) has been studied by means of STD NMR . The results obtained initiated the synthesis of a number of moenomycin derivatives modified in unit A including a moenomycin-ampicillin conjugate and determination of their antibiotic activities . A protocol is described that allows studying the interaction of moenomycin analogues with PBP 1b by fluorescence correlation spectroscopy.

Bioorg Med Chem, 2003 Jul 3, 11(13), 2791 - 801
Association of chromatin with anticancer antibiotics, mithramycin and chromomycin A3; Mir MA et al.; Mithramycin and chromomycin A(3) are two anticancer antibiotics, which inhibit protein biosynthesis via transcription inhibition . They bind reversibly to DNA with (G.C) base specificity . At and above physiological pH in the absence of DNA, they form two types of complexes with Mg(2+), complex I (1:1 in terms of antibiotic: Mg(2+)) and complex II (2:1 in terms of antibiotic: Mg(2+)) . These are the DNA binding ligands . In vivo, the antibiotics interact with chromatin, a protein-DNA complex . In order to understand the mode of action of these antibiotics at molecular level, we have carried out spectroscopic, gel electrophoretic and UV melting studies of complex I of these antibiotics with rat liver chromatin, nucleosome core particle and DNA stripped of all chromosomal proteins . Analysis of the results has led us to propose that the antibiotic: Mg(2+) complex binds to both nucleosomal and linker DNA in native chromatin . Histone proteins reduce the binding potential and accessibility of the complexes to the minor groove of (G.C) rich regions of chromosomal DNA . The antibiotic: Mg(2+) complex stabilizes DNA duplex and histone- DNA contacts in chromatin fiber . It also leads to the aggregation of chromatin fibers . From a comparison of the association of the antibiotic: Mg(2+) complexes with different levels of chromatin structure and their effects upon the structure, we suggest that the sugar moieties of the antibiotics play a role in the binding process . Significance of these results to understand the molecular basis of the transcription inhibition potential of the antibiotics in eukaryotes is discussed.

Biochem Biophys Res Commun, 2003 Jun 20, 306(1), 87 - 92
DNA cleavage characteristics of non-protein enediyne antibiotic N1999A2; Miyagawa N et al.; N1999A2 (NA2) is a new non-protein antitumor antibiotic that contains a stable 9-membered ring enediyne chromophore similar to a neocarzinostatin chromophore (NCS-chr) . We have compared DNA cleavage reactions between NA2 and NCS-chr, and also clarified some characteristics of DNA strand scission by NA2 . It was found that: (1) NA2 is considerably stable in nature, (2) the compound intercalates into base pairs of a DNA minor groove and decreases its base-attacking frequency in the order of T>A>> C>G, (3) the base-sequence specificity 5(')-GGT/3(')-CCA presented by NA2 is significantly related to recognition of the base pair with the naphthoate moiety, and (4) the different cleavage property between NCS-chr and NA2 is associated with the presence or absence of an aminoglycoside residue . Based on the results of the site-specific cleavage by NA2 for certain bulged DNAs and a fluorescence study of NA2-DNA oligomer complexes, the DNA interaction mode of NA2 has also been examined . These results provide important information to design a new enediyne molecule for a DNA target.

Biochem Pharmacol, 2003 Jun 1, 65(11), 1767 - 75
Non-caspase-mediated apoptosis contributes to the potent cytotoxicity of the enediyne antibiotic lidamycin toward human tumor cells; Wang Z et al.; Enediyne antibiotics have been reported to be the most potent cytotoxic antitumor agents . The pathway by which these compounds cleave DNA and induce apoptosis of tumor cells may be different from the caspase-mediated pathways that initiate typical apoptosis . In this report, we studied the apoptosis induced by lidamycin (LDM), a member of the enediyne antibiotic family, and compared the characteristics of LDM-induced apoptosis with those of typical apoptosis induced by mitomycin C or etoposide . Chromatin condensation occurred very rapidly and appeared as speckles in human hepatoma BEL-7402 and breast carcinoma MCF-7 cells after treatment with 1 microM LDM . In addition, co-staining the cells with the mitochondria-specific dye Mitosensor and the DNA-specific dye Hoechst 33342 enabled the visualization of mitochondria in normal control and LDM-treated cells but not in mitomycin C-treated cells . Neither the caspase inhibitor VAD-fmk nor the caspase-3 inhibitor DEVD-fmk was able to inhibit the DNA ladder patterns caused by LDM in BEL-7042 or MCF-7 cells . Smaller fragments of histone H1 cleaved by LDM were detected by SDS-PAGE, indicating that the site of LDM action is the internucleosomal structure . Although caspase-9, caspase-3/7, and caspase-6 activities were increased in BEL-7402 cells, and caspase-7 activity was increased in MCF-7 cells after treatment with 1 microM LDM, this occurred much later, indicating that chromatin condensation reached the maximal level rapidly while caspase activities still remained low . Taken together, these results demonstrate that LDM induced rapid DNA cleavage and chromatin condensation independently of caspase activities; this may contribute to its highly potent cytotoxicity toward tumor cells.

J Chromatogr A, 2003 Apr 25, 994(1-2), 227 - 32
Enantiomeric separation of acidic compounds of pharmaceutical interest by capillary electrochromatography employing glycopeptide antibiotic stationary phases; Fanali S et al.; Enantiomeric separation of some selected acidic compounds of pharmaceutical interest belonging to the group of non-steroidal anti-inflammatory drugs were separated by capillary electrochromatography employing silica based glycopeptide antibiotic stationary phases, namely vancomycin or a teicoplanin derivatives (Hepta-Tyr) . The vancomycin stationary phase allowed to achieve the chiral resolution of some racemic studied compounds only using mobile phases containing ammonium formate at a relatively low pH 2.5-3.5 and acetonitrile . Employing the teicoplanin derivative stationary phase, good enantiomeric resolution was achieved eluting with mobile phases containing sodium phosphate pH 6-acetonitrile . Enantiomers were moved to the detector because a relatively high reversed electroosmotic flow (due to the positive charge of the stationary phase) and to the electrophoretic mobility of analytes.

J Chromatogr A, 2003 Apr 25, 994(1-2), 75 - 84
Determination of the antibiotic chloramphenicol in meat and seafood products by liquid chromatography-electrospray ionization tandem mass spectrometry; Mottier P et al.; A confirmatory method based on isotope dilution liquid chromatography-electrospray ionization tandem mass spectrometry is described for the determination of the antibiotic chloramphenicol (CAP) in foods . The method is quantitative and entails liquid-liquid extraction followed by a clean-up step on a silica gel solid-phase extraction cartridge . Mass spectral acquisition is done in the negative ion mode applying multiple reaction monitoring of two diagnostic transition reactions for CAP (m/z 321 --> 257 and m/z 321--> 152) . In addition, the presence of two chlorine atoms in the CAP molecule provides further analyte certainty by assessing the 37Cl/35Cl ratio using the transition reactions m/z 323 --> 257 and m/z 323 --> 152 . Validation of the method in chicken meat is conducted according to the latest European Union criteria for the analysis of veterinary drug residues at levels of 0.05, 0.10, and 0.20 microg/kg, employing {2H5}-chloramphenicol as internal standard . The decision limit and the detection capability were calculated at 0.01 microg/kg and 0.02 microg/kg, respectively . At the lowest fortification level (i.e . 0.05 microg/kg), precision values below 14 and 17% were achieved under repeatability and within-laboratory reproducibility conditions, respectively . The accuracy of the method was within 20, 15, and 5% of the target values at the 0.05, 0.10, and 0.20 microg/kg fortification levels, respectively . The applicability of this procedure was demonstrated by the analysis of other meat (turkey, pork, beef) and seafood (fish, shrimps) products . The method is robust and suitable for routine quality control operations, and more than 200 sample injections were performed without excessive pollution of the mass spectrometer or loss of LC column performance.

Pharm World Sci, 2003 Apr, 25(2), 52 - 5
Hospital pharmacists' reinforcement of guidelines for switching from parenteral to oral antibiotics: a pilot study; von Gunten V et al.; OBJECTIVE: The cost of antibiotics in hospitals may be reduced by streamlining, and, particularly, by early switching from the intravenous (i.v.) to the oral route of administration . The aim of the study was to evaluate the feasibility and impact of guidelines for switching, reinforced by pharmacists . METHOD: Patients admitted to internal medicine wards and treated with i.v . antibiotics for various infections were included for six weeks before (group A) and six weeks after (group B) the intervention . Differences in patient characteristics and their outcomes were sought between the two groups . RESULTS: The 26 patients in group B stayed longer in hospital than the 29 in group A (13.3 vs . 9.7 days; P = 0.05) . They also tended to need more time to reach the pre-defined criteria for switching (3.6 vs . 2.4 days; P = 0.09) . From that point on, they were switched more rapidly to oral antibiotics (1.5 vs . 3.2 days; P = 0.02), which resulted in a trend toward a lower treatment cost until their discharge (44 vs . 92 euros; P = 0.08) . No difference was found between the 2 groups for the duration of the i.v . therapy, or the total in-hospital cost of antibiotics . CONCLUSION: Pharmacists may help implement and reinforce guidelines for switching to oral antibiotics . The evaluation of such interventions implies the choice of appropriate outcomes and the awareness of confounding factors.

Mikrobiol Z, 2003 Jan-Apr, 65(1-2), 168 - 81
{Streptomycetes--producers of polyketide antibiotics}; Matseliukh AB; The review is dedicated to biosynthesis of polyketides compounds by streptomycetes . It contains new data about structure of streptomycete chromosome, structure and action mechanism of polyketidesynthases of I and II types and gene clusters determining the biosynthesis of polyketides . A new promising approach is considered--the combinatorial biosynthesis of hybrid "unnatural" antibiotics by means of gene engineering construction of recombinant strains bearing the biosynthetic genes of bacterial aromatic polyketidesynthases.

Probl Tuberk Bolezn Legk, 2003, (4), 22 - 6
{Role of test therapy with broad-spectrum antibiotics in the diagnosis of nonbacterial tuberculosis}; Gubkina MF; Test therapy with broad-spectrum antibiotics in the diagnosis of abacillary tuberculosis is indicated in the acute onset of the disease, in focal and infiltrative lung tissue changes, marked pulmonary symptoms (cough, auscultative lung changes, fever) . Test therapy can be performed at any stage of diagnosis: in the outpatient setting, in a somatic or tuberculosis hospital . During test therapy, it is irrational to frequently change antibiotics or to use drugs having antituberculous activity (such as fluoroquinolones, rifampicin, most aminoglycosides) . Positive X-ray changes after a course of test therapy with non-specific antibiotics is a diagnostic criterion which suggests that the disease of non-tuberculosis etiology.

Biochem Soc Trans, 2003 Jun, 31(Pt 3), 487 - 92
Antibiotic glycosyltransferases; Walsh CT et al.; In the biosynthesis of several classes of antibiotics, sugars are attached to aglycone scaffolds by antibiotic-specific glycosyltransferases in the latter stages of the pathways . Two glycosylation pathways will be examined: the glycopeptide antibiotics of the vancomycin class and the aminocoumarin antibiotics of the novobiocin class . An oxidatively cross-linked heptapeptide scaffold is sequentially glucosylated and vancosaminylated by GtfE and GtfD, respectively, in vancomycin maturation, while in chloroeremomycin assembly the same heptapeptide is glucosylated by GtfB, then epivancosaminylated at two distinct sites by GtfA and GtfC . The specificity and mechanism of these glycosyltransferases will be discussed . In novobiocin biosynthesis, three enzymes (NovM, NovP and NovN) are thought to act sequentially to transfer an L-noviose moiety to the novobiocic acid aglycone (NovM), followed by 4'-hydroxyl methylation (NovP) and 3'-hydroxyl carbamoylation to produce the mature antibiotic structure, targeting the GyrB subunit of DNA gyrase . Initial characterization of NovM and NovP will be discussed.

Pediatr Pulmonol, 2003 Jul, 36(1), 43 - 8
Duration of effect of intravenous antibiotics on spirometry and sputum cytokines in children with cystic fibrosis; Cunningham S et al.; Intravenous (IV) antibiotics are a mainstay of therapy in children with cystic fibrosis . It is unclear, however, over what period associated improvements in pulmonary function are maintained, and to what extent the underlying inflammatory process is impeded in children admitted for a course of IV antibiotics . This was a prospective, interventional study of 14 children (median age, 14 years; interquartile range, 10-14) with cystic fibrosis who were regular sputum producers and who required admission for a 2-week course of IV antibiotics . Children performed spirometry and provided a sputum sample prior to starting IV antibiotics and then weekly for 6 weeks, the first 2 weeks of which IV antibiotics were given . Sputum IL-8, TNF-alpha, IL-6, IL-10, MIP1-alpha, and elastase were measured . Seven children were asked to repeat the protocol in a subsequent exacerbation to assess similarities in response to therapy . Significant improvements were seen in forced expired volume in 1 sec (FEV(1)) in association with IV antibiotics (27% relative improvement in predicted from baseline to end of week 1, median FEV(1) 41.3% increasing to 52.2%), but this continued only 1 week following cessation of antibiotics . Although IL-8 demonstrated a trend for reduction in association with antibiotics, no significant profile was demonstrated for any of the cytokines assessed . IL-10 was detectable in 64% of samples (all <100 pg/ml) . In children with two episodes assessed, although there was a close correlation of FEV(1) and FVC between exacerbations (before antibiotics), no significant correlation was seen for IL-8, TNF-alpha, or IL-10 measured in both sets of samples at any sample point (indeed, a discordant response was seen between sample points in the two exacerbations) . Although FEV(1) temporarily improves in response to admission for IV antibiotics, no such response is seen in sputum cytokine values . In addition, assessment of cytokines in subsequent exacerbations does not show a similar pattern of response to treatment .

Zhonghua Er Bi Yan Hou Ke Za Zhi, 2000 Apr, 35(2), 94 - 7
{The role of mtDNA deletion in the sensitivity to aminoglycoside antibiotic induced deafness}; Kong W et al.; OBJECTIVE: To establish an animal model of mitochondrial DNA (mtDNA) deletion and investigate the possible role of mtDNA deletion in aminoglycoside antibiotic induced deafness . METHODS: Thirty wistar rats (4 months) were randomly divided into group A and B . Doxorubicin (DOX) was subcutaneously injected at doses of 2 mg/kg twice per week for 3 months in group A and then kanamycin (KM) was intraperitoneally injected 500 mg/kg per day for 10 consecutive days . The treatments of group B were identical to group A, except normal saline was substituted for DOX . The thresholds of auditory brainstem response (ABR) were measured before and after the drug administrations . The inner ear membranous labyrinthine tissue was harvested and mtDNA was amplified to identify 4,834 bp deletion by PCR technique . RESULTS: The elevation of the mean ABR thresholds in group A(67.08 +/- 8.59) dB peSPL was significantly higher than that in group B (12.71 +/- 4.42) dB peSPL after KM administration (P < 0.001) . In group A, 9 of the 15 rats demonstrated 4,834 bp mtDNA deletion . However, mtDNA 4,834 bp deletion was negative in group B animals . CONCLUSION: DOX can induce mtDNA deletion in the inner ear tissue of the rat . mtDNA deletion in the inner ear may play an important role in the hypersensitivity to aminoglycoside antibiotic ototoxicity.

Appl Microbiol Biotechnol, 2003 Jun, 61(5-6), 512 - 6 Epub 2003 Mar 22.
Deletion of scbA enhances antibiotic production in Streptomyces lividans; Butler MJ et al.; Antibiotic production in many streptomycetes is influenced by extracellular gamma-butyrolactone signalling molecules . In this study, the gene scbA, which had been shown previously to be involved in the synthesis of the gamma-butyrolactone SCB1 in Streptomyces coelicolor A3(2), was deleted from the chromosome of Streptomyces lividans 66 . Deletion of scbA eliminated the production of the antibiotic stimulatory activity previously associated with SCB1 in S . coelicolor . When the S . lividans scbA mutant was transformed with a multi-copy plasmid carrying the gene encoding the pathway-specific activator for either actinorhodin or undecylprodigiosin biosynthesis, production of the corresponding antibiotic was elevated significantly compared to the corresponding scbA(+) strain carrying the same plasmid . Consequently, deletion of scbA may be useful in combination with other strategies to construct host strains capable of improved bioactive metabolite production.

J Antibiot (Tokyo), 2003 Mar, 56(3), 232 - 42
Nocathiacins, new thiazolyl peptide antibiotics from Nocardia sp . II . Isolation, characterization, and structure determination; Leet JE et al.; A new group of thiazolyl peptide antibiotics, the nocathiacins, was isolated from cultured broth of Nocardia sp . The major analogs nocathiacins I-III (1-3) were purified using silica gel and Sephadex LH-20 chromatography techniques . The structures of nocathiacins I-III were determined by spectroscopic (2D-NMR, MSn) methods, and share structural similarities to glycothiohexide-alpha (4).

Semin Ophthalmol, 2002 Sep-Dec, 17(3-4), 153 - 61
Antibiotic therapy in post-operative endophthalmitis; Wang RC et al.; Endophthalmitis following routine cataract surgery is a rare but potentially devastating complication resulting in severe vision loss . Various prophylaxis treatments have been tried . However, none have been demonstrated to completely eliminate the risk . The Endophthalmitis Vitrectomy Study (EVS) helped establish clinical guidelines in the treatment of post-operative endophthalmitis in a prospective, randomized, multicenter trial . The strength and limitation of the study will be discussed as well as the current knowledge of the pharmacokinetics of intravitreous injection of antibiotics . Additionally, the common pathologic organisms, the use of antibiotic therapy, steroids, and vitrectomy will be discussed.

Dermatol Clin, 2003 Apr, 21(2), 337 - 48
Antibiotic use in dermatologic surgery; Babcock MD et al.; Few situations in dermatologic surgery require prophylactic antibiotics . The AHA has decreased the dose for endocarditis prophylaxis from antibiotics before and after the procedure to only 1 hour prior to the procedure . In the 1997 guidelines, fewer procedures are listed as requiring antibiotics compared with prior guidelines . In fact, several authors have questioned the efficacy of prophylactic antibiotics . The sequela of endocarditis or an infected prosthetic joint are certainly serious and possibly life-threatening conditions, yet this should not be a justification for using a therapy that is not proven and has potential serious side effects of its own . The authors suggest not using antibiotics on clean or clean-contaminated wounds regardless of cardiac history . Patients with prosthetic joint replacements probably do not need prophylactic antibiotics in cutaneous surgery unless mucosa is invaded; in such cases the guidelines set by the ADA and the AAOS should be followed . The authors believe that antibiotics should be reserved for contaminated or infected wounds when their application is therapeutic . Table 2 contains a summary of the authors' recommendations for the use of antibiotics in cutaneous surgery . Each patient should be evaluated on an individual basis, and consultation with the patient's primary physician, cardiologist, or orthopedist should be sought when the need arises.

Vet Ther, 2003 Spring, 4(1), 94 - 100
Effects of an ethyl lactate shampoo in conjunction with a systemic antibiotic in the treatment of canine superficial bacterial pyoderma in an open-label, nonplacebo-controlled study; de Jaham C; An open-label, nonplacebo-controlled study was designed to compare systemic cephalexin therapy versus systemic cephalexin and ethyl lactate shampoo therapy in the treatment of canine superficial bacterial pyoderma . Twenty client-owned dogs diagnosed with generalized superficial bacterial pyoderma (SP) were alternately assigned to oral treatment with cephalexin (25 to 30 mg/kg every 12 hours) or treatment with cephalexin (as for Group 1) and twice-weekly shampooing with a 10% ethyl lactate shampoo, which was left in contact with the dog's skin for 10 minutes . On Days 14 and 28, skin lesion severity scores, assessed by the investigators, were significantly (P <.01) lower for the group treated with cephalexin and shampoo than for the group treated with cephalexin only . On Day 14, dog owners gave better scores to dogs treated with cephalexin and shampoo for haircoat appearance and body odor than for dogs treated only with cephalexin . Clinical and cytologic resolution of SP occurred significantly (P <.02) sooner in the cephalexin/shampoo group (29.4 days) than in the cephalexin only group (37.8 days).

J Pharm Pharm Sci, 2003 Jan-Apr, 6(1), 67 - 83
Development of liposomal polyene antibiotics: an historical perspective; Ng AW et al.; PURPOSE: The purpose of this review article is to review the development of a number of liposomal polyene antibiotics . BACKGROUND: In the past thirty years, the increase in life-threatening pre-systemic and systemic fungal infections within cancer, diabetic and AIDS patients have reached alarming proportions . A number of antifungal agents have been developed to combat this problem . In particular, polyene antibiotics such as Amphotericin B (AmB) and Nystatin (Nys) have remained the most effective and widely used agents in the treatment of these infections . However, their administration is limited by dose-dependent toxicities . One such dose-limiting toxicity is renal toxicity . Polyene antibiotic-induced renal toxicity is believed to be mediated by the drug anchoring to cholesterol within the mammalian cell membrane, resulting in pore formation, abnormal electrolyte flux, decrease in adenosine triphosphate (ATP), and eventually a loss of cell viability . CONCLUSION: In the 1980s and 90s a number of promising lipid-based AmB and Nys formulations were developed to overcome these toxicities . This article will review the development of these liposomal polyene antibiotics.

Trop Med Int Health, 2003 May, 8(5), 392 - 401
Antibiotic therapy in murine filariasis (Litomosoides sigmodontis): comparative effects of doxycycline and rifampicin on Wolbachia and filarial viability; Volkmann L et al.; The symbiosis of filarial nematodes and rickettsial Wolbachia endobacteria has been exploited as a target for antibiotic therapy of filariasis . Depletion of Wolbachia after tetracycline treatment results in filarial sterility because of interruption of embryogenesis and inhibits larval development and adult worm viability . The aim of this study was to investigate if antibiotic intervention of BALB/c mice infected with the rodent filaria Litomosoides sigmodontis with rifampicin or the combination of rifampicin and doxycycline can be used to shorten the treatment period . Both regimens, when given over a period of 14 days initiated with infection, were sufficient to deplete Wolbachia as evidenced by immunohistology and semiquantitative PCR . Worm development and filarial load were significantly reduced in experiments followed up until 63 days p.i . The therapy inhibited embryogenesis and led to filarial sterility . In contrast, treatment with doxycycline alone for 21 days led only to a modest reduction of Wolbachia, filarial growth retardation, worm viability and fertility . In conclusion, the combination of antirickettsial drugs could be used as a suitable tool to explore the minimum duration of therapy required for the depletion of Wolbachia in parasitized hosts subsequent to the onset of patency in human and animal filariasis and the prevention of adverse reactions in human infections.

Semin Pediatr Infect Dis, 2003 Jan, 14(1), 60 - 3
Biography: Selman A . Waksman, PhD (1888-1973): pioneer in development of antibiotics and Nobel Laureate; Ligon-Borden BL; Selman Abraham Waksman is regarded today as the foremost authority on soil biology . A Nobel Prize recipient for his work on antibiotics, he also coined the term . Waksman started life in humble surroundings in Priluka, the Ukraine, and later, as a young man, emigrated to the United States, where he later became a renowned scientist . His work on antibiotics has changed the lives of many people, far more than he could possibly have imagined . This brief biography seeks to honor this individual and his contributions to the war against infectious diseases .

Br J Community Nurs, 2003 May, 8(5), 209 - 13
Patient group directions for antibiotic supply in Walk-in Centres: how legal are they?
Deave T, Weiss M, Salisbury C.
Until recently antibiotics were only available on prescription . Nurses in NHS Walk-in Centres (WiCs) now supply and administer antibiotics in accordance with patient group directions (PGDs) . The aim of this study was to investigate the process of antibiotic supply from WiCs . Antibiotic PGDs from ten WiCs were selected and medical notes of 50 patients who received an antibiotic at these WiCs were examined to determine compliance with PGD specifications . No consistency of approach in format and content of PGDs was found . PGDs from six WiCs complied with 15/20 or fewer PGD requirements . In the examination of patients' records, 65% of all relevant PGD requirements were explicitly recorded . The breadth and variability of PGDs demonstrates local needs and priorities; however, low compliance levels with PGD requirements provide cause for concern . This article discusses the legality of PGDs, equity in both service provision and advice offered, compliance of medical notes with PGD requirements, implications for patients and WiC nurses, and training implications . Incomplete documentation makes it impossible to verify the quality of care provided across and within WiCs . It also suggests that uncertainty remains around the supply of medicines under PGDs.

J Dermatolog Treat, 2003 Jan, 14(1), 54 - 6
A case of recurrent acute generalized exanthematous pustulosis due to beta-lactam antibiotics: a case report; Mysore V et al.; A case of acute generalized exanthematous pustulosis (AGEP) is presented . The case is notable for the recurrent episodes of AGEP, caused by three beta-lactam antibiotics (piperacillin, ceftazidime, and meropenem) in septicemic patient . The case represents the first report of the reaction developing in response to these three antibiotics . The report is also notable for the spontaneous resolution of the rash in all the three episodes.

Chest, 2003 May, 123(5), 1503 - 11
Impact of initial antibiotic choice on clinical outcomes in community-acquired pneumonia: analysis of a hospital claims-made database; Brown RB et al.; BACKGROUND: Much controversy exists regarding the initial choice of antibiotics and selected outcomes for patients with community-acquired pneumonia (CAP) . METHODS: The investigators analyzed a hospital claims-made database to assess the impact of initial antibiotic choice on 30-day mortality, total hospital costs, and hospital length of stay (LOS) . Fine risk groups allowed for stratification for variations in the severity of illness . Patients were divided into five monotherapy groups (ie, ceftriaxone, "other" cephalosporins, fluoroquinolones, macrolides, or penicillins) and four groups that received dual therapy (ie, the agents listed above, except macrolides) plus macrolides . Patients also were stratified by age (ie, > 65 years of age and < 65 years of age) . Severely ill patients were excluded . RESULTS: Overall, 44,814 persons met the criteria for inclusion . Among monotherapy patients, those who received macrolides had the least mortality but were the least ill . Patients who received dual therapy generally had shorter LOSs, lower total hospital charges, and decreased mortality compared with those who received monotherapy . Differences among dual-therapy regimens regarding outcomes studies were noted . Patients who were < 65 years of age had lower mortality rates, shorter LOSs, and lower hospital charges than did the more elderly patients . Within this group, those who received dual therapy had better outcomes than those who received monotherapy . CONCLUSIONS: We confirmed the value of dual therapy employing macrolides as a second agent in decreasing mortality from CAP, and we provided similar data regarding shorter LOSs and lower hospital charges . This appears to hold for a younger population . Differences among dual-therapy regimens (all employing macrolides) appear to exist and may be clinically relevant.

Pharmacoepidemiol Drug Saf, 2003 Apr-May, 12(3), 213 - 9
Antibiotic prescribing for otitis media: how well does it match published guidelines?
McEwen LN, Farjo R, Foxman B.
Otitis media (OM) accounts for approximately 31 million physician visits annually, and is typically treated with antibiotics . Amoxicillin is the recommended first-line treatment; appropriate antibiotic use slows the development of resistance . We analyzed insurance claims from families of employees working at a single company to determine if OM treatments (1) matched published standards; and (2) varied by patient characteristics, type of physician practice or geographic location . Persons diagnosed with OM between 1996 and 1999 were matched to prescription drug claims for those who filled an antibiotic prescription within 3 days of diagnosis . Physicians prescribed amoxicillin for only 31% of acute cases and 19% of recurrent cases . For acute infections in children < or = 2 years the prescribed duration often matched the standard of 10 days, but for persons > 2 years the prescribed duration was often longer than the suggested duration of 5-7 days . For persons of all ages with recurrent infections, the prescribed duration was often shorter than suggested (10 days versus > or = 14 days) . There were only modest variations by urban/rural location or provider type.

Ann Intern Med, 2003 May 6, 138(9), 697 - 704
Duration of antibiotic therapy for early Lyme disease . A randomized, double-blind, placebo-controlled trial; Wormser GP et al.; BACKGROUND: Treatment of patients with early Lyme disease has trended toward longer duration despite the absence of supporting clinical trials . OBJECTIVE: To evaluate different durations of oral doxycycline treatment and the combination of oral doxycycline and a single intravenous dose of ceftriaxone for treatment of patients with early Lyme disease . DESIGN: Randomized, double-blind, placebo-controlled trial . SETTING: Single-center university hospital . PATIENTS: 180 patients with erythema migrans . INTERVENTION: Ten days of oral doxycycline, with or without a single intravenous dose of ceftriaxone, or 20 days of oral doxycycline . MEASUREMENTS: Outcome was based on clinical observations and neurocognitive testing . Efficacy was assessed at 20 days, 3 months, 12 months, and 30 months . RESULTS: At all time points, the complete response rate was similar for the three treatment groups in both on-study and intention-to-treat analyses . In the on-study analysis, the complete response rate at 30 months was 83.9% in the 20-day doxycycline group, 90.3% in the 10-day doxycycline group, and 86.5% in the doxycycline-ceftriaxone group (P > 0.2) . The only patient with treatment failure (10-day doxycycline group) developed meningitis on day 18 . There were no significant differences in the results of neurocognitive testing among the three treatment groups and a separate control group without Lyme disease . Diarrhea occurred significantly more often in the doxycycline-ceftriaxone group (35%) than in either of the other two groups (P < 0.001) . CONCLUSIONS: Extending treatment with doxycycline from 10 to 20 days or adding one dose of ceftriaxone to the beginning of a 10-day course of doxycycline did not enhance therapeutic efficacy in patients with erythema migrans . Regardless of regimen, objective evidence of treatment failure was extremely rare.

Infez Med, 1999, 7(1), 8 - 23
{Benefit/risk ratio of antibiotic therapy}; Rossi F et al.; This publication evaluates critically the benefit/risk profile of several antibiotics currently at our disposal . The considered antibiotics are divided into pharmacological classes, because generally the drugs of the same class share the same adverse events . Moreover, the high therapeutic profile of the antibiotics puts them at the top of the safest drugs . Therefore the choice of an antibiotic is based above all on the evaluation of the patient and of the pathology to be treated, in terms of severity and possibility of achieving a response to treatment . An accurate anamnesis, the identification of the correct dosage and of the therapy duration minimise the potential risks of the chosen treatment . Detailed knowledge of the safety profile of these drugs is a further element in order for the antibiotic to perform at its best

Pediatrics, 2003 May, 111(5 Pt 1), e548 - 54
Effectiveness of an educational intervention in modifying parental attitudes about antibiotic usage in children; Taylor JA et al.; OBJECTIVE: To determine the effectiveness of educational materials in improving the attitudes of parents of young children about the judicious use of antibiotics . METHODS: We conducted a randomized controlled trial by recruiting parents of children who were younger than 24 months and being seen for any reason in primary care pediatric offices . At the time of enrollment, study parents indicated their level of agreement with 16 statements, including 9 statements about antibiotic usage and 7 about injury prevention . After being randomized, parents received either a pamphlet and a videotape promoting the judicious use of antibiotics (intervention group) or brochures about effective injury prevention (control group) . Six weeks after enrollment, each group received another copy of the pamphlet or brochures and a follow-up questionnaire with the identical 16 statements . Responses on both questionnaires were transformed to an ordinal scale for analysis . Scores on the follow-up questionnaire for each statement about antibiotic use and injury prevention in the 2 groups were compared using linear regression, after controlling for the score obtained for the statement at enrollment . RESULTS: We enrolled a total of 499 eligible parents in the study; 358 (72%) completed the follow-up questionnaires . At study entry, there were no significant differences between parents in the intervention and control groups regarding attitudes for 15 of the 16 statements assessed . However, 6 weeks after receiving the antibiotic educational materials, parents in the intervention group had significantly different attitude scores for 5 of the 9 statements about the antibiotic use . In each case, the scores reflected attitudes that would promote the judicious use of antibiotics . We found significant attitudinal change for statements about the use of antibiotics for specific conditions in children; there were no differences between the 2 groups for more general or theoretical statements about antibiotic use . CONCLUSIONS: A simple educational effort was successful in modifying parental attitudes about the judicious use of antibiotics . Information about specific childhood conditions may be more effective in changing attitudes than more general information about antibiotic usage.

J Pharm Pharmacol, 2003 Mar, 55(3), 313 - 21
Influence of co-administered antibiotics on the pharmacokinetic fate in rats of paeoniflorin and its active metabolite paeonimetabolin-I from Shaoyao-Gancao-tang; He JX et al.; The effects of orally co-administered antibiotics on the pharmacokinetics of paeoniflorin (PF) and paeonimetabolin-I (PM-I), a bioactive metabolite derived from PF by intestinal bacteria, from the traditional Chinese formulation, Shaoyao-Gancao-tang (SGT), were investigated in rats to clarify the effect of administering SGT together with some synthetic drugs . Co-administration of the antibiotics amoxicillin and metronidazole (AMPC-MET) significantly increased the area under the plasma concentration versus time curve (AUC) of PF, whereas it markedly decreased that of PM-I, to 2.6% of the normal AUC by administration of a single dose, and less than 1% by a 3-day pretreatment . Similar effects were observed using the combination of ofloxacin with SGT . The PF-metabolizing activity of intestinal bacteria was reduced to 16% and 33% of normal levels by treatment with AMPC-MET and ofloxacin, respectively, which caused alterations of that degree in the extent of absorption of PF and PM-I, but did not affect their rate of absorption or elimination . The present study suggests that it may not be appropriate to use SGT simultaneously with antibiotics such as AMPC-MET or ofloxacin, and also reveals the important role of intestinal bacteria in the pharmacokinetics of the active components of this traditional Chinese formulation.

J AOAC Int, 2003 Mar-Apr, 86(2), 236 - 40
Simultaneous determination of different antibiotic residues in bovine and in porcine kidneys by solid-phase fluorescence immunoassay; Okerman L et al.; Parallux, a solid-phase fluorescence immunoassay (SPFIA) developed for antibiotic residue detection in milk, was used for analysis of bovine and porcine kidney tissue . Four tetracyclines, 2 broad-spectrum cephalosporins, 3 beta-lactam antibiotics, and cephapirin were detected in one run after minimal sample preparation . This commercially available test system is designed as cartridges, each with a combination of 1-4 tests . One cartridge can be used to detect 4 analytes in the same sample, or 1 or 2 analytes in different samples . The cartridge with the combination tetracyclines-ceftiofur-penicillin-cephapirin was selected because tetracyclines, beta-lactam antibiotics as well as cephalosporins, are registered for oral or parenteral use in bovines and pigs in Europe . The test is qualitative and is recommended only for screening . Tetracycline, oxytetracycline, chlortetracycline, and doxycycline were easily detected at 300 ppb with the tetracyclines channel; ceftiofur at 1000 ppb and cefquinome at 200 ppb with the ceftiofur channel; penicillin G, ampicillin, and amoxicillin at 50 ppb with the penicillin channel; and cephapirin at 100 ppb with the cephapirin channel . These levels are equal to or lower than the corresponding maximal residue limits in kidney tissue . Cephalexin was not detected . The SPFIA test can be used as an alternative to classical inhibition tests and for post-screening inhibitor- positive kidneys, because it detects 3 specific groups of antibiotics, which enables selection of specific confirmatory methods for identification and quantification.

Int J Clin Pract, 2003 Apr, 57(3), 167 - 9
Why do family doctors prescribe antibiotics for upper respiratory tract infection?
Lam TP, Lam KF.
The prescribing behaviour of family doctors in Hong Kong towards upper respiratory tract infections (URTIs), and the major clinical factors that might affect such behaviour, were studied . Members of the Hong Kong College of Family Physicians were surveyed; 801 completed the questionnaire with an overall response rate of 65% . Purulent nasal discharge, purulent sputum, persistent fever over three days, patients looking unwell, exudates on throat, inflamed eardrums and cervical lymphadenopathy made more than half the respondents 'likely' or 'very likely' to prescribe antibiotics . Those in private practice and those who graduated in Hong Kong were more likely to prescribe antibiotics, while fellows of the College were less likely to do so . Vocational training and higher qualifications in family medicine/general practice, however, revealed minimal effect . Our results showed that many doctors are still prescribing antibiotics when they encounter URTI patients presenting with clinical factors that have been proven to have no or little benefit from antibiotics.

Clin Rev Allergy Immunol, 2003 Jun, 24(3), 221 - 8
Hypersensitivity reactions to non-beta-lactam antibiotics; Tilles SA et al.; As alternatives to beta lactam antibiotics continue to be developed, an increasing number of patients are experiencing hypersensitivity reactions to these agents . Unfortunately, unlike penicillin, there are no validated skin testing reagents to aid in confirming the presence of specific IgE antibodies to these drugs . This review summarizes what is known about hypersensitivity reactions to non-beta lactam antibiotics, and includes practical approaches to readministering these drugs in selected situations . Sulfonamides, vancomycin, macrolides, tetracyclines, fluoroquinolones, and anti-virals are included in the discussion.

Clin Rev Allergy Immunol, 2003 Jun, 24(3), 201 - 20
Hypersensitivity reactions to beta-lactam antibiotics; Solensky R; Clinicians commonly encounter patients with a history of allergy to penicillin and other beta-lactam antibiotics, since about 10% of the population reports such an allergy . At the same time, it is known that about 90% of these patients are not truly allergic and could safely receive beta-lactam antibiotics . Instead, these patients are treated unnecessarily with alternate broad-spectrum antibiotics, which increases costs and contributes to the development and spread of multiple drug-resistant bacteria . In the case of penicillin, relevant allergenic determinants that elicit immune responses are known . Hence, validated diagnostic skin testing to detect the presence of drug-specific IgE antibodies is available . For non-penicillin beta-lactams, the immunogenic determinants that are produced by degradation are unknown, and diagnostic skin testing is of more limited value . Ideally, patients with a history of penicillin allergy should be evaluated when they are well and not in immediate need of antibiotic therapy . Patients who are found to be penicillin skin test-negative may be safely treated with all beta-lactam antibiotics . Penicillin skin test-positive patients should only receive a penicillin-class antibiotic via rapid desensitization, and only in cases when an alternative agent cannot be substituted . Penicillin skin test-positive patients may be safely treated with monobactams . The extent of allergic cross-reactivity between penicillin arid cephalosporins/carbapenems is uncertain; therefore penicillin skin test-positive patients should only receive these antibiotics via cautious graded challenge or desensitization . Identification of patients who erroneously carry a label of beta-lactam allergy leads to improved utilization of antibiotics and slows the spread of multiple drug-resistant bacteria.

Biomed Chromatogr, 2003 Mar-Apr, 17(2-3), 172 - 81
Analysis of glycopeptide antibiotics using micellar electrokinetic chromatography and borate complexation; Lucas C et al.; Micellar electrokinetic chromatography (MEKC) was investigated as a technique for the separation and analysis of the following related glycopeptide antibiotics: alpha-avoparcin, beta-avoparcin, ristocetin A, ristocetin B and vancomycin . Sodium dodecyl sulfate (SDS) micelles were employed as the pseudostationary phase in conjunction with borate or CHES buffers at pH 9.2 . A complete separation of the glycopeptides was achieved only when two separation mechanisms were employed simultaneously: (i) differential partitioning of the glycopeptides into SDS micelles; and (ii) differential complexation of the glycopeptides with the borate anion from the borate buffer . Quantitatively, linearity was confirmed for each antibiotic from 0.5 to 40 ppm, with correlation coefficients (r(2)) ranging from 0.9996 (vancomycin and beta-avoparcin) to 0.9986 (alpha-avoparcin) . Detection limits ranging from 0.01 ppm (vancomycin) to 0.2 ppm (avoparcin) were achieved, and the mean recovery of avoparcin at the 10 ppm level was 99.2% .

Bull Exp Biol Med, 2003 Jan, 135(1), 103 - 5
Comparison of cytotoxicity of aminoglycoside antibiotics using a panel cellular biotest system; Chernikov VG et al.; The cytotoxicity of four aminoglycoside antibiotics was studied by estimation of the dose-effect relationship using a panel cellular biotest system including cell cultures for test objects . The cultures represented 4 differentiation types: normal human fibroblasts and myoblasts, human or Syrian hamster hepatoma cells, and mouse/mouse hybridoma cells . It was found that three widely used antibiotics gentamicin, kanamycin, and neomycin exhibit similar, but not identical cytotoxicity parameters and differ distinctly from geneticin . Hence, the proposed panel biotest system helps to quantitatively evaluate and differentiate the effects of bioactive substances with similar chemical structure.

Pancreas, 2003 May, 26(4), 363 - 7
The effect of antibiotic and probiotic combination therapy on secondary pancreatic infections and oxidative stress parameters in experimental acute necrotizing pancreatitis; Akyol S et al.; INTRODUCTION: Ciprofloxacin and meropenem have effects on intestinal bacteria that are responsible for pancreatic infection, and on the basis of recent data it has been argued that probiotics, especially those used in the food industry, could improve efforts to prevent and treat secondary pancreatic infections by inhibiting bacterial translocation . AIMS: To evaluate the effects of probiotic treatment alone or in combination with early administration of two different antibiotics on serum amylase, pancreatic histopathology, bacterial translocation, and oxidative markers . METHODOLOGY: Acute pancreatitis was induced in rats with 3% sodium taurocholate (1 mL/kg intraductally), except in group VI (sham group) . After the stabilization period, the rats were divided into seven groups (n = 20) randomly . At hour 6 after injection, group I rats received probiotic Saccharomyces boulardii (25 mg/d orally q.d.), group II received meropenem (60 mg/kg intraperitoneally b.i.d.), group III received ciprofloxacin (40 mg/kg intraperitoneally b.i.d.), group IV received the same dose of probiotic plus meropenem, and group V received probiotic plus ciprofloxacin . Treatment was not given to group VI (sham group) and group VII (pancreatitis group) . At hour 48 after induction, specimens were collected . RESULTS AND CONCLUSION: Although histopathologic scores in treatment groups were found to be lower than in group VII, the difference was statistically significant only in group V (p < 0.001) . In evaluation of oxidative stress, we found that MDA levels decreased and SOD levels increased in treatment groups in comparison with levels in group VII . Probiotic treatment alone reduced bacterial translocation . Probiotic-antibiotic combination therapy was shown to improve histopathologic scores and oxidative parameters.

Presse Med, 2003 Apr 5, 32(13 Pt 1), 615 - 9
{The impact of fusafungine on the prescription of antibiotics in the treatment of rhinopharyngitis}; Laccourreye O et al.; OBJECTIVE: The analysis in France, during the period 01/12/99 to 30/11/2000, of the prescription of systemic antibiotics in patients with rhinopharyngitis and of the variables statistically related to such prescriptions and the potential role of fusafungine in the form of a rhinopharyngeal spray . METHODS: A retrospective study, based on a panel of 1,010 general practitioners, in a cohort of 30,568 patients presenting with rhinopharyngitis . The fusafungine group consisted of 16,076 patients who had rhinopharyngitis and in whom fusafungine was prescribed . The control group consisted of 14,492 patients with rhinopharyngitis without prescription of fusafungine . The overall rate of antibiotic prescription was documented . A stepwise statistical analysis was conducted to specify the variables statistically associated with the prescription of a systemic antibiotic . The rate of prescription of a systemic antibiotic and the cost of the treatment were also compared within both groups . RESULTS: The overall rate of systemic antibiotic prescription was 52.9%, falling from 60.4% in the group without fusafungine down to 46.2% in the group with fusafungine (p<0.01) whichever the systemic antibiotic prescribed . The stepwise analysis documented various variables that appear to be related to the systemic antibiotic prescription . A saving of 0.7 euros per prescription was noted in the fusafungine group . CONCLUSION: Although various variables appear to influence systemic antibiotic prescription in patients with rhinopharyngitis, our study shows that prescription of fusafungine in spray from led to statistically significant reduction in systemic antibiotic prescription.

Minerva Ginecol, 2003 Apr, 55(2), 175 - 87
{Use of antibiotics in prevention and therapy in obstetrics and gynaecologic surgery}; Nedicova N et al.; BACKGROUND: The antibiotic treatments employed in 1999 in cases of gynaecologic and obstetric surgery in the first clinic of the Gynaecology and Obstetrics Department of the University of Turin have been evaluated . METHODS: 1131 gynaecological operations (major interventions, minor interventions, laparoscopies) and 492 laparotomic operations in obstetrics (mostly Cesareans) were assessed . Modalities of administration of chemoantibiotics (CAB) both at the prophylaxis stage and during the therapy stage were evaluated . RESULTS: A great application of chemoantibiotic prophylaxis (CABP) was noted as regards the gynaecological interventions (57.4% of cases) and low resort to chemoantibiotic therapy (CABT) (9%), thus highlighting the effectiveness of prophylaxis in reducing the incidence of infectious complications in the postoperative course in gynaecological surgery . As for obstetrics, the low percentage resort to CABP (36%) and the high resort to CABT (26%) were noted . It is proposed to obviate this fact by increasing the number of cases of CABP for obstetrics so as to reduce the massive recourse to CABT . CONCLUSIONS: Finally, some pharmacoeconomic remarks are offered regarding the rationalisation of the use of CABs in hospital surgical obstetrics and gynaecology.

Infez Med, 2000, 8(3), 156 - 166
{Pharmaco-economic evaluation of antibiotic therapy in a ward for infections diseases}; Sabbatani S et al.; For all hospitalized patients admitted in the first six months of 1999, we recorded the data relative to antibiotic therapy (TA) administered, establishing the period of treatment in days and the dosage, including any variations during the period in question . We calculated the prescribed daily dose (PDD) and were thus able to establish the expense incurred in antibiotic therapy, comparing the real overall cost per product used . For all patients, the discharge diagnosis was reported, and the whole case-study was aggregated into homogeneous groups . PDD was compared with DDD (defined daily doses) . The Pareto curve was used to highlight the antibiotics with higher overall cost . Besides cotrimoxazole, ceftriaxone and ciprofloxacin were the antibiotics most frequently prescribed, while ceftriaxone, imipenem-cilastatine and vancomycin were the antibiotics incurring the greatest expense . With reference to the average duration of the treatment cycle, ceftriaxone (9.75 dd) and ciprofloxacin tbl (6.75 dd) were the only antibiotics (in monotherapy) used for less than 10 treatment days . Special attention was paid to analysing the TA costs in treating pneumonia, which accounted for the highest percentage of cases (50 cases) . Ceftriaxone, especially pulmonary infections, was the most commonly used drug . In hospitalized subjects treated who show good therapeutic response, we recommend early discharge and continuation of the therapy at home (switch therapy) . This strategy will allow the patient to return to his/her family in good time, also thereby reducing hospital management costs.

Infez Med, 2000, 8(2), 95 - 100
{Epidemiology and sensitivity to antibiotics in paediatric respiratory infections over a 4-year period . Retrospective study of 460 H . influenzae, S . pneumoniae and M . catarrhalis strains}; Manno G et al.; H . influenzae, S . pneumoniae and M . catarrhalis are the most common bacterial pathogens causing respiratory infections in children . Resistance to antibiotics may vary according to the geographical area . It is therefore important that the resistance pattern of such pathogens is determined by surveillance studies carried out both on a national scale and by individual laboratories . In this study, we determined retrospectively the prevalence of H . influenzae, S . pneumoniae and M . catarrhalis in upper respiratory tract infections involving subjects of paediatric age, with reference to the type of clinical sample (pharingeal swab and nasal swab), symptomatology and age group . Moreover, for the above micro-organisms the pattern of sensitivity to antibiotics was assessed . In the observation period (January 1996-December 1999), at the day hospital of the Paediatric Pneumology Division of the Gaslini Institute in Genova, in 476 patients between 0 and 15 years of age a total of 460 respiratory pathogens were isolated: 164 S . pneumoniae strains, 163 of H . influenzae (96 belonging to type B and 67 non-attributable to any type) and 133 of M . catarrhalis . As regards sensitivity to antibiotics, ceftriaxone and amoxycillin/clavulanic acid proved to be the most active molecules in all the studied strains.

Infez Med, 2000, 8(2), 74 - 81
{Antibiotics and kidney}; Nardiello S et al.; Renal excretion is the most important route of elimination for the majority of antibiotics, and some antibiotics may cause renal injury by direct and/or immunologic mechanisms . These conditions determine a dose relationship between antibiotic therapy and renal function . In this review we report some practical guidelines for the correct administration of antibiotics in patients with decreased renal function . Currently used antibiotics that are most frequently associated to nephrotoxicity are also examined, and for each of them the incidence and degree of renal damage, pathogenic mechanisms and preventive measures are reported . This review emphasizes the need for a careful assessment of renal function in patients with acute and chronic infections undergoing antibiotic therapy.

Amino Acids, 2003 Apr, 24(3), 311 - 23
Solution phase synthesis of the 14-residue peptaibol antibiotic trichovirin I; Bruckner H et al.; The 14-residue peptaibol antibiotic trichovirin I 4A of the structure Ac-Aib-L-Asn-L-Leu-Aib-L-Pro-L-Ala-L-Val-Aib-L-Pro-Aib-L-Leu-Aib-L-Pro-L-Leuol (Aib = alpha-aminoisobutyric acid, Leuol = leucinol) was synthesized by stepwise conventional solution phase synthesis using the Z/O tBu(OMe) strategy and HOBt/EDC as coupling reagents . Intermediates were fully characterized and the identity of the synthetic peptide with the component 4A of the natural, microheterogeneous peptide mixture was proven by electrospray mass spectrometry, HPLC, and bioassay.

Anal Bioanal Chem, 2003 Apr, 375(7), 942 - 7 Epub 2003 Mar 15.
Determination of antibiotics such as macrolides, ionophores and tiamulin in liquid manure by HPLC-MS/MS; Schlusener MP et al.; A method for the analysis of several macrolide and ionophore antibiotics as well as tiamulin in liquid manure was developed . Reversed-phase liquid chromatography and atmospheric pressure chemical ionisation (APCI) tandem mass spectrometry was used for detection.High-performance liquid chromatographic (HPLC) separation of the antibiotics was achieved in 35 min . The analytes were extracted with ethyl acetate and the extracts were cleaned up by solid-phase extraction on a diol SPE cartridge . Recovery experiments with spiked liquid manure concentrations varying from 6 to 2,000 microg kg(-1) gave constant recovery rates . The recovery rates for the macrolides erythromycin, roxithromycin and oleandomycin were 75-94%, that for the ionophore salinomycin was 119%, while that for the pleuromutilin tiamulin was 123%, when using a macrolide internal standard . The relative standard deviation was found to be 15-36% and the limits of detection were 0.4-11.0 micro g kg(-1).The maximum concentrations found in manure samples were 43 micro g kg(-1) for tiamulin and 11 micro g kg(-1) for salinomycin.

Microb Drug Resist, 2003 Spring, 9(1), 93 - 7
Effect of restoration of children's teeth with mercury amalgam on the prevalence of mercury- and antibiotic-resistant oral bacteria; Pike R et al.; The purpose of this study was to determine whether placement of mercury amalgam restorations in children's teeth induces an increase in oral bacteria resistant to mercury, penicillin, ampicillin, erythromycin, or tetracycline . Dental plaque and saliva samples from 16 children without mercury amalgam restorations were screened for bacteria resistant to mercury or to one of the antibiotics prior to, and 1 month after, placement of the amalgam restoration . Following amalgam placement, there was no significant increase in the number of children harboring bacteria resistant to mercury, penicillin, ampicillin, erythromycin, or tetracycline; neither was there an increase in the proportions of such organisms . This study has shown that the presence of mercury restorations in children's teeth has little effect on the prevalence of mercury- or antibiotic-resistant oral bacteria.

Infez Med, 2002 Sep, 10(3), 169 - 75
{Outpatient Parenteral Antibiotic Therapy (OPAT): the Italian registry}; Esposito S et al.; In the early eighties, in the US the advantages (reduced costs, no hospitalisation trauma in children, no immobilization syndrome in elderly, reduction of nosocomial and acquired infections by multi-resistant organisms) of OPAT were identified and suitable therapeutic programs were established . Following the US experience, other countries set up their own OPAT programs which vary considerably from country to country because of different ways in which infections are managed in different parts of the world and because of different reimbursement systems . In order to understand the ways of managing OPAT and its results, a National OPAT Registry was set up in 1999 in Italy belonging to a wider International OPAT database, which collects data also from USA, Canada, Spain, Uruguay and Argentina . Up to now 396 patients and as many antibiotic courses have been included in the National Registry by eight different centres . The analysis of data permits to get information about the criteria of patient's selection, treatment (route of administration, site of care, choice of antibiotic, dosage and duration), outcomes and possible side-effects . Italian results offer a quite peculiar picture of OPAT in this country when comparing data with those of other countries . In contrast with other countries where soft tissue infections and osteomyelitis are the most frequent diagnoses for including patients in OPAT programmes, in Italy pneumonia and bronchitis are the top two amenable infections . Ceftriaxone, Teicoplanin and Amikacin are absolutely the top three antibiotics selected for OPAT in Italy which confirm that a single daily dose regimen represents a great advantage in terms of compliance . Finally, a large percentage of antibiotic courses (50%) are carried out by using the i.m . administration route, which is very unusual in other countries . OPAT Registry is still ongoing and it will give us more detailed information in the future about the management of infections in the outpatient setting, but it already permits to define an actual picture of OPAT in our country and/or to compare and correlate data and information from different countries.

Indian J Ophthalmol, 2003 Mar, 51(1), 39 - 44
Role of prophylactic intravitreal antibiotics in open globe injuries; Narang S et al.; PURPOSE: To determine the efficacy of prophylactic intravitreal antibiotics in reducing the incidence of endophthalmitis after trauma . METHODS: This was a prospective, randomised, case control study of 70 consecutive patients with open globe injury . The patients were prospectively randomised into group I (32 eyes) and group II (38 eyes) . Group I patients were given prophylactic intravitreal injection of vancomycin 1 mg and ceftazidime 2.25 mg at the conclusion of primary repair . Group II patients were not given prophylactic intravitreal antibiotics . All the patients received intravenous ciprofloxacin . RESULTS: The incidence of endophthalmitis was higher in group II (7 of 38 eyes; 18.42%) compared to group I (2 of 32 eyes; 6.25%) . Both the patients who developed endophthalmitis despite prophylactic intravitreal antibiotics in group I had an initially undetected intraocular foreign body (eyelash) in the vitreous cavity . CONCLUSIONS: Prophylactic intravitreal broad spectrum antibiotic injection decreases the risk of post-traumatic endophthalmitis.

Biochemistry, 2003 Apr 15, 42(14), 4179 - 89
Initial characterization of novobiocic acid noviosyl transferase activity of NovM in biosynthesis of the antibiotic novobiocin; Freel Meyers CL et al.; The aminocoumarin class of antibiotics, exemplified by novobiocin, is composed of tripartite l-noviosylaminocoumarin prenylbenzoate natural products . The decorated noviosyl sugar component interacts with the target bacterial enzyme DNA gyrase . We have subcloned the putative 40 kDa l-noviosyl transferase from Streptomyces spheroides into Escherichia coli, expressed it in soluble form, and purified it to homogeneity as a C-terminal His(8) fusion protein . The aglycone novobiocic acid, obtained from selective degradation of novobiocin, and TDP-l-noviose, obtained by an 11-step chemical synthesis from l-rhamnose, were shown to be robust substrates for NovM to produce the desmethyldescarbamoyl novobiocin intermediate with a k(cat) of >300 min(-1) . NovM displays activity with variant coumarin aglycones, suggesting it may be a promiscuous catalyst for noviosylation of a range of planar scaffolds . Conversely, NovM shows no activity with and is inhibited by TDP-l-rhamnose (K(i) = 83.5 +/- 5.5 microM), the sugar donor that most closely structurally resembles the natural substrate TDP-l-noviose . The NovM reaction products generated during the course of this work will serve as substrates for subsequent analysis of the NovP and NovN tailoring enzymes that impart the noviose decorations required for DNA gyrase binding and antibiotic activity.

J Am Acad Orthop Surg, 2003 Jan-Feb, 11(1), 38 - 47
Use of antibiotic-impregnated cement in total joint arthroplasty; Joseph TN et al.; The use of antibiotic-impregnated cement in revision of total hip arthroplasty procedures is widespread, and a substantial body of evidence demonstrates its efficacy in infection prevention and treatment . However, it is not clear that it is necessary or desirable as a routine means of prophylaxis in primary total joint arthroplasty . In the management of infected implant sites, antibiotic-impregnated cement used in one-stage exchange arthroplasties has lowered reinfection rates . In two-stage procedures, use of beads and either articulating or nonarticulating antibiotic-impregnated cement spacers also has lowered reinfection rates . In addition, spacers reduce "dead space," help stabilize the limb, and facilitate reimplantation . Problems associated with antibiotic-impregnated cement in total joint arthroplasty include weakening of the cement and the generation of antibiotic-resistant bacteria in infected implant sites.

Antibiot Khimioter, 2002, 47(11), 13 - 7
{Efficacy of some new antibiotics in treating experimental brucellosis}; Maletskaia OV; Brucella pathogens are highly susceptible in vitro to pefloxacin, lomefloxacin, meropenem and azithromycin . High efficacy of these drugs was demonstrated for experimental brucellosis treatment, azithromycin being the most active . Meropenem and azithromycin implementation resulted in more rapid and full normalization of the bactericidial and energy systems of the experimental animals peripheral blood cells.

Appl Microbiol Biotechnol, 2003 May, 61(3), 179 - 88 Epub 2002 Dec 18.
Polyene antibiotic biosynthesis gene clusters; Aparicio JF et al.; Over the past 15 years the biosynthetic gene clusters for numerous bioactive polyketides have been intensively studied and recently this work has been extended to the antifungal polyene macrolides . These compounds consist of large macrolactone rings that have a characteristic series of conjugated double bonds, as well as an exocyclic carboxyl group and an unusual mycosamine sugar . The biosynthetic gene clusters for nystatin, pimaricin, amphotericin and candicidin have been investigated in detail . These clusters contain the largest modular polyketide synthase genes reported to date . This body of work also provides insights into the enzymes catalysing the unusual post-polyketide modifications, and the genes regulating antibiotic biosynthesis . The sequences also provide clues about the evolutionary origins of polyene biosynthetic genes . Successful genetic manipulation of the producing organisms leading to production of polyene analogues indicates good prospects for generating improved antifungal compounds via genetic engineering.

Eur J Ophthalmol, 2003 Mar, 13(2), 155 - 61
The effects of some antibiotics on sheep lens glucose 6-phosphate dehydrogenase in vitro; Beydemir S et al.; PURPOSE: To investigate the in vitro effects of gentamicin sulfate, vancomycin hydrochloride, sodium cefazolin and ceftriaxone on glucose 6-phosphate dehydrogenase enzyme (G6PD) purified from sheep lenses . METHODS: G6PD was purified from sheep lenses with a yield of 66.8% and a specific activity of 7.8 U/mg proteins, and 10,400-fold using ammonium sulfate fractionation and 2',5'-ADP Sepharose 4B affinity gel . The enzyme activity was determined by Beutler's method . RESULTS: Gentamicin sulfate and vancomycin hydrochloride strongly inhibited the enzyme in vitro . The concentrations causing 50% inhibition (IC50 were 15.34, and 8.0 mM, respectively . Conversely, cefazolin sodium strongly activated this enzyme, and ceftriaxone caused milder activation . CONCLUSIONS: If a patient with G6PD deficiency requires gentamicin sulfate or vancomycin hydrochloride, routine ophthalmic did not inhibit this enzyme . Postmortem studies are now needed to investigate the activity of G6PD and how it is affected by these antibiotics.

Arch Intern Med, 2003 Apr 14, 163(7), 797 - 802
Antibiotic therapy for ambulatory patients with community-acquired pneumonia in an emergency department setting; Malcolm C et al.; BACKGROUND: Little attention has been paid to the factors that influence choice of antibiotic therapy for patients with community-acquired pneumonia who are treated on an ambulatory basis in an emergency department setting . METHODS: Prospective observational study of all patients who presented to the 6 hospitals for adults in the Capital Health Authority, Edmonton, Alberta, with community-acquired pneumonia (as diagnosed by the emergency department physician) from November 15, 2000, through April 30, 2001, and who were treated on an ambulatory basis . RESULTS: The study population consisted of 768 patients, mean age 51 years . The antibiotics most commonly prescribed were azithromycin (36%), levofloxacin (32%), and clarithromycin (17%) . Site of care differences were evident in the frequency of clarithromycin (P<.001) and levofloxacin (P =.01) prescription . Multiple logistic regression analysis showed that older age, presence of chronic obstructive pulmonary disease, antibiotic therapy at the time of presentation, and site of care were factors independently predictive of levofloxacin use (P<.05 for all factors) . Levofloxacin prescription did not follow our indications for its use in 51% of the 245 patients who were treated with this antibiotic . The failure rate (defined as admission to the hospital within 3 weeks of emergency department visit) was low (2.2%) . CONCLUSIONS: Patient factors and site of care influence the choice of antibiotic therapy in an ambulatory setting, and 50% of levofloxacin use was inappropriate according to our definition.

Arch Pediatr Adolesc Med, 2003 Apr, 157(4), 369 - 74
Acute care and antibiotic seeking for upper respiratory tract infections for children in day care: parental knowledge and day care center policies; Friedman JF et al.; BACKGROUND: Children who attend day care are high consumers of antibiotics . Studies suggest that physicians prescribe unnecessary antibiotics for upper respiratory tract infections (URIs) for children who attend day care on the basis of perceived pressure from parents and/or day care centers . OBJECTIVE: To determine both parental and day care-level predictors of acute care and antibiotic seeking for children who attend day care . METHODS: We conducted a day care center-based cross-sectional survey of parents and day care center staff . Two hundred eleven parents of children attending 36 day care centers in Massachusetts completed a survey . Day care center staff completed a separate survey addressing their day care center's policies for ill children . RESULTS: Few parents reported day care staff pressure to seek care from a physician (3.9%) or antibiotics (1.9%) . In multivariate models, higher parental knowledge about URIs was related to decreased acute care seeking for 3 upper respiratory symptoms (clear rhinorrhea, green rhinorrhea, and cough) in the absence of fever (odds ratios and 95% confidence intervals: 0.45 {0.31-0.65}, 0.66 {0.52-0.85}, and 0.57 {0.45-0.72}, respectively) . Parent-reported acute care seeking was not related to a day care center's polices for exclusion or physician clearance for these illnesses . Similar results were also found for the parental belief that antibiotics expedite return to day care for these symptoms . CONCLUSION: Although it has been suggested that inappropriate day care center policies for exclusion motivate parental acute care and antibiotic seeking, this study suggests that parental knowledge is a more important predictor of these reported behaviors than are day care center policies.

Kaohsiung J Med Sci, 2003 Jan, 19(1), 6 - 12
Biological evaluation of an antibiotic DC-81-indole conjugate agent in human melanoma cell lines; Hu WP et al.; Pyrrolo{2, 1-c}{1, 4}benzodiazepines (PBDs) are potent inhibitors of nucleic acid synthesis because of their ability to recognize and bind to specific sequences of DNA and form a labile covalent adduct . DC-81, an antitumor antibiotic produced by Streptomyces species, is a PBD . We combined DC-81 and an indole carboxylate moiety to synthesize a hybrid designed to have much higher sequence selectivity in DNA interactivity . In this paper, the cytotoxic potency of the hybrid in human melanoma cell lines was studied . XTT assay demonstrated that the DC-81-indole conjugate possessed cytotoxicity against human melanoma cell lines.

Shock, 2003 Apr, 19(4), 310 - 3
Effects of age on mortality and antibiotic efficacy in cecal ligation and puncture; Turnbull IR et al.; The incidence and mortality of sepsis increase with age, consequently, 80% of the clinical mortality from sepsis occurs in patients over age 65 . Despite this aged clinical population, most research models of sepsis use 6- to 16-week-old mice as patient surrogates . This age range of mice corresponds to human ages 10 to 17 years . To assess the influence of age on rodent CLP and on antibiotic therapy, we studied young (4 month), mature (12 month), and aged (24 month) mice . Male C57BL/6 mice (n = 27-30 in each age group) were subjected to cecal ligation and puncture (CLP), two punctures with a 25-gauge needle . Mice were observed untreated for 10 days . Young mice had 20% mortality, mature mice had 70% mortality (P = 0.0013 vs . young), and aged mice had 75% mortality (P = 0.0001 vs . young) . To assess the effects of age on antibiotic therapy, mice were subjected to CLP as above (n = 38-40 in each age group) . Mice were then randomized to treatment with intraperitoneal injections of ceftriaxone and metronidazole or normal saline . Therapy was initiated 12 h after CLP, and injections were repeated every 12 h for 7 days . Young mice saw a 56% decrease in mortality from CLP with antibiotic therapy (P = 0.001), and mature mice had a 30% decrease in mortality (P = 0.06) . Aged mice saw no benefit from antibiotic therapy . We also compared plasma cytokine levels between young and aged mice after CLP . When compared with young mice, aged mice had higher levels of IL-6 and TNF-alpha 24 h after CLP . However, high IL-6 was predictive of mortality at any age . Mice appear to have age-dependent responses to intra-abdominal sepsis and to appropriate therapy.

Mol Biol Rep, 2003 Mar, 30(1), 9 - 14
Kinetics of inhibition of ribonuclease P activity by peptidyltransferase inhibitors . Effect of antibiotics on RNase P; Kalavrizioti D et al.; A cell-free system derived from Dictyostelium discoideum has been used to study the kinetics of inhibition of RNase P by puromycin, amicetin and blasticidin S . Detailed kinetic analysis showed that the type of inhibition of RNase P activity by puromycin is simple competitive, whereas the type of inhibition by amicetin and blasticidin S is simple non-competitive . On the basis of Ki values amicetin is stronger inhibitor than puromycin and blasticidin S.

HNO, 2003 Apr, 51(4), 315 - 20
{The treatment of necrotizing otitis externa with a combination of surgery, antibiotics, specific immunoglobulins and hyperbaric oxygen therapy . Results of the Ulm Treatment Concept}; Tisch M et al.; BACKGROUND: Even today, necrotizing otitis externa is still a life-threatening condition . The standard treatment concepts based on antibiotic therapy, topical treatment and--if necessary--surgical debridement of necrotic tissue, remain ineffective in many cases . In advanced stages, necrotizing otitis externa can therefore be expected to result in severe functional impairment or even a fatal outcome . PATIENTS AND METHODS: We describe our experience with a multimodal treatment concept that we have been using with great success at the Federal Armed Forces Hospital in Ulm since 1987 . This treatment is based on four pillars: 1 . Surgical debridement, 2 . Use of a combination of antibiotics, and 3 . Administration of specific immunoglobulins, accompanied by, 4 . Hyperbaric oxygen therapy RESULTS: Over a period of more than 5 years 16 of the 22 patients treated on the basis of this multimodal concept remained free of recurrences . In addition, significant reductions in analgesic use and in the insulin doses needed by diabetic patients were possible . CONCLUSIONS: The treatment concept under scrutiny has proved particularly successful . The various modes involved and the results of this combined therapy are discussed.

Anal Bioanal Chem, 2003 May, 376(1), 42 - 8 Epub 2003 Apr 10.
Resonance Rayleigh scattering spectra for studying the interaction of aminoglycoside antibiotics with pontamine sky blue and their analytical applications; Hu XL et al.; In a weakly acid medium, some aminoglycoside antibiotics, such as kanamycin (KANA), gentamicin (GEN), tobramycin (TOB), and neomycin (NEO), or acid bisazo dye pontamine sky blue (PSB) can only produce very weak resonance Rayleigh scattering (RRS) signals . However, when the two agents react with each other to form the ion association complexes, the RRS intensity can be enhanced greatly and a new RRS spectrum and a significant enhancement of the RRS intensity in the wavelength range 350-600 nm can be observed . The maximum scattering peak is at 580 nm . There is a linear relationship between the RRS intensity and the antibiotic concentration in the range 0.01-6.0 microg mL(-1) at 580 nm . This RRS method has therefore been developed for the determination of trace levels of aminoglycoside antibiotics . The detection limits (3 sigma) of the four antibiotics, whose order of sensitivity is KANA>NEO>TOB>GEN, are 5.8-6.9 ng mL(-1) . This method has a good selectivity and has been successfully applied to the quick determination of antibiotics not only for injections and ear drops, but clinic serum samples as well . In addition, quantum chemistry-based analysis of the reaction mechanism, the factors influencing the RRS spectra, and the reasons for the enhancement of RRS are discussed.

J Am Soc Mass Spectrom, 2003 Apr, 14(4), 302 - 10
An antibiotic linked to peptides and proteins is released by electron capture dissociation fourier transform ion cyclotron resonance mass spectrometry; Fagerquist CK et al.; Desfuroylceftiofur (DFC) is a bioactive beta-lactam antibiotic metabolite that has a free thiol group . Previous experiments have shown release of DFC from plasma extracts after addition of a disulfide reducing agent, suggesting that DFC may be bound to plasma and tissue proteins through disulfide bonds . We have reacted DFC with {Arg(8)}-vasopressin (which has one disulfide bond) and bovine insulin (which has three disulfide bonds) and analyzed the reaction products by use of electron capture dissociation Fourier transform ion cyclotron resonance mass spectrometry (ECD FT-ICR MS), which has previously shown preferential cleavage of disulfide bonds . We observe cleavage of DFC from vasopressin and insulin during ECD, suggesting that DFC is indeed bound to peptides and proteins through disulfide bonds . Specifically, we observed dissociative loss of one, as well as two, DFC species during ECD of {vasopressin + 2(DFC-H) + 2H}(2+) from a single electron capture event . Loss of two DFCs could arise from either consecutive or simultaneous loss, but in any case implies a gas phase disulfide exchange step . ECD of {insulin + DFC + 4H}(4+) shows preferential dissociative loss of DFC . Combined with HPLC, ECD FT-ICR-MS may be an efficient screening method for detection of drug-biomolecule binding.

J Chromatogr A, 2003 Mar 21, 990(1-2), 259 - 69
Development of a capillary zone electrophoresis-electrospray ionisation tandem mass spectrometry method for the analysis of fluoroquinolone antibiotics; McCourt J et al.; The applicability of a capillary zone electrophoresis-electrospray ionisation tandem mass spectrometric (CZE-ESI-MS-MS) method for the separation of nine fluoroquinolones was investigated . Method optimisation involved systematic trouble-shooting starting with the type and duration of capillary pre-washing and conditioning, the choice of both the CE run buffer, MS sheath liquid, CE run potential, ESI spray voltage, sheath gas flow-rate, MS capillary voltage and CE capillary and MS capillary temperatures . Another extremely important factor was found to be the degree to which the CE capillary protrudes into the ESI chamber as well as whether or not sheath gas and spray voltage are employed during the CE injection or not . The importance of the latter has, to our knowledge, not been addressed elsewhere . Nine fluoroquinolones have been separated and detected in a single run by this technique.

J Chromatogr A, 2003 Mar 21, 990(1-2), 143 - 51
Use of short-end injection capillary packed with a glycopeptide antibiotic stationary phase in electrochromatography and capillary liquid chromatography for the enantiomeric separation of hydroxy acids; Fanali S et al.; A new chiral stationary phase (CSP) was prepared by reacting MDL 63,246 (Hepta-Tyr), a glycopeptide antibiotic belonging to the teicoplanin family, with 5-microm diol-silica particles . The CSP mixed with 5-microm amino silica particles (3:1) was packed into 75-microm fused-silica capillaries for only 6.6 cm and used for electrochromatographic experiments analyzing several hydroxy acid enantiomers . A reversed electroosmotic flow carried both analytes and mobile phase towards the anode in a short time (1-3 min), being baseline resolved all the studied analytes . In order to achieve the fastest enantiomeric resolution of the studied hydroxy acids, the effect of several experimental parameters such as mobile phase composition (organic modifier type and concentration, pH of the buffer and ionic strength), capillary temperature and applied voltage on enantioresolution factor, retention time, enantioselectivity were evaluated . The packed capillary column allowed the separation of mandelic acid enantiomers in less than 72 s with resolution factor Rs=2.18 applying a voltage of 30 kV and eluting with a mobile phase composed by 50 mM ammonium acetate (pH 6)-water-acetonitrile (1:4:5, v/v) . The CSP was also tested in the capillary liquid chromatography mode resolving all the studied enantiomers applying 12 bar pressure to the mobile phase {50 mM ammonium acetate (pH 6)-water-methanol-acetonitrile, 1:4:2:3, v/v)}, however, relatively long analysis times were observed (12-20 min).

Clin Infect Dis, 2003 Apr 15, 36(8), 1006 - 12 Epub 2003 Apr 03.
Empirical antibiotic choice for the seriously ill patient: are minimization of selection of resistant organisms and maximization of individual outcome mutually exclusive?
Paterson DL, Rice LB.
Mortality related to serious infections in intensive care units (ICUs) is highest if empirical therapy is not active against the organism causing the infection . However, excessive empirical therapy undoubtedly contributes to bacterial resistance to antibiotics, in turn potentially contributing to poor patient outcome . We have reviewed 3 strategies that are increasingly practiced to reduce the hazards of broad empirical therapy, while aiming to ensure that empirical therapy is adequate . The most widely practiced strategy is discontinuation or streamlining of empirical therapy when culture results are available . The second approach is to withdraw certain antibiotic classes (most notably, third-generation cephalosporins) from the ICU antibiotic armamentarium . The third strategy employed is antibiotic cycling . Although this has also appeared to be a successful strategy, currently published studies have used historical controls and thus may be subject to significant bias . Computer-assisted antibiotic prescribing in ICUs may supplement or replace such strategies in the future.

Se Pu, 2002 Nov, 20(6), 519 - 25
{New species of selectors of chiral stationary phase in high performance liquid chromatography--macrocyclic antibiotics}; Ding GS et al.; The recent development and applications of chiral stationary phase (CSP) of macrocyclic antibiotics are reviewed . The characteristics of its chiral separation are discussed according to the structures and the comparisons are made between macrocyclic antibiotics-CSPs and the other CSPs.

Curr Top Med Chem, 2003, 3(9), 949 - 61
Macrolide antibiotics: binding site, mechanism of action, resistance; Gaynor M et al.; Macrolides are among the most clinically important antibiotics . However, many aspects of macrolide action and resistance remain obscure . In this review we summarize the current knowledge, as well as unsolved questions, regarding the principles of macrolide binding to the large ribosomal subunit and the mechanism of drug action . Two mechanisms of macrolide resistance, inducible expression of Erm methyltransferase and peptide-mediated resistance, appear to depend on specific interactions between the ribosome-bound macrolide molecule and the nascent peptide . The similarity between these mechanisms and their relation to the general mode of macrolide action is discussed and the discrepancies between currently available data are highlighted.

Curr Med Chem Anti-Canc Agents, 2002 Mar, 2(2), 215 - 54
Recent developments in the design, synthesis and structure-activity relationship studies of pyrrolo{2,1-c}{1,4}benzodiazepines as DNA-interactive antitumour antibiotics; Kamal A et al.; Pyrrolo{2,1-c}{1,4}benzodiazepines (PBDs) are naturally occurring compounds isolated from various Streptomyces species . The PBDs exert their biological activity through covalent binding and exhibit cytotoxicity . Extensive studies have been carried out on the synthetic strategies of PBDs, and a sound understanding of structure activity relationships within this class of compounds has been developed . The PBDs have shown to interfere with the interaction of endonuclease enzymes of DNA and block the transcription by inhibiting RNA polymerase in a sequence specific manner . These processes have been thought to account for the biological activity of PBDs . The PBDs have also been used as a scaffold to attach different type of moieties leading to novel sequence selective DNA cleaving and cross-linking agents . The design and synthesis of C8-linked PBD dimers and other hybrids of PBDs has given a new insight towards the development of molecules with enhanced DNA binding affinity and sequence specificity compared to the naturally occurring PBDs . This improvement in the biological profile has been explained on the basis of certain factors like DNA cross-linking and doubling of DNA binding sites . There seems to be enough potential for further changing the substitution pattern and to design structurally modified PBDs by retaining the PBD core intact . In this review both the synthetic strategies and the structure-activity relationships, particularly the DNA binding and cytotoxicity studies of PBDs have been discussed.

J Pediatr Surg, 2003 Apr, 38(4), 590 - 3
Prophylactic oral antibiotics in prevention of recurrent cholangitis after the Kasai portoenterostomy; Bu LN et al.; PURPOSE: The aim of this study was to evaluate the efficacy of trimethoprim-sulfamethoxazole (TMP/SMZ) and neomycin as the prophylactic agents against the recurrence of cholangitis in children with biliary atresia (BA) after a Kasai portoenterostomy . METHODS: Nineteen BA patients aged 0 to 2 years, who had one episode of cholangitis after a Kasai portoenterostomy, were recruited in this study . Patients were assigned randomly into 2 groups: one (9 cases) with TMP/SMZ (TMP 4 mg/kg/d and SMZ 20 mg/kg/d, divided in 2 doses) and the other (10 cases) with neomycin (25 mg/kg/d, qid, 4 days a week) . Another 18 BA patients aged 0 to 2 years, with cholangitis but not put on long-term prophylaxis, served as the historical control group . RESULTS: The mean prophylactic periods were 14.6 months and 14.7 months in the TMP/SMZ and neomycin groups . Patients who received prophylaxis with either TMP/SMZ or neomycin had lower recurrence rates of cholangitis than those in the control group (P =.042 and.011) . There was no difference in the recurrence rates of cholangitis between the TMP/SMZ and neomycin groups (P =.641) . The survival rates were higher in the TMP/SMZ and neomycin groups than in the control group (P =.09 and.018) . CONCLUSIONS: Use of TMP/SMZ or neomycin is effective as a prophylactic agent against the recurrence of cholangitis after the Kasai portoenterostomy, but there is no difference in efficacy between these 2 regimens .

J Radiat Res (Tokyo), 2002 Dec, 43(4), 361 - 70
High-dose antibiotic therapy is superior to a 3-drug combination of prostanoids and lipid A derivative in protecting irradiated canines; Kumar KS et al.; There is an urgent need to develop non-toxic radioprotectors . We tested the efficacy of a 3-drug combination (3-DC) of iloprost, misoprostol, and 3D-MPL (3-deacylated monophosphoryl lipid A) and the effects of postirradiation clinical support with high doses of antibiotics and blood transfusion . Canines were given 3-DC or the vehicle and exposed to 3.4 Gy or 4.1 Gy of 60Co radiation . Canines irradiated at 4.1 Gy were also given clinical support, which consisted of blood transfusion and antibiotics (gentamicin, and cefoxitin or cephalexin) . Peripheral blood cell profile and 60-day survival were used as indices of protection . At 3.4 Gy, 3-DC- or vehicle-treated canines without postirradiation clinical support survived only for 10 to 12 days . Fifty percent of the canines treated with 3-DC or vehicle and provided postirradiation clinical support survived 4.1-Gy irradiation . Survival of canines treated with vehicle before irradiation significantly correlated with postirradiation antibiotic treatments, but not with blood transfusion . The recovery profile of peripheral blood cells in 4.1 Gy-irradiated canines treated with vehicle and antibiotics was better than drug-treated canines . These results indicate that therapy with high doses of intramuscular aminoglycoside antibiotic (gentamicin) and an oral cephalosporin (cephalexin) enhanced survival of irradiated canines . Although blood transfusion correlated with survival of 3-DC treated canines, there were no additional survivors with 3-DC treated canines than the controls.

FEMS Microbiol Lett, 2003 Mar 28, 220(2), 215 - 21
The promoter of a cold-shock-like gene has pleiotropic effects on Streptomyces antibiotic biosynthesis; Martinez-Costa OH et al.; We have isolated a Streptomyces hygroscopicus chromosomal DNA fragment able to induce production of the blue-pigmented antibiotic actinorhodin in Streptomyces lividans . The 1.9-kb fragment contains four orfs (orf1-4) of which only orf2 and orf3 were complete . The minimal region involved in activation of actinorhodin production is limited to 165 bp corresponding to the promoter region of orf3 . The truncated Orf1 show homologies with threonine synthases, Orf2 is similar to other proteins of unknown function, Orf3 (here named Csp1) is homologous to cold-shock-induced proteins of the Csp family, and Orf4 encodes the N-terminal region of GroEL2 . Transcription of csp1 seems to be subjected to temporal control but is not obviously induced by cold shock . Interestingly, the csp1-groEL2 region pleiotropically regulates the production of antibiotics from Streptomyces coelicolor and Streptomyces nodosus.

J Int Acad Periodontol, 2002 Jul, 4(3), 77 - 87
Scaling and root-planing treatment with adjunctive subgingival minocycline . A clinical pilot study over six months, of sites adjacent to and remote from the antibiotic application; Henderson RJ et al.; AIM: A clinical trial was performed to determine if a single dose of subgingival minocycline has (i) a clinical spillover effect at adjacent and remote sites and (ii) an adjunctive effect to scaling and root-planing . MATERIALS AND METHODS: Each of the 15 adult subjects included in the study had to present with at least two pairs of adjacent 6-9 mm pockets each pair located on adjacent teeth in an interproximal space, on opposite sides of the mouth . Each study site was required to have at least 3 mm loss of attachment . Following a baseline examination including assessments of plaque, pocket depth (PD), clinical attachment levels (CAL) and bleeding on probing (BOP), instruction in oral hygiene was given . Each subject was treated with a single episode of scaling and root-planing (SRP), of approximately 90 minutes duration using ultrasonic and hand instrumentation under local anaesthetic, if indicated . This was followed by a single application of 1 mg of minocycline in the form of Minocycline Periodontal Therapeutic System (MPTS) into one of the four sites selected at random by another clinician, who also randomly selected one of the two sites on the opposite side of the mouth to be designated the Remote site . Clinical re-examinations were performed at 3- and 6-months . RESULTS: At six months the CAL gains at the MPTS sites were statistically significantly different when compared with the Adjacent sites (P=0.04) . The proportion of sites demonstrating a CAL gain (> or = 2 mm) was higher in the MPTS group (73%) compared with the Adjacent (40%) and Remote sites (53%) . Periodontal therapy, (MPTS+SRP) and (SRP alone) resulted in a statistically significant reduction in mean pocket depths (P<0.01) . However no statistically significant differences in pocket depths were found between treatment groups over the six months of the study . The proportion of sites demonstrating a clinically significant reduction in PD (> or = 2 mm) was higher in the MPTS sites (80%) compared with the Adjacent sites (53%) and Remote sites (53%) . BOP was significantly reduced at all sites over the duration of the study except at the Adjacent sites at three months (P<0.05) . CONCLUSION: No apparent clinical spillover effect of minocycline was demonstrated over the six months of the study . There was a trend for greater improvement in all clinical parameters at the MPTS sites compared with the Adjacent and Remote sites except for plaque scores . This trend needs to be examined in a study with a sufficient number of subjects to allow statistical significance.

Curr Opin Investig Drugs, 2003 Feb, 4(2), 140 - 8
Macrolide antibiotic interaction and resistance on the bacterial ribosome; Poehlsgaard J et al.; Our understanding of the fine structure of many antibiotic target sites has reached a new level of enlightenment in the last couple of years due to the advent, by X-ray crystallography, of high-resolution structures of the bacterial ribosome . Many classes of clinically useful antibiotics bind to the ribosome to inhibit bacterial protein synthesis . Macrolide, lincosamide and streptogramin B (MLSB) antibiotics form one of the largest groups, and bind to the same site on the 50S ribosomal subunit . Here, we review the molecular details of the ribosomal MLSB site to put into perspective the main points from a wealth of biochemical and genetic data that have been collected over several decades . The information is now available to understand, at atomic resolution, how macrolide antibiotics interact with their ribosomal target, how the target is altered to confer resistance, and in which directions we need to look if we are to rationally design better drugs to overcome the extant resistance mechanisms.

J Pharm Biomed Anal, 2003 Apr 10, 31(6), 1079 - 88
Determination of the antibiotic drug pefloxacin in bulk form, tablets and human serum using square wave cathodic adsorptive stripping voltammetry; Beltagi AM; A simple, rapid, reliable and fully validated square wave cathodic adsorptive stripping voltammetric procedure has been developed for the determination of the antibiotic pefloxacin drug in bulk form, tablets and human serum, based on its electrochemical reduction at a hanging mercury drop electrode . The Britton-Robinson buffer of pH 7.0 was found to be reasonable as a supporting electrolyte for assay of the drug . Pefloxacin drug, at the optimized conditions, showed a single 2-electron well-defined peak at -1.07 V (versus Ag/AgCl/KCl(s)) using an accumulation potential of -0.40 V . This peak may be attributed to the reduction of the C=O group . A mean recovery of 99.54%+/-0.23 and a detection limit of 1.65 x 10(-10) M pefloxacin were achieved . After being validated, the proposed procedure was successfully applied for the determination of the drug in tablets and human serum with mean recoveries of 99.57+/-0.48 and 98.55+/-0.78%, respectively . A detection limit of 4.50 x 10(-10) M was achieved for the determination of the drug in human serum . Results of the proposed procedure were comparable with those obtained by reported methods.

Artif Intell Med, 2003 Mar, 27(3), 259 - 82
A multi-agent system approach for monitoring the prescription of restricted use antibiotics; Godo L et al.; Hospitals have a specified set of antibiotics for restricted use (ARU), very expensive, which are only recommended for special pathologies . The pharmacy department daily checks the prescription of this kind of antibiotics since it is often the case that, after a careful analysis, one can get the same therapeutic effects by using normal antibiotics which are much cheaper and usually less aggressive . In this paper, we describe a multi-agent system to help in the revision of medical prescriptions containing antibiotics of restricted use . The proposed approach attaches an agent to each patient which is responsible of checking different medical aspects related to his/her prescribed therapy . A pharmacy agent is responsible for analyzing it and suggesting alternative antibiotic treatments . All these agents are integrated in a hospital distributed scenario composed by many different kinds of software and human agents . This patient-centered multi-agent scenario is specified using the design methodology of Electronic Institutions.

J Cataract Refract Surg, 2003 Mar, 29(3), 595 - 7
Entry of antibiotic ointment into the anterior chamber after uneventful phacoemulsification; Aralikatti AK et al.; A 77-year-old woman had uneventful phacoemulsification . Postoperative examination revealed that chloramphenicol ointment instilled in the conjunctival fornix had entered the anterior chamber and smeared the intraocular lens (IOL) . Immediate surgical removal of the ointment with IOL exchange was performed . The eye settled in 6 weeks with a best corrected visual acuity of 6/9 . This case raises concerns about the integrity of clear corneal incisions and the need for postoperative review of uneventful phacoemulsification surgery.

Biochim Biophys Acta, 2003 Apr 1, 1611(1-2), 161 - 70
Relevance of drug uptake, cellular distribution and cell membrane fluidity to the enhanced sensitivity of Down's syndrome fibroblasts to anticancer antibiotic-mitoxantrone; Przybylska M et al.; Sensitivity of human fibroblasts derived from Down's syndrome (DS) individuals (S-240, T-158, T-74, T-164) and normal donors (S-126, WA-1) to anticancer antibiotic-mitoxantrone (1,4-dihydroxy-5,8-bis((2-((2-hydroxy-ethyl)amino)ethyl)amino)-9,10-anthracenedione dihydrochloride; MIT) and its relationship to the transport rate, cellular distribution and interaction with cell membrane were studied . The survival assay showed that MIT was more toxic to trisomic fibroblast lines than to normal cells . Studies of transport kinetics indicated that the amount of drug taken up and extruded by DS cells was diminished, compared to control cells . In contrast, the cellular level of MIT associated with DNA was greater in trisomic than in normal cells . The fluorescence anisotropy measurements of TMA-DPH and 12-AS demonstrated that the fluidity of the polar region of the outer lipid monolayer of DS cell membrane was decreased in comparison with normal cells . MIT treatment decreased fluidity of the inner hydrophobic region of plasma membrane, but only slightly influenced the fluidity of the outer surface of the cell membrane . Finally, we concluded that lowered membrane fluidity, diminished amount of MIT extruded by cells and the enhanced level of the drug associated with DNA could be responsible for the enhanced sensitivity of DS fibroblasts to the MIT treatment.

Clin Pediatr (Phila), 2003 Mar, 42(2), 113 - 9
White blood cell count can aid judicious antibiotic prescribing in acute upper respiratory infections in children; Casey JR et al.; Fifty percent or more of children with upper respiratory infections (URIs) and nonspecific febrile illnesses (e.g., children febrile, anorexic, decreased activity, irritable) receive unnecessary antibiotics from community-based physicians . This study was undertaken to show that white blood cell (WBC) count testing can aid physicians in avoiding antibiotic prescribing when managing children with URIs, and nonspecific febrile illnesses . A prospective, 3-year study was conducted in a community-based pediatric practice . A weekly convenience sample (Tuesdays) of acute URI and febrile patients ages 3 months to 21 years was studied . Data collected on enrollment included: age, gender, duration of illness, recent/current antibiotic use, temperature, symptoms, signs, laboratory testing (WBC count, cultures), diagnosis and treatment . Similar data on any illness visits in the previous 2 weeks and the subsequent 2 weeks after enrollment were collected . Viral culture specimens were obtained on a subset . The use of the WBC count was assessed, including obviating antibiotic prescription, frequency of related follow-up visits, and the occurrence of subsequent bacterial infections . Of 1,956 patients with respiratory or febrile illness enrolled, 1,219 (62%) had a diagnosis established by history and examination (e.g., acute otitis media) and 737 (38%) did not . Of the 737 patients without an established diagnosis, 386 (52%) did not receive an antibiotic because they did not appear particularly ill, their temperature was less than 101 degrees F, and parents were not demanding antibiotics, leaving 351 (48%) patients who appeared ill, had a temperature greater than 101 degrees F, and parents were demanding an antibiotic or physicians were inclined to give an antibiotic . A WBC count was performed on these 351 children; 337 children (96%) had a WBC count less than 15,000/mm3, and 14 (4%) had a WBC 15,000/mm3 or greater . An antibiotic was prescribed for 13 of the 14 children with a WBC count greater than 15,000/mms . With this approach, return office visits in the following 2 weeks were infrequent (13% of 737 patients), and no child had significant bacterial illness that was missed . With selective use of WBC count testing

Invest Ophthalmol Vis Sci, 2003 Apr, 44(4), 1464 - 9
Antibiotic dosage in trachoma control programs: height as a surrogate for weight in children; Munoz B et al.; PURPOSE: National programs for trachoma control are implementing mass treatment programs in which azithromycin is used as part of the control strategy . Dose is determined by weight, which can be difficult to determine in field conditions . The purposes of this study were to determine whether an accurate dose could be determined by using height as a surrogate for weight and whether a single model of height-based dosage would be applicable in more than one setting . METHODS: Data on height, weight, age, and gender of 5558 children aged 6 months to15 years were obtained from Kongwa and Rombo, Tanzania; Malakal, Sudan; Jareng, The Gambia; and Daboya, Ghana . Models for predicting weight by measuring height were developed that incorporated country-specific parameters . Doses of azithromycin assumed suspension of 40 mg/mL and 250-mg tablets that could be halved . Tolerance limits were defined as 15 to 30 mg/kg . RESULTS: A regression model, predicting log weight as a function of log height, was the best fit and explained 94% of the variance . In children less than 1 year of age or 60 cm in height, dose determined by weight was preferred . Dosage by height resulted in more than 97% of children receiving doses within the tolerance limits . Children aged 1 to 2 years were the group most likely to be over- or undermedicated, but this occurred in only 6% of this age group . CONCLUSIONS: Height-based determination of dosage of azithromycin in trachoma control programs appears to be feasible, using the height-based schedule proposed . One model was adequate for all the countries in the study . Further expansion to other countries is warranted.

J Am Chem Soc, 2003 Apr 2, 125(13), 3988 - 94
Configurational entropy and cooperativity between ligand binding and dimerization in glycopeptide antibiotics; Jusuf S et al.; Oligomerization and ligand binding are thermodynamically cooperative processes in many biochemical systems, and the mechanisms giving rise to cooperative behavior are generally attributed to changes in structure . In glycopeptide antibiotics, however, these cooperative processes are not accompanied by significant structural changes . To investigate the mechanism by which cooperativity arises in these compounds, fully solvated molecular dynamics simulations and quasiharmonic normal-mode analysis were performed on chloroeremomycin, vancomycin, and dechlorovancomycin . Configurational entropies were derived from the vibrational modes recovered from ligand-free and ligand-bound forms of the monomeric and dimeric species . Results indicate that both ligand binding and dimerization incur an entropic cost as vibrational activity in the central core of the antibiotic is shifted to higher frequencies with lower amplitudes . Nevertheless, ligand binding and dimerization are cooperative because the entropic cost of both processes occurring together is less than the cost of these processes occurring separately . These reductions in configurational entropy are more than sufficient in magnitude to account for the experimentally observed cooperativity between dimerization and ligand binding . We conclude that biochemical cooperativity can be mediated through changes in vibrational activity, irrespective of the presence or absence of concomitant structural change . This may represent a general mechanism of allostery underlying cooperative phenomena in diverse macromolecular systems.

Cell Mol Biol Lett, 2003, 8(1), 161 - 70
Organization of antibiotic amphotericin B in model lipid membranes . A mini review; Gruszecki WI et al.; Amphotericin B (AmB) is a polyene antibiotic frequently applied in the treatment of fungal infections . According to the general understanding, the mode of action of AmB is directly related to the molecular organization of the drug in the lipid environment, in particular to the formation of pore-like molecular aggregates . Electronic absorption and fluorescence techniques were applied to investigate formation of molecular aggregates of AmB in the lipid environment of liposomes and monomolecular layers formed at the argon-water interface . It appears that AmB dimers, stabilized by van der Waals interactions, are present in the membrane environment along with the aggregates formed by a greater number of molecules . Linear dichroism measurements reveal that AmB is distributed between two fractions of molecules, differently oriented with respect to the bilayer . Molecules in one fraction remain parallel to the plane of the membrane and molecules in the other one are perpendicular . Scanning Force Microscopy imaging of the surface topography of the monolayers formed with AmB in the presence of lipids reveals formation of pore-like structures characterized by the external diameter close to 17 A and the internal diameter close to 6 A . All the findings are discussed in terms of importance of the molecular organization of AmB in the pharmacological action, as well as of the toxic side effects of the drug.

Nucleic Acids Res . 2003 Apr 1;31(7):e32.
Bypassing antibiotic selection: positive screening of genetically modified cells with an antigen-dependent proliferation switch; Kawahara M et al.; While antibiotic selection has been routinely used for the selection of genetically modified cells, administration of cytotoxic drugs often leads to deleterious effects not only to inert cells but also to transfected or transduced ones . In this study, we propose an Antigen-MEdiated Genetically modified cell Amplification (AMEGA) system employing antibody/receptor chimeras without antibiotic selection . Based on a rational design where the extracellular domains of dimeric erythropoietin receptor (EpoR) or gp130 were substituted with heterodimeric V(H)/V(L) regions of anti-hen egg lysozyme (HEL) antibody and EpoR D2 domains, the genes encoding the chimeras as well as a model transgene, enhanced green fluorescent protein (EGFP), were retrovirally infected into IL-3-dependent Ba/F3 cells followed by direct HEL selection in the absence of IL-3 . After a single round of selection, EGFP-positive cells were selectively amplified, resulting in a population of almost 100% positive cells . The AMEGA without antibiotic selection will not harm normal cells, which will be especially useful for increasing the efficacy for stem cell-based gene therapy.

Bioorg Med Chem Lett, 2003 Mar 24, 13(6), 1169 - 73
A new and improved method for deglycosidation of glycopeptide antibiotics exemplified with vancomycin, ristocetin, and ramoplanin; Wanner J et al.; A general method for the deglycosidation of glycopeptide antibiotics has been developed . Treatment of vancomycin, ristocetin, and ramoplanin with anhydrous HF results in efficient cleavage of the sugars to provide the corresponding aglycons in high yield.

Rev Med Chir Soc Med Nat Iasi, 2002 Apr-Jun, 107(2), 414 - 20
{Methods of advanced purification-the challenge for biosynthetic antibiotics industry}; Oniscu C et al.; Reactive extraction, permeation through liquid membranes and direct extraction are some of the new techniques applied for separation and advanced purification of biosynthetic antibiotics . Compared with the conventional separation techniques, the main advantages of these extraction methods are: high separation efficiency, the avoidance of antibiotics chemical and thermal inactivation, high purity of obtained antibiotics . Furthermore, using reactive extraction or permeation through liquid membrane, the antibiotics can be selective separated from their biosynthesis precursors or from the secondary biosynthetic compounds . This paper is a review on separation of Penicillins and Erythromycin by means of these extraction techniques, being underlined their advantages, applications and problems concerning the separation process scale-up.

Kansenshogaku Zasshi, 2003 Jan, 77(1), 24 - 8
{10-yearly monitoring of prevalence of MRSA and antibiotic usage in a neonatal intensive care unit}; Sakata H; From 1992 to 2001, we studied the prevalence of infants colonized MRSA and antibiotic usage for very-low-birth-weight infants in a neonatal intensive care unit at Asahikawa Kosei Hospital . We investigated nasopharyngeal swabs and stool samples every week after admission, and occasionally skin swabs, eye discharges and urines . Seventeen infants contracted nosocomial blood stream infection caused by MRSA which occurred between 1993 and 1996 . Rate of infants colonized MRSA to all inpatients was 14.9% in 1992, which increased to 40.0% in 1994, and decreased to 7.1% in 2001 . In each birth-weight group, rates of > or = 1,500 g, 1,000-1,499 g, and < 1,000 g infants were 6.5%, 45.0% and 60.0% in 1992, 24.5%, 100%, and 100% in 1994, 6.2%, 10.5%, and 21.4% in 2001 . The longest period of antibiotic usage was 148.4 per 1000 patient-day in 1995 and decreased to 32.6 per 1,000 patient-day in 2001 . The total value of antibiotics in 1995 was about yen 3,050,000, but in 2001 was about yen 470,000.

Int J Antimicrob Agents, 2003 Mar, 21(3), 267 - 73
Beta-lactamase production in Prevotella and in vitro susceptibilities to selected beta-lactam antibiotics {corrected}; Dubreuil L et al.; This study looked for beta-lactamase production in 100 Prevotella isolates . MICs were determined for amoxycillin, ticarcillin, amoxycillin+clavulanate, cephalothin, cefuroxime, cefixime, cefpodoxime and cefotaxime using the reference agar dilution method (standard M11 A4, NCCLS) . Beta-lactamase activity was detected in 58 of the 100 isolates, 24 of 46 black-pigmented Provotella and 34 of 54 non-pigmented Prevotella . All beta-lactamase-negative strains were susceptible to all beta-lactam antibiotics with the exception of cefuroxime and cefixime . Overall, resistance rates of Prevotella strains were lower for ticarcillin (8%) and celefotaxime (12%) than for the other cephalosporins . All Prevotella isolates were susceptible to amoxycillin and were all inhibited by 2 mg/l or less amoxycillin {corrected}.

Int J Antimicrob Agents, 2003 Mar, 21(3), 222 - 8
Does short-course antibiotic therapy better meet patient expectations?
Perez-Gorricho B, Ripoll M; PACE Study Group.
A pan-European market research study of 3254 patients designed to determine patient attitudes, expectations and behaviour to antibiotic management of mild-moderate RTIs, identified three key drivers of perceived antibiotic efficacy: length of antibiotic course, time to onset of symptom relief and time to complete resolution of symptoms . Azithromycin was selected as "drug therapy of shortest dosage schedule" for common outpatient infections . The results demonstrate that once-daily, short-course treatment is perceived to be significantly more effective than longer antibiotic courses and thus, better meets patient expectations of therapy . This perception of efficacy with short-course therapy also correlates with overall satisfaction with management by the physician and compliance with therapy . These findings have important implications for the way physicians manage patients with mild-moderate RTIs.

Int J Antimicrob Agents, 2003 Mar, 21(3), 215 - 21
Antibiotic safety assessment; Rouveix B; Antibiotics usually have positive risk-benefit ratios, their adverse effects being generally mild and reversible on treatment cessation . However, severe adverse drug reactions (ADR), associated with significant mortality and morbidity have resulted in the withdrawal of several active antibiotics, including new fluoroquinolones . Adverse reactions to antibiotics are often poorly documented . The purpose of this article is to examine current tools for investigating and preventing antibiotic toxicity and to suggest future lines of investigation . Structure/ADR relationships have been investigated with various antibiotics (beta-lactams, macrolides, quinolones, etc.) in an attempt to reduce the risk of adverse reactions . Some reactions can be linked to the drug's stereochemical composition . In the case of quinolones for instance, particularly ofloxacin and its derivatives, experimental data show that individual enantiomers have different toxicities . Another major factor that influences the risk of ADRs in a given population is metabolic variability, due to genetic differences in the relevant drug-metabolizing enzymes . Idiosyncratic antibiotic toxicity can be caused by a chemically reactive metabolite . Recent advances in molecular biology, and especially in individual genomic characterization (DNA chip technology, etc.), could in future be useful for identifying patients who are at a special risk of ADR . Finally, certain pharmacokinetic parameters (AUC, Cmax, etc.) can be used to predict adverse effects.

Indian J Exp Biol, 2002 Mar, 40(3), 277 - 81
Effect of co-administration of piperine on pharmacokinetics of beta-lactam antibiotics in rats; Hiwale AR et al.; Co-administration of piperine, an alkaloid isolated from Piper nigrum L . enhanced bioavailability of beta lactam antibiotics, amoxycillin trihydrate and cefotaxime sodium significantly in rats . The improved bioavailability is reflected in various pharmacokinetic parameters viz . tmax, Cmax, t(1/2) and AUC, of these antibiotics . The increased bioavailability could be attributed to the effect of piperine on microsomal metabolising enzymes or enzymes system.

Am J Obstet Gynecol, 2003 Mar, 188(3), 816 - 9
Placental passage of clarithromycin surpasses other macrolide antibiotics; Witt A et al.; OBJECTIVE: Infection of the amnion cavity with Ureaplasma urealyticum continues to be a therapeutic challenge . The transplacental transfer rates of macrolide antibiotics are low, and tetracyclines and quinolones are contraindicated in pregnancy . The aim of this study was to investigate placental transfer of clarithromycin in a well-studied placental perfusion model to determine whether clarithromycin surpasses the transfer rate of other macrolide antibiotics in similar models . STUDY DESIGN: Ten placentas that were obtained immediately after delivery were perfused with clarithromycin (3 microg/mL) plus a reference substance (antipyrine) . Open circulation placental preparations were used to evaluate steady-state pharmacodynamics and transplacental gradient formation . Drug concentrations were measured by high-performance liquid chromatography . RESULTS: The mean transplacental transfer of clarithromycin was 6.1% (95% CI, 1.8%) . CONCLUSION: Because of its enhanced placental passage compared with other macrolide antibiotics, clarithromycin that is given after the first trimester (after embryogenesis) may be an appropriate candidate in treatment trials of genital mycoplasma and ureaplasma infections during pregnancy.

Org Lett, 2003 Mar 20, 5(6), 843 - 4
Synthesis of the benz{a}anthraquinone core of angucyclinone antibiotics; Kalogerakis A et al.; {reaction: see text} A general method for the synthesis of benz{a}anthraquinones is reported . The key step is a catalytic cobalt-mediated {2+2+2}-cycloaddition of a triyne, which affords an angularly substituted tetracycle . Oxidation of this core gives the typical structure of angucyclinone antibiotics.

Mayo Clin Proc, 2003 Mar, 78(3), 321 - 32
Chlamydia pneumoniae and coronary artery disease: the antibiotic trials; Higgins JP; Parallel with the mounting evidence that atherosclerosis has a major inflammatory component, provoking agents that may initiate and drive this process have been sought . Infectious agents such as Chlamydia pneumoniae have been alleged to be activators of inflammation that may contribute to atherosclerosis and thus coronary artery disease (CAD) and its associated complications . A logical pneumoniae extension of this theory whether treating C pneumoniae infection with antibiotics and/or modulating inflammatory processes can affect CAD and its sequelae . This article discusses the potential role of C pneumoniae in atherosclerosis, its detection, and the rationale for antibiotics . Additionally, it summarizes the current randomized clinical trials of antichlamydial antibiotics in patients with CAD and draws conclusions based on the results.

Nurs Times, 2003 Jan 28-Feb 3, 99(4), 36 - 9
The supply of antibiotics by NHS walk-in centre nurses using PGDs; Brooks N et al.; Patient group directions (PGDs) have become a feature of NHS walk-in centres enabling nurses to supply and administer drugs in response to the generalised direction of a doctor . In light of the issues surrounding the use of antibiotics a clinical audit was undertaken to assess nurses' competence and record-keeping in relation to supplying antibiotics according to PGDs . This study goes some way to demonstrate that nurses are supplying and administering antibiotics judiciously and safely according to local PGDs.

Electrophoresis, 2003 Mar, 24(5), 904 - 12
A glycopeptide antibiotic chiral stationary phase for the enantiomer resolution of hydroxy acid derivatives by capillary electrochromatography; Fanali S et al.; Separation of hydroxy acid enantiomers was achieved by using capillary electrochromatography (CEC) employing a chiral stationary phase (CSP) based on MDL 63,246 (Hepta-Tyr), a macrocyclic antibiotic of the teicoplanin family . The chiral selector was chemically bonded to 5 num diol-modified silica particles and the CSP mixed with amino silica (3:1 w/w) was packed into a 75 num ID fused-silica capillary . The CEC experiments were carried out by using an aqueous reversed-phase mode for the enantiomeric resolution of hydroxy acid compounds . Good enantioresolution was achieved for mandelic acid (MA), m-hydroxymandelic acid (m-OH-MA), p-OH-MA, and 3-hydroxy-4-methoxymandelic acid (3-OH-4-MeO-MA) . The CEC system was less enantioselective towards 2-phenyllactic acid (2-PhL) and 3-PhL while mandelic acid methyl ester (MA-Et-Est) enantiomers were not resolved . Several experimental parameters, such as organic solvent type and concentration, buffer pH, capillary temperature, on enantioresolution factor, retention time, and retention factor were studied.

Electrophoresis, 2003 Mar, 24(5), 808 - 15
On-column derivatization of the antibiotics teicoplanin and ristocetin coupled to affinity capillary electrophoresis; Silverio CF et al.; Binding constants between the glycopeptides teicoplanin (Teic) and ristocetin (Rist) and their derivatives to D-Ala-D-Ala terminus peptides were determined by on-column receptor synthesis coupled to partial-filling affinity capillary electrophoresis (PFACE) or affinity capillary electrophoresis (ACE) . In these techniques, the column is first partially filled with increasing concentrations of D-Ala-D-Ala terminus peptides . This is followed by plugs of buffer, antibiotic and two noninteracting standards, and acetic and/or succinic anhydride (and buffer in the case of ACE) . The order of the reagent plugs containing the antibiotic and anhydride varies with the charge of the glycopeptide . Upon electrophoresis, the antibiotic reacts with the anhydride yielding a derivative of Teic or Rist . Continued electrophoresis results in the overlap of the derivatized antibiotic and the plug of D-Ala-D-Ala peptide . Analysis of the change in the relative migration time ratio (RMTR) of the new glycopeptide relative to the standards, as a function of the concentration of the D-Ala-D-Ala ligand yields a value for the binding constant K(b) . The techniques described here can be used to assess how the derivatization of drugs alters their affinities for target molecules.

J Hosp Infect, 2003 Mar, 53(3), 183 - 6
Correlation between candiduria and departmental antibiotic use; Weinberger M et al.; The incidence of candiduria is increasing in teaching hospitals . We examined the hypothesis that this trend was correlated with the amount of departmental antibiotic consumption . In the setting of a large teaching hospital in Israel, the correlation coefficient between departmental intravenous antibiotic consumption (expressed as daily defined dose (DDD)/1000 patient-days) and the incidence of candiduria per 1000 patient-days was 0.47 (P=0.03) . For broad-spectrum antibiotics, the corresponding correlation coefficient was 0.66 (P=0.001) . The strongest correlation with candiduria was shown for the use of meropenem (r=0.79, P<0.001) and ceftazidime (r=0.66, P=0.001) . This is the first time that departmental habits of antibiotic use have been shown to be strongly correlated with the incidence of candiduria in hospitalized patients . These results add an important new dimension to the strategy of restricting broad-spectrum antibiotics.

Mol Microbiol, 2003 Mar, 47(6), 1723 - 32
Association of mycothiol with protection of Mycobacterium tuberculosis from toxic oxidants and antibiotics; Buchmeier NA et al.; Mycothiol, MSH or 1D-myo-inosityl 2-(N-acetyl-L-cysteinyl)amido-2-deoxy-alpha-D-glucopyranoside, is an unusual conjugate of N-acetylcysteine (AcCys) with 1D-myo-inosityl 2-acetamido-2-deoxy-alpha-D-glucopyranoside (GlcN-Ins), and is the major low-molecular-mass thiol in mycobacteria . Mycothiol has antioxidant activity as well as the ability to detoxify a variety of toxic compounds . Because of these activities, MSH is a candidate for protecting Mycobacterium tuberculosis from inactivation by the host during infections as well as for resisting antituberculosis drugs . In order to define the protective role of MSH for M . tuberculosis, we have constructed an M . tuberculosis mutant in Rv1170, one of the candidate MSH biosynthetic genes . During exponential growth, the Rv1170 mutant bacteria produced approximately 20% of wild-type levels of MSH . Levels of the Rv1170 substrate, GlcNAc-Ins, were elevated, whereas those of the product, GlcN-Ins, were reduced . This establishes that the Rv1170 gene encodes for the major GlcNAc-Ins deacetylase activity (termed MshB) in the MSH biosynthetic pathway of M . tuberculosis . The Rv1170 mutant grew poorly on agar media lacking catalase and oleic acid, and had heightened sensitivities to the toxic oxidant cumene hydroperoxide and to the antibiotic rifampin . In addition, the mutant was more resistant to isoniazid, suggesting a role for MSH in activation of this prodrug . These data indicate that MSH contributes to the protection of M . tuberculosis from oxidants and influences resistance to two first-line antituberculosis drugs.

Pharmacoepidemiol Drug Saf, 2003 Jan-Feb, 12(1), 9 - 15
Agreement between patient self-report and a Veterans Affairs national pharmacy database for identifying recent exposures to antibiotics; Metlay JP et al.; PURPOSE: The dramatic rise in antibiotic drug resistance among community pathogens has stimulated interest in the epidemiological relationship between antibiotic exposure and drug resistance . In assessing the strength of this relationship, studies are hampered by the lack of data on the accuracy of subject self-report of antibiotic exposure . The authors compared self-report with pharmacy dispensing data to determine the accuracy of self-reported antibiotic exposure . METHODS: The study design was a cross-sectional survey of veterans seen at the Philadelphia Veterans Affairs (VA) Medical Center in 1999 and 2000 . Subjects reported exposures to antibiotics, antihypertensive drugs and nonsteroidal anti-inflammatory drugs through a structured telephone interview . The instrument included open-ended questions, condition-specific prompts and drug-specific prompts . Subject responses were linked to a national VA pharmacy database that served as the reference standard for evaluating self-reported exposures . RESULTS: The authors found that the sensitivity of self-report of antibiotic exposure increased with increasing use of prompts . A comprehensive assessment of antibiotic exposure identified 73% of antibiotic exposures, compared to 73% of antihypertensive drug exposures and 92% of nonsteroidal anti-inflammatory drug exposures . CONCLUSIONS: Assessment of antibiotic exposure appears to be comparable to assessment of other chronic and episodic drugs . Multistep assessment of exposure improves the sensitivity of assessment.

Antibiot Khimioter, 2002, 47(9), 3 - 8
{Radioprotective and antineoplastic activity of polyene antibiotics combined with dimethyl sulfoxide}; Ibragimova VKh et al.; Radioprotective and antineoplastic activity of polyene, its derivatives and combinations with dimethyl sulfoxide (DMSO) was studied . The most potent radioprotective effect was demonstrated by methylated levorin, original levorin and by its isomer--isolevorin . Survival rate of the animals on 12th day after X-ray exposure was 100, 60, 60 per cent, at the control group 33.6, 20 and 0 per cent consequently . Levorin and alkyl derivatives of amphotericin B--methamphocin and buthamphocin inhibited growth of ascites and solid tumors to 46.3-79.0 per cent when compared to control group . Polyen antibiotics combined with DMSO also demonstrated antineoplastic activity at the animals treated with carcinogenic agent--diethyl nitrosoamine (DENA) . 5-month survival of the animals was 76 per cent at nystatin and levorin group and 35.7 per cent at the control group (animals treated with DENA only).

Bioorg Med Chem Lett, 2003 Mar 10, 13(5), 901 - 3
Synthesis of (+),(-)-neamine and their positional isomers as potential antibiotics; Ryu do H et al.; The syntheses of (+)-neamine 1, (-)-neamine ent-1 and their positional isomers 2, 3, ent-2 and ent-3 are reported as potential new scaffolds for novel aminoglycoside antibiotics . These isomers exhibit similar inhibitory activities, as shown using an in vitro translation assay . A simple model is proposed to explain this lack of stereospecific binding to the ribosomal RNA.

J Antimicrob Chemother, 2003 Mar, 51(3), 683 - 9
Socioeconomic factors and prescription of antibiotics in 0- to 2-year-old Danish children; Thrane N et al.; OBJECTIVES: The aim was to examine the impact of socioeconomic factors on the use of systemic antibiotics during the first 2 years of life . METHODS: This was a population-based cohort study of 5024 Danish children born in 1997 . The study was conducted by linking records drawn from public administrative registries . The main predictor variables were mother's education level, household income and cohabitation status . The outcome was the number of antibiotic courses (0, 1-5, > or =6) during the first 2 years of life . RESULTS: A total of 3273 children (65.1%) received 1-5 antibiotic courses, and 337 (6.7%) received > or =6 courses of antibiotics during the first 2 years of life . The risk of receiving > or =6 courses of antibiotics was increased in children of mothers with a low educational level (< or =10 years) compared with vocational education {OR 1.3 (95% CI 1.0-1.7)} . Children of mothers with a higher education >4 years had a reduced risk of receiving > or =6 courses {OR 0.3 (95% CI 0.1-0.7)} . Children from high-income families had a reduced risk (not statistically significant) of receiving antibiotics, compared with children from middle-income families {1-5 and > or =6 courses: adjusted OR 0.6 (95% CI 0.3-1.2)} . Children of single mothers had an increased risk of receiving antibiotics, particularly if the child did not attend day care . CONCLUSIONS: Socioeconomic factors have some impact on antibiotic prescription in young children . Children of mothers with only basic schooling were at highest risk of receiving multiple prescriptions, whereas children of mothers with a high education, and/or high household income, had the lowest risk.

Vestn Ross Akad Med Nauk, 2002, (12), 15 - 20
{Achievements and problems in studies of antibiotic peptides of an organic origin}; Kokriakov VN et al.; The paper contains the original data of the authors and literature survey in the field of studies of the structure and functions of antibiotic peptides . Physical-and-chemical as well as structural properties of a new subfamily of defensins, i.e . minidefensins (theta-defensins), are described in detail . Mechanisms of the antibiotic action of defensins and bactenecins as well as their role in regulating the body immune reactions are discussed.

Ophthalmic Epidemiol, 2003 Feb, 10(1), 31 - 6
Pattern of antibiotic use in a trachoma-endemic region of Nepal: implications for mass azithromycin distribution; Schiedler V et al.; PURPOSE: To investigate antibiotic utilization in a rural district of western Nepal that is currently receiving azithromycin as part of a trachoma program and is being monitored by the Centers for Disease Control and Prevention (CDC) for drug resistance . METHODS: Antibiotic purchase receipts were collected for 3 months from all medicine halls, pharmacies, and government sub-health posts in a sub-district of Western Nepal . Supplementary surveys of antibiotic sales were performed in different seasons . RESULTS: Macrolides account for 3.9% of total antibiotic use, far less than quinolones, penicillins, tetracyclines, and sulfonamides . CONCLUSIONS: If trachoma programs in Western Nepal generate transient macrolide resistance in pneumococcus and other bacteria, the epidemiological impact may not be great, as macrolides are not commonly used in the area.

Antimicrob Agents Chemother, 2003 Mar, 47(3), 1062 - 7
Amino acid sequence requirements at residues 69 and 238 for the SME-1 beta-lactamase to confer resistance to beta-lactam antibiotics; Majiduddin FK et al.; Carbapenem antibiotics have been used to counteract resistant strains of bacteria harboring beta-lactamases and extended-spectrum beta-lactamases . Four enzymes from the class A group of beta-lactamases, NMC-A, IMI-1, SME-1, and KPC-1, efficiently hydrolyze carbapenem antibiotics . Sequence comparisons and structural information indicate that cysteines at amino acid residues 69 and 238, which are conserved in all four of these enzymes, form a disulfide bond that is unique to these beta-lactamases . To test whether this disulfide bond is required for catalytic activity, the codons for residues Cys69 and Cys238 were randomized individually and simultaneously by PCR-based mutagenesis to create random replacement libraries for these positions . Mutants that were able to confer resistance to ampicillin, imipenem, or cefotaxime were selected from these libraries . The results indicate that positions Cys69 and Cys238 are critical for hydrolysis of all of the antibiotics tested, suggesting that the disulfide bond is generally required for this enzyme to catalyze the hydrolysis of beta-lactam antibiotics.

Med J Aust, 2003 Mar 3, 178(5), 210 - 3
Effect of computerised prescribing on use of antibiotics; Newby DA et al.; OBJECTIVES: To examine whether the use of current prescribing software systems might raise rates of repeat prescribing, with a consequent increase in use of antibiotics in the community . DESIGN AND SETTING: A prospective audit of consecutive prescriptions for amoxycillin, cefaclor, roxithromycin and amoxycillin/clavulanate presented to community pharmacies in the Hunter region of New South Wales and a follow-up survey of people who received a repeat prescription, October to November 2000 . MAIN OUTCOME MEASURES: The frequency of repeat prescription ordering on computer-generated and handwritten prescriptions; the proportion of people who filled their repeat prescription . RESULTS: Data were collected for 1667 prescriptions presented to 35 pharmacies; 126 people who received repeat prescriptions completed the survey . The rate of repeat prescription ordering on computer-generated prescriptions was 69%, compared with 40% for handwritten prescriptions (odds ratio, 3.3; 95% CI, 2.6-4.2) . Computer-generated repeat prescriptions were as likely to be filled as hand-written prescriptions (61% and 69%, respectively) . CONCLUSIONS: The default settings on computerised prescribing packages result in a significant increase in the use of antibiotics . We estimate these settings result in about 500 000 additional prescriptions being filled annually in Australia for the four antibiotics in the study.

Med J Aust, 2003 Mar 3, 178(5), 207 - 9
A simple intervention to improve hospital antibiotic prescribing; South M et al.; OBJECTIVE: To evaluate changes in prescribing behaviour after distribution of antibiotic guidelines printed on a 9 x 6 cm laminated card suitable for clipping to a hospital identification badge . INTERVENTION: Guidelines for appropriate antibiotic prescribing for 20 common and important paediatric infections were printed on a laminated 9 x 6 cm card suitable to clip to a hospital identification badge and distributed to all medical staff . DESIGN: We collected data from medical records for three marker conditions (tonsillitis, pneumonia, and orbital/periorbital cellulitis) on samples of patients from the six-month periods either side of the month in which the cards were distributed . Prescribers were unaware of the study and investigators analysed the prescriptions without knowledge of the period in which they were written . Prescriptions were rated for appropriate choice of antibiotic and appropriate dose . Data were also collected on antibiotic costs . MAIN OUTCOME MEASURES: Proportion of cases in which antibiotic choice was appropriate; proportion of cases in which antibiotic dose was appropriate; annualised costs of third-generation cephalosporins . RESULTS: For tonsillitis there was little change in prescribing practice after the cards were introduced . For pneumonia, cases with appropriate choice increased from 77% to 92% (P = 0.028) and cases with appropriate dose increased from 48% to 81% (P = 0.001) . For orbital/periorbital cellulitis, cases with appropriate choice increased from 19% to 78% (P < 0.001) and cases with appropriate dose increased from 30% to 51% (P = 0.11) . Annualised costs of third-generation cephalosporins were $193 245 pre-cards and $89 814 post-cards . CONCLUSION: The cards appeared to have a beneficial effect on prescribing practice for the three marker conditions . This simple intervention is likely to be cost-effective and useful in reducing inappropriate use of antibiotics.

Jpn J Antibiot, 2002 Sep, 55 Suppl A, 79 - 85
{Beta-lactamase activity and susceptibilities to antibiotics among some species of bacteria isolated from medical institution between December 1999 and February 2000}; Tanimoto A et al.; We studied the beta-lactamase activity and susceptibilities to antibiotics in 604 strains among 10 species of bacteria isolated from 10 medical institutions in Tottori and Shimane Prefectures between December 1999 and February 2000 . beta-Lactamase activity was measured by the nitrocefin test and penicillinase/cephalosporinase activities were measured by acidometry . beta-Lactamase activity was detected in 72.1% of S . aureus, 18.8% of H . influenzae, and 96.3% of M . catarrhalis . Penicillinase/cephalosporinase activities were detected in 17.8%/22.2% of E . coli, 9.7%/0.0% of K . pneumoniae, 18.6%/95.3% of E . cloacae, 12.7%/79.4% of S . marcescens, and 7.1%/31.8% of P . aeruginosa . Three of 72 strains (4.2%) of K . pneumoniae and 5 of 90 strains (5.6%) of E . coli were assessed as ESBL-producing bacteria using the NCCLS proposed screening method based on routine susceptibility testing results . BLNAR were detected in 13 of 69 strains (18.8%) of H . influenzae.

Indian J Exp Biol, 2002 Aug, 40(8), 960 - 2
Fishmeal extract agar--a new antibiotic sensitivity test medium; Subbannayya K et al.; Fishmeal extract agar is a new antibiotic sensitivity test medium . It is simpler and cheaper than Mueller-Hinton agar and comparable in its efficacy to the latter . It can also be used for isolation of moderately fastidious and non-fastidious bacteria from clinical specimens . Fishmeal extract broth can be used as a base for biochemical tests used for the identification of bacterial isolates.

J Basic Microbiol, 2003, 43(1), 18 - 27
Genotypic and phenotypic characteristics of antibiotic-producing soil Streptomyces investigated by RAPD-PCR; Gharaibeh R et al.; Random amplified polymorphic DNA (RAPD) analysis has been used to determine the relatedness of 73 antibiotic-producing soil Streptomyces isolates that were recovered from different soil habitats in Jordan based on their RAPD-PCR fingerprints . Genetic polymorphisms between these isolates showed three common bands of 2777, 800 and 250 bp shared by approximately (95%) of them . Some specific bands were also observed . Further analysis of RAPD patterns with the UPGMA resulted in clustering the tested isolates into two main super clusters . Super cluster I was more homogenous than super cluster II and contained all the reference strains . However, super cluster II consists of unrelated isolates within five small groups . As RAPD fingerprints of the tested isolates linked to their phenotypes, differentiation between isolates with different cultural properties was observed.

J Am Chem Soc, 2003 Feb 26, 125(8), 2044 - 5
Shishijimicins A-C, novel enediyne antitumor antibiotics from the ascidian Didemnum proliferum(1); Oku N et al.; Three new compounds of the enediyne antibiotics, shishijimicins A-C (1-3), have been isolated from the ascidian Didemnum proliferum . They encompass a novel sugar component, which is a conjugation product of a hexose and a beta-carboline, attached to the calicheamicinone aglycone . Their structures have been determined by interpretation of spectral data . Shishijimicins showed extremely potent cytotoxicity against HeLa cells with IC(50) values of 1.8-6.9 pM.

J Biol Chem, 2003 Apr 25, 278(17), 14788 - 97 Epub 2003 Feb 14.
Inhibition of transfer messenger RNA aminoacylation and trans-translation by aminoglycoside antibiotics; Corvaisier S et al.; Transfer messenger RNA (tmRNA) directs the modification of proteins of which the biosynthesis has stalled or has been interrupted . Here, we report that aminoglycosides can interfere with this quality control system in bacteria, termed trans-translation . Neomycin B is the strongest inhibitor of tmRNA aminoacylation with alanine (K(i) value of approximately 35 micro m), an essential step during trans-translation . The binding sites of neomycin B do not overlap with the identity determinants for alanylation, but the aminoglycoside perturbs the conformation of the acceptor stem that contains the aminoacylation signals . Aminoglycosides reduce the conformational freedom of the transfer RNA-like domain of tmRNA . Additional contacts between aminoglycosides and tmRNA are within the tag reading frame, probably also disturbing reprogramming of the stalled ribosomes prior protein tagging . Aminoglycosides impair tmRNA aminoacylation in the presence of all of the transfer RNAs from Escherichia coli, small protein B, and elongation factor Tu, but when both proteins are present, the inhibition constant is 1 order of magnitude higher . SmpB and elongation factor Tu have RNA chaperone activities, ensuring that tmRNA adopts an optimal conformation during aminoacylation.

Rev Med Chil, 2002 Nov, 130(11), 1265 - 72
{Impact of regulatory measures in the trends of community consumption of antibiotics in Chile}; Bavestrello L et al.; BACKGROUND: The indiscriminate use of antibiotics increases the appearance of bacterial resistance and forces the use of more expensive alternatives . The Chilean Ministry of Health is regulating the consumption of antibiotics since September 1999 . These regulatory measures restricted the sale of antibiotics only when these were prescribed by an MD or an DS . AIM: To study the impact of these regulatory measures on antibiotics sales in pharmacies . MATERIAL AND METHODS: A retrospective analysis of antibiotics sales in pharmacies from 1996 to 2000 . The information was obtained from the International Marketing System (IMS Health), an auditing system of pharmacy sales . The consumption unit used was the Defined Daily Dose per 1000 inhabitants/day (DDD) . RESULTS: There was an important reduction in DDD, after the introduction of regulatory measures, for amoxicillin, ampicillin, erythromycin, trimethoprim/sulpha, chroramphenicol, cloxacillin and phenoxymethylpenicillin . There was also a important fall in sales, expressed in dollars . CONCLUSIONS: The regulatory measures of the Ministry of Health, had an immediate and great impact on antibiotics sales in Chile.

Lik Sprava, 2002, (7), 15 - 21
{Antibiotics in the treatment of syphilis (history, modern state of the problem, perspectives)}; Zav'ialov AI; Submitted in the report are data in brief outline on therapy of syphylis with mercury, arsenic, bismuth preparations and their use-associated complications . Historical stages of discovery, production, use of penicillin and its durant forms are described together with those of other antibiotics in the treatment os syphylitic infection in the USSR and abroad . A comparative efficiency of antibioticotherapy versus therapeutic modalities (combined and permanent) is given.

J Fam Pract, 2003 Feb, 52(2), 140 - 8
Why do physicians think parents expect antibiotics? What parents report vs what physicians believe; Stivers T et al.; OBJECTIVE: To examine the relation between parent expectations for antibiotics, parent communication behaviors, and physicians' perceptions of parent expectations for antibiotics . STUDY DESIGN: A nested cross-sectional study with parallel measures of parents presenting children for acute respiratory infections (previsit) and physicians (postvisit) and audiotaping of the encounters . POPULATION: Ten physicians in 2 private pediatric practices (1 community-based and 1 university-based) and a consecutive sample of 306 eligible parents (response rate, 86%) who were attending sick visits for their children between October 1996 and March 1997 . OUTCOMES MEASURED: Communication behaviors used by parents expecting antibiotics and physicians' perceptions of parents' expectations . RESULTS: Parents' use of "candidate diagnoses" during problem presentation increased the likelihood that physicians would perceive parents as expecting antibiotics (from 29% to 47%; P=.04), as did parents' use of "resistance to the diagnosis" (an increase from 7% to 20%) . In the multivariate model, parents' use of candidate diagnoses increased the odds that a doctor would perceive a parental expectation for antibiotics by more than 5 times (odds ratio, 5.23; 95% confidence interval, 3.74-7.31; Plt.001), and parents' use of resistance to a viral diagnosis increased these odds by nearly 3 times (odds ratio, 2.73; 95% confidence interval, 1.97-3.79; Plt.001) . CONCLUSIONS: Parents perceived as expecting antibiotics may be seeking reassurance that their child is not seriously ill or that they were correct to obtain medical care . Physicians were significantly more likely to perceive parents as expecting antibiotics if they used certain communication behaviors . This study revealed an incongruity between parents' reported expectations, their communication behaviors, and physicians' perceptions of parents' expectations.

JAMA, 2003 Feb 12, 289(6), 719 - 25
Predictors of broad-spectrum antibiotic prescribing for acute respiratory tract infections in adult primary care; Steinman MA et al.; CONTEXT: Broad-spectrum antibiotics are commonly prescribed, but little is known about the physicians who prescribe and the patients who take these agents . OBJECTIVE: To identify factors associated with prescribing of broad-spectrum antibiotics by physicians caring for patients with nonpneumonic acute respiratory tract infections (ARTIs) . DESIGN, SETTING, AND PATIENTS: Cross-sectional study using data from the National Ambulatory Medical Care Survey between 1997 and 1999 . Information was collected on a national sample of 1981 adults seen by physicians for the common cold and nonspecific upper respiratory tract infections (URTIs) (24%), acute sinusitis (24%), acute bronchitis (23%), otitis media (5%), pharyngitis, laryngitis, and tracheitis (11%), or more than 1 of the above diagnoses (13%) . MAIN OUTCOME MEASURE: Prescription of broad-spectrum antibiotics, defined for this study as quinolones, amoxicillin/clavulanate, second- and third-generation cephalosporins, and azithromycin and clarithromycin . RESULTS: Antibiotics were prescribed to 63% of patients with an ARTI, ranging from 46% of patients with the common cold or nonspecific URTIs to 69% of patients with acute sinusitis . Broad-spectrum agents were chosen in 54% of patients prescribed an antibiotic, including 51% of patients with the common cold and nonspecific URTIs, 53% with acute sinusitis, 62% with acute bronchitis, and 65% with otitis media . Multivariable analysis identified several clinical and nonclinical factors associated with choice of a broad-spectrum agent . After adjusting for diagnosis and chronic comorbid illnesses, the strongest independent predictors of broad-spectrum antibiotic prescribing were physician specialty (odds ratio {OR}, 2.4; 95% confidence interval {CI}, 1.6-3.5 for internal medicine physicians compared with general and family physicians) and geographic region (OR, 2.6; 95% CI, 1.4-4.8 for Northeast and OR, 2.4; 95% CI, 1.4-4.2 for South {both compared with West}) . Other independent predictors of choosing a broad-spectrum agent included black race, lack of health insurance, and health maintenance organization membership, each of which was associated with lower rates of broad-spectrum prescribing . Patient age, sex, and urban vs rural location were not significantly associated with prescribing choice . CONCLUSIONS: Broad-spectrum antibiotics are commonly prescribed for the treatment of ARTIs, especially by internists and physicians in the Northeast and South . These high rates of prescribing, wide variations in practice patterns, and the strong association of nonclinical factors with antibiotic choice suggest opportunities to improve prescribing patterns.

Anal Chem, 2003 Feb 1, 75(3), 678 - 84
Chiral analysis using the kinetic method with optimized fixed ligands: applications to some antibiotics; Wu L et al.; A new version of the kinetic method for chiral analysis, which employs a fixed (nondissociating) ligand as well as the usual analyte and chiral reference ligands, is introduced to simplify the kinetics of this experiment . Singly charged clusters containing the divalent transition metal ion MnII, a peptide which serves as a fixed ligand, an amino acid chiral reference, and the analyte 4-benzyl-2-oxazolidinone were generated by electrospray ionization (ESI) . The cluster ion of interest was mass-selected, and the kinetics of its competitive unimolecular dissociations was investigated in an ion trap mass spectrometer . The chiral selectivity (R(fixed)chiral), the ratio of the two fragment ion abundances when the cluster contains one pure enantiomer of the analyte expressed relative to that for the other enantiomer, varies with increasing size of the fixed peptide ligands . The metal-ligand and the ligand-ligand interactions that produce chiral discrimination are optimized in the tetrapeptide fixed ligand Gly-Gly-Ala-Gly, as shown by data for 15 fixed ligands . The difference in the free energies of activation for the two competitive reactions is estimated to be approximately 7 kJ/mol for this particular fixed ligand . The sensitive nature of the methodology and the linear relationship between the logarithm of the fragment ion abundance ratio and the optical purity (intrinsic to the kinetic method) allows mixtures to be analyzed for as little as 1% enantiomeric excess (ee), by simply recording the ratios of fragment ion abundances in a tandem mass spectrum . These features are demonstrated in the case of the pharmacologically important 4-benzyl-2-oxazolidinones and in the case of penicillamine.

Org Lett, 2003 Feb 20, 5(4), 443 - 5
Synthesis of new 14-membered macrolide antibiotics via a novel ring contraction metathesis; Lazarova TI et al.; {reaction: see text} A novel ring opening ring closing metathesis (ROM-RCM) was demonstrated for cyclic conjugated dienes, effecting the excision of a C(2)H(2) unit and a net ring contraction . Applying the ring contraction metathesis, new 14-membered ring macrolide antibiotics were synthesized in a single step from existing 16-membered ring macrolides . This new class of macrolide antibiotics will provide access to new therapeutics for the treatment of macrolide-resistant bacterial infections.

Rev Esp Quimioter, 2002 Mar, 15(1), 61 - 70
{Use of systemic antibiotics in Valladolid (1996-2000)}; Pastor Garcia E et al.; A longitudinal retrospective study was conducted to analyze the changes in the use of systemic antibiotics from 1996 to 2000 in the province of Valladolid, Spain . The use of systemic antibiotics was determined according to the defined daily dose and showed a progressive increase during the first four years of the study, followed by a large decrease in the year 2000 . When examined by subgroup, wide spectrum penicillins accounted for almost 60% of the antibiotics consumed, and were therefore responsible for this change . Macrolides represented 16.4% of the consumption, which increased during the whole study period . Quinolones, with 9.3% of the total, showed a slow but steady increase . Cephalosporins accounted for 8.1%, with their use decreasing since 1998 . It was concluded that wide spectrum penicillins were the most used systemic antibiotics in the study population, although a decreasing trend in their use and an increase in the use of macrolides and quinolones was observed.

Arch Pediatr Adolesc Med, 2003 Feb, 157(2), 145 - 9
Maternal antibiotics and decreased periventricular leukomalacia in very low-birth-weight infants; Paul DA et al.; OBJECTIVE: To investigate the effect of maternal antibiotics, given in the predelivery period, on neonatal outcomes . DESIGN: Retrospective cohort study . SETTING: A single level 3 neonatal intensive care unit . PATIENTS: All infants with birth weights 1500 g or less cared for from July 1994 to July 2000 (n = 834) were included in the study . Mothers were classified as receiving antibiotics if they received any parenteral antibiotics in the predelivery period . Infants whose mothers received antibiotics were compared with infants whose mothers received no antibiotics . MAIN OUTCOME MEASURES: The main outcome variables studied included intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), sepsis, and mortality . RESULTS: Of 834 mothers, 374 (45%) received antibiotics prior to delivery . On univariate analysis, there were no differences in the relative risk (RR) of mortality (1.26; 95% confidence interval {CI}, 0.86-1.79) or grades 3 to 4 IVH (RR, 1.39; 95% CI, 0.82-1.90) between the antibiotics and no-antibiotics groups . Infants born to mothers receiving antibiotics had an increased risk of culture-proven sepsis (RR, 1.4; 95% CI, 1.02-1.64) and a decreased risk of cystic PVL (RR, 0.26; 95% CI, 0.09-0.79) compared with infants whose mothers did not receive antibiotics . After controlling for confounding variables, maternal antibiotics were not associated with a decrease in the risk of mortality (adjusted risk {AR}, 1.0; 95% CI, 0.5-2.1), grades 3 to 4 IVH (AR, 1.0; 95% CI, 0.5-1.9), or sepsis (AR, 0.9; 95% CI, 0.7-1.4) . However, the use of maternal antibiotics was associated with a decreased risk of developing cystic PVL (AR, 0.09; 95% CI, 0.02-0.5) . CONCLUSIONS: In our population of very low-birth-weight infants, maternal antibiotics were associated with a decreased risk of cystic PVL . Maternal antibiotics do not change the risk of mortality, sepsis, or severe IVH.

Yao Xue Xue Bao, 2001 Mar, 36(3), 174 - 8
{Characterization of cell death induced by anticancer antibiotic lidamycin in human hepatoma BEL-7402 cells}; He QY et al.; AIM: To study the features of cell death induced by the anticancer antibiotic lidamycin (LDM) in human hepatoma BEL-7402 cells . METHODS: Chromatin condensation was observed by co-staining with fluorescent dyes, hoechst 33342 and propidium iodide . "G1 sub-peak" was detected by flow cytometry and DNA ladder was observed using agarose gel electrophoresis . The caspase-3, 6 activities were measured with kits specific for them . RESULTS: Typical apoptotic chromatin condensations appeared when the BEL-7402 cells were treated with the conventional antitumor agent mitomycin C30 mumol.L-1 for 12 h . However, an abnormal type of chromatin condensation occurred when the cells were treated with LDM 1 mumol.L-1 for 6 h, which was characterized with keeping the completeness of nuclear membrane and not forming apoptotic bodies . The DNA ladder patterns were observed using agarose gel electrophoresis . The "G1 sub-peak" occurred only in the cells treated with LDM for 24 h, though chromatin condensation was earlier detected in treatment with LDM for 6 h . The caspase-3, 6 activities were increased about 5 and 4 folds, after the cells were treated with LDM 1 mumol.L-1 for 6 h, as did mitomycin C . The time of initiating chromatin condensation was earlier than that of the high peak activities of caspase-6 . CONCLUSION: The characterization of cell death induced by lidamycin in the human hepatoma BEL-7402 cells differs from typical apoptosis . The results make it helpful to explain the molecular mechanism of the highly potent cytotoxicities of lidamycin toward tumor cells.

Yao Xue Xue Bao, 2002 Mar, 37(3), 204 - 6
{Analysis of the response factors of different aminoglycoside antibiotics detected by evaporative light-scattering detector}; Wang MJ et al.; AIM: To analyze if the response factors of different aminoglycoside antibiotics detected by evaporative light-scattering detector (ELSD) are the same . If they are, then ELSD can be applied to the quality analysis of this class of antibiotics . METHODS: The response factors of five different aminoglycosides (amikacin, sisomicin, netilmicin, etimicin and vertilmicin) detected by ELSD were determined by using a Diamonsil C18 column (150 mm x 4.6 mm, 5 microns) as analytical column and 0.2 mol.L-1 trifluoroacetic acid-methanol (94:6) as mobile phase at a flow rate of 0.6 mL.min-1, the temperature of the drift tube was set at 110 degrees C, and the flow of carrier gas at 2.80 L.min-1 . Detector responses (A) and the amount of injection of each substance (m) were fitted to the logarithmic regression: logA = blogm + loga . RESULTS: The linear regression equation obtained were amikacin: Y = 1.46X + 5.07, gamma = 0.9997; sisomicin: Y = 1.51X + 5.03, gamma = 0.9997; netilmicin: Y = 1.52X + 4.88, gamma = 1.000; etimicin: Y = 1.46X + 4.85, gamma = 0.9999; vertilmicin: Y = 1.41X + 4.90, gamma = 0.9998 . The differences between them were negligible . CONCLUSION: Different aminoglycosides can give the same responses with ELSD detection . So, the HPLC-ELSD methods can be applied to the analysis of impurities, the control of the ratio of multi-components drug and the determination of new substances by using another substance as reference, etc.

Curr Med Chem, 2003 Mar, 10(5), 427 - 36
Vascular actions of anthracycline antibiotics; Wakabayashi I et al.; Anthracycline antibiotics are of particular value in the therapy of malignant diseases and exert profound effects not only on tumor cells but also on cells in the cardiovascular system . These quinone drugs affect vascular tone by a multitude of mechanisms, including acute modulation of Ca(2+) homeostasis, altered expression of membrane proteins and enzymes that are involved in the control of smooth muscle contraction, and generation of autoregulatory mediators, such as nitric oxide and endothelin . Anthracyclines interfere with blood coagulation-fibrinolysis balance due to its effects on the production of prostacyclin, plasminogen activator and plasminogen activator inhibitor in the endothelium . Moreover, anthracyclines are thought to be the modulators of angiogenesis . The intensity and quality of anthracycline actions on blood vessel function are highly variable and may depend not only on the chemical structure of anthracycline but also on the type of blood vessel as well as the metabolic and redox status of the vascular tissue . Vascular actions of anthracyclines are possibly involved in both beneficial as well as toxic and undesirable side-effects such as tumor progress . Further investigations are required to clarify the relation between specific modifications of vascular cell function and clinical events observed during antineoplastic therapy with anthracyclines.

Clin Infect Dis, 2003 Feb 15, 36(4), 389 - 95 Epub 2003 Jan 31.
Addition of a macrolide to a beta-lactam-based empirical antibiotic regimen is associated with lower in-hospital mortality for patients with bacteremic pneumococcal pneumonia; Martinez JA et al.; To assess the association between inclusion of a macrolide in a beta-lactam-based empirical antibiotic regimen and mortality among patients with bacteremic pneumococcal pneumonia, 10 years of data from a database were analyzed . The total available set of putative prognostic factors was subjected to stepwise logistic regression, with in-hospital death as the dependent variable . Of the 409 patients analyzed, 238 (58%) received a beta-lactam plus a macrolide and 171 (42%) received a beta-lactam without a macrolide . Multivariate analysis revealed 4 variables to be independently associated with death: shock (P<.0001), age of >or=65 years (P=.02), infections with pathogens that have resistance to both penicillin and erythromycin (P=.04), and no inclusion of a macrolide in the initial antibiotic regimen (P=.03) . For patients with bacteremic pneumococcal pneumonia, not adding a macrolide to a beta-lactam-based initial antibiotic regimen is an independent predictor of in-hospital mortality . However, only a randomized study can definitively determine whether this association is due to a real effect of macrolides.

J Antimicrob Chemother, 2003 Feb, 51(2), 391 - 6
Cost-minimization analysis and audit of antibiotic management of bone and joint infections with ambulatory teicoplanin, in-patient care or outpatient oral linezolid therapy; Nathwani D et al.; Bone and joint infections are significant causes of morbidity, mortality and healthcare costs . The cost of treatment for such infections is driven primarily by the length of hospital stay . Many of these infections will require treatment with prolonged periods of parenteral antibiotic therapy . Clinicians and healthcare managers are being attracted increasingly by administering treatment in the ambulatory setting as this offers clinical, economic and quality of life advantages from both the hospital's and patient's perspective . Our retrospective audit of managing 55 treatment episodes of bone and joint infections with teicoplanin delivered in the outpatient or home setting revealed that the mean cost of care per episode of infection was less with treatment in the ambulatory setting ( pound 1749.15) compared with the in-patient setting ( pound 11 400) or compared with the hypothetical situation of treatment with oral linezolid in the home setting ( pound 2546) . Teicoplanin therapeutic drug monitoring appears to be valuable in establishing optimal serum levels, which appear to correlate with good clinical outcomes . The potential for alternative day or thrice weekly dosing with teicoplanin may offer further cost advantages whilst maintaining equivalent clinical effectiveness.

Indian J Exp Biol, 2001 Jun, 39(6), 604 - 6
JU-2, a novel phosphorous-containing antifungal antibiotic from Streptomyces kanamyceticus M8; Datta I et al.; A novel phosphorous-containing antifungal antibiotic JU-2 was isolated from Streptomyces kanamyceticus M8 . Quantitative chemical analysis shows the presence of two phenylalanines, two glucose, one linoleic acid, one crucic acid and one phosphonamide moiety per molcule of the antibiotic . JU-2 shows strong inhibitory activity against various pathogenic and non-pathogenic fungi but no activity against bacteria and yeast.

Epidemiol Infect, 2002 Dec, 129(3), 507 - 13
Antibiotic use, gastroenteritis and respiratory illness in South Australian children; Talbot-Smith A et al.; This study examines the incidence of antibiotic-associated diarrhoea (AAD) in children in the community setting . Parents of 965 children aged 4-6 years and resident in rural/semi-rural South Australia completed a questionnaire on socio-demographic factors, and a 6-week daily diary detailing symptoms of gastroenteritis, antibiotic use, respiratory illness, and contact with someone with gastroenteritis . The incidence of AAD was 32.3 %, falling to 23.5% when episodes associated with a respiratory illness were excluded . Respiratory illness in the previous 3 days (OR 6.76, 95% CI 4.87, 9.38), and contact with someone with gastroenteritis in the previous 14 days (OR 1.8, 95% CI 1.48, 2.19), were both associated with gastroenteritis . After adjusting for these, only the first day of antibiotic use was associated with gastroenteritis (OR 3.8, 95% CI 1.8, 8.06) . Potential confounding factors, in particular inter-current respiratory illness, need to be considered when examining AAD.

Wei Sheng Wu Xue Bao, 1999 Dec, 39(6), 510 - 4
{Transposition of Tn5096 in a agricultural antibiotic 120 roducer Streptomyces hygrospinocus var . beijingensis RF220}; Zhang Y et al.; No transformant was obtained when pCZA168(bla, tsr, Tn5096, ColEI rep . Strep repts) was used to transform S . hygropinocus RF220 . pIJ702 isolated from S . hygroscopicus N103 was transformed into RF220 at a low frequency . pIJ702 plasmid was cured in RF220 transformant and it was re-transformed into its cured FR220 strain, but the transformation frequency was not increased significantly, suggesting that restriction-modification system in FR220 was existent and complicated . Four transformants containing pCZA168 were obtained, when the RF220 strain was grown in medium with ampicillin, glycine and the protoplast was stored at -70 degrees C . Restriction analysis of plasmid from transformants indicated that the DNA fragment from E . coli in pCZA168 was deleted . With transposition of Tn5096, two mutants blocked in antibiotic biosynthesis of 120 and some mutants with variation in antibiotic level were obtained, this showed that the Tn5096 transposed in different positions of chromosomal DNA in RF220 and resulted in the production of 120 in different level.

Wei Sheng Wu Xue Bao, 1999 Feb, 39(1), 84 - 6
{Taxonomy of the producing strain of agricultural antibiotic 2-16}; Shi Y et al.; In screening process of new agricultural, a streptomycetes, 2-16, was isolated from the soil sample collected in Huangsan . The secondary metabolites produced by the strain had strong inhibition to Sclerotinia sclerotiorum . By identification, this strain was regarded as new variety of Streptomyces ahygroscopicus and was called Streptomyces ahygroscopicus var . huangsanensis.

Indian Pediatr, 2003 Jan, 40(1), 7 - 12
Inappropriate antibiotic prescription to children with acute respiratory infection in Brazil; da Cunha AJ et al.; OBJECTIVE: To determine the rate of inappropriate antibiotic prescription and to describe the types of antibiotics prescribed by health workers to children with acute respiratory infection (ARI) . DESIGN: Cross-sectional survey conducted in 6 state capitals of Brazil . METHODS: A representative sample of facilities was selected in each state using a cluster sampling method based on the mean number of visits of children less than 5 years of age . In each facility, consultations were observed and children were reassessed following standard guidelines . Health worker s diagnosis and treatment were compared with a gold standard and inappropriate antibiotic prescriptions noted . RESULTS: 1565 children with ARI from 156 health facilities (73% health centers) were included in study . Most children had a common cold (77.5%) . Antibiotics were inappropriately prescribed in 9.2% (95% CI: 7.8, 10.7) of ARI cases (range: 2.8% to 25%) . Most frequently prescribed antibiotics were those recommended by the ARI Program . Seventy-six percent of health workers explained to guardians how to use antibiotics at home and 3.9% demonstrated the first dose . Antibiotics were available in 84% of health facilities . CONCLUSION: Inappropriate prescription of antibiotics varied geographically in Brazil . More training and supervision is needed to decrease it.

Protein Pept Lett, 2002 Dec, 9(6), 533 - 43
Antibiotic properties of novel synthetic temporin A analogs and a cecropin A-temporin A hybrid peptide; Wade D et al.; Temporin A, 18 analogs, and a cecropin A-temporin A hybrid peptide were tested with antibiotic sensitive and resistant bacteria, fungi, human erythrocytes, and in clotting assays.Several peptides were active in these assays, and some analogs (D-TA, W1-TA, and Con-L4,G10) may be useful lead compounds for further antibiotics development.The activity of temporin A was found to be dependent upon several of its structural features, including amino acid composition and sequence, chirality, helicity, and positive charge.

Acta Orthop Scand, 2002 Dec, 73(6), 688 - 90
Mechanical characteristics of antibiotic-laden bone cement; Armstrong MS et al.; We studied the mechanical characteristics of cement-antibiotic combinations in vitro . Palacos R was tested without antibiotics, with gentamicin alone and with gentamicin plus vancomycin or flucloxacillin . Palacos LV was studied only with gentamicin added . CMW 1 was studied with gentamicin added, with gentamicin plus vancomycin, and with gentamicin plus flucloxacillin . We performed four-point bending tests on beams of cement to establish bending strength and modulus, and compared the values to ISO standards . Density was also assessed . Palacos R was the strongest of the cements (bending strength 80 MPa) . Palacos formulations (apart from Palacos LV) had a higher density and bending modulus than CMW 1 . Statistical comparison of various cements with plain Palacos R showed lower density in 4 of the mixtures, and lower bending strength and modulus in 6 of the mixtures . Palacos R/gentamicin plus vancomycin and CMW 1/gentamicin plus vancomycin had bending strength slightly above minimum ISO standards, suggesting that the addition of vancomycin during cement mixing may compromise the outcome in revision surgery for sepsis.

Se Pu, 1999 Nov, 17(6), 588 - 9
{Detection of residual antibiotics in honey by capillary high performance liquid chromatography}; Huang HN et al.; The quantitative analysis of the three antibiotics-tetracycline(TC), oxytetracycline(OTC) and chlortetracyclinum(CTC) was carried out with a self-packed Hypersil C18 150 mm x 0.5 mm i.d . column . As little as 0.5 nanogram of antibiotics can be well detected, the capillary high performance liquid chromatographic method is 100 times more sensitive than that with ordinary HPLC method . The coefficients of linear correlation of mass concentration from 0.5 nanogram to 20 nanogram were rOTC = 0.99695, rTC = 0.99778 and rOTC = 0.98836 . It showed that capillary HPLC is a good method used for sensitive analysis of antibiotics in honey.

Ann Pharmacother, 2003 Feb, 37(2), 187 - 91
Pharmacy-based intervention to reduce antibiotic use for acute bronchitis; Hickman DE et al.; BACKGROUND: Intervention programs can reduce inappropriate antibiotic use for the treatment of acute bronchitis in a closed health maintenance organization model . OBJECTIVE: To evaluate the impact of a pharmacy-based intervention program intended to reduce antibiotic use in the treatment of acute bronchitis in a community-based physician group model . SUBJECTS: Adult and pediatric patients with an office or urgent care visit for acute bronchitis during the baseline and study periods were included in the study . The clinicians were primary care physicians, nurse practitioners, and physician assistants in a suburban community-based physician group setting . METHODS: All patients treated for acute bronchitis from January 1 through June 30, 1998, were evaluated for initial receipt of antibiotics and use of clinic resources (office visits, additional antibiotics) . From September through December of 1998, physicians were provided literature from the Centers for Disease Control and Prevention (CDC), cough and cold package inserts, and newsletters intended to educate the providers regarding the inappropriateness of antibiotics in the treatment of acute bronchitis . Patient-directed literature from the CDC was placed in the examination rooms and clinic waiting areas beginning September 1998 . From January 1 through June 30, 1999, all patients treated for acute bronchitis were assessed for receipt of antibiotics and use of clinic resources . A separate geographic clinic site served as a control during both study periods . RESULTS: During 1998, 888 of 1840 patients (48.3%) received antibiotics for treatment of acute bronchitis; this total decreased to 924 of 2392 (38.6%; p < or = 0.001) in 1999, a reduction of 20% . The rate of antibiotic prescribing in control patients was unchanged during the concomitant time periods (142/446, 31.8% vs . 102/321, 31.8%) . The rate of subsequent physician visits was similar (8% vs . 9%) between patients receiving antibiotics and those who did not . However, significantly more patients initially receiving antibiotics required a subsequent antibiotic prescription (45/1812, 2.5% vs . 24/2420, 1.0%; p < or = 0.001) . CONCLUSIONS: A pharmacy-based intervention program reduces the incidence of inappropriate antibiotic use in the treatment of acute bronchitis . Reduced antibiotic prescribing does not increase consumption of healthcare resources; patients who receive antibiotics for acute bronchitis are more likely to subsequently require additional antibiotic prescriptions . While a significant decrease in antibiotic use was realized, other interventions are required to further reduce the prevalence of antibiotic use in acute bronchitis.

Wei Sheng Wu Xue Bao, 1998 Feb, 38(1), 32 - 6
{Nucleotide sequence analysis of an antibiotic biosynthesis gene of Streptomyces globisporus}; Mao X et al.; Antitumor antibiotic C-1027 produced by Streptomyces globisporus has very high biological activity both in vivo and in vitro . Research works showed that one of biosynthesis gene of C-1027 is in the F2 DNA fragment . The plasmid pUC18 was used as vector to subclone the F2 DNA fragment . The nucleotide sequence analysis for F2 DNA fragment was carried out . Results showed that there is an open reading frame encoding for 122 amino acids . According to EMBO and GeneBanks data, this sequence may be a new one.

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 1998 Mar, 15(1), 69 - 72
{Study on antibiotic rate-limiting barrier membrane by radio-frequency glow discharge plasma deposition}; Li T et al.; A method that forming antibiotic rate-controling membrance on surface of polyurethane and ciprofloxacin matrix by RF-GDPD was studied . The surface characterization of film was analysed by XPS . The elution of antibiotic drug in vitro was discussed.

Wei Sheng Wu Xue Bao, 2000 Dec, 40(6), 646 - 51
{A actinomycete strain C3905 producing antitumor antibiotic sandramycin from Antarctica}; Hu J et al.; A nocardioform actinomycete strain C3905 was isolated from a soil sample collected in King Geoge island, Antarctica . Its aerial mycelium is white, substrate mycelium is colorless to cream or pink . The hyphae of mycelium 0.5 micron-0.8 micron in diameter and they fragment into irregular rod to coccoid elements with smooth surface . Cell wall type I . The mycolic acids are lacking . Mk-9(H4) is the predominant menaquinone component . Phospholipid type PI . The G + C content of DNA is 68.3-68.9 mol% . Facultative psychrophile . The optimum temperature for growth is 15 degrees C-20 degrees C . Produces antitumor antibiotic sandramycin . Based on the characteristics above as well as the investigation of the molecular genetics . We propose that strain C3905 should be placed in the Nocardioides albus as a variant, named Nocardioides albus var . antarcticus.

Am J Infect Control, 2003 Feb, 31(1), 18 - 25
Trends in antibiotic use and cost and influence of case-mix and infection rate on antibiotic-prescribing in a long-term care facility; Mylotte JM et al.; BACKGROUND: Antibiotic use and cost indicators have been developed specifically for the long-term care facility (LTCF) setting . Approximately 50% of the variation in these indicators was explained by the variation in infection rate . The objectives of this study were to further assess the utility of the antibiotic use and cost indicators in a different LTCF and to determine the correlation of case-mix and these indicators . METHODS: Antibiotic use and cost indicators were collected monthly by unit (N = 10) and by physician (N = 6) at a 433-bed LTCF in Syracuse, New York, from February 1999 to September 2001 . Indicators included incidence (number of antibiotic courses per 1000 resident care-days) of antibiotic use, antibiotic utilization ratio ({AUR}; ratio of the number of antibiotic-days to the number of resident care-days), cost per antibiotic-day, and cost per resident care-day . Case-mix variation was measured with the case-mix index (CMI) of the Resource Utilization Group II system . Simple linear and multilinear regression analyses were used to evaluate correlations of continuous variables . RESULTS: Among the 10 units or 6 physicians, there was a significant difference in the average values for all indicators . Correlation between unit- or physician-specific CMI and antibiotic use or cost indicators or infection rate was poor . However, there was a significant positive correlation between unit- or physician-specific infection rate and incidence of antibiotic use, AUR, and cost per resident care-day but not cost per antibiotic-day . With use of multilinear regression analysis to control for CMI and cost per antibiotic-day, infection rate was a significant predictor of incidence of antibiotic use (R2 = 0.65; P <.001) and AUR (R2 = 0.78; P <.001) . CONCLUSIONS: This study provides further evidence that the antibiotic use and cost indicators developed specifically for LTCFs can detect significant variation among units within a facility and among physicians . However, there was no correlation between CMI and antibiotic use or cost indicators . After controlling for case-mix variation and cost per antibiotic-day, variation in infection rate explained most of the variation in incidence of antibiotic use and AUR.

J Photochem Photobiol B, 2003 Jan, 69(1), 49 - 57
Dimers of polyene antibiotic amphotericin B detected by means of fluorescence spectroscopy: molecular organization in solution and in lipid membranes; Gruszecki WI et al.; Fluorescence emission from amphotericin B dissolved in 2-propanol-water was recorded in the spectral region 500-650 nm . The fluorescence excitation spectrum corresponds to the absorption spectrum of the monomeric drug . The large energy shift between the excitation and emission bands indicates that emission takes place from an energy level different than that responsible for absorption . These levels were attributed to the 2(1)A(g) and 1(1)B(u) states, respectively . Excitation of the same sample with short wavelength radiation (below 350 nm) yields light emission between 400 and 550 nm . The fluorescence excitation spectrum corresponding to this emission band displays distinct maxima at 350, 334 and 318 nm . This band was analyzed in terms of the exciton splitting theory and assigned to amphotericin B in a dimeric form, in which chromophores are spaced by 4.9 A . The binding energy of the dimers, determined to be 4.9 kJ/mol, indicates that the structures are stabilized by van der Waals interactions . The same type of molecular structures was also detected in the lipid membranes formed with dipalmitoylphosphatidylcholine . Linear dichroism of amphotericin B embedded in lipid multibilayers indicates that molecules are distributed between two fractions: parallel (38%) and perpendicular (62%) with respect to the membrane . The biological importance of such membrane organization is discussed.

J Antibiot (Tokyo), 2002 Nov, 55(11), 952 - 61
New antibiotics miyakamides produced by a fungus; Shiomi K et al.; New antibiotics, miyakamides A1, A2, B1, and B2, were isolated from the cultured broth of Aspergillus flavus Link var . columnaris FKI-0739 together with known compounds, parasiticolide A, hydroxyaspergillic acid, and kojic acid . The structure of miyakamide A1 is N-acetyl-L-phenylalanyl-N-methyl-L-phenylalanyl-(alphaZ)-alpha,beta-didehydrotryptamine, and miyakamide A2 is E isomer of A1 at didehydrotryptamine . The structure of miyakamide B1 is N-acetyl-L-tyrosyl-N-methyl-L-phenylalanyl-(alphaZ)-alpha,beta-didehydrotryptamine, and B2 is E isomer of B1 . Both miyakamides A1 and B1 existed as equilibrium isomers in solvents, and this isomerism was associated with cis-trans rotation of the amide bond between two amino acids . Conformational isomerism between two amino acids of miyakamides A2 and B2 is cis-form . Miyakamides showed growth inhibitory activity against brine shrimp, Artemia salina.

Health Serv Res, 2002 Dec, 37(6), 1603 - 23
An observational study of antibiotic prescribing behavior and the Hawthorne effect; Mangione-Smith R et al.; OBJECTIVES: To assess whether prospective, observational study procedures, including questionnaires and audio recording, are associated with different patterns of physician diagnostic decision making and antibiotic prescribing . DATA SOURCES/SETTING: (1) Survey data from a prospective observational study of treatment patterns for children with acute upper respiratory illnesses (10/96-3/97) and (2) retrospective medical record abstraction data of nonobserved encounters for the same problems occurring during (10/96-3/97) and one year after (10/97-3/98) the observational study period . Ten pediatricians in two community practices were studied . STUDY DESIGN: Patterns of diagnoses recorded in the medical record and antibiotics ordered for visits occurring outside of the observational study (same time period and one year later) were compared with the pattern of diagnoses and antibiotics ordered during the observational study . DATA COLLECTION/EXTRACTION METHODS: For the observational study (10/96-2/97), diagnosis and treatment choices were obtained from questionnaires completed by physicians immediately following the visit . For the nonstudy encounters (10/96-3/97 and 10/97-3/98), data were abstracted from medical records one year after the observational study was completed . PRINCIPAL FINDINGS: The proportion of viral cases in which an antibiotic was prescribed was 29 percentage points lower for the observational study compared to the retrospective analysis (p < .05) . In one of two study sites, the proportion of cases assigned a bacterial diagnosis was 29 percentage points lower in the observational study period compared to the retrospective study (p <.05) . CONCLUSIONS: Observational study procedures including questionnaires and audio recording can affect antibiotic prescribing behavior . Future observational studies aimed at examining the frequency of inappropriate antibiotic prescribing should measure and adjust for the Hawthorne effect; without such adjustments, the results will likely underestimate the true degree of the problem . Future interventions aimed at decreasing inappropriate antibiotic prescribing should consider "harnessing" the Hawthorne effect through performance feedback to participating physicians.

Community Dent Oral Epidemiol, 2003 Feb, 31(1), 40 - 51
Medically administered antibiotics, dietary habits, fluoride intake and dental caries experience in the primary dentition; Mariri BP et al.; OBJECTIVES: Dental caries continues to be a major public health problem in the US and other nations, particularly among younger children . Unfortunately, understanding of factors contributing to caries in this age group is incomplete and further studies are necessary . The purpose of this study was to assess factors related to extensive caries experience among children aged 4-7 years, including antibiotic use, dietary patterns, fluoride intakes, and tooth brushing habits . METHODS: The case-control study was nested within a longitudinal cohort study of children's oral health . The larger cohort study collected data on fluoride intakes and behavioral factors, including antibiotic use and dietary patterns of children periodically from birth . A single dental examination was completed for each child at a time between the ages of 4-7 years . A case-control design was used to compare children with severe caries experience (6 or greater dmfs) to those with no caries experience . Cases (n = 39) included all who met the criteria and had sufficient longitudinal data (n = 39) while a control group was selected to have comparable mean age, exam dates, and an equal number of boys and girls . RESULTS: Backward elimination logistic regression controlling for demographic variables showed severe caries experience to be related to greater regular pop/other sugared beverage intake, greater frequency of starch foods, and greater frequency of eating occasions . Mother's education and fluoride intake from water were inversely related to severe caries experience . Antibiotic use was generally higher in the control group, but was not significantly different than in the severe caries group . CONCLUSIONS: Although we cannot rule out the possibility that antibiotics may be associated with increased or decreased caries risk, our data suggest that they play only a minor role in caries prevention compared to fluoride . Dietary sugar continues to be a significant risk factor for caries in the primary dentition.

Se Pu, 2001 Jan, 19(1), 91 - 3
{Detection of residual antibiotics in honey with capillary electrophoresis}; Chen TB et al.; Five antibiotics compounds, tetracycline (TC), oxytetracycline (OTC), doxycycline (DOC), chlortetracycline (CTC) and chloramphenicol (CP), were successfully separated and determined by high performance capillary electrophoresis(HPCE) . Effects of buffer pH, various organic additives and temperature on electrophoretic separation of antibiotics were investigated . Satisfactory separation of these five antibiotics was achieved in the buffer of pH 3.2, 0.02 mol/L Na2HPO4-0.01 mol/L citric acid with addition of 4% (V/V) N-methylmorpholine and 12% (V/V) acetonitrile within 20 minutes . The calibration graphs were linear by plotting the peak area against the sample concentration over the range of 150 micrograms/L to 750 micrograms/L and the correlation coefficients were greater than 0.9917 . The detection limits were 10 micrograms/L for CP, 20 micrograms/L for TC, OTC and DOC and 40 micrograms/L for CP (signal to noise ratio > 5) . HPCE method was successfully applied to the analysis of trace antibiotics in honey.

Lin Chuang Er Bi Yan Hou Ke Za Zhi, 2001 Apr, 15(4), 149 - 51
{Determination of the point of gene mutation in two types of tissue from the aminoglycoside antibiotics induced deaf patients}; Xu L et al.; OBJECTIVE: To elucidate the gene mutation presents in hair follicle cells, just as blood cells, in the aminoglycoside antibiotics induced deaf patients(AAID) . METHOD: Mitochondrial DNA of blood cells and/or hair follicle cells from 8 members of 3 aminoglycoside antibiotics induced deafness families were analysed using PCR-SSCP and Alw 26 I digestian . RESULT: Our result showed that a gene mutation at nucleotide 1555 in 12 S rRNA of mitochondrial DNA appeared in blood cells and/or hair follicle cells of 7 subjects among those 8 members . Only a father with normal hearing did't exhibit such a mutation . CONCLUSION: This indicated that hairs could be used as a sample instead of blood to perform gene examination for AAID.

Se Pu, 2002 Jan, 20(1), 49 - 51
{Determination of tetracyclines antibiotics by reversed-phase high performance liquid chromatography}; Wang L et al.; A method for the determination of 7 tetracycline antibiotics (TCs) by reversed-phase high performance liquid chromatography is described . TCs were successfully separated on a Diamonsil C18 column (250 mm x 4.6 mm i.d., 5 microns) using methanol-acetonitrile-0.01 mol/L oxalic acid (pH 2.0) (11:22:67, volume ratio) as mobile phase at a flow rate of 0.8 mL/min and detected at 267 nm within 22 min . Effects of the pH value of the mobile phase, concentration of the mobile phase buffer, elution composition and detection wavelength on the response and retention were studied . Tetracycline (TC) and oxytetracycline(OTC) in medicinal tablets were quantitated by standard added method . It has been proven that the method is fast, accurate and suitable for routine analysis.

Z Gastroenterol, 2003 Jan, 41(1), 5 - 10
{Ceftriaxone versus Levofloxacin for antibiotic therapy in patients with acute cholangitis}; Kiesslich R et al.; INTRODUCTION: For the therapy of acute cholangitis complete biliary drainage and antibiotic therapy is needed . The aim of the current study was to compare intravenous therapy of acute cholangitis with Ceftriaxone or Levofloxacin in a prospective and randomized fashion . METHODS: Patients with biliary obstruction and clinical signs of infection received in addition to 1.5 g Metronidazole either 500 mg Levofloxacin/die or 2 g Ceftriaxone/die . Early on during ERCP, bile was aspirated via the cannulation catheter and cultured for bacteria under aerobic and anaerobic conditions . Minimal inhibitory concentrations of the respective antibiotics were determinate for each isolate . The clinical course was followed for at least 6 days with clinical and laboratory data . RESULTS: 60 patients with clinical signs of acute cholangitis were randomised . In 40 patients (66 %) biliary colonization with bacteria could be identified . In all bacterial species Levofloxacin showed significantly lower rates of in-vitro resistance as compared to Ceftriaxone . However, the percentage of patients with a clinical cure or significant improvement was the same in the two groups . CONCLUSIONS: The clinical effect of Levofloxacin and Ceftriaxone in patients with acute cholangitis showed no significant differences . Because of improved in-vitro efficiency, a calculated therapy with Levofloxacin might be advantageous.

Emerg Med J . 2003 Jan;20(1):66.
Antibiotics in orbital floor fractures; Martin B et al.; A short cut review was carried out to establish whether prophylactic antibiotics are indicated in patients with undisplaced maxillary or orbital floor fractures . Altogether 214 papers were found using the reported search, but none presented any evidence to answer the clinical question . More research is needed in this area and, in the mean time, local advice should be followed.

BMJ . 2003 Jan 18;326(7381):138.
Why do general practitioners prescribe antibiotics for sore throat? Grounded theory interview study; Kumar S et al.; OBJECTIVES: To understand why general practitioners prescribe antibiotics for some cases of sore throat and to explore the factors that influence their prescribing . DESIGN: Grounded theory interview study . SETTING: General practice . PARTICIPANTS: 40 general practitioners: 25 in the maximum variety sample and 15 in the theoretical sample . RESULTS: General practitioners are uncertain which patients will benefit from antibiotics but prescribe for sicker patients and for patients from socioeconomically deprived backgrounds because of concerns about complications . They are also more likely to prescribe in pressured clinical contexts . Doctors are mostly comfortable with their prescribing decisions and are not prescribing to maintain the doctor-patient relationship . CONCLUSIONS: General practitioners have reduced prescribing for sore throat in response to research and policy initiatives . Further interventions to reduce prescribing would need to improve identification of patients at risk of complications and be workable in busy clinical situations.

J Enzyme Inhib Med Chem, 2002 Aug, 17(4), 271 - 7
Purification and characterization of glucose 6-phosphate dehydrogenase from sheep erythrocytes and inhibitory effects of some antibiotics on enzyme activity; Beydemir S et al.; Glucose 6-phosphate dehydrogenase (D-glucose 6-phosphate: NADP+ oxidoreductase, EC 1.1.1.49; G6PD) was purified from sheep erythrocytes, using a simple and rapid method . The purification consisted of three steps; preparation of haemolysate, ammonium sulphate fractionation and 2', 5'-ADP Sepharose 4B affinity chromatography . The enzyme was obtained with a yield of 37.1% and had a specific activity of 4.64 U/mg proteins . Optimal pH, stable pH, molecular weight, and KM and Vmax values for NADP+ and glucose 6-phosphate (G6-P) substrates were also determined for the enzyme . The overall purification was about 1,189-fold . A temperature of +4 degrees C was maintained during the purification process . In order to control the purification of the enzyme SDS polyacrylamide gel electrophoresis (SDS-PAGE) was done in 4% and 10% acrylamide concentration for stacking and running gel, respectively . SDS-PAGE showed a single band for enzyme . Enzymatic activity was spectrophotometrically measured according to Beutler's method at 340 nm . In addition, in vitro effects of gentamicin sulphate, penicillin G potassium, amicasin on sheep red blood cell G6PD enzyme activity were investigated . These antibiotics showed inhibitory effects on enzyme activity . I50 values were determined from Activity%-{Drug} graphs and Ki values and the type of inhibition (noncompetitive) were determined by means of Lineweaver-Burk graphs.

Org Lett, 2003 Jan 23, 5(2), 109 - 12
Novel antibiotics: macrocyclic peptides designed to trap Holliday junctions; Bolla ML et al.; {reaction: see text} Described are the syntheses of eight macrocyclic peptides designed to trap Holliday junctions in bacteria, thereby inhibiting bacterial growth . These macrocycles were designed from linear dimerized hexapeptides that bind to the C-2 symmetrical Holliday junction . They were synthesized from three monomers using a combinatorial-like strategy that permits elucidation of the monomer role in accumulation of Holliday junctions and antibiotic activity . These macrocycles are an important step in designing and synthesizing a new class of antibiotics.

Chest, 2003 Jan, 123(1), 261 - 5
Tissue reparative effects of macrolide antibiotics in chronic inflammatory sinopulmonary diseases; Garey KW et al.; It is well established that macrolide antibiotics are efficacious in treating sinopulmonary infections in humans . However, a growing body of experimental and clinical evidence indicates that they also express distinct salutary effects that promote and sustain the reparative process in the chronically inflamed upper and lower respiratory tract . Unlike the anti-infective properties, these distinct effects are manifested at lower doses, usually after a relatively prolonged period (weeks) of treatment, and in the absence of an identifiable, viable pathogen . Long-term, low-dose administration of macrolide antibiotics has been used most commonly for sinusitis, diffuse panbronchiolitis, asthma, bronchiectasis, and cystic fibrosis . It is associated with down-regulation of nonspecific host inflammatory response to injury and promotion of tissue repair . Although large-scale trials are lacking, the prolonged use of these drugs has not been associated with emergence of clinically significant bacterial resistance or immunosuppression . Long-term, low-dose administration of 14- and 15-membered ring macrolide antibiotics may represent an important adjunct in the treatment of chronic inflammatory sinopulmonary diseases in humans.

LDI Issue Brief, 2001 Mar, 6(6), 1 - 4
When data conflict with practice: rethinking the use of prophylactic antibiotics before dental treatment; Strom BL; Concern is growing about the overuse of antibiotics and the subsequent rise in antibiotic-resistant bacteria . Antibiotics are commonly used to prevent heart valve infections in susceptible patients undergoing dental or other surgical procedures . Although this practice has been standard for nearly 50 years, little evidence exists that it works . This Issue Brief summarizes a population-based study that challenges the link between dental procedures and heart valve infections, and illustrates the difficulty in incorporating new evidence into existing guidelines and longstanding practices.

J Antibiot (Tokyo), 2002 Oct, 55(10), 893 - 8
Chalcomycin B, a new macrolide antibiotic from the marine isolate Streptomyces sp . B7064; Asolkar RN et al.; In our screening of marine streptomycete isolates for bioactive components, a new macrolide antibiotic designated as chalcomycin B (1b) was isolated from the culture broth of a marine Streptomycete isolate B7064 together with chalcomycin (1a) as the active principles . The structure of the new antibiotic was determined by EI and ESI MS, 1H, 13C and 2D NMR spectroscopy and by comparison of the NMR data with those of chalcomycin.

J Antibiot (Tokyo), 2002 Oct, 55(10), 863 - 72
GEX1 compounds, novel antitumor antibiotics related to herboxidiene, produced by Streptomyces sp . II . The effects on cell cycle progression and gene expression; Sakai Y et al.; Six GEX1 compounds, GEX1A/herboxidiene and its related 5 novel compounds, were isolated from a culture broth of Streptomyces sp . GEX1 compounds induced both G1 and G2/M arrest in a human normal fibroblast cell line, WI-38 . All six compounds up-regulated luciferase reporter gene expression directed by enhancer/promoter of various genes, such as cdc2, IL-2 and SV40 early genes . All GEX1 compounds showed cytotoxic activities in the same order of the up-regulating activities on gene expression, suggesting that these two activities are related . Despite the up-regulating activities on the reporter gene expression, GEX1A/herboxidiene did not enhance the expression of any endogenous genes involved in the cell cycle, proliferation and apoptosis . Although the unique effects of GEX1 compounds on cell cycle and the reporter gene expression were similar to those of trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), GEX1A/herboxidiene did not affect histone acetylation in cells . In addition, GEX1A/herboxidiene treatment gave rise to the shorter sized transcripts of the cdc25A and cdc2 genes as well as the normal sized ones . These results suggest that GEX1 compounds modulate gene expression by an unknown mechanism.

Structure (Camb), 2003 Jan, 11(1), 43 - 53
Comparison of X-ray crystal structure of the 30S subunit-antibiotic complex with NMR structure of decoding site oligonucleotide-paromomycin complex; Lynch SR et al.; Aminoglycoside antibiotics that bind to 16S ribosomal RNA in the aminoacyl-tRNA site (A site) cause misreading of the genetic code and inhibit translocation . Structures of an A site RNA oligonucleotide free in solution and bound to the aminoglycosides paromomycin or gentamicin C1a have been determined by NMR . Recently, the X-ray crystal structure of the entire 30S subunit has been determined, free and bound to paromomycin . Distinct differences were observed in the crystal structure, particularly at A1493 . Here, the NMR structure of the oligonucleotide-paromomycin complex was determined with higher precision and is compared with the X-ray crystal structure of the 30S subunit complex . The comparison shows the validity of both structures in identifying critical interactions that affect ribosome function.

Arch Pediatr Adolesc Med, 2003 Jan, 157(1), 54 - 9
Association between antibiotic use and primary idiopathic intussusception; Spiro DM et al.; BACKGROUND: Intussusception is the leading cause of intestinal obstruction in young children . Antibiotics are the most frequently prescribed medication in the pediatric population and have common adverse effects on the gastrointestinal tract . OBJECTIVE: To determine whether a relationship exists between primary idiopathic intussusception and antibiotic drug use . DESIGN: Case-control study . PARTICIPANTS: Ninety-three case patients with intussusception and 353 injury controls younger than 4 years who were seen at the emergency department of the Children's Hospital of Alabama between January 1, 1996, and April 30, 2001, were included . Controls were matched to cases by quarter and year of time of diagnosis, age, and sex . MAIN OUTCOME MEASURES: Odds ratios and 2-sided 95% confidence intervals were estimated using conditional logistic regression . Prevalence of antibiotic use in an age-standardized, representative sample of US children from NHANES III (Third National Health and Nutrition Examination Survey) was used for external comparisons . RESULTS: Antibiotic use within 48 hours of diagnosis was found in 23 cases (25%) and 33 controls (9%) (odds ratio, 4.15; 95% confidence interval, 2.17-7.92; attributable risk, 18.7%) . Antibiotic use among US children according to NHANES III was 10.7% . In cases, the beta-lactam class accounted for 78% of all medications used . Cephalosporin use was associated with more than a 20-fold increased risk of intussusception . CONCLUSION: An association between antibiotic drug use and intussusception was identified.

Stat Methods Med Res, 2002 Dec, 11(6), 491 - 512
Decision analytical economic modelling within a Bayesian framework: application to prophylactic antibiotics use for caesarean section; Cooper NJ et al.; Economic evaluation of health care interventions based on decision analytic modelling can generate valuable information for health policy decision makers . However, the usefulness of the results obtained depends on the quality of the data input into the model; that is, the accuracy of the estimates for the costs, effectiveness, and transition probabilities between the different health states of the model . The aim of this paper is to review the use of Bayesian decision models in economic evaluation and to demonstrate how the individual components required for decision analytical modelling (i.e., systematic review incorporating meta-analyses, estimation of transition probabilities, evaluation of the model, and sensitivity analysis) may be addressed simultaneously in one coherent Bayesian model evaluated using Markov Chain Monte Carlo simulation implemented in the specialist Bayesian statistics software WinBUGS . To illustrate the method described, a simple probabilistic decision model is developed to evaluate the cost implications of using prophylactic antibiotics in caesarean section to reduce the incidence of wound infection . The advantages of using the Bayesian statistical approach outlined compared to the conventional classical approaches to decision analysis include the ability to: (i) perform all necessary analyses, including all intermediate analyses (e.g., meta-analyses) required to derive model parameters, in a single coherent model; (ii) incorporate expert opinion either directly or regarding the relative credibility of different data sources; (iii) use the actual posterior distributions for parameters of interest (opposed to making distributional assumptions necessary for the classical formulation); and (iv) incorporate uncertainty for all model parameters.

Am Surg, 2002 Dec, 68(12), 1072 - 4
Oral antibiotics in the management of perforated appendicitis in children; Gollin G et al.; After appendectomy for perforated appendicitis children have traditionally been managed with intravenous broad-spectrum antibiotics for 5 to 10 days and then until fever and leukocytosis have resolved . We prospectively evaluated a protocol of hospital discharge on oral antibiotics when oral intake is tolerated-regardless of fever or leukocytosis-in a consecutive series of 80 children between one and 15 years of age who underwent appendectomy (38 open and 42 laparoscopic) for perforated appendicitis . At discharge subjects began a 7-day course of oral trimethoprim/sulfamethoxazole and metronidazole . Patients were discharged between 2 and 18 days postoperatively (mean 5.3 days) . Sixty-six were discharged on oral antibiotics, and 28 of these had persistent fever or leukocytosis . Two patients (2.5%) developed postoperative intra-abdominal abscesses while inpatients . Wound infections developed in seven patients (8.8%) four of whom were on intravenous antibiotics . Among the 66 children who were discharged on oral antibiotics without having had an inpatient infectious complication there were three wound infections (4.4%) . None of these patients had a fever or leukocytosis at discharge . We conclude that after appendectomy for perforated appendicitis children may be safely discharged home on oral antibiotics when enteral intake is tolerated regardless of fever or leukocytosis.

Int J Qual Health Care, 2002 Dec, 14(6), 503 - 8
Prophylactic antibiotic prescription for cesarean section; Liabsuetrakul T et al.; OBJECTIVES: To assess the use of prophylactic antibiotics for cesarean section, and to identify factors associated with a doctor's intraoperative prescription . DESIGN: A hospital-based, cross-sectional study . STUDY PARTICIPANTS: All 967 medical records of women undergoing cesarean section from January 1998 to February 1999 in a university hospital, Southern Thailand . MAIN MEASURES: Independent variables consisted of patient and doctor factors . The outcome variable was whether any antibiotics were given intraoperatively . Multivariate logistic regression with random effects was used to identify factors associated with the doctor's prescription . RESULTS: Prophylactic antibiotics were prescribed in 82% of all patients . One hundred and eighty-eight patients (21%) received antibiotics postoperatively . Of the patients receiving intraoperative antibiotics after cord clamping, 8% received only a single dose and 53% received an additional postoperative prescription . The most commonly used antibiotic was ampicillin . Intraoperative prescription was significantly associated with longer duration of ruptured membranes, higher number of vaginal examinations and doctors' age . Doctors aged 30-39 years had three and seven times the likelihood of prescribing intraoperative antibiotics compared with their younger and older colleagues, respectively . CONCLUSIONS: Administration of single-dose prescriptions was still an uncommon practice . Prophylaxis was given more commonly to patients with well known risks for infection, and was given by doctors aged 30-39 years.

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