Antibiotics

Rapid Commun Mass Spectrom, 2003, 17(2), 149 - 54
Fragmentation study of salinomycin and monensin A antibiotics using electrospray quadrupole time-of-flight mass spectrometry; Miao XS et al.; The fragmentation pathways of two selected ionophore antibiotics, salinomycin and monensin A, were studied using electrospray (ES) orthogonal acceleration quadrupole time-of-flight mass spectrometry in positive-ion mode . The identity of fragment ions was determined by accurate-mass measurements . In ES mass spectra, ion signals of relatively high intensity were observed for {M+Na}(+) and {M-H+2Na}(+) for each antibiotic . Each of the ion species {M+Na}(+) and {M-H+2Na}(+) for salinomycin and {M-H+2Na}(+) for monensin A were isolated in turn and subjected to fragmentation . In the fragmentation of {M+Na}(+) and {M-H+2Na}(+) from salinomycin, only Cbond;C single bond cleavage and dehydration were observed . Product ion mass spectra obtained from {M-H+2Na}(+) of monensin A showed that ether ring opening, Cbond;C single bond cleavage and dehydration fragmentations had occurred . Fragment ions containing two sodium atoms were observed in the product ion mass spectrum of {M-H+2Na}(+) from salinomycin, but not from monensin A . Both type A (containing the terminal carboxyl group) and type F (containing the terminal hydroxyl group) fragment ions were observed in the product ion mass spectra of sodium adduct ions of salinomycin and monensin A .

Acta Orthop Traumatol Turc, 2002, 36(1), 63 - 71
{Mechanical strength of antibiotic-impregnated bone cement on Day 0 and Day 15: a biomechanical study with Surgical Simplex P and teicoplanin}; Gogus A et al.; OBJECTIVES: To determine the maximum amount of a specific antibiotic added to 40 g acrylic bone cement in terms of the effect on mechanical properties of the bone cement on Day 0 and after antibiotic release on Day 15 . METHODS: In an experimental design, eight teicoplanin doses (0, 400 mg, 800 mg, 1200 mg, 1600 mg, 2000 mg, 3200 mg and 4000 mg) were added to bone cement (Surgical Simplex P) . Specimens were prepared using the third generation cementing technique to determine the compressive strength and four-point bending strength according to ASTM and ISO standards, respectively . For each concentration, 10 samples were prepared for Day 0 and Day 15 . Mechanical tests were performed on Day 0 and after antibiotic leaching in water at 37 degrees C on Day 15 . 0 mg specimens served as controls and mechanical strengths for each antibiotic concentration on Day 0 and Day 15 were compared . RESULTS: In compression tests, Day 0 samples showed no significant differences, whereas Day 15 samples starting with 800 mg exhibited significant decreases in compressive strength . However, the compressive strengths were above the minimum standard of 70 MPa set by ASTM at all concentrations and in all groups . Four-point bending tests demonstrated significant decreases in strength starting with 1200 mg in Day 0 samples, and with 400 mg in Day 15 samples . Four-point bending strengths of 2000 mg, 3200 mg, and 4000 mg samples decreased below, or approximated closely the minimum standard of 50 MPa set by ISO on Day 15 . CONCLUSION: Our results suggest that the maximum amount of teicoplanin dose to be safely added to 40 g of Surgical Simplex P is 1600 mg when third generation cement mixing and application techniques are employed.

Int J Antimicrob Agents, 2003 Jan, 21(1), 63 - 6
Rational antibiotic use and academic staff; Cagri Buke A et al.; This study was devised to determine the knowledge, attitude and behaviour of an educated group of people towards antibiotic use and self-medication with antibiotics . Of 1380 members of academic staff (excluding those from the Faculty of Medicine) of Ege University, 602 were chosen by systematic sampling methods . Two groups were formed . Group A included academic staff from the Faculties of Dentistry and Pharmacy and Group B, members of all other faculties . The mean age was 37.4+/-11.0 and 47.0% were females . The mean antibiotic knowledge score was 7.16+/-3.32 . Self-medication with antibiotics was admitted by 45.8% of the total samle and 15.6% of the respondents used antibiotics until their symptoms disappeared regardless of the period of prescription . In Group A 48.8% and in Group B 80.7% of the respondents believed that antibiotics could be used for common cold . It is concluded that priority should be given to knowledge-based behaviour education programmes for the more highly educated community; there must also be restriction on the sale of antibiotics without prescription.

Biochim Biophys Acta, 2003 Jan 10, 1609(1), 39 - 44
Uptake of dipeptide and beta-lactam antibiotics by the basolateral membrane vesicles prepared from rat kidney; Sugawara M et al.; The transport of dipeptides and beta-lactam antibiotics across the rat renal basolateral membrane was examined . The initial uptake of glycylsarcosine and cefadroxil by rat renal basolateral membrane vesicles was inhibited by the presence of all the di- and tripeptides and beta-lactam antibiotics that were tested in this study . However, the uptake of both substrates was not inhibited by glycine, an amino acid . The initial uptake of zwitterionic beta-lactam antibiotics, cefadroxil, cephradine, and cephalexin, was stimulated by preloaded glycylsarcosine (countertransport effect) . On the other hand, the uptake of dianionic beta-lactam antibiotics, ceftibuten and cefixime, was not affected . A concentration-dependent initial uptake of glycylsarcosine and cefadroxil suggested the existence of a carrier-mediated mechanism, whereas the transport of ceftibuten did not show any saturated uptake . The transporter that participates in the permeation of dipeptides and beta-lactam antibiotics across basolateral membranes showed lower affinity than did PEPT1 and PEPT2 . This is the first study that showed an evidence for a peptide transporter, expressed in the rat renal basolateral membrane, that recognizes zwitterionic beta-lactam antibiotics using basolateral membrane vesicles isolated from normal rat kidney.

J Infect, 2003 Jan, 46(1), 30 - 4
Antibiotic prescribing and penicillin-resistant pneumococci in a Merseyside Health District; Vardhan MS et al.; OBJECTIVES: To measure the effects of antibiotic prescribing changes in the community on the prevalence of penicillin-resistant pneumococci . METHODS: Penicillin-resistant pneumococci were isolated from clinical samples taken from 549 patients between January 1987 and December 2000 . Changes in the percentage of penicillin-resistant pneumococci isolated over the 14-year period and changes in prescribing practices were determined . RESULTS: Between January 1987 and December 2000, the prevalence of penicillin resistant pneumococci increased from 1.4% to a peak of 12.9% in 1997, subsequently falling to 8.9% after changes in antibiotic prescribing practices in the community.Over 65% of isolates were community acquired with 53% of patients having received antibiotics in the 3 months prior to their first isolate . Thirteen patients had a history of recent travel abroad . CONCLUSION: Reduction in antibiotic prescribing in general practice was followed by a reduction in the prevalence of penicillin-resistant pneumococci.

J Nat Prod, 2002 Dec, 65(12), 1953 - 5
Biosynthesis of the lipophilic side chain in the cyclic hexadepsipeptide antibiotic IC101; Umezawa K et al.; Antibiotic IC101 is a cyclic hexadepsipeptide having a C(15) lipophilic side chain . The side chain was shown to be synthesized in Streptomyces from acetate, propionate, and 3-methylbutyrate derived from leucine . Thus, the terminal isopentyl structure came from leucine and not from the mevalonate pathway.

Biochemistry, 2002 Dec 31, 41(52), 15795 - 802
Molecular characterization of NikD, a new flavoenzyme important in the biosynthesis of nikkomycin antibiotics; Venci D et al.; Nikkomycin antibiotics are potent inhibitors of chitin synthase, effective as therapeutic antifungal agents in humans and easily degradable insecticides in agriculture . NikD is a novel flavoprotein that catalyzes the oxidation of Delta(1)- or Delta(2)-piperideine-2-carboxylate, a key step in the biosynthesis of nikkomycin antibiotics . The resulting dihydropicolinate product may be further oxidized by nikD or converted to picolinate in a nonenzymic reaction . Saturated nitrogen heterocycles (L-pipecolate, L-proline) and 3,4-dehydro-L-proline act as alternate substrates . The ability of nikD to oxidize 3,4-dehydro-L-proline, but not 1-cyclohexenoate, suggests that the enzyme is specific for the oxidation of a carbon-nitrogen bond . An equivalent reaction is possible with the enamine (Delta(2)), but not the imine (Delta(1)), form of the natural piperideine-2-carboxylate substrate . Apparent steady-state kinetic parameters for the reaction of nikD with Delta(1)- or Delta(2)-piperideine-2-carboxylate (k(cat) = 64 min(-1); K(m) = 5.2 microM) or 3,4-dehydro-L-proline (k(cat) = 18 min(-1); K(m) = 13 mM) were determined in air-saturated buffer by measuring hydrogen peroxide formation in a coupled assay . NikD appears to be a new member of the monomeric sarcosine oxidase (MSOX) family of amine oxidizing enzymes . The enzyme contains 1 mol of flavin adenine dinucleotide (FAD) covalently linked to Cys321 . The covalent flavin attachment site and two residues that bind substrate carboxylate in MSOX are conserved in nikD . NikD, however, exhibits an unusual long-wavelength absorption band, attributed to charge-transfer interaction between FAD and an ionizable (pK(a) = 7.3) active-site residue . Similar long-wavelength absorption bands have been observed for flavoproteins containing an active site cysteine or cysteine sulfenic acid . Interestingly, Cys273 in nikD aligns with an active-site histidine in MSOX (His269) that is, otherwise, a highly conserved residue within the MSOX family.

J Crit Care, 2002 Dec, 17(4), 251 - 4
Purulent pneumococcal pericarditis: a rarity in the antibiotic era; Hastbacka J et al.; PURPOSE: The purpose of this report is to show that even while properly treated, pneumococcal disease may proceed to a life-threatening condition including purulent pericarditis and multiple organ failure . PATIENTS AND METHODS: This is a case-report describing one patient treated in the intensive care unit (ICU) of Helsinki University Central Hospital in March 2001 . CONCLUSIONS: In the antibiotic era, purulent pericarditis is an extremely rare yet possible condition complicating pneumococcal disease . Because of the growing incidence of penicillin resistance of this community-acquired pathogen, purulent pericarditis may become more common . Early detection and treatment of this otherwise fatal condition may lead to a good outcome .

Chem Pharm Bull (Tokyo), 2002 Dec, 50(12), 1570 - 3
Physicochemical analyses of phase transition and dehydration processes of a new oral 1beta-methylcarbapenem antibiotic agent, CS-834; Kobayashi K et al.; The characterizations of the anhydrate (A-form), monohydrate (B1-form), and dihydrate (B2-form) of CS-834 were investigated by powder X-ray diffraction, differential scanning calorimetry (DSC), thermogravimetry-differential thermal analysis (TG-DTA), infrared spectroscopy, and Karl Fischer moisture titration . The typical DSC curve of the B2-form showed five endothermic peaks at 35.0, 46.4, 56.2, 99.2, and 190.4 degrees C and an exothermic peak at 123.4 degrees C . In TG-DTA analysis, the three peaks at 35.0, 46.4, and 56.2 degrees C had a total weight loss of 7.3%, corresponding to the release of two water molecules . From morphological observation under thermomicroscopy, the endothermic peak at 99.2 degrees C was attributed to the melting of the dehydrous crystals (B0-form) and the exothermic peak at 123.4 degrees C to the recrystallization to the A-form crystals . The endothermic peak at 190.4 degrees C was due to the melting of the A-form crystals . After incubation for 6.0 h at 35, 50, 60, and 80 degrees C, the powder X-ray diffraction patterns of the B2-form indicated that it was converted into the A-form via the B1-form and B0-form . Thus CS-834 exists in homologous hydrous crystal forms in multiple-phase transformations with the dehydration of two water molecules.

Antimicrob Agents Chemother, 2003 Jan, 47(1), 413 - 5
Antibiotic susceptibilities of Anaplasma (Ehrlichia) phagocytophilum strains from various geographic areas in the United States; Maurin M et al.; We tested the antibiotic susceptibilities of eight strains of Anaplasma phagocytophilum (the agent of human granulocytic ehrlichiosis) collected in various geographic areas of the United States, including Minnesota, Wisconsin, California, and New York . The results are homogeneous and show that doxycycline, rifampin, and levofloxacin are the most active antibiotics against these strains in vitro.

Antimicrob Agents Chemother, 2003 Jan, 47(1), 181 - 7
The proton channel is the minimal structure of ATP synthase necessary and sufficient for microcin h47 antibiotic action; Rodriguez E et al.; It had been previously determined that the presence of F(o)F(1) ATP synthase was required for microcin H47 antibiotic action . In this work, microcin-resistant atp mutants were genetically analyzed . Their mutations, originated by Tn5 insertion, in all cases were found to affect determinants for the F(o) portion of ATP synthase . To discern if microcin action required the presence of the entire complex or if the F(o) proton channel would suffice, recombinant plasmids carrying different segments of the atp operon were constructed and introduced into an atp deletion strain . The phenotypic analysis of the strains thus obtained clearly indicated that the presence of the F(o) proton channel was absolutely required for microcin H47 action, while the F(1) catalytic portion was found to be dispensable . Furthermore, when any of the three components of the proton channel was missing, total resistance to the antibiotic ensued . Complementation analysis between atp::Tn5 chromosomal mutations and recombinant atp plasmid constructions further supported the idea that the proton channel would be the minimal structure of the ATP synthase complex needed for microcin H47 antibiotic action.

Chem Biol, 2002 Dec, 9(12), 1268 - 70
Combinatorial glycosylation of glycopeptide antibiotics; Baltz RH; The glycosyltransferases GtfE and GtfD from the vancomycin producer Amycolatopsis orientalis have promiscuous substrate and NDP-sugar specificities . They have been used to generate novel glycopeptide antibiotics containing the heptapeptide scaffolds of vancomycin and teichoplanin.

PDA J Pharm Sci Technol, 2002 Nov-Dec, 56(6), 312 - 7
ICH Q7A; 4.40 containment of beta-lactam antibiotics: an industry perspective; Kasai T et al.; The ICH Q7A guidance was finalized at the Fifth International Conference on Harmonization in San Diego, Nov . 9-11, 2000, and has been implemented in Japan since Nov . 2, 2001 . However, in ICH Q7A; 4.40, Containment, there is no clear stipulation about whether a dedicated or multi-purpose facility should be employed in the production of highly sensitizing materials of different types of beta-lactam antibiotics, such as cephalosporins and cephems . This study presents the threshold levels for the induction of anaphylaxis by beta-lactam antibiotics to show that it is possible to use a multi-purpose facility for the production of several different types of beta-lactam antibiotics except for penicillins, if there are validated cleaning standards based on threshold values.

Infect Immun, 2003 Jan, 71(1), 456 - 64
Inhibition of Mycobacterium tuberculosis glutamine synthetase as a novel antibiotic strategy against tuberculosis: demonstration of efficacy in vivo; Harth G et al.; Tuberculosis remains one of humankind's greatest killers, and new therapeutic strategies are needed to combat the causative agent, Mycobacterium tuberculosis, which is rapidly developing resistance to conventional antibiotics . Using the highly demanding guinea pig model of pulmonary tuberculosis, we have investigated the feasibility of inhibiting M . tuberculosis glutamine synthetase (GS), an enzyme that plays a key role in both nitrogen metabolism and cell wall biosynthesis, as a novel antibiotic strategy . In guinea pigs challenged by aerosol with the highly virulent Erdman strain of M . tuberculosis, the GS inhibitor L-methionine-SR-sulfoximine (MSO) protected the animals against weight loss, a hallmark of tuberculosis, and against the growth of M . tuberculosis in the lungs and spleen; MSO reduced the CFU of M . tuberculosis at 10 weeks after challenge by approximately 0.7 log unit compared with that in control animals . MSO acted synergistically with isoniazid in protecting animals against weight loss and bacterial growth, reducing the CFU in the lungs and spleen by approximately 1.5 log units below the level seen with isoniazid alone . In the presence of ascorbate, which allows treatment with a higher dose, MSO was highly efficacious, reducing the CFU in the lungs and spleen by 2.5 log units compared with that in control animals . This study demonstrates that inhibition of M . tuberculosis GS is a feasible therapeutic strategy against this pathogen and supports the concept that M . tuberculosis enzymes involved in cell wall biosynthesis, including major secretory proteins, have potential as antibiotic targets.

Ned Tijdschr Tandheelkd, 2002 Nov, 109(11), 444 - 8
{Are antibiotics effective in the treatment of periodontitis?}; Collaert B et al.; Antibiotics are promoted for the treatment of periodontitis as an adjunct to mechanical debridement . Numerous studies have shown that some topically and systemically administered antibiotics provide an improved short-term clinical effect if used as an adjunct to scaling and rootplaning . However, the few long-term studies (> 5 years) question the clinical relevance.

J Pharm Biomed Anal, 2003 Jan 15, 30(6), 1765 - 71
Sensitive determination of a beta-lactam antibiotic, cefaclor by liquid chromatography with chemiluminescence detection; Kai M et al.; We present a sensitive method for the determination of cefaclor (CCL), a beta-lactam antibiotic . It was based on the chemical derivatization of the drug with 4-(2'-cyanoisoindolyl)phenylisothiocynate (CIPIC) under the reaction conditions with heating at 80 degrees C for 7 min in the presence of pyridine . The CIPIC reagent could react with the primary amino group of the drug to form the CIPIC-conjugated CCL . The derivatives emitted not only fluorescence (FL) at maximum emission wavelength of 410 nm with irradiation at 310 nm, but also chemiluminescence (CL) in the presence of H(2)O(2), borate buffer (pH 9.6) and acetonitrile . After separation of the CIPIC derivatives of CCL and cephradine as internal standard in human serum by reversed-phase liquid chromatography, the derivatives could be monitored with both FL and CL detections . The detection limit (S/N=3) in the chromatograph was 1 pmol by the CL detection and 10 pmol by the FL detection . The proposed CL method permitted the most sensitive determination of CCL in the human serum after its oral administration.

J Fam Pract, 2002 Nov, 51(11), 954 - 9
Delayed antibiotic prescriptions: what are the experiences and attitudes of physicians and patients?
Arroll B, Goodyear-Smith F, Thomas DR, Kerse N.
OBJECTIVE: To explore the experiences and opinions of family physicians and patients regarding the delay of antibiotic prescriptions, to be dispensed if symptoms persist or worsen over time, in treating upper respiratory tract infections . STUDY DESIGN: Qualitative study using semistructured interviews conducted in family practice in Auckland, New Zealand . POPULATION: Thirteen physicians recruited from a study of family physicians' reported antibiotic prescribing and 13 patients recruited from the intervention arm of a randomized controlled trial on delayed antibiotic prescribing . OUTCOMES MEASURED: Patients' and physicians' experiences of delayed antibiotic prescriptions for upper respiratory tract infections . RESULTS: The primary themes identified were value judgments of antibiotics, decreased antibiotic use, patient-centered factors, effects on the physician-patient relationship, patient convenience, adverse effects of delaying prescription, and selectivity for use of antibiotics . Many themes were common to both patients and physicians . Physicians valued empowering patients' decision making about their health care management more highly than did patients . Decreasing antibiotic use was not a key factor for most patients . Both groups acknowledged the value in saving patients time and money . Physicians viewed the strategy as giving patients reassurance and meeting their expectations for antibiotics . Negative implications included perception of physician incompetence and physician loss of management control . Opinions were mixed regarding which patients, under which conditions, were suitable for delayed antibiotic prescriptions . CONCLUSIONS: Although delayed antibiotic prescriptions are effective in decreasing antibiotic use for conditions not clinically warranting antibiotics, neither patients nor physicians universally endorsed this strategy . Research to establish formalized recommendations for patient suitability and instructions for use would be of value.

J Gen Appl Microbiol, 2001 Apr, 47(2), 85 - 97
The formation and structures of cystites of Arthrobacter ureafaciens NRIC 0157T induced by antibiotics; Tanaka N et al.; The cystite formation of Arthrobacter ureafaciens NRIC 0157(T) was induced by some antibiotics, and the addition of tetracycline at a lag phase was effective for cystite formation in YPM liquid medium . Cystites differed from vegetative cells in the cell wall structure, protein content, and water content . Furthermore, the characteristics and structures of cystites induced by tetracycline were similar to those of cystites produced by nutritional imbalance in CT medium . Consequently, various triggers would induce cystite formation . It is interesting that cystite formation was found in part of the Arthrobacter strains and seemed to correlate with the type of peptidoglycan.

Microbiology, 2002 Dec, 148(Pt 12), 3901 - 11
Molecular cloning and sequence analysis of the clorobiocin biosynthetic gene cluster: new insights into the biosynthesis of aminocoumarin antibiotics; Pojer F et al.; The biosynthetic gene cluster of the aminocoumarin antibiotic clorobiocin was cloned by screening of a cosmid library of Streptomyces roseochromogenes DS 12.976 with two heterologous probes from the novobiocin biosynthetic gene cluster . Sequence analysis revealed 27 ORFs with striking similarity to the biosynthetic gene clusters of novobiocin and coumermycin A(1) . Inactivation of a putative aldolase gene, cloR, by in-frame deletion led to the abolishment of the production of clorobiocin . Feeding of the mutant with 3-dimethylallyl-4-hydroxybenzoic acid (Ring A of clorobiocin) restored clorobiocin production . Here, it is suggested that the formation of Ring A of clorobiocin may proceed via a retro-aldol reaction catalysed by CloR, i.e . by a mechanism different from the previously elucidated benzoic acid biosynthetic pathway in Streptomyces maritimus . A comparison of the gene clusters for clorobiocin, novobiocin and coumermycin A(1) showed that the structural differences between the three antibiotics were reflected remarkably well by differences in the organization of their respective biosynthetic gene clusters.

J Emerg Med, 2002 Nov, 23(4), 327 - 8
Antibiotics after rattlesnake envenomation; LoVecchio F et al.; To record the outcome, with regard to infection rate, of patients with rattlesnake bites (RSBs) who do not receive prophylactic antibiotics, a prospective observational study was performed of patients with RSBs treated at our institution during a consecutive 18-month period . The inclusion criteria were RSBs <24 h old and completion of follow-up (telephone call, mail reply, medical toxicologist, or private physician examination) 7-10 days following envenomation . Fifty-six consecutive patients (Median age: 32.8 years {range 4-67 years}) were enrolled . One patient was excluded because of presentation 38 h after envenomation and two patients failed to complete the required follow-up . One patient received a dose of antibiotics before transfer . Antibiotics were discontinued upon arrival . Of the total 56 RSB patients, 34 (61%) RSBs involved the upper extremity and 22 (39%) involved the lower extremity . Six patients (11%) applied ice and two (4%) used a tourniquet before evaluation . The mean arrival time was 2.7 h (Range <1-24 h) . Forty-three patients (81%) received antivenin . Fifty-three patients (100%) had extremity swelling and 38 patients (72%) had tender proximal lymph nodes . Of the 53 patients who completed the study, 3 (6%) received antibiotics from their primary care physicians at 7-10 day follow-up, with no cases (0%) of documented infection . Prophylactic antibiotics are not indicated in patients with rattlesnake bites.

J Biol Chem, 2003 Feb 28, 278(9), 7381 - 9 Epub 2002 Dec 06.
Spectroscopic characterization of the electronic changes in the active site of Streptomyces antibioticus tyrosinase upon binding of transition state analogue inhibitors; Bubacco L et al.; The dinuclear copper enzyme tyrosinase (Ty) from genetically engineered Streptomyces antibioticus has been investigated in its paramagnetic half-met form {Cu(I)-Cu(II)} . The cw EPR, pulsed EPR, and hyperfine sublevel correlation spectroscopy (HYSCORE) experiments on the half-met-Ty and on its complexes with three different types of competitive inhibitor are reported . The first type includes p-nitrophenol, a very poor substrate for the monooxygenase activity of Ty . The second type comprises hydroxyquinones, such as kojic acid and l-mimosine, and the third type of inhibitor is represented by toluic acid . The electronic and structural differences of the half-met-Ty form induced at the cupric site by the different inhibitors have been determined . Probes of structural effects are the hyperfine coupling constants of the non coordinating Ndelta histidyl nitrogens . By using the available crystal structures of hemocyanin as a template in combination with the spectroscopic results, a structural model for the active site of half-met-Ty is obtained and a model for the binding modes of both mono- and diphenols could be proposed.

J Clin Periodontol, 2002 Nov, 29(11), 975 - 86
Meta-analysis of the effect of scaling and root planing, surgical treatment and antibiotic therapies on periodontal probing depth and attachment loss; Hung HC et al.; OBJECTIVE: This paper reports a meta-analysis of studies that have investigated the effect of scaling and root planing on periodontal probing depth and attachment loss . MATERIAL AND METHODS: The criteria used for inclusion of studies were as follows: root planing and scaling alone was one of the primary treatment arms; patients or quadrants of each patient were randomly assigned to study groups; 80% of patients enrolled were included in first year follow-up examinations; periodontal probing depth and attachment loss were reported in mm; the sample size of each study and substudy was reported . Sample size was used to weight the relative contribution of each study since standard errors were not reported by many studies and sample size is highly correlated with standard error and therefore statistically able to explain a substantial portion of the standard error on studies that use similar measures . RESULTS: The meta-analysis results show that periodontal probing depth and gain of attachment level do not improve significantly following root planing and scaling for patients with shallow initial periodontal probing depths . However, there was about a 1-mm reduction for medium initial periodontal probing depths and a 2-mm reduction for deep initial periodontal probing depths . Similarly, there was about a 0.50-mm gain in attachment for medium initial periodontal probing depth measurements and slightly more than a l-mm gain in attachment for deep initial periodontal probing depth measurements . Surgical therapy for patients with deep initial probing depths showed better results than scaling and root planing in reducing probing depths . When patients were followed up over 3 years or more, these differences were reduced to less than 0.4 mm . Antibiotic therapy showed similar results to scaling and root planing . However, a consistent improvement in periodontal probing depth and gain of attachment is demonstrated when local antibiotic therapy is combined with root planing and scaling.

J Clin Pharm Ther, 2002 Dec, 27(6), 431 - 40
Ethical dilemmas in antibiotic prescribing: analysis of everyday practice; Bjornsdottir I et al.; OBJECTIVE: To explore general practitioners' (GP's) views on their obligations with respect to diagnosing infections and prescribing antibiotics . METHODS: The GP's reflections and prioritization were studied by means of interviews and observations . We analysed how their prioritization complied with an ethical guidance that ranked patient autonomy and welfare highest, then competence obligations and obligations to society, followed by fraternal obligations . RESULTS: Balancing of pros and cons was prominent in our informants' decision making but often resulted in decisions that deviated from the ethical guidance . The ranking varied much between the GPs . The highest priorities in the GPs' practice were related to the patient's everyday life (sometimes autonomy, sometimes beneficence in a broad sense), doctor-patient relationship (communication competence), the patient's perceived importance on the job market (society) and relationship with colleagues (fraternal) . Perceived lack of resources and uncertainty with respect to both diagnostic and treatment decisions frequently influenced decision making.

Arch Microbiol, 2002 Dec, 179(1), 66 - 9 Epub 2002 Nov 09.
A possible role of poly-3-hydroxybutyric acid in antibiotic production in Streptomyces; Verma S et al.; The occurrence of poly-3-hydroxybutyric acid (PHB) in 12 different strains of the genus Streptomyces was investigated . Gas chromatographic estimation indicated that all the strains produced PHB and the range of maximum PHB accumulation was between 1.5 and 11.8% dry cell weight . PHB was isolated from Streptomyces coelicolor A3(2) M145 and characterized using Fourier transform-infrared (FT-IR) spectroscopy . The correlation between PHB utilization and antibiotic production in S . coelicolor A3(2) M145, was studied; results indicated a possible role of PHB as a carbon reserve material used for antibiotic production.

Kulak Burun Bogaz Ihtis Derg, 2002 Sep-Oct, 9(5), 352 - 7
{The efficacy of combined medical treatment (antihistaminics, steroids, and macrolide antibiotics) in patients with nasal polyposis: preliminary results}; Kuran G et al.; OBJECTIVES: We evaluated the efficacy of combined medical treatment in cases with bilateral nasal polyposis without a history of any surgical or medical treatment . PATIENTS AND METHODS: Twenty-five patients (19 males, 6 females; mean age 45 years; range 30 to 60 years) who had not received any treatment for bilateral nasal polyposis were included . Treatment was comprised of an oral anti-histaminic agent (single dose daily for 3 weeks), and a topical steroid (as a nasal spray, twice daily for 6 months) and a single dose of intramuscular systemic steroid . Patients who did not respond to this therapy at the end of three weeks were administered a macrolide antibiotic (clarithromycin) . The results were evaluated before treatment, and three weeks and six months after treatment with the use of a patient questionnaire, computed tomography and endoscopic examination findings . RESULTS: The patients' complaints improved by 85.5% and 79% at the end of three weeks and six months, respectively (p<0.005) . Radiologic improvement was found to be 64% at the end of six months (p<0.005) . The overall decrease in the size of the polyps was significant (p<0.005) . No treatment-associated complications were encountered . CONCLUSION: Significant improvement achieved favors the use of combined medical treatment before surgery in selected patients with nasal polyposis.

Am Surg, 2002 Jan, 68(1), 29 - 35
Infection in penetrating abdominal trauma: risk factors and preventive antibiotics; Fabian TC; Infection remains the greatest risk for victims of penetrating abdominal injury with major infections occurring in 10 to 15 per cent . Attributable mortality is approximately 30 per cent of those who develop major abdominal infections . In addition to this morbidity infection adds approximately $43,000.00 of hospital charges per infected patients . This article addresses two significant areas: risk factors and antibiotic utilization . The most important risk factor is the presence of hollow viscus injury; colonic wounding carries the highest incidence of infection relative to intra-abdominal organs injured . Pancreatic and liver injuries significantly increase infection risk when combined with hollow viscus wounds . The degree of injury as measured by the volume of hemorrhage and the presence of shock as well as the anatomic degree of injury likewise correlates with the incidence of septic morbidity . Antibiotic utilization is addressed by the three issues of antibiotic agents of choice, duration of administration, and optimal dosing . Regimens of choice should include anaerobic coverage . Twenty-four hours of antibiotic administration is satisfactory with currently available agents . Evidence-based medicine analyses from the Eastern Association for the Surgery of Trauma have addressed those two issues . There are few data on optimal dosing . Increased volumes of distribution and rates of excretion have been demonstrated in trauma patients . This would suggest that higher-than-normal doses should be used . Laboratory studies would support such an approach . However, significant clinical research is desirable to address issues of concentration-dependent bacterial killing and time-dependent killing . Those pharmacodynamic considerations are variable among antibiotic classes.

Allergy, 2002 Dec, 57(12), 1151 - 8
Oral antibiotic adverse reactions after penicillin skin testing: multi-year follow-up; Macy E et al.; BACKGROUND: Long-term follow-up data on adverse drug reactions after oral antibiotic use in penicillin allergy history positive individuals with penicillin skin test done in advance of need are rare . METHODS: Oral antibiotic associated adverse drug reactions in 83 penicillin skin test positive individuals were compared to a sex, age, and length of follow-up matched sample of 166 penicillin skin test negative individuals, all of whom had at least one post penicillin skin test oral antibiotic . The mean post penicillin skin test follow-up interval was 34.5 +/- 16.6 months . There were 1655 total oral antibiotic exposures . RESULTS: In penicillin skin test positive individuals, the adverse drug reaction rate was not significantly different with cephalosporin or non-beta-lactam use (P = 0.12) . In penicillin skin test negative individuals the adverse drug reaction rate was significantly lower with cephalosporin vs . non-beta-lactam use (P = 0.005) . Penicillin was safely used in penicillin skin test negative individuals . Overall cephalosporins caused fewer adverse drug reactions independent of penicillin skin test status (P = 0.005) . CONCLUSIONS: Penicillin skin testing was only able to predict penicillin associated adverse drug reactions in penicillin skin test positive individuals . Excluding accidental penicillin exposure in penicillin skin test positive individuals, non-beta-lactams were associated with adverse drug reactions more often than penicillins or cephalosporins, independent of the penicillin skin test result . Cephalosporins were used as or more safely than non-beta-lactams in both penicillin skin test positive and negative individuals.

J R Coll Surg Edinb, 2002 Oct, 47(5), 700 - 4
The effects of desferrioxamin and vitamin E as supplements to antibiotics in the treatment of peritonitis in rats; Soybir N et al.; AIM: The aim of the study was to determine the effects of vitamin E and the iron chelating agent desferrioxamin (Dfx), supplemented by clindamycin and gentamycin therapy, on peritonitis caused by caecal ligation of a puncture wound in an experimental model . MATERIALS AND METHODS: One hundred and twenty Spraque Dawley rats were divided into eight groups . Three groups were used as controls; intraperitoneal (i.p.), subcutaneous (s.c.) and i.p . and s.c., respectively . Group 4 was treated with Dfx, Group 5 with vitamin E and Group 6 with antibiotics . Group 7 was treated with vitamin E in combination with antibiotics, and Group 8 with a combination of antibiotics and Dfx . The rats were studied for 14 days following treatment, and survivors then humanely dispatched . Post-mortem examination was undertaken on all the rats studied . RESULTS: In the control groups, mortality at 14 days was 66% . Rats treated with antibiotics alone (Group 5) had a mortality rate of 40% . Those treated with a combination of antibiotics and vitamin E (Group 7), however, had a mortality rate of only 14%, and those treated with antibiotics and Dfx had a mortality rate of only 7% . CONCLUSION: This study suggests that treatment of peritonitis in rats with a combination of Dfx and antibiotics has a significant beneficial effect on survival, in comparison with treatment with antibiotics alone.

J Chromatogr A, 2002 Nov 8, 976(1-2), 195 - 206
Validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of 11 (fluoro)quinolone antibiotics in swine kidney; Toussaint B et al.; A LC-MS-MS method has been validated for the simultaneous quantification of 11 (fluoro)quinolone antibiotics at the maximum residue level (MRL) in swine kidney . The studied compounds were danofloxacine, cinoxacine, ciprofloxacine, noxacine, enrofloxacine, flumequine, marbofloxacine, nalidixic acid, norfloxacine, ofloxacine and oxolinic acid . The method involves solid-phase extraction of these compounds followed by LC-MS-MS analysis using an electrospray ionisation interface . Limits of quantification < or = 50 microg/kg could be obtained in swine kidney, much lower than every MRL . The validation is discussed . This work was carried out in order to support the European Union policy on consumer health

J Chromatogr A, 2002 Nov 8, 976(1-2), 65 - 78
Liquid chromatography-ion trap tandem mass spectrometry for the characterization of polypeptide antibiotics of the colistin series in commercial samples; Govaerts C et al.; A selective reversed-phase liquid chromatography-tandem mass spectrometry method is described for the characterization of related substances in the colistin complex . Mass spectral data were acquired on an LCQ ion trap mass spectrometer equipped with an electrospray ionization probe operated in the positive ion mode . The main advantage of this technique is the characterization of novel related substances without time-consuming isolation and purification procedures . Using this method seven new related substances were partially identified in colistin bulk sample and tablets . Four components were assigned as isomers of the main components of colistin.

J Antimicrob Chemother, 2002 Dec, 50(6), 989 - 97
Antibiotic prescribing in general practice: striking differences between Italy (Ravenna) and Denmark (Funen); Vaccheri A et al.; OBJECTIVE: To compare antibiotic prescribing in primary care in two European populations, one in Denmark (Funen), the other in Italy (Ravenna) . METHODS: Reimbursement data (1999) were retrieved from the Odense Pharmacoepidemiologic Database (Denmark) and the Emilia Romagna Health Authority Database (Italy) . The extent of antibiotic use (ATC J01) was analysed as the number of defined daily doses per 1000 inhabitants per day (DDD/1000 inhabitants/day), and as annual prevalence of use . A qualitative analysis was carried out according to the Drug Utilization 90% (DU90%) approach . RESULTS: Antibiotic consumption was 16.5 DDD/1000 inhabitants/day in Ravenna and 10.4 DDD/1000 inhabitants/day in Funen; the annual prevalence of use was 40 and 30 subjects/100 inhabitants, respectively . Italian children received a greater amount (four-fold in DDDs) of antibiotics than Danish ones, whereas consumption was only slightly higher in Italy than in Denmark in the other age groups . In Italy, injectable antibiotics (third generation cephalosporins or aminoglycosides) accounted for 4% of total DDDs and 11% of exposed subjects . In Funen, use of injectable antibiotics was negligible . The bulk of prescription (90% of total DDDs) was made up of eight (out of 38) different antibiotics in Denmark, mainly narrow-spectrum penicillins and macrolides (1st: phenoxymethylpenicillin), and of 18 (out of 74) antibiotics in Italy, mainly broad-spectrum penicillins, macrolides, fluoroquinolones and cephalosporins . CONCLUSIONS: These data show remarkable differences in antibiotic prescribing between Italy and Denmark, and suggest possible overuse and misuse of antibiotics in Italy.

Med Decis Making, 2002 Nov-Dec, 22(6), 498 - 505
Antibiotic prescribing decisions of generalists and infectious disease specialists: thresholds for adopting new drug therapies; Metlay JP et al.; The objective of this study was to examine whether physicians are willing to continue to use older antibiotics in the face of drug resistance in order to preserve newer antibiotics forfuture use . The study was a national sample of 398 generalist physicians and 429 infectious disease (ID) specialists . Clinical vignettes prompted respondents to select the level of resistance to a hypothetical older antibiotic at which they would prefer a newer antibiotic without any current resistance in the treatment of a patient with pneumococcalpneumonia . Vignettes varied in the site of care of the patient as a proxyfor variation in disease severity . Respondents significantly reduced their threshold for switching to a newer antibiotic as disease severityincreased . Generalists were more responsive to disease severity than LD specialists . Thus, the adoption of recommendations to limit overuse of newer antibiotics may be variable across clinical settings and providers, reducing the impact of these recommendations on emerging resistance.

J Antibiot (Tokyo), 2002 Sep, 55(9), 801 - 6
Endophenazines A-D, new phenazine antibiotics from the athropod associated endosymbiont Streptomyces anulatus II . Structure elucidation; Krastel P et al.; A detailed screening of the secondary metabolite pattern produced by different athropod associated strains of the species Streptomyces anulatus resulted in the isolation and structure elucidation of the endophenazines A-D (2, 4-6) . The structures were assigned by spectroscopic methods and chemical transformations . 4 represents a chromophoric system based on a phenazin-7-one, 5 and 6 are new 5,10-dihydrophenazine derivatives.

Eur J Pharm Sci, 2002 Dec, 17(4-5), 229 - 38
Solid state 'adsorption' of fine antibiotic powders onto sorbitol: effects of particle size, state of sorbed water and surface free energy characteristics; Nikolakakis I et al.; A study has been made on the effects of the state of sorbed water, surface free energy characteristics and particle size on the 'adsorption' of fine antibiotic powders (ampicillin and amoxycillin trihydrates, cephalexin monohydrate and erythromycin ethylsuccinate) onto a special type of sorbitol (instant) . 'Adsorption' was assessed by sieving before and after mixing, surface free energy characteristics were derived from contact angle measurements and state of sorbed water from sorption/desorption isotherms at different relative humidity, at 25 and 45 degrees C . It was found that sorbed water was externally located on sorbitol and erythromycin ethylsuccinate and internally on ampicillin, amoxycillin trihydrates and on cephalexin monohydrate, but in a different way of association as strongly bound hydrate and loosely bound hydrate water (reversible and exothermic for the latter) . Erythromycin, with the highest interfacial energy value, resulted in greater extent of 'adsorption' than cephalexin of similar particle size, which had the lowest interfacial energy . The presence of sorbed water increased the 'adsorption' of ampicillin and amoxycillin trihydrates due to the contribution of capillary forces and due to their ability of hydrogen bonding at plactisized regions of sorbitol with higher moisture content and molecular mobility . The plactisizing effect of water sorbed on sorbitol is demonstrated by a logarithmic decrease of the yield pressure/elastic recovery ratio . The 'adsorption' of the low interfacial energy cephalexin monohydrate did not increase with the presence of water sorbed on sorbitol, presumably due to the lack of intermolecular hydrogen bonding ability, while 'adsorption' of erythromycin ethylsuccinate decreased, probably due to masking of the interparticle forces (van der Waal and electrostatic).

Ann Pharmacother, 2002 Dec, 36(12), 1851 - 5
Quality-of-life assessment in an outpatient parenteral antibiotic program; Goodfellow AF et al.; OBJECTIVE: To measure changes and to identify predictors of change of health-related quality of life (HRQoL) for enrollees into an outpatient parenteral antibiotic therapy (OPAT) program . METHODS: A multidisciplinary, single-center, prospective investigation was conducted at a 1000-bed Canadian adult tertiary-care teaching hospital . Over a 15-month study period, consenting patients who were enrolled in the OPAT program completed paired Short Form-36 (SF-36) questionnaires within 48 hours prior to discharge from the hospital and again 26-30 days after discharge . Sociodemographic data and clinical variables were also collected for the purpose of determining potential predictors of change in quality of life . RESULTS: During the study period, 134 patients were enrolled in the OPAT program and 82 completed the paired SF-36 questionnaires . Study participants experienced a significant improvement in 3 SF-36 domains (physical functioning, bodily pain, role emotional) and the mental component summary scale (MCS) scores when they were transferred from the hospital to home setting . The SF-36 scores for all domains and summary scales were lower than the Canadian population average (all p < 0.001) . Multiple linear-regression analysis revealed that infectious disease diagnosis and baseline physical component summary scale (PCS) scores were predictors of the change in the PCS score when patients transferred from the hospital to the home setting . Length of hospital stay and baseline MCS scores were predictors of the change in MCS scores when patients transferred from the hospital to the home setting . CONCLUSIONS: This study reveals that some domains in HRQoL appear to improve 4 weeks after discharge for adults enrolled in an OPAT program and that there are different predictors for changes in physical and mental health.

Ther Drug Monit, 2002 Dec, 24(6), 728 - 36
Monitoring adverse drug reactions to sulfonamide antibiotics in human immunodeficiency virus-infected individuals; Neuman MG et al.; Patients infected with the human immunodeficiency virus (HIV) are at higher risk for adverse drug reactions from trimethoprim-sulfamethoxazole (TMP-SMX) than the HIV-negative population . Studying the HIV-positive population the authors aimed to validate the predictive and diagnostic value of the lymphocyte toxicity assay (LTA) for adverse drug reactions . Patient lymphocytes were analyzed for toxicity to SMX and TMP . Of 35 enrolled HIV patients, 18 had TMP-SMX hypersensitivity syndrome reaction (HSR); 10 tolerated the drug; and 5 had never received the drug . When cases with HSR were compared with controls that tolerated the drugs, cytotoxicity was higher for cases: 29.5% +/- 10.1% versus 19.3% +/- 11.2% for SMX (P < 0.022) and 25.0% +/- 11.9% versus 16.3% +/- 11.0% for TMP (P < 0.04) . The authors' proposed threshold value for assigning positive results for TMP and SMX hypersensitivities was 22.5% . The LTA has a strong potential for use as a diagnostic tool to assess TMP-SMX hypersensitivity in HIV-infected individuals . Larger patient populations, as well as in vitro studies are needed to further address the reasons for elevated results in immunocompromised patients and to validate the usefulness of the test.

Ann Biol Clin (Paris), 2002 Nov-Dec, 60(6), 655 - 61
{Interest in therapeutic drug monitoring of the main antibiotics}; Davani S et al.; The therapeutic drug monitoring aims at optimising the prescribed dosages to improve efficacy and prevent toxicity . The aim of this study were to review the main pharmacodynamic and pharmacokinetic properties of aminoglycosides, glycopeptides and ceftazidime . Then, the therapeutic drug monitoring of these antibiotics and their methods of analysis is reviewed.

Chem Biol, 2002 Nov, 9(11), 1209 - 17
Analysis of the pi-pi stacking interactions between the aminoglycoside antibiotic kinase APH(3')-IIIa and its nucleotide ligands; Boehr DD et al.; A key contact in the active site of an aminoglycoside phosphotransferase enzyme (APH(3')-IIIa) is a pi-pi stacking interaction between Tyr42 and the adenine ring of bound nucleotides . We investigated the prevalence of similar Tyr-adenine contacts and found that many different protein systems employ Tyr residues in the recognition of the adenine ring . The geometry of these stacking interactions suggests that electrostatics play a role in the attraction between these aromatic systems . Kinetic and calorimetric experiments on wild-type and mutant forms of APH(3')-IIIa yielded further experimental evidence of the importance of electrostatics in the adenine binding region and suggested that the stacking interaction contributes approximately 2 kcal/mol of binding energy . This type of information concerning the forces that govern nucleotide binding in APH(3')-IIIa will facilitate inhibitor design strategies that target the nucleotide binding site of APH-type enzymes.

Chem Biol, 2002 Nov, 9(11), 1175 - 87
Structure, biosynthetic origin, and engineered biosynthesis of calcium-dependent antibiotics from Streptomyces coelicolor; Hojati Z et al.; The calcium-dependent antibiotic (CDA), from Streptomyces coelicolor, is an acidic lipopeptide comprising an N-terminal 2,3-epoxyhexanoyl fatty acid side chain and several nonproteinogenic amino acid residues . S . coelicolor grown on solid media was shown to produce several previously uncharacterized peptides with C-terminal Z-dehydrotryptophan residues . The CDA biosynthetic gene cluster contains open reading frames encoding nonribosomal peptide synthetases, fatty acid synthases, and enzymes involved in precursor supply and tailoring of the nascent peptide . On the basis of protein sequence similarity and chemical reasoning, the biosynthesis of CDA is rationalized . Deletion of SCO3229 (hmaS), a putative 4-hydroxymandelic acid synthase-encoding gene, abolishes CDA production . The exogenous supply of 4-hydroxymandelate, 4-hydroxyphenylglyoxylate, or 4-hydroxyphenylglycine re-establishes CDA production by the DeltahmaS mutant . Feeding analogs of these precursors to the mutant resulted in the directed biosynthesis of novel lipopeptides with modified arylglycine residues.

J Am Soc Mass Spectrom, 2002 Nov, 13(11), 1313 - 21
Multiple-stage mass spectrometric analysis of complex oligosaccharide antibiotics (everninomicins) in a quadrupole ion trap; Chen G et al.; Electrospray ionization (ESI) quadrupole ion-trap tandem mass spectrometry (MS/MS) was utilized to characterize a class of complex oligosaccharide antibiotics (everninomicins) that include SCH 27899, everninomicin-D, amino everninomicin (SCH 27900), and SCH 49088 (containing a hydroxylamino-ether sugar) . The addition of sodium chloride (approximately 1 microg/mL) facilitates the formation of abundant metal complex ions, and this was used because protonation does not readily occur for most of these compounds . The multiple-stage mass analysis (MS(n)) of the sodiated species provides an important series of fragment ions that are specific for sugar sequence and for some sugar-ring opening . These data suggest a general charge-remote fragmentation pattern with the sodium cation residing in a specific, central location of the sugar chain and fragmentation occurring to trim the end of the molecule . For protonated everninomicin (SCH 27900), however, the proton appears to be mobile during the collisional activation process, opening different fragmentation pathways depending on the proton location . The use of water and acetonitrile with 0.1% acetic acid as the solvent in ESI-MS promotes rapid hydrolysis of the central ortho ester, resulting in the formation of abundant sodiated products that are hydrated . These product ions of the hydrated molecules are likely formed by the same charge-remote fragmentation processes as those that occur for the unhydrolyzed precursor.

Crit Care Med, 2002 Nov, 30(11), 2580 - 3
Recurrent fatal drug-induced toxic epidermal necrolysis (Lyell's syndrome) after putative beta-lactam cross-reactivity: Case report and scrutiny of antibiotic imputability; Paquet P et al.; OBJECTIVE: A series of antibiotics may be responsible for toxic epidermal necrolysis . We report two successive episodes of toxic epidermal necrolysis in the same patient . Drug imputability criteria designate a cross-reactivity between two antibiotics of different chemical classes but sharing the beta-lactam ring in common . DESIGN: Descriptive case report and review of the literature . SETTING: Medical intensive care unit in a university medical center . PATIENT AND MAIN RESULTS: A 75-yr-old woman developed a first episode of toxic epidermal necrolysis (involving 40% of the body surface) after intake of cefotaxime, a third-generation cephalosporin . Perfusions of high-dose immunoglobulins rapidly improved the lesions, followed by partial reepithelialization in 5 days . Sepsis required the administration of meropenem, which is a carbapenem antibiotic . The epidermal destruction immediately recurred, with extension to previously uninvolved skin areas and fatal consequences . CONCLUSIONS: The beta-lactam ring present in cephalosporins and carbapenems represents the putative chemical structure responsible for the presently reported cross-reactivity to two antibiotics of different classes . Drugs having any chemical similarity to the initial culprit compound should be strictly avoided when possible in the management of toxic epidermal necrolysis.

Exp Cell Res, 2002 Nov 15, 281(1), 86 - 100
Azithromycin, a lysosomotropic antibiotic, has distinct effects on fluid-phase and receptor-mediated endocytosis, but does not impair phagocytosis in J774 macrophages; Tyteca D et al.; Pretreatment of J774 mouse macrophages by the dicationic macrolide antibiotic, azithromycin (AZ), selectively inhibited fluid-phase endocytosis of horseradish peroxidase and lucifer yellow, but not phagocytosis of latex beads . AZ delayed sequestration of receptor-bound transferrin and peroxidase-anti-peroxidase immune complexes into cell-surface endocytic pits and vesicles, but did not slow down the subsequent rate of receptor-mediated endocytosis . AZ down-regulated cell surface transferrin receptors, but not Fc gamma receptors, by causing a major delay in the accessibility of internalized transferrin receptors to the recycling route, without slowing down subsequent efflux, resulting in redistribution of the surface pool to an intracellular pool . Acidotropic accumulation of AZ was associated with an extensive vacuolation of late endosomes/lysosomes, and these compartments became inaccessible to horseradish peroxidase and immune complexes, but not to latex beads . The inhibitory profile of AZ cannot be solely accounted for by vacuolation and interference with acidification . AZ may help in dissecting various steps of the endocytic apparatus such as lateral mobility of receptors at the plasma membrane, formation of clathrin-independent endocytic vesicles, orientation of transferrin receptors into the recycling route, and fusogenicity with lysosomes.

J Orthop Trauma, 2002 Nov-Dec, 16(10), 723 - 9
Intramedullary infections treated with antibiotic cement rods: preliminary results in nine cases; Paley D et al.; The treatment of intramedullary infections after nailing usually includes removal of the rod, debridement of the canal, and, in many cases, insertion of antibiotic-impregnated cement beads . These beads offer no mechanical support and are difficult to remove if left in place for more than 2 weeks . We present an alternative for filling the medullary canal's noncollapsible dead space with an antibiotic-impregnated cement rod . This rod can be custom-made at the time of surgery, using different diameter chest tubes as molds and embedding a 3-mm beaded guidewire within the cement . The smooth molded surface of this nail makes extraction of the cement rod relatively easy . The cement rod also provides some limited temporary support to the fracture or nonunion site while the infection is being treated . After 6 weeks, the rod can be removed and replaced with a definitive metal intramedullary nail, with or without bone grafting to treat the previously infected fracture or nonunion site . We retrospectively reviewed nine cases of intramedullary infection treated with antibiotic-impregnated molded cement rods . These included six femora, two tibiae, and one humerus . The cause of infection was lengthening or transport over nail in six cases, fixator-augmented nailing of osteotomies in two, and fracture fixation in one . The follow-up period after surgery ranged from 38 to 48 months . No recurrent infection occurred during this follow-up period, and no patient required antibiotics after the rod was removed . In all cases, the canal cultures were negative after rod removal . The cement rod was removed between 29 and 753 days after implantation . Fracture of the rod occurred in one case in which the rod was left in place for more than 1 year . We conclude that this method is a relatively simple and inexpensive alternative for the treatment of intramedullary infections.

Dent Clin North Am, 2002 Oct, 46(4), 653 - 64
Antibiotics and oral contraceptives; DeRossi SS et al.; With the exception of rifampin-like drugs, there is a lack of scientific evidence supporting the ability of commonly prescribed antibiotics, including all those routinely employed in outpatient dentistry, to either reduce blood levels and/or the effectiveness of oral contraceptives . To date, all clinical trials studying the effects of concomitant antibiotic therapy (with the exception of rifampin and rifabutin) have failed to demonstrate an interaction . Like all drugs, oral contraceptives are not 100% effective with the failure rate in the typical United States population reported to be as high as 3% . It is thus possible that the case reports of unintended pregnancies during antibiotic therapy may simply represent the normal failure rate of these drugs . Considering that both drug classes are prescribed frequently to women of childbearing potential, one would expect a much higher rate of oral contraceptive failure in this group of patients if a true drug:drug interaction existed . On the other hand, if the interaction does exist but is a relatively rare event, occurring in, say, 1 in 5000 women, clinical studies such as those described in this article would not detect the interaction . The pharmacokinetic studies of simultaneous antibiotic and oral contraceptive ingestion, and the retrospective studies of pregnancy rates among oral contraceptive users exposed to antibiotics, all suffer from one potential common weakness, i.e., their relatively small sample size . Sample sizes in the pharmacokinetic trials ranged from 7 to 24 participants, whereas the largest retrospective study of pregnancy rates still evaluated less than 800 total contraceptive users . Still, the incidence of such a rare interaction would not differ from the accepted normal failure rate of oral contraceptive therapy . The medico-legal ramifications of what looks like at best a rare interaction remains somewhat "murky." On one hand, we have medico-legal experts advising the profession to exercise caution and warn all oral contraceptive users of a potential reduction in efficacy during antibiotic therapy . These opinions are not evidence-based and rely heavily on one or two legal proceedings that cannot even be substantiated . On the other hand, there is one recently published legal proceeding in which the outcome was in favor of the oral surgeon . There is clearly a need for additional scientific research in oral contraceptive users that incorporates larger sample sizes, different time courses (prophylactic use versus standard 7-10 day use versus extended use), and different delivery systems (systemic administration versus local-controlled delivery) of antibiotic therapy . Though experts on this topic still recommend informing oral contraceptive users of the potential for a rare interaction, and for clinicians to advise them to employ additional barrier techniques of birth control during antibiotic therapy and for at least 1 week beyond the last dose {40}, it is hoped that a set of guidelines regarding this controversy will eventually be published that is evidence-based, and not solely the results of anecdotal reports, expert opinions, and legal proceedings.

Clin J Oncol Nurs, 2002 Nov-Dec, 6(6), 337 - 40
Neutropenic fever: one institution's quality improvement project to decrease time from patient arrival to initiation of antibiotic therapy; Baltic T et al.; Neutropenic fever is an oncologic emergency that requires prompt assessment and treatment with antibiotics . Although the term "prompt" is not defined in numbers of minutes in the biomedical literature, the literature does indicate that the sooner antibiotics are initiated, the greater the likelihood of a positive clinical outcome . At Dartmouth-Hitchcock Medical Center in Lebanon, NH, the oncology team was concerned about the length of time before adult inpatients with febrile neutropenia received their initial dose of antibiotics (cycle time) . The purpose of this quality improvement project was to reduce treatment delays in patients with febrile neutropenia . A multidisciplinary team charted the existing admission process and identified three areas for improvement: (a) inpatient orders, (b) the admission communication process, and (c) multidisciplinary staff accountability . Following implementation, the hematology and oncology clinical nurse specialist completed a chart review of all patients with febrile neutropenia, which revealed a nearly 50% reduction in cycle time on the inpatient unit.

Drug Metab Dispos, 2002 Dec, 30(12), 1393 - 9
Mechanism for the tissue distribution of grepafloxacin, a fluoroquinolone antibiotic, in rats; Suzuki T et al.; This study was carried out to investigate the most important factor(s) governing the tissue distribution of grepafloxacin (GPFX), a fluoroquinolone antibiotic, in rats . The tissue-to-blood concentration ratio (K(p)) of GPFX at steady state during constant infusion was highest in the lung, followed by the pancreas, kidney, and spleen . After bolus injection, GPFX was efficiently taken up by most of the organs examined, the uptake clearance other than the lung being almost blood flow-limited . Approximately 10% of the intravenously injected dose was rapidly trapped by the lung, but GPFX distribution rapidly decreased within 30 s due to the washout by the plasma flow . Thus, the higher distribution of GPFX to the lung compared with the other organs cannot be accounted for by a difference in its uptake or efflux . Subcellular fractionation after the infusion indicated that GPFX is primarily distributed to the organelle fractions in most organs, 60% of lung-associated GPFX being recovered in the nucleus and plasma membrane fraction . Such subcellular distribution in the lung was proportional to the phosphatidylserine (PhS) content of each fraction . The steady-state K(p) value in each tissue in vivo also correlated with the tissue content of PhS . GPFX preferentially binds to PhS, compared with other phospholipids, and this binding was inhibited by weakly basic drugs, such as quinidine, imipramine, and propranolol, that have also been reported to bind to PhS . The association of GPFX with PhS synthase transformants of Chinese hamster ovary (CHO-K1) cells depends on the PhS content of each cell line, this association being also inhibited by basic drugs . These results suggest that binding of GPFX to PhS is the major determinant of the high distribution of GPFX to the lung.

Paediatr Drugs, 2002, 4(12), 817 - 37
Antibiotics and breast-feeding: a critical review of the literature; Chung AM et al.; Continuous breast-feeding, an integral component of the postpartum period, is often threatened upon maternal initiation of antibiotics . The real risk of antibiotic use while breast-feeding must be carefully analysed with regard to all the variables that influence the extent of antibiotic distribution into breast milk, including breast milk composition, physicochemical properties of the antibiotic (molecular weight, lipid solubility, pH, protein binding), length of feeding, and maternal disposition . In addition, infant disposition, including ability to absorb, metabolize, eliminate, and tolerate any amounts of antibiotic, must also be considered prior to maternal administration of antibiotic . The milk to plasma (M/P) ratio is a frequently quoted parameter used to predict drug distribution into breast milk . However, its utility is questionable and often fraught with misinterpretation . An alternative approach when the amount of antibiotic concentration in breast milk is known (through clinical trials) is to calculate an estimated or expected infant drug exposure factoring in known/expected milk consumption, drug concentration and bioavailability . In this review, the following antibiotic classes and current literature regarding their distribution into breast milk are critically reviewed: beta-lactam antibiotics, fluoroquinolones, sulfonamides, macrolides, aminoglycosides, tetracyclines, nitrofurantoin, metronidazole, vancomycin, clindamycin and chloramphenicol . In the majority of instances, these antibiotics do not distribute into breast milk in sufficient concentrations to be of any clinical consequence in the breast-feeding infant.

Neth J Med, 2002 Aug, 60(7 Suppl), 78 - 80; discussion 80-2
Pharmacoepidemiological modelling: Markov models of antibiotic use in patients with diabetes; Leufkens HG; The importance of time patterns in drug exposure is increasingly recognised in the evaluation of determinants and outcomes of pharmacotherapy . Data on patterns of drug exposure over time in individual patients and populations have been found to provide important 'fingerprint' information on temporal relations between disease course and severity, drug effects, and prognosis . However, data on prescriptions of medicines always need to be interpreted in the light of complementary data on clinical status, diagnosis, co-morbidity and the like.

Fam Pract, 2002 Dec, 19(6), 638 - 40
The more time spent on listening, the less time spent on prescribing antibiotics in general practice; Lundkvist J et al.; OBJECTIVE: To analyse the variation between primary care centres (PCCs) with regard to prescribing antibiotics and to investigate whether the variation can be explained by factors related to patient satisfaction and to socio-demographic characteristics of the populations in the catchment areas of the PCCs . METHODS: The frequency of prescription of antibiotics by GPs at the PCCs was used as the dependent variable in a multivariate regression analysis . Questionnaire data for patient satisfaction and register data for socio-demographic characteristics were used as explanatory variables . The study was set in a county in south-east Sweden, and 6734 patients consulting GPs at 39 out of the 41 PCCs in the county participated . Variables correlating with the frequency of antibiotics prescription at PCC level and with patient satisfaction were the main outcome measures . RESULTS: A seven-fold variation in the extent of the prescription of antibiotics between the PCCs was observed . In the multivariate analysis, a high antibiotic prescription rate relates to high overall patient satisfaction with GP consultation as well as to the share of males in the listed population but to low satisfaction with the time spent by the GP on listening to the patient . CONCLUSION: A high frequency of prescription of antibiotics at a PCC may reflect a general disposition among GPs to give priority to maintaining good relations with the patients . However, a low level of prescription may be consistent with patient satisfaction if more time is spent on listening to and informing the patients . Thus more time spent on listening to the patients may reduce the prescription of antibiotics without reducing patient satisfaction.

Microbiology, 2002 Nov, 148(Pt 11), 3365 - 73
Genetic and physiological characterization of rpoB mutations that activate antibiotic production in Streptomyces lividans; Lai C et al.; Antibiotic production in Streptomyces lividans can be activated by introducing certain mutations (rif) into the rpoB gene that confer resistance to rifampicin . Working with the most typical (rif-17) mutant strain, KO-417, the rif-17 mutation was characterized . The rif-17 mutation was shown to be responsible for activating antibiotic production and for reducing the growth rate of strain KO-417, as demonstrated by gene-replacement experiments . Gene-expression analysis revealed that introduction of rif into S . lividans elevates expression of the pathway-specific regulatory gene actII-ORF4 to nearly the same level seen in Streptomyces coelicolor . The rif effect on antibiotic production was still evident in the genetic background of relC, indicating that the rif mutation can provoke its effect without depending on ppGpp . Accompanying the restoration of antibiotic production, rif mutants also exhibited a lower rate of RNA synthesis compared to the parental strain when grown in a nutritionally rich medium, suggesting that the mutant RNA polymerases may behave like 'stringent' RNA polymerases . These results indicate that the rif mutation can alter the gene-expression pattern independent of ppGpp . The impaired growth of strain KO-417 (rif-17) was largely restored by introducing the second rif mutation (rif-18) just adjacent to the rif-17 position . Proteome analysis using two-dimensional PAGE revealed that the rif mutant strain KO-418 (rif-17 rif-18) displayed a temporal burst of expression especially of two enzymes, glutamine synthetase (type II) and oxidoreductase, during the late growth phase.

J Bacteriol, 2002 Dec, 184(23), 6417 - 23
The rpoZ gene, encoding the RNA polymerase omega subunit, is required for antibiotic production and morphological differentiation in Streptomyces kasugaensis; Kojima I et al.; The occurrence of pleiotropic mutants that are defective in both antibiotic production and aerial mycelium formation is peculiar to streptomycetes . Pleiotropic mutant KSB was isolated from wild-type Streptomyces kasugaensis A1R6, which produces kasugamycin, an antifungal aminoglycoside antibiotic . A 9.3-kb DNA fragment was cloned from the chromosomal DNA of strain A1R6 by complementary restoration of kasugamycin production and aerial hypha formation to mutant KSB . Complementation experiments with deletion plasmids and subsequent DNA analysis indicated that orf5, encoding 90 amino acids, was responsible for the restoration . A protein homology search revealed that orf5 was a homolog of rpoZ, the gene that is known to encode RNA polymerase subunit omega (omega), thus leading to the conclusion that orf5 was rpoZ in S . kasugaensis . The pleiotropy of mutant KSB was attributed to a 2-bp frameshift deletion in the rpoZ region of mutant KSB, which probably resulted in a truncated, incomplete omega of 47 amino acids . Furthermore, rpoZ-disrupted mutant R6D4 obtained from strain A1R6 by insertion of Tn5 aphII into the middle of the rpoZ-coding region produced neither kasugamycin nor aerial mycelia, similar to mutant KSB . When rpoZ of S . kasugaensis and Streptomyces coelicolor, whose deduced products differed in the sixth amino acid residue, were introduced into mutant R6D4 via a plasmid, both transformants produced kasugamycin and aerial hyphae without significant differences . This study established that rpoZ is required for kasugamycin production and aerial mycelium formation in S . kasugaensis and responsible for pleiotropy.

South Med J, 2002 Oct, 95(10), 1163 - 7
Are pediatricians adhering to principles of judicious antibiotic use for upper respiratory tract infections?
Nambiar S, Schwartz RH, Sheridan MJ.
BACKGROUND: In 1997, the Centers for Disease Control and Prevention (CDC), in collaboration with other professional organizations, released principles for judicious use of antibiotics in pediatric upper respiratory illnesses (URI) . This study compared use of antibiotics for URI in children before (1995) and after (1998) publication of the principles and compared survey responses with practice habits . METHODS: A questionnaire was mailed to a sample of pediatricians in northern Virginia . Office records of a randomly selected subset of pediatricians were reviewed . RESULTS: Seventy-five percent of pediatricians completed the questionnaire; 51/149 (34%) chose to prescribe antibiotics for purulent rhinorrhea of less than 10 days' duration . This was significantly lower than that reported in the 1995 survey . However, review of office records of a random sample of these pediatricians revealed no significant difference in antibiotic use in children with uncomplicated URI in the 2 years studied . CONCLUSIONS: Injudicious antibiotic use for URI is prevalent among pediatricians in northern Virginia . Actual practice habits are at variance with response to case vignettes.

Australas J Dermatol, 2002 Nov, 43(4), 262 - 8
Prospective study of depressive symptoms and quality of life in acne vulgaris patients treated with isotretinoin compared to antibiotic and topical therapy; Ng CH et al.; There have been recent concerns about the possible association between isotretinoin therapy and depressive symptoms . We conducted a prospective study to evaluate depressive symptoms and quality of life in acne patients having either isotretinoin or antibiotics/topical treatments . There were 215 patients (mean age 20 years) included in the study . Depression, quality of life and acne severity ratings were administered at baseline, 1 month, 3 months and end of treatment or 6 months, and compared between both treatment groups . The changes in the mean depression scores did not differ significantly between both groups (P = 0.62) . The incidence of isotretinoin patients with moderate depressive symptoms remained relatively unchanged from baseline . The changes in the quality-of-life measures scores between treatment groups showed no significant difference . No correlation between isotretinoin dose and depression score was found . Although five isotretinoin patients were withdrawn during the study because of worsening of mood, no definite causal relationship was established . This pilot study does not appear to support any direct link between depression and isotretinoin, apart from being a rare unpredictable idiosyncratic side-effect . However, because of the study limitations, a larger study is needed to confirm the findings.

Eur J Biochem, 2002 Nov, 269(22), 5527 - 35
Identification of a set of genes involved in the biosynthesis of the aminonucleoside moiety of antibiotic A201A from Streptomyces capreolus; Saugar I et al.; A novel cosmid (pABC6.5) whose DNA insert from Streptomyces capreolus, the A201A antibiotic producer, overlaps the inserts of the previously reported pCAR11 and pCAR13 cosmids, has been isolated . These two latter cosmids were known to contain the aminonucleoside antibiotic A201A resistance determinants ard2 and ard1, respectively . Together, these three cosmids have permitted the identification of a DNA stretch of 19 kb between ard1 and ard2, which should comprise a large region of a putative A201A biosynthetic (ata) gene cluster . The sequence of the 7 kb upstream of ard1 towards ard2 reveals seven consecutive open reading frames: ataP3, ataP5, ataP4, ataP10, ataP7, ata12 and ataPKS1 . Except for the last two, their deduced products present high similarities to an identical number of counterparts from the pur cluster of Streptomyces alboniger that were either known or proposed to be implicated in the biosynthesis of the N6,N6-dimethyl-3'-amino-3'-deoxyadenosine moiety of puromycin . Because A201A contains this chemical moiety, these ataP genes are most likely implicated in its biosynthesis . Accordingly, the ataP4, ataP5 and ataP10 genes complemented specific puromycin nonproducing Deltapur4, Deltapur5 and Deltapur10 mutants of S . alboniger, respectively . Amino acid sequence comparisons suggest that ata12 and ataPKS1 could be implicated in the biosynthesis of the d-rhamnose and alpha-p-coumaric acid moieties of A201A . Further sequencing of 2 kb of DNA downstream of ard1 has disclosed a region which might contain one end of the ata cluster.

Emerg Med J . 2002 Nov;19(6):556.
Towards evidence based emergency medicine: best BETs from Manchester Royal Infirmary . Routine use of antibiotic ointment and wound healing; Van Zyl A et al.; A short cut review was carried out to establish whether topical antibiotics improved the outcome of simple wounds . Altogether 71 papers were found using the reported search, of which one presented the best evidence to answer the clinical question . The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of this best paper are tabulated . A clinical bottom line is stated.

Emerg Med J, 2002 Nov, 19(6), 553 - 4
Towards evidence based emergency medicine: best BETs from Manchester Royal Infirmary . Antibiotics in patients with isolated chest trauma requiring chest drains; Butler J et al.; A short cut review was carried out to establish whether the administration of antibiotics reduces the incidence of intrathoracic infection in patients who have had a chest drain inserted after trauma . Altogether 321 papers were found using the reported search, of which two presented the best evidence to answer the clinical question . The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these best papers are tabulated . A clinical bottom line is stated.

Emerg Med J, 2002 Nov, 19(6), 552 - 3
Antibiotics in compound depressed skull fractures; Ali B et al.; A short cut review was carried out to establish whether antibiotics reduce the incidence of meningitis in patients with compound depressed skull fracture . Altogether 198 papers were found using the reported search, of which one presented the best evidence to answer the clinical question . The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this best paper are tabulated . A clinical bottom line is stated.

Int J Colorectal Dis, 2002 Sep, 17(5), 355 - 8
Single-dose metronidazole versus 5-day multi-drug antibiotic regimen in excision of pilonidal sinuses with primary closure: a prospective randomised controlled double-blinded study; Chaudhuri A et al.; BACKGROUND AND AIMS: This pilot study examines whether single-dose intravenous metronidazole preoperatively is at least as effective as a broad-spectrum multi-drug regimen in preventing infection-related wound complications following excision of pilonidal sinuses with primary closure . PATIENTS AND METHODS: A double-blinded study with 50 patients randomised to receiving either a single drug (intravenous metronidazole 500 mg) prophylaxis preoperatively or multi-drug cover (intravenous cefuroxime 1.5 g and metronidazole 0.5 g preoperatively, and oral co-amoxiclav 375 mg 8-hourly postoperatively) . They will be reviewed 1, 2 and 4 weeks postoperatively . The wound will be graded as: I, healthy; II, redness and swelling of edges; III, abscess related to a suture; IV, spreading wound infection; V, wound breakdown . Other factors considered are the distance from the lowest wound margin to the anal verge, and previous pilonidal sinus surgery . RESULTS: Results awaited . CONCLUSION: Single-dose metronidazole seems an appropriate and low-cost antibiotic to consider for prophylaxis in pilonidal sinus surgery . This study will form the base for a trial to be conducted in larger numbers as a randomised controlled trial in order to have statistical power.

Ann Oncol, 2002 Nov, 13(11), 1810 - 8
Phase I and pharmacokinetic study of docetaxel in combination with epirubicin and cyclophosphamide in advanced cancer: dose escalation possible with granulocyte colony-stimulating factor, but not with prophylactic antibiotics; Rischin D et al.; BACKGROUND: The objective of this phase I trial was to determine the maximally tolerated doses of the combination of docetaxel, epirubicin and cyclophosphamide . PATIENTS AND METHODS: Patients with advanced cancer, World Health Organization (WHO) performance status 0 to 2, who had received up to one prior chemotherapy regimen were treated with docetaxel, epirubicin and cyclophosphamide repeated every 21 days . The cyclophosphamide dose was fixed at 600 mg/m(2) and the dose levels studied were: docetaxel/epirubicin; 60/60, 75/60, 75/75, 75/90, 85/90 and 85/105 mg/m(2) . There was provision for the addition of prophylactic ciprofloxacin and granulocyte colony-stimulating factor (G-CSF) in separate steps if dose-limiting toxicity (DLT) was neutropenia related . RESULTS: Forty-three patients were entered and all were assessable for toxicity . Dose-limiting toxicity, predominantly febrile neutropenia, was surprisingly seen at the first dose level . The addition of prophylactic ciprofloxacin did not permit dose escalation, but dose escalation was possible with the addition of G-CSF . The highest administered dose level with G-CSF was docetaxel 85 mg/m(2) and epirubicin 105 mg/m(2) with DLTs in five of six patients . Treatment was well tolerated in 10 patients treated at the recommended dose level (85/90) with only one patient experiencing DLT . Responses were seen in a range of malignancies including breast and anaplastic thyroid cancers . No significant pharmacokinetic interaction was observed, but a transient increase in epirubicinol plasma concentration occurred during and after docetaxel infusion . CONCLUSIONS: The recommended dose level of docetaxel 85 mg/m(2), epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2) with G-CSF support has a favorable toxicity profile and is suitable for further investigation in phase II and III trials.

Pharmacol Res, 2002 Nov, 46(5), 395 - 400
Adverse drug reactions to antibiotics observed in two pulmonology divisions of catanzaro, Italy: a six-year retrospective study; Gallelli L et al.; We retrospectively analysed adverse drug reactions (ADRs) associated with antibiotic therapy and reported over a 6-year period, from January 1995 to December 2000, in clinical notes of two Pulmonology Units of "Mater Domini" University Hospital and "Pugliese-Ciaccio" Hospital, both located in Catanzaro, Italy.Antibiotics were responsible for 92 (44.9%) out of 205 episodes of ADRs . In particular, 22 episodes (23.9%) were observed after penicillin G administration, 19 episodes (20.7%) following ceftazidime and cefotaxime administration, 16 episodes (17.4%) after therapy with ampicillin, and 35 reactions (38%) were further reported during treatments with other antibiotics . We determined that the drug-ADR relationship was certain in 63% of the reports; withdrawal of the suspected drug led to recovery in 95% of cases . In conclusion, this retrospective evaluation demonstrated that antibiotics are a common cause of ADRs in hospitalised patients and, therefore, drug surveillance can successfully identify targeted adverse events.

J Biomed Mater Res, 2002, 63(6), 800 - 6
Effect of antibiotics on the properties of poly(methylmethacrylate)-based bone cement; He Y et al.; The goal of this study was to examine the relationship between gentamicin concentration in Palacos R bone cement (in the mass fraction range of 0-9.4%) and various properties of the cement . The results from the thermal, density, and static compression tests show that gentamicin favors the cement polymerization in its final steps, and forms a diphasic structure with the cement {poly(methylmethacrylate)} matrix . The static compression properties in the dry state are only slightly modified by the presence of the antibiotic . Concerning aging in water at 37 degrees C, two types of behavior can be distinguished: below a critical concentration, approximately 3-4%, the extraction of gentamicin by water is slow and there is only a slight change of static compression properties . In contrast, above this critical concentration, the gentamicin extraction is fast and almost complete after 48 weeks, and there is a considerable loss of static compression properties .

J Periodontol, 2002 Oct, 73(10), 1188 - 96
Rationale for use of antibiotics in periodontics; Walker C et al.; The purpose of this review is to provide the clinician with some practical rationale for the selection and use of antibiotics in the treatment of destructive periodontal diseases . We have attempted to integrate approximately 20 years of periodontal literature describing antibiotic therapy with personal experience and 21st century ideas . This article addresses antibiotic use during treatment of aggressive periodontitis with emphasis on juvenile disease and adult refractory diseases . The literature review revealed few large, controlled studies that compared efficacy of adjunctive antibiotic use to mechanical therapy alone . Even fewer studies evaluated the efficacy of one antibiotic relative to another . However, based on the evidence available, certain conclusions were drawn . Adjunctive use of an antibiotic along with mechanical debridement is recommended for the treatment of Actinobacillus actinomycetemcomitans-associated periodontitis as an acceptable therapeutic regimen . Due to the emergence of tetracycline-resistant A . actinomycetemcomitans, the combination of metronidazole and amoxicillin may be preferable . In aggressive refractory periodontitis, compelling evidence exists that the use of an appropriate adjunctive antibiotic frequently gives a more favorable clinical response than mechanical therapy alone . Unfortunately, the selection of antibiotic is not as clear and is probably case-dependent . Positive responses have been reported with amoxicillin/clavulanic acid, clindamycin, metronidazole, and the combination therapy metronidazole plus amoxicillin . The introduction of local delivery antibiotics specifically for the treatment of periodontitis offers a novel concept for the treatment of localized disease . The latter, in particular, may prove useful in the treatment of recurrent disease activity or where only a few individual sites are involved.

Am J Med Qual, 2002 Sep-Oct, 17(5), 195 - 9
An evidence-based clinical pathway for bronchiolitis safely reduces antibiotic overuse; Wilson SD et al.; The overuse of antibiotics in the management of bronchiolitis is widely known, yet physician practice has been slow to change . We report here on the success of a clinical pathway in reducing antibiotic overuse in the inpatient management of bronchiolitis . The charts of 181 children admitted for bronchiolitis were reviewed to determine whether antibiotic use was reduced in patients managed using a clinical pathway compared with a matched group of patients managed without use of the pathway (non-pathway group) . Only 9% of the pathway patients received antibiotics compared with 27% of the nonpathway group . No negative effects were seen on other quality measures including unplanned return for care . Furthermore, for patients managed using the clinical pathway, cost and length of stay were significantly reduced . Overall, the study suggests that implementation of a clinical pathway may be an effective means to change physician practice and reduce the unnecessary use of antibiotics, while maintaining or improving other aspects of quality of care.

Zhonghua Liu Xing Bing Xue Za Zhi, 2002 Aug, 23(4), 301 - 3
{Study on intervention and comparison of rational use of antibiotics on perioperative period of clean incision and clean-defiled incision}; Wang Y et al.; OBJECTIVE: To explore a set of scientific evaluation and intervention methods on perioperatur period which fits for China's situation, and to promote the development of rational drug use . METHODS: Two would tertiary general hospitals were selected and separated in to intervention group and control group . Intervention was carried out and compared at the same period on inpatient surgical cases of thryroidectomy, mastectomy, cholescystectomy, and hysteromyomectomy plus appendix . RESULTS: The average drug costs was decreased from 1 601.27 yuan to 1 489.59 yuan and the average antibiotics use from 740.20 yuan to 352.03 yuan (P < 0.01) in the intervention group pre and post intervention . There was a remarkable improvement on the rationality of antibiotics use in intervention group, from 31.35% to 91.81% (P < 0.01) pre and post intervention, implemented in the hospital . CONCLUSION: It is practicable and effective to implement rational drug use where intervention was carried out, since it plays an active role on promoting safely, effectively and economic antibiotic use in China.

Life Sci, 2002 Nov 22, 72(1), 49 - 57
Mitochondrial cytochrome c oxidase as a target site for cephalosporin antibiotics in renal epithelial cells (LLC-PK(1)) and renal cortex; Kiyomiya K et al.; We reported previously that treatment of the pig kidney proximal tubular epithelial cell line LLC-PK(1) with cephaloridine (CLD) decreased the activity of cytochrome c oxidase in the mitochondria of the cells followed by increases in lipid peroxidation and cell necrosis . In this study, we investigated the effects of CLD on the activity of cytochrome c oxidase in mitochondria isolated from LLC-PK(1) cells and purified the enzyme from mitochondria of the rat renal cortex . The activity of cytochrome c oxidase in the isolated mitochondria from LLC-PK(1) cells was significantly decreased from 1 h after addition of 1 mM CLD . Other cephalosporin antibiotics, cefazolin and cefalotin, also decreased the activity of cytochrome c oxidase in the isolated mitochondria . The activity of cytochrome c oxidase purified from the mitochondria of the rat renal cortex was also decreased from 2 h after addition of 1 mM CLD in a non-competitive manner . These results suggest that the direct inhibition of cytochrome c oxidase activity in the mitochondrial electron transport chain by cephlosporins may result from the observed nephrotoxicity.

J Pharm Biomed Anal, 2002 Nov 7, 30(4), 1093 - 102
Analysis of beta-lactam antibiotics by high performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry using bromoform; Horimoto S et al.; The novel identification method for a heat-unstable antibiotic, FC/TA-891 and its active metabolite (FCE22101) by high-performance liquid chromatography (HPLC)-atmospheric pressure chemical ionization mass spectrometry (APCI-MS) employing bromoform as an ionization acceleration solvent, was applied to eight penicillins and 13 cephalosporins which are groups of beta-lactam antibiotics . The conditions of HPLC-APCI-MS were examined with ampicillin . Bromoform or chloroform was added to the mobile phase in HPLC to compare the difference between bromine and chlorine adducted ions . For all penicillins except sulbenicillin, both chlorine adducted and bromine adducted ions were observed with a flow injection method . The results indicated that the relative sensitivity ratios of bromine adducted ions to {M-H}(-) were higher than those of chlorine adducted ions . These bromine adduct ions could be clearly distinguished from other ions due to its isotopical ratio (1:1), leading to an easy identification of the compounds . For 13 cephalosporins, bromine adducted ions were detected in nine compounds, and chlorine adducted ions were detected in four compounds . The separation of four antibiotics was investigated with an HPLC column to apply this technique to the actual analysis . The capability was equal as in the flow injection method and it found that this technique, i.e . APCI-MS with bromoform could be applicable in the separation analysis.

Bioorg Khim, 2002 Sep-Oct, 28(5), 474 - 80
{1H-NMR analysis of the heteroassociation of caffeine with the antibiotic actinocyl-bis(3-dimethylaminopropylamine) in aqueous solution}; Veselkov AN et al.; The heteroassociation of caffeine (CAF) and the synthetic antibiotic actinocyl-bis(3-dimethylaminopropylamine) (ACT) was studied in aqueous solution by one- and two-dimensional 1H NMR spectroscopy at 500 MHz . The equilibrium reaction constants, thermodynamic parameters (delta H and delta S) of ACT heteroassociation with CAF, the limiting values of proton chemical shifts of their molecules in the heteroassociation complex, and the spatial structure of the ACT-CAF complex were determined from the experimental dependences of proton chemical shifts of the aromatic molecules on concentration and temperature . The parameters of CAF heteroassociation with the phenoxazone antibiotic actinomycin D and its synthetic analogue ACT were comparatively analyzed and conclusions were made on the crucial role of stacking interactions of the chromophores of CAF and the phenoxazone antibiotics in the formation of the heterocomplexes in aqueous solution.

Mol Microbiol, 2002 Oct, 46(2), 505 - 17
Molecular characterization and analysis of the biosynthetic gene cluster for the azoxy antibiotic valanimycin; Garg RP et al.; Streptomyces viridifaciens MG456-hF10 produces the antibiotic valanimycin, a naturally occurring azoxy compound . Valanimycin is known to be derived from valine and serine with the intermediacy of isobutylamine and isobutylhydroxylamine, but little is known about the stages in the pathway leading to the formation of the azoxy group . In previous studies, a cosmid containing S . viridifaciens DNA was isolated that conferred valanimycin production upon Strepto-myces lividans TK24 . Subcloning of DNA from the valanimycin-producing cosmid has led to the identi-fication of a 22 kb segment of DNA sufficient to allow valanimycin production in S . lividans TK24 . Sequencing of this DNA segment and the surrounding DNA revealed the presence of 20 genes . Gene disruption experiments defined the boundaries of the valanimycin gene cluster, which appears to contain 14 genes . The cluster includes an amino acid decar-boxylase gene (vlmD), a valanimycin resistance gene (vlmF ), at least two regulatory genes (vlmE, vlmI ), two genes encoding a flavin monooxygenase (vlmH, vlmR), a seryl tRNA synthetase gene (vlmL ) and seven genes of unknown function . Overproduction and characterization of VlmD demonstrated that it catalyses the decarboxylation of l-valine . An unusual feature of the valanimycin gene cluster is that four genes involved in branched amino acid biosynthesis are located near its 5' end.

J Med Assoc Thai, 2002 Aug, 85 Suppl 2, S739 - 42
Prevention of antibiotic-associated diarrhea in infants by probiotics; Jirapinyo P et al.; Probiotics administration has been claimed to prevent antibiotic-associated diarrhea . The investigators thus conducted a double blind, placebo controlled study of providing probiotics to infants and children with severe bacterial infections and receiving broad spechum antibiotics . The results of the study showed that the group receiving probiotics had fewer diarrheal episodes (37.5%) than the control group (80%), although the numbers were too small for statistical analysis . In conclusion, probiotics administration to patients receiving high doses of broad spectrum antibiotics may prevent the occurrence of antibiotic-associated diarrhea . A further study with a larger number is required.

J Orthop Surg (Hong Kong), 2002 Jun, 10(1), 53 - 60
The treatment of chronic osteomyelitis with a biodegradable antibiotic-impregnated implant; Gitelis S et al.; The use of local antibiotics from a biodegradable implant for chronic osteomyelitis is an attractive alternative . The implant delivers high tissue levels, obliterates dead space, aids bone repair and does not need to be removed . The purpose of this paper is to review our early clinical experience with custom-made calcium sulfate (Osteoset bone void filler) antibiotic-impregnated implants.

Patient Educ Couns, 2002 Oct -Nov, 48(2), 161 - 9
Cross-cultural differences in lay attitudes and utilisation of antibiotics in a Belgian and a Dutch city; Deschepper R et al.; Cultural differences are probably an important factor in the considerable variation in antibiotic use between countries . The objective of this study was to explore local cultural differences in the lay perspective on coping with URTD and using antibiotics . We interviewed 30 persons in a Dutch and a Belgian city . Twenty-one were interviewed a second time after 3 months . Between the first and second interview, they noted in a diary all URTD episodes experienced by themselves and their family members (N=69) and how they coped with them . The Dutch participants labelled most URTD episodes as "common cold" or "flu" . The Flemish participants labelled most of their URTD episodes as "bronchitis" and used more antibiotics . Four categories of antibiotic users could be distinguished . Participants with a Protestant background were more sceptical about medicines than those with a Catholic background . A thorough understanding of the cultural context is necessary to design effective campaigns to promote rational antibiotic use.

Pediatr Cardiol, 2003 Jul-Aug, 24(4), 344 - 9 Epub 2002 Oct 29.
Knowledge, compliance and practice of antibiotic endocarditis prophylaxis of patients with congenital heart disease; Knirsch W et al.; The aim of this study was to determine the knowledge, compliance, and practice of antibiotic endocarditis prophylaxis (AEP) for patients with congenital heart disease (CHD) during various diagnostic or therapeutic procedures . Patients (296) and their parents were interrogated during a visit with an 18-question survey pertaining to the practice of AEP . Most patients (91.6%) had acyanotic congenital heart disease, usually preoperative (45.3%), or had high risk of infective endocarditis due to previous endocarditis (2.0%), cyanosis (8.4%), or prosthetic valves (5.4%) . Potential sources for failure of AEP were (1) no existence of a wallet card (6.8%), no communication between patient and doctor concerning the potential risk of endocarditis during a visit (13.2%), or no sufficient anamnestic inquiry by the physician before procedures were performed (43.2%) . The patients underestimated (4.4%) or had no knowledge of the individual risks of endocarditis (37.5%) or underestimated indication for AEP (11.1%) . AEP was often not performed at all (60.5%) . Bad dental status with no previous dental therapy (35.5%) and a high rate of caries (17.2%) or gingivitis (7.4%) even in young children was frequent . AEP for patients with CHD has not been sufficiently used because of the patient's, and the physician's failure to take the necessary steps, the cardiac diagnosis, or the dental health status . Alternative strategies in prophylaxis for AEP are discussed here.

Biofizika, 2002 Sep-Oct, 47(5), 833 - 41
{Biophysical and medical and biological aspects of use of polyene antibiotics in combination with dimethylsulfoxide}; Ibragimova VKh et al.; Modern conceptions of the physicochemical properties of dimethylsulfoxide and polyene antibiotics are reviewed . The results of investigations of independent and mutual effects of polyene antibiotics and dimethylsulfoxide on membrane permeability were analysed . The own experimental data of radioprotective and antitumour action of complex dimethylsulfoxide-polyene antibiotics are presented, and the perspectives of their use in medicine are described.

Mediators Inflamm, 2002 Aug, 11(4), 235 - 44
Inhibitory action of a macrolide antibiotic, roxithromycin, on co-stimulatory molecule expressions in vitro and in vivo; Suzuki M et al.; OBJECTIVE: The influence of a macrolide antibiotic, roxithromycin (RXM), on co-stimulatory molecule expression was examined in vitro and in vivo . MATERIALS AND METHODS: Spleen cells obtained from BALB/c mice 10 days after immunization with 8.0 microg of hemocyanin absorbed to 4.0 mg of aluminum hydroxide were cultured in the presence of 100.0 microg/ml of hemocyanin and various concentrations of RXM . We first examined the influence of RXM on cell activation by examining the proliferative response of cells and cytokine production . We also examined the influence of RXM on co-stimulatory molecule (CD40, CD80 and CD86) expressions on cultured splenic B-lymphocytes induced by in vitro antigenic stimulation using flow cytometry . In the second part of experiments, non-immunized and immunized mice were treated orally with 2.5 mg/kg of RXM once a day for 4 or 8 weeks . Splenic B lymphocytes were obtained from these mice 24 h after antigenic challenge, and co-stimulatory molecule expressions were examined by flow cytometer . RESULTS: Cell activation induced by in vitro antigenic stimulation was suppressed by RXM when cells were cultured in the presence of more than 5.0 microg/ml of the agent . Addition of RXM at a concentration of 5.0 microg/ml into cell cultures also suppressed co-stimulatory molecule (CD40, CD80 and CD86) expressions on splenic B lymphocytes, which was enhanced by antigenic stimulation in vitro . Oral RXM administration for 4 weeks clearly suppressed the enhancement of CD40 and CD86 (but not CD80) expressions on splenic B lymphocytes induced by antigenic stimulation in vivo . This suppressive activity of RXM on co-stimulatory molecule (CD40 and CD86) expressions was further strengthened by the treatment of mice for 8 weeks . Long-term treatment with oral RXM also suppressed CD80 expressions, which was not suppressed by 4-week treatment . CONCLUSION: The present results suggest that RXM exerts its immunomodulating effects through suppression of both cell activation and co-stimulatory molecule expressions induced by antigenic stimulation . These suppressive activities of RXM might contribute, in part, to the therapeutic mode of action of RXM on inflammatory diseases.

Mol Genet Genomics, 2002 Oct, 268(2), 179 - 89 Epub 2002 Aug 15.
A rifampicin resistance mutation in the rpoB gene confers ppGpp-independent antibiotic production in Streptomyces coelicolor A3(2); Xu J et al.; In Streptomyces coelicolor A3(2), deletion of relA or a specific mutation in rplK ( relC) results in an inability to synthesize ppGpp (guanosine 5'-diphosphate 3'-diphosphate) and impairs production of actinorhodin . We have found that certain rifampicin-resistant ( rif) mutants isolated from either relA or relC strains regain the ability to produce actinorhodin at the same level as the wild-type strain, although their capacity to synthesize ppGpp is unchanged . These rif mutants were found to have a missense mutation in the rpoB gene that encodes the RNA polymerase beta-subunit . This rpoB mutation was shown to be responsible for the observed changes in phenotype, as demonstrated by gene replacement experiments . Gene expression analysis revealed that the restoration of actinorhodin production in both relA and relC strains is accompanied by increased expression of the pathway-specific regulator gene actII-ORF4, which is normally decreased in the rel mutants . In addition to the restoration of antibiotic production, the rif mutants also exhibited a lower rate of RNA synthesis compared to the parental strain when grown in a rich medium, suggesting that these mutant RNA polymerases behave like "stringent" RNA polymerases . These results indicate that rif mutations can alter gene expression patterns independently of ppGpp . We propose that RNA polymerases carrying particular rif mutations in the beta-subunit can functionally mimic the modification induced by binding of ppGpp.

Br J Clin Pharmacol, 2002 Oct, 54(4), 445 - 8
In vitro permeation of beta-lactam antibiotics across rat jejunum and its correlation with oral bioavailability in humans; Saitoh H et al.; AIMS: To investigate the correlation between in vitro permeation of 11 beta-lactam antibiotics across rat jejunum and their oral bioavailability in humans . METHODS: The absorptive and secretory permeation across rat jejunum was evaluated and apparent permeability coefficients (P(app)) were determined . RESULTS: A steep, sigmoid-type curve was obtained for the relationship between P(app) in the absorptive permeation and human oral bioavailability . When the ratios of P(app) in the absorptive direction to P(app) in the secretory direction were plotted against human oral bioavailability, a much improved correlation was obtained (r = 0.98, P < 0.001) . The addition of glycylglycine to both mucosal and serosal media modified the permeation of ceftibuten and cephalexin from the absorptive to the secretory direction . CONCLUSIONS: For 11 beta-lactam antibiotics rat intestinal permeation correlated well with human oral bioavailability, especially when corrected for secretory transport.

J Biotechnol, 2002 Nov 13, 99(3), 215 - 22
Enzymatic synthesis of beta-lactam antibiotics via direct condensation; Ulijn RV et al.; In this paper, the feasibility of precipitation driven synthesis of acidic and zwitterionic beta-lactam antibiotics is studied . As an example of the first type, penicillin G was produced in good yield (160 mmol kg(-1)) directly from the free acid and amine aqueous substrate suspension, where the synthesis product precipitated . Such a precipitation driven synthesis via direct reversal of the hydrolytic reaction is thermodynamically unfavourable for zwitterionic beta-lactam antibiotics, such as amoxicillin . In this paper, a novel method is suggested to help favour precipitation of (poorly soluble) product salts by deliberate addition of certain counter-ions . After screening a number of different counter-ions, it was found that the amoxicillin anion forms a poorly soluble salt with Zn(2+) . Despite increased beta-lactam degradation due to the presence of zinc ions, in a synthetic reaction with 0.1 M ZnSO(4) present the synthetic yield could be increased at least 30-fold.

Int J Antimicrob Agents, 2002 Oct, 20(4), 253 - 7
Over-the-counter acquisition of antibiotics in the Maltese general population; Borg MA et al.; Few studies have studied the frequency of over-the-counter acquisition of antibiotics in western countries . In order to provide an insight into these practices in Malta, attitudes towards antibiotic use in the general public were researched through a structured interview . Nineteen percent admitted that they took antibiotics without prescription and 11% of parents replied that they had given antibiotics to their children without prescription . These antibiotics were mainly self-administered for upper respiratory tract symptoms, particularly sore throat, with community pharmacies being the major source in more than 85% of cases . The study indicates the need for an educational campaign on proper antibiotic use amongst the Maltese general public.

Antimicrob Agents Chemother, 2002 Nov, 46(11), 3348 - 55
Mycothiol-deficient Mycobacterium smegmatis mutants are hypersensitive to alkylating agents, free radicals, and antibiotics; Rawat M et al.; Mycothiol (MSH; 1D-myo-inosityl 2-{N-acetyl-L-cysteinyl}amido-2-deoxy-alpha-D-glucopyranoside) is the major low-molecular-weight thiol produced by mycobacteria . Mutants of Mycobacterium smegmatis mc(2)155 deficient in MSH production were produced by chemical mutagenesis as well as by transposon mutagenesis . One chemical mutant (mutant I64) and two transposon mutants (mutants Tn1 and Tn2) stably deficient in MSH production were isolated by screening for reduced levels of MSH content . The MSH contents of transposon mutants Tn1 and Tn2 were found to be less than 0.1% that of the parent strain, and the MSH content of I64 was found to be 1 to 5% that of the parent strain . All three strains accumulated 1D-myo-inosityl 2-deoxy-alpha-D-glucopyranoside to levels 20- to 25-fold the level found in the parent strain . The cysteine:1D-myo-inosityl 2-amino-2-deoxy-alpha-D-glucopyranoside ligase (MshC) activities of the three mutant strains were < or =2% that of the parent strain . Phenotypic analysis revealed that these MSH-deficient mutants possess increased susceptibilities to free radicals and alkylating agents and to a wide range of antibiotics including erythromycin, azithromycin, vancomycin, penicillin G, rifamycin, and rifampin . Conversely, the mutants possess at least 200-fold higher levels of resistance to isoniazid than the wild type . We mapped the mutation in the chemical mutant by sequencing the mshC gene and showed that a single amino acid substitution (L205P) is responsible for reduced MSH production and its associated phenotype . Our results demonstrate that there is a direct correlation between MSH depletion and enhanced sensitivity to toxins and antibiotics.

Adv Drug Deliv Rev, 2002 Oct 16, 54(7), 963 - 86
Polyanhydride implant for antibiotic delivery--from the bench to the clinic; Li LC et al.; A polyanhydride implant (Septacin) containing gentamicin sulfate was developed for sustained local delivery of the drug to the site of infection in the treatment of osteomyelitis . Laboratory-scale injection molding equipment was utilized to fabricate the implant for in vitro characterization . Molding conditions were optimized to produce implants with a skin-core structure which was found to be critical in preventing the initial cracking of the implant during in vitro drug release test in water . A manufacturing process consisting of twin-screw extrusion, pelletizing, and injection molding was developed . Polymer-drug pellets were characterized with respect to copolymer molecular weight and drug content uniformity . The implants were terminally sterilized by gamma-radiation which was found to cause increase in copolymer molecular weight as a result of polymer chain extension . The stability of Septacin was evaluated as a function of storage temperature and time . A marked decline in copolymer molecular weight occurred in samples stored above freezing temperatures and significantly slower drug-release profiles were also exhibited by these samples . In vivo drug release from Septacin in rats showed that the gentamicin plasma levels were extremely low, indicating the low systemic exposure to gentamicin . Furthermore, Septacin samples have demonstrated efficacy in the rat skin-abscess and horse-joint infection models . Results from a human in vivo study also showed high local drug concentrations at implantation sites while systemic exposure to the drug was minimal.

J Chromatogr B Analyt Technol Biomed Life Sci, 2002 Nov 15, 780(1), 83 - 92
Multiresidue analysis of fluoroquinolone antibiotics in chicken tissue using liquid chromatography-fluorescence-multiple mass spectrometry; Schneider MJ et al.; An efficient liquid chromatographic method for the multiresidue analysis of fluoroquinolone antibiotics in chicken tissue has been developed in which quantitation using fluorescence and confirmation with multiple mass spectrometry (MS(n)) was achieved simultaneously . Using this method, eight fluoroquinolones were analyzed in fortified samples of chicken liver and muscle tissue with recoveries at levels of 10-200 ng/g generally in the range of 60-93%, except for desethylene ciprofloxacin, which consistently gave recoveries >or=45% . Relative standard deviations were excellent in all cases, and the limits of detection in ng/g were determined as follows in liver and (muscle): desethylene ciprofloxacin 0.3 (0.1), norfloxacin 1.2 (0.2), ciprofloxacin 2 (1.5), danofloxacin 0.2 (0.1), enrofloxacin 0.3 (0.2), orbifloxacin 1.5 (0.5), sarafloxacin 2 (0.6), difloxacin 0.3 (0.2) . Confirmation of the identities of the fluoroquinolones was achieved by monitoring the ratios of two prominent product ions in MS(2) (desethylene ciprofloxacin) or MS(3) (all others) . Levels of confirmation as related to ion ratio variability criteria were established . Enrofloxacin and ciprofloxacin were also determined in enrofloxacin incurred chicken liver and muscle using this method.

J Pediatr Surg, 2002 Oct, 37(10), 1430 - 4
A prospective comparison of antibiotic usage in pediatric surgical patients: the safety, advantage, and effectiveness of the Surgical Infection Society guidelines versus a common practice; Gorecki W et al.; BACKGROUND: The Surgical Infection Society (SIS) guidelines for antibiotic (Ab) usage minimally changed the surgical practice . The authors believed that clinical evidence of the safety, advantage, and effectiveness of SIS guidelines may improve inappropriate usage of Ab . METHODS: A group of dedicated surgeons attempted to use Ab appropriately to SIS guidelines in their patients (group A) . A comparison was made with a concurrent cohort of patients (group B), treated by surgeons who were nonsupporters of SIS guidelines . The trial was conducted in 378 children between March 1999 and May 2000 . The outcome measures were morbidity and mortality rates, Ab treatment duration, timing of administration, unjustified spectrum, and switch of Ab . Analysis of variance and Chi2 test were used in statistics . P value less than.05 was considered significant (s) . RESULTS: Group A included 124 patients and Group B, 254 . There were no intergroup differences in age, sex, and clean/contaminated/dirty ratio of procedures . The mean duration of Ab treatment was 3.9 days in group A, versus 7.1 days in group B (s), with overall rate of appropriateness of 77% versus 36% (s) and no differences in mortality and morbidity rates . CONCLUSION: Perhaps these results may change Ab usage in pediatric surgery .

Clin Invest Med, 2002 Oct, 25(5), 185 - 90
Outpatient parenteral antibiotic therapy: evolution of the Calgary adult home parenteral therapy program; Laupland KB et al.; In the past 25 years, outpatient antibiotic therapy has been recognized as a cost-effective, safe and patient-accepted means of managing patients with chronic infections who require prolonged parenteral therapy but otherwise do not need admission to hospital . We describe the home parenteral therapy program in Calgary, which reflects the next generation of outpatient antibiotic therapy in Canada because of its unique inclusion of patients with acute infections . The Calgary home parenteral therapy program has evolved from a few, small, single-site programs to a multisite, region-wide program that each year treats thousands of patients who require long- and short-term parenteral therapy . With escalating health care budgets and increased demand on acute-care hospital beds, existing programs in other centres may benefit from the Calgary experience, and this home parenteral therapy model may serve as a template for developing new outpatient antibiotic therapy programs in other regions.

Scand J Infect Dis, 2002, 34(9), 657 - 9
Educational intervention for parents and healthcare providers leads to reduced antibiotic use in acute otitis media; Smabrekke L et al.; We used a controlled before-and-after design with the aims of reducing both the total consumption of antibiotics and the use of broad-spectrum antibiotics against acute otitis media (AOM), and to study to what extent prescriptions for antibiotics against AOM were dispensed . Information on evidence-based treatment of uncomplicated AOM was provided to doctors and nurses, and written guidelines were implemented . Pamphlets and oral information concerning symptomatic treatment and the limited effect of antibiotic use in AOM were given to parents . Eligible patients were 819 children aged 1-15 y . The proportion of patients receiving a prescription for antibiotics was reduced from 90% at baseline to 74% during the study period . The proportion of prescriptions for penicillin V increased from 72% at baseline to 85% during the study period . There were no significant changes at the control site . The proportion of dispensed prescriptions was 70% both at baseline and during the study period . Educational efforts reduced the total consumption of antibiotics and the use of broad-spectrum antibiotics for AOM in children aged 1-15 y at an emergency call service . Data on antibiotic use in AOM based only on prescribing overestimates the use of antibiotics.

J Infect Chemother, 2002 Sep, 8(3), 247 - 51
Bacteremic and leukopenic pneumococcal pneumonia: successful treatment with antibiotics, pulse steroid, and continuous hemodiafiltration; Yokoyama T et al.; We describe a case of bacteremic, leukopenic pneumococcal pneumonia with respiratory failure, accompanied by diabetic ketoacidosis and hypothermia . Pulmonary leukostasis may play a role in the pathogenesis of the acute respiratory distress syndrome (ARDS) in pneumococcal pneumonia . The patient recovered with mechanical ventilation, intravenous antibiotics, pulse-steroid therapy, and continuous hemodiafiltration (CHDF) . In particular, administration of steroid and the use of CHDF may improve the status of pulmonary leukostasis in leukopenic pneumococcal infection.

J Environ Sci Health B, 2002 Sep, 37(5), 485 - 92
Methionine auxotroph Escherichia coli growth assay kinetics in antibiotic and antifungal amended selective media; Froelich CA et al.; The objective of this work was to determine if Escherichia coli methionine bioassay characteristics were influenced by selective media amended with antibiotics and the antifungal compound cycloheximide . Bacterial cells were grown in minimal media with increasing concentrations of methionine and were incubated at 37 degrees C with vigorous agitation for 6 hours . Addition of antistatic agents to the media did not change the growth kinetic response (P>0.05) to methionine concentration (3.4 to 26.8 microM) . This supports the utility of this strain as a methionine bioassay organism for feed and other environmental sources.

Med Decis Making, 2002 Sep-Oct, 22(5 Suppl), S17 - 25
Modeling the public health response to bioterrorism: using discrete event simulation to design antibiotic distribution centers; Hupert N et al.; BACKGROUND: Post-exposure prophylaxis is a critical component of the public health response to bioterrorism . Computer simulation modeling may assist in designing antibiotic distribution centers for this task . METHODS: The authors used discrete event simulation modeling to determine staffing levels for entry screening, triage, medical evaluation, and drug dispensing stations in a hypothetical antibiotic distribution center operating in low, medium, and high disease prevalence bioterrorism response scenarios . Patient arrival rates and processing times were based on prior mass prophylaxis campaigns . Multiple sensitivity analyses examined the relationship between average staff utilization rate (UR) (i.e., percentage of time occupied in patient contact) and capacity of the model to handle surge arrivals . RESULTS: Distribution center operation required from 93 staff for the low-prevalence scenario to 111 staff for the high-prevalence scenario to process approximately 1000 people per hour within the baseline model assumptions . Excess capacity to process surge arrivals approximated (1-UR) for triage staffing . CONCLUSIONS: Discrete event simulation modeling is a useful tool in developing the public health infrastructure for bioterrorism response . Live exercises to validate the assumptions and outcomes presented here may improve preparedness to respond to bioterrorism.

J Orthop Trauma, 2002 Oct, 16(9), 622 - 7
The use of an antibiotic-impregnated, osteoconductive, bioabsorbable bone substitute in the treatment of infected long bone defects: early results of a prospective trial; McKee MD et al.; OBJECTIVE: We sought to evaluate the use of a bioabsorbable, tobramycin-impregnated bone graft substitute (calcium sulfate alpha-hemihydrate pellets) in the treatment of patients with infected bony defects and nonunions . STUDY DESIGN/METHODS: Twenty-five patients (15 male and 10 female, mean age 43 years (range 27-69 years) requiring surgical debridement of culture-positive long bone infection (16 with associated nonunion) were entered into an ongoing consecutive, prospective clinical trial . Involved bones included the tibia ( 15), femur ( 6), ulna ( 3), and humerus ( 1) . All defects were posttraumatic in origin, and each patient had had previous surgery at the involved site (mean 4.3 surgeries; range 1-8 surgeries) . The duration of infection ranged from 4 months to 20 years (mean 43 months) . According to the Cierny-Mader classification system, there was 1 stage I (medullary osteomyelitis), 6 stage III (localized osteomyelitis), and 18 stage IV (diffuse osteomyelitis) lesions . There were 4 normal (A) hosts and 21 locally and/or systemically compromised (B) hosts . Mean bone defect/void was 30.5 cm (range 3-192 cm ) . RESULTS: Mean follow-up was 28 months (range 20-38 months) . Radiographically, pellets were resorbed at a mean of 2.7 months postoperatively . Infection was eradicated in 23 of 25 patients (92%) . Isolated bony defects healed in all nine patients without further treatment . Fourteen of 16 patients with nonunion achieved union, although nine required autogenous bone grafting . Union was achieved in five of seven nonunion patients treated with bone graft substitute in isolation . Complications included refracture (three), recurrence of infection (two), persistent nonunion (two), and superficial wound necrosis (one) . Eight patients developed sterile draining sinuses that healed upon radiographic resorption of the pellets . CONCLUSIONS: In patients with posttraumatic osteomyelitis, the bone graft substitute was effective in eradicating bone infection in 23 of 25 patients . Isolated bony defects healed reliably (nine of nine) following addition of bone graft substitute alone . The role of the bone graft substitute in isolation in the treatment of nonunion is unclear at present.

Compr Ther, 2002 Fall, 28(3), 201 - 7
Guidelines for community-acquired pneumonia in the US and Canada: a practical approach to antibiotic selection; Ramirez JA; Several US and Canadian national organizations have published guidelines for antibiotic therapy of patients with community-acquired pneumonia (CAP) . This review paper will present the clinician with a practical approach to antibiotic selection based on current guidelines.

Chem Commun (Camb), 2002 Sep 21, (18), 2112 - 3
Acid-accelerated DNA-cleaving activities of antitumor antibiotic varacin; Lee AH et al.; It is demonstrated in this report that the authentic molecular structure of antibiotic varacin is capable of causing DNA-cleavage with high efficiency in the presence of thiols . In addition, it is found that the DNA-cleaving activity by varacin is apparently promoted by its acidic environments.

Ear Nose Throat J, 2002 Sep, 81(9), 648 - 52
Nebulized antibiotics for the treatment of acute exacerbations of chronic rhinosinusitis; Scheinberg PA et al.; We studied the effectiveness of aerosol delivery of antibiotics to the sinuses via a nebulizer in 41 patients who had chronic, recurrent sinusitis that had persisted despite endoscopic sinus surgery and that had not responded to multiple courses of oral antibiotics . We compared pre- and post-treatment symptom scores in five categories: nasal obstruction, facial pain, pressure, mucopurulent rhinorrhea, and malaise . Following 3 to 6 weeks of treatment, 34 patients (82.9%) experienced either an excellent or good response to treatment . Side effects were infrequent, mild, and transient . We conclude that nebulized antibiotics should be considered for all patients with chronic sinusitis who have undergone functional endoscopic sinus surgery and who have failed to respond to oral antibiotics or who do not tolerate them.

Dis Colon Rectum, 2002 Sep, 45(9), 1267 - 70
Regression of CD5-positive and Helicobacter pylori-negative mucosa-associated lymphoid tissue lymphoma of the rectum after administration of antibiotics: report of a case; Hisabe T et al.; We report a case of mucosa-associated lymphoid tissue lymphoma of the rectum that regressed after antibiotics administration . A 70-year-old female complained of abdominal discomfort . Colonoscopy performed in July 1998 showed a hemispheric protrusion of the rectum, the surface of which was covered with normal rectal mucosa . Pathologic diagnosis of a biopsy specimen was low-grade mucosa-associated lymphoid tissue lymphoma . Gastroscopy showed multiple erosions of the antrum, and was negative by both culture and histology . After informed consent the patient was treated with a 14-day course of lansoprazole, amoxicillin, and clarithromycin for the eradication of . Repeat colonoscopy ten days after initiation of treatment showed that the rectal tumor had disappeared, and this was confirmed by histologic examination . There was no recurrence during 20 months of follow-up.

Dialogue Diarrhoea . 1988 Jun;(33):2.
Iran: attitudes to treatment and use of antibiotics; Bhardwa RC; PIP: The inclusion of leaf concentrate in the diet of children has been found to reduce the risk of diarrhea . In addition, it has been observed that leaf concentrate, when incorporated into diets of well nourished children, can reduce the severity and length of diarrhea episodes . Leaf concentrate is a rich, natural source of B-carotene (pro-vitamin A) . Amaranthus leaves contain B-carotene, and one study has found that when cooked, pureed amaranthus leaves are served with the standard ORT solution, there is significant improvement in children . Leaf concentrate (LC) could be as effective as bananas in supplying potassium as it contains similar levels . The consumption of LC following a diarrhea episode could provide the much needed "catch up" proteins that insure proper growth . Because LC is soft and digestible, it can be included in a child's diet even before the last stages of diarrhea illness .

Chembiochem, 2002 Jun 3, 3(6), 559 - 65
A surface plasmon resonance analysis of the interaction between the antibiotic moenomycin A and penicillin-binding protein 1b; Stembera K et al.; The antibiotic moenomycin A inhibits the biosynthesis of peptidoglycan, the main structural polymer of the bacterial cell wall . The inhibition is based on a reversible binding of the antibiotic to one of the substrate binding sites in enzymes such as penicillin-binding protein (PBP) 1b . A novel assay based on surface plasmon resonance (SPR) has been established that can be used to investigate selective binding of the moenomycin sugar moiety and other transglycosylase inhibitors to this enzyme . Suitable ligands were prepared from moenomycin A and coupled to SPR sensor surfaces . Moenomycin analogues with structural variations were used to perform competitive SPR experiments with PBP 1b . The SPR results confirm for the first time that the trisaccharide fragment of moenomycin A (C-E-F-G-H-I) is the minimal structure that possesses all moieties sufficient for biological activity and for affinity towards PBP 1b . The method seems to be appropriate for use in screens for transglycosylase inhibitors that bind to the moenomycin-binding site of the enzyme.

Appl Environ Microbiol, 2002 Oct, 68(10), 4731 - 9
Engineering of primary carbon metabolism for improved antibiotic production in Streptomyces lividans; Butler MJ et al.; Deletions were made in Streptomyces lividans in either of two genes (zwf1 and zwf2) encoding isozymes of glucose-6-phosphate dehydrogenase, the first enzyme in the oxidative pentose phosphate pathway (PPP) . Each mutation reduced the level of Zwf activity to approximately one-half that observed in the wild-type strain . When the mutants were transformed with multicopy plasmids carrying the pathway-specific transcriptional activator genes for either the actinorhodin (ACT) or undecylprodigiosin (RED) biosynthetic pathway, they produced higher levels of antibiotic than the corresponding wild-type control strains . The presumed lower flux of carbon through the PPP in each of the Deltazwf mutants may allow more efficient glucose utilization via glycolysis, resulting in higher levels of antibiotic production . This appears to occur without lowering the concentration of NADPH (the major biochemical product of the oxidative PPP activity) to a level that would limit antibiotic biosynthesis . Consistent with this hypothesis, deletion of the gene (devB) encoding the enzyme that catalyzes the next step in the oxidative PPP (6-phosphogluconolactonase) also resulted in increased antibiotic production . However, deletion of both zwf genes from the devB mutant resulted in reduced levels of ACT and RED production, suggesting that some of the NADPH made by the PPP is utilized, directly or indirectly, for antibiotic biosynthesis . Although applied here to the model antibiotics ACT and RED, such mutations may prove to be useful for improving the yield of commercially important secondary metabolites.

Org Lett, 2002 Oct 3, 4(20), 3383 - 6
Stereostructure of a novel cytotoxic 18-membered macrolactone antibiotic FD-891; Eguchi T et al.; The absolute stereochemistry of FD-891, a novel cytotoxic 18-membered macrolactone antibiotic, was determined by a synthetic approach as well as X-ray diffraction of degradative derivatives . The absolute configuration of FD-891 turned out to be as shown above . The stable conformer of FD-891 was also discussed with respect to biological activity by comparison with the structurally related concanamycin A on the bases of molecular mechanics calculations . {structure: see text}

J Med Strasb, 1982 Jan, 13(1), 77 - 8
{The "pill" and antibiotics: examples of drug interactions of metabolic origin}; Imbs JL et al.; PIP: The action and effectiveness of most estroprogestational contraceptive agents can be impaired by interference with administration of certain antibiotics which can modify the hepatic estrogen metabolism . Such antibiotics are: 1) rifampicin, which can inactivate the action of ethinyl estradiol; spotting can be present; 2) ampicillin, chloramphenicol, neomycin, nitrofurantoin, sulfamethoxypyridazine, and penicillin; these agents modify the intestinal bacterial flora, thus reducing the effectiveness of contraception; and 3) troleandomycin, which increases hepatic risk .

Rev Gastroenterol Peru, 1997, 17 Suppl 1, 136 - 150
{ANTIBIOTICS IN GASTROINTESTINAL INFECTIONS}; Zolezzi A DR; In gastroenterology, the antibiotics are widely used for the treatment of gastrointestinal infections and also as prophylaxis for gastrointestinal procedures . Therefore, it is very important to know the characteristics of each and every antibiotic to use the most effective with the least adverse effects.This review gives a brief summary mentioning the most frequent adverse effects produced by antibiotics in the gastrointestinal tract.

Contracept Technol Update, 1995 Jun, 16(6), 72, 77 - 8
Data lacking to support antibiotics at IUD insertion; Role of antibiotics for the prevention of cardiovascular disease; Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA . mgabay@uic.edu

OBJECTIVE: To evaluate the data regarding the use of antibiotic therapy for the prevention of cardiovascular events . DATA SOURCES: Pertinent literature was identified through a MEDLINE search (1966-September 2001) and through other secondary literature databases and/or bibliographies of pertinent articles . DATA SYNTHESIS: Cardiovascular disease is a common cause of morbidity and mortality among the general population, with well-defined risk factors (e.g., diabetes, hypertension, hyperlipidemia, cigarette smoking, genetic predisposition) . Clinical data evaluating the association between the aforementioned risk factors and the development of atherosclerosis and subsequent cardiovascular disease are substantial; however, these risk factors may only partially explain the high prevalence of cardiovascular disease . The presence of Chlamydia pneumoniae within atherosclerotic lesions has been documented and may be an additional risk factor for the development and progression of cardiovascular disease . CONCLUSIONS: The results of primary and secondary prevention trials have shown conflicting evidence with regard to the beneficial effects of antibiotic therapy to reduce cardiovascular events . Currently, the lack of certainty in published data does not support the use of antibiotics for the prevention of cardiovascular disease . Clinicians should continue to emphasize interventions proven to reduce adverse cardiovascular events such as smoking cessation, reduction of hyperlipidemia, and control of hypertension.

Chem Commun (Camb), 2001 Sep 21, (18), 1752 - 3
Characterisation of a hydroxymandelate oxidase involved in the biosynthesis of two unusual amino acids occurring in the vancomycin group of antibiotics; Li TL et al.; ORF22 from the chloroeremomycin gene cluster has been cloned, expressed and characterised as a hydroxymandelate oxidase (HmO) that is involved in the formation of both (S)-4-hydroxyphenylglycine and (S)-3,5-dihydroxyphenylglycine.

Chem Commun (Camb), 2001 Oct 21, (20), 2156 - 7
Biosynthesis of the vancomycin group of antibiotics: characterisation of a type III polyketide synthase in the pathway to (S)-3,5-dihydroxyphenylglycine; Li TL et al.; 3,5-dihydroxyphenylacetate, a precursor for the non-proteinogenic amino acid 3,5-dihydroxyphenylglycine occurring in glycopeptide antibiotics, is determined to be catalysed by a type III polyketide synthase using malonyl-CoA as a starter unit.

Wiad Lek, 2002, 55(5-6), 276 - 81
{Effect of antibiotic therapy on levels of proinflammatory cytokines: interleukin IL-1, IL-6 and tumor necrosis factor TNF-alpha in serum of patients with Lyme borreliosis}; Kondrusik M et al.; We estimated serum concentrations of cytokines: IL-1, IL-6, TNF-alpha in patients with diagnosed Lyme disease treated for 14 days with antibiotics . The detection of proinflammatory cytokines was performed by ELISA tests . The examination was carried out before and after the treatment . The comparison with control group stated statistically significant higher concentration of IL-1, IL-6 and TNF-alpha before and after the treatment . Comparing the concentrations of cytokines after treatment with control group showed normalization only in a few cases . In the majority of cases serum cytokines concentrations remained significantly higher . That is why we conclude that 14-day-therapy with antibiotic in patients with Lyme disease may not be sufficient.

J Pharmacol Exp Ther, 2002 Oct, 303(1), 218 - 25
Divergent proarrhythmic potential of macrolide antibiotics despite similar QT prolongation: fast phase 3 repolarization prevents early afterdepolarizations and torsade de pointes; Milberg P et al.; Macrolide antibiotics are known to have a different proarrhythmic potential in the presence of comparable QT prolongation in the surface ECG . Because the extent of QT prolongation has been used as a surrogate marker for cardiotoxicity, we aimed to study the different electrophysiological effects of the macrolide antibiotics erythromycin, clarithromycin, and azithromycin in a previously developed experimental model of proarrhythmia . In 37 Langendorff-perfused rabbit hearts, erythromycin (150-300 microM, n = 13) clarithromycin (150-300 microM, n = 13), and azithromycin (150-300 microM, n = 11) led to similar increases in QT interval and monophasic action potential (MAP) duration . In bradycardic (atrioventricular-blocked) hearts, eight simultaneously recorded epi- and endocardial MAPs demonstrated increased dispersion of repolarization in the presence of all three antibiotics . Erythromycin and clarithromycin led to early afterdepolarizations (EADs) and torsade de pointes (TdP) after lowering of potassium concentration . In the presence of azithromycin, no EAD or TdP occurred . Erythromycin and clarithromycin changed the MAP configuration to a triangular pattern, whereas azithromycin caused a rectangular pattern of MAP prolongation . In 13 additional hearts, 150 microM azithromycin was administered after previous treatment with 300 microM erythromycin and suppressed TdP provoked by erythromycin . In conclusion, macrolide antibiotics lead to similar prolongation of repolarization but show a different proarrhythmic potential (erythromycin > clarithromycin > azithromycin) . In the presence of azithromycin, neither EAD nor TdP occur . This effect may be related to a rectangular pattern of action potential prolongation, whereas erythromycin and clarithromycin cause triangular action potential prolongation and induce TdP.

Gut, 2002 Oct, 51(4), 490 - 5
Impact of acid secretion, gastritis, and mucus thickness on gastric transfer of antibiotics in rats; Sherwood PV et al.; BACKGROUND AND AIMS: The success of Helicobacter pylori eradication regimens depends on gastric pH, inflammation, and mucus thickness . Our aim was to investigate the effects of acid secretion, inflammation, and mucolysis on gastric antibiotic transfer . SUBJECTS AND METHODS: A total of 134 anaesthetised rats were given metronidazole, amoxicillin, or clarithromycin intravenously and gastric contents were aspirated via an indwelling cannula . Acid secretion was controlled by either omeprazole or pentagastrin while gastritis was induced by infection with H pylori or dosing with iodoacetamide . Mucolysis was achieved by instilling pronase into the gastric lumen . RESULTS: Metronidazole transfer increased with acid secretion and fell with omeprazole, independently of gastric pH . Clarithromycin was also transferred with acid but was then rapidly degraded . Omeprazole prevented this degradation, raising gastric luminal concentrations . Omeprazole did not alter amoxicillin transfer . Gastritis induced by H pylori did not alter gastric transfer of metronidazole and amoxicillin but that of clarithromycin was increased by 23% . However, gastritis induced by iodoacetamide reduced clarithromycin transfer without any effect on metronidazole or amoxicillin transfer . Pronase treatment increased amoxicillin transfer fourfold and metronidazole by 66% but reduced clarithromycin transfer by 35% . CONCLUSIONS: Metronidazole and clarithromycin are predominantly transferred with gastric acid rather than by an acid trapping mechanism . Pronase increases the appearance of amoxicillin and metronidazole in gastric secretions.

Antimicrob Agents Chemother, 2002 Oct, 46(10), 3327 - 30
Inhibition of secretion of interleukin-1alpha and tumor necrosis factor alpha by the ketolide antibiotic telithromycin; Araujo FG et al.; The antibiotic telithromycin was examined for its effect on secretion of interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, IL-10, and tumor necrosis factor alpha (TNF-alpha) by lipopolysaccharide (LPS)-stimulated monocytes of eight human donors . Secretion of each cytokine was significantly increased by LPS alone, whereas treatment with telithromycin significantly inhibited secretion of IL-1alpha and TNF-alpha but not secretion of IL-1beta, IL-6, and IL-10 . Telithromycin had immunomodulatory effects as a result of alteration of secretion of IL-1alpha and TNF-alpha by monocytes.

Eur Cytokine Netw, 2002 Jul-Sep, 13(3), 324 - 30
Cytokine pattern in cystic fibrosis patients during antibiotic therapy and gene therapy using adenoviral vector; Reix P et al.; Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene . Despite improvements in treatment, pulmonary disease still remains the primary cause of death among these patients . In order to introduce a normal CFTR gene copy into airway epithelial cells, adenoviral vectors (AV) have been developed . AV are known to induce an inflammatory reaction that limits transgene expression, and can be potentially harmful . No human study has clearly monitored simultaneously, systemic and local inflammatory reaction, during AV administration . We report here the levels of C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 receptor antagonist (IL-1Ra) in plasma and bronchoalveolar lavage fluid (BALF) from six cystic fibrosis patients receiving AV encoding CFTR (AdCFTR) . AdCFTR was administered to three cohorts of two patients into the nose on day 0, at doses ranging from 105 to 4 x 108 plaque-forming units (pfu), followed, on day 1, by aerosolization of 107 to 5.4 x 108 pfu . In order to ensure that patients were in the best clinical condition, and to further attenuate the broncho-pulmonary inflammation secondary to bacterial infection, they received antibiotic therapy, two weeks prior to AdCFTR administration, until 9 to 11 days after . We found that antibiotics markedly decreased CRP, TNF-alpha, IL-6, IL-1Ra levels in blood . In BALF, antibiotics slightly decreased TNF-alpha levels but had no effect on IL-8 and IL-1Ra, while IL-6 levels increased . AdCFTR administration did not induce any systemic or local cytokine release . In both blood and BALF, CRP, IL-8, IL-1Ra, TNF-alpha decreased, while IL-6 levels increased between day -7 and day 3 . One patient presented an asymptomatic increase of all parameters in the BALF on day 7 . Twenty one days later, he displayed a clinical deterioration suggestive of an exacerbation . In conclusion, this study demonstrates that antibiotic administration tends to attenuate systemic but not local broncho-pulmonary inflammation in CF patients . In the setting of our study, AdCFTR administration did not induce cytokine release . Further studies are necessary to investigate other inflammatory markers and the mechanisms involved during AV-mediated gene transfer for a better understanding of the immune reaction, which continues to hamper the development of gene therapy for CF patients.

Eur J Biochem, 2002 Sep, 269(18), 4533 - 41
Solution NMR structure of five representative glycosylated polyene macrolide antibiotics with a sterol-dependent antifungal activity; Volpon L et al.; Glycosylated polyene macrolide antibiotics, as nystatins and amphotericins, are amphiphilic structures known to exert antifungal activity by disrupting the fungal cell membrane, leading to leakage of cellular materials, and cell death . This membrane disruption is strongly influenced by the presence and the exact nature of the membrane sterols . The solution structures of five representative glycosylated members, three tetraenes (pimaricin, nystatin A1 and rimocidin) and two heptaenes (candidin and vacidin A) have been calculated using geometric restraints derived from 1H-NMR data and random searches of their conformational space . Despite a different apparent structural order, the NMR solutions structure indicate that the hydroxyl groups all clustered on one side of the rod-shaped structures, and the glycosyl moieties are structurally conserved both in their conformation and their apparent order . The molecular structures afford an understanding of their selective interaction with the membrane sterols and the design of new polyene macrolides with improved activities.

Chest, 2002 Sep, 122(3), 913 - 9
An intervention to improve antibiotic delivery and sputum procurement in patients hospitalized with community-acquired pneumonia; Lawrence SJ et al.; STUDY OBJECTIVES: To determine if an educational intervention targeting emergency department (ED) and medicine staff could successfully decrease the time to antibiotic delivery (door-to-drug delivery time {DDD}) for patients admitted through the ED with community-acquired pneumonia (CAP) . DESIGN: Prospective, multidisciplinary team-based educational project . Demographics, outcomes, and processes of care including DDD and sputum procurement for patients with CAP were determined during a baseline period and compared to the same parameters for patients with CAP presenting after the educational intervention was administered to ED and medicine staff . SETTING: Barnes-Jewish Hospital, a large Midwest teaching institution affiliated with the Washington University School of Medicine . PATIENTS: Consecutive adult patients admitted through the ED with CAP . INTERVENTION: Multidisciplinary in-service education administered to ED physicians and nurses, and medicine housestaff, which emphasized the importance of rapid antibiotic delivery and procurement of preantibiotic expectorated sputum . RESULTS: Mean DDD improved from 413 to 291 min (p = 0.02), with more patients receiving antibiotics in the ED (46% vs 69%; adjusted odds ratio {OR}, 2.3; 95% confidence interval {CI}, 1.0 to 4.9) . Sputum procurement improved from 11.5 to 25.4% (adjusted OR, 3.3; 95% CI, 1.1 to 9.9) . There were no observed differences for inpatient mortality or length of stay . CONCLUSION: This multidisciplinary team intervention significantly improved the time to initiation of antibiotics and procurement of sputum for patients with CAP.

Trop Med Int Health, 2002 Sep, 7(9), 803 - 10
Private pharmacies in Hanoi, Vietnam: a randomized trial of a 2-year multi-component intervention on knowledge and stated practice regarding ARI, STD and antibiotic/steroid requests; Chalker J et al.; OBJECTIVES: To assess the effectiveness of a multi-component intervention on knowledge and reported practice amongst staff working in private pharmacies in Hanoi regarding four conditions: urethral discharge {sexually transmitted diseases (STD)}, acute respiratory infection (ARI), and non-prescription requests for antibiotics and steroids . METHOD: Randomized controlled trial with staff working in 22 matched pair intervention and control private pharmacies who were administered a semistructured questionnaire on the four conditions before and 4 months after the interventions . The interventions focused on the four conditions and were in sequence (i) regulations enforcement; (ii) face-to-face education and (iii) peer influence . Outcome measures were knowledge and reported change in practice for correct management of tracer conditions . RESULTS: The intervention/control-pairs (22 after drop-outs) were analysed pre- and post-intervention using the Wilcoxon signed rank test . STD: More drug sellers stated they would ask about the health of the partner (P = 0.03) and more said they would advise condom use (P = 0.01) and partner notification (P = 0.04) . ARI: More drug sellers stated they would ask questions regarding fever (P = 0.01), fewer would give antibiotics (P = 0.02) and more would give traditional medicines (P = 0.03) . Antibiotics request: Fewer said they would sell a few capsules of cefalexin without a prescription (P = 0.02) . Steroid requests: No statistical difference was seen in the numbers who said they would sell steroids without a prescription as numbers declined in both intervention and control groups (P = 0.12) . CONCLUSION: The three interventions in series over 17 months were effective in changing the knowledge and reported practice of drug sellers in Hanoi.

Drugs Exp Clin Res, 2002, 28(2-3), 99 - 104
A multiple-antibiotic resistance-independent active chloramphenicol efflux in an Escherichia coli clinical isolate; Bellaaj A et al.; The clinical isolate, Escherichia coli 1941, exhibits high resistance to chloramphenicol and tetracycline (minimum inhibitory concentrations of 512 micrograms/ml) . Neither resistance is linked to the large conjugative plasmid present in the strain . The intracellular accumulation of radiolabeled chloramphenicol increased about 9-fold after the addition of the energy uncoupler carbonyl cyanide m-chlorophenol-hydrazone to an E . coli 1941 culture, indicating the presence of an active efflux mechanism . Sequence analysis and expression study suggested that the multiple-antibiotic resistance marRAB locus and the AcrAB drug-efflux pump were not involved in this active efflux of chloramphenicol.

Biochem Biophys Res Commun, 2002 Sep 13, 297(1), 71 - 7
Aminoglycoside antibiotics induce pH-sensitive activation of the calcium-sensing receptor; McLarnon S et al.; The aminoglycoside antibiotic (AGA) neomycin is a known agonist of the extracellular calcium-sensing receptor (CaR) . To test whether other AGA drugs stimulate the CaR, we studied the relative effects of four AGAs on intracellular Ca(2+) concentration ({Ca(2+)}(i)) using CaR-transfected human embryonic kidney (HEK)-293 cells . Gentamicin, tobramycin, and neomycin evoked dose-dependent increases in {Ca(2+)}(i) with EC(50) values of 258, 177, and 43 microM, respectively, in CaR-transfected, but not in non-transfected cells . Kanamycin was ineffective at doses <1mM . Thus, AGAs stimulate the CaR with a rank order of potency that correlates positively with the number of their attached amino groups . The CaR is expressed on the apical surface of renal proximal tubule cells, which is also the site of AGA endocytosis and nephrotoxicity . In the current study, reducing extracellular pH from 7.4 to 6.9, to mimic the luminal pH of the proximal tubule, enhanced the sensitivity of the CaR to tobramycin, suggesting that the AGAs may be more potent CaR agonists in the proximal tubule than elsewhere . This pH effect was not observed when stimulating CaR with the non-ionizable agonist, Gd(3+), suggesting that the enhanced AGA effect is due to increased ionization of the drug . Thus, we show that a number of AGA drugs are capable of CaR activation and that their potency most likely relates to the number of their amino side chains and to their pH-dependent charge characteristics . The contribution of CaR activation to the pharmacological/toxicological effects of these AGAs remains to be determined.

Lakartidningen, 2002 Aug 8, 99(32-33), 3211 - 3
{Every tenth hospitalized patient is given antibiotics for a nosocomial infection}; Struwe J et al.; In a point-prevalence survey at Huddinge University Hospital, Sweden, 237/723 (33%) of patients admitted to non-psychiatric units received antibiotics . Among these, 181 received treatment for an infection and 56 as prophylaxis . We found that 11% of all patients were treated with antibiotics for a nosocomial infection and that an additional 8% received antibiotics as prophylaxis for nosocomial infections . The high rate of infections emphasizes the importance of integrating surveillance of nosocomial infections into the quality system.

J Biol Chem, 2002 Nov 8, 277(45), 43352 - 8 Epub 2002 Sep 05.
Structural basis for the inhibition of the biosynthesis of biotin by the antibiotic amiclenomycin; Sandmark J et al.; The antibiotic amiclenomycin blocks the biosynthesis of biotin by inhibiting the pyridoxal-phosphate-dependent enzyme diaminopelargonic acid synthase . Inactivation of the enzyme is stereoselective, i.e . the cis isomer of amiclenomycin is a potent inhibitor, whereas the trans isomer is much less reactive . The crystal structure of the complex of the holoenzyme and amiclenomycin at 1.8 A resolution reveals that the internal aldimine linkage between the cofactor and the side chain of the catalytic residue Lys-274 is broken . Instead, a covalent bond is formed between the 4-amino nitrogen of amiclenomycin and the C4' carbon atom of pyridoxal-phosphate . The electron density for the bound inhibitor suggests that aromatization of the cyclohexadiene ring has occurred upon formation of the covalent adduct . This process could be initiated by proton abstraction at the C4 carbon atom of the cyclohexadiene ring, possibly by the proximal side chain of Lys-274, leading to the tautomer Schiff base followed by the removal of the second allylic hydrogen . The carboxyl tail of the amiclenomycin moiety forms a salt link to the conserved residue Arg-391 in the substrate-binding site . Modeling suggests steric hindrance at the active site as the determinant of the weak inhibiting potency of the trans isomer.

Rev Esp Salud Publica, 2002 Jul-Aug, 76(4), 293 - 300
{The influence of population structure on systemic antibiotic consumption . Valladolid, Spain}; Enrique PG et al.; BACKGROUND: The high degree to which systemic antibiotics are consumed in our country makes a study of those factors determining the spread thereof necessary . Different parameters are involved in the unequal spread of their consumption, including: a) the epidemiology of the infectious processes b) the population-dependent factors and c) factors depending upon the prescribing physicians . This study is aimed at analyzing those determining factors depending upon the population (type of population and age) . METHODS: A longitudinal retrospective study based on systemic antibiotic consumption data provided by the company International Marketing Services (IMS) for the January 1, 1996-December 31, 2000 period . The consumption indicator used was the number of daily doses defined per 1000 inhabitants/day (DID) . Six geographical areas in the province of Valladolid were placed under study, three of which were urban and the other three mainly rural . RESULTS: The overall consumption by area was as follows: Medina del Campo (25.9DID), the capital city of Valladolid (23.4DID), Laguna de Duero (22.6DID), Northern Area (22.4DID), Southern Area (21.4DID) and, lastly, the Central Area (20.2DID) . The specific consumption by areas revealed a greater consumption of amoxicillin in the three urban areas, amoxicillin-clavulanic acid and the major macrolides in Medina del Campo, quinolone antibiotics in the Northern Area and tetracyclines and sulfonamides in the capital city of Valladolid . CONCLUSIONS: Major overall consumption-related differences were found to exist among areas, the maximums being found in the urban areas . These differences were more marked on when studying the geographic spread of the consumption of the main active ingredients.

J Arthroplasty, 2002 Sep, 17(6), 785 - 7
A simple method for construction of an articulating antibiotic-loaded cement spacer; Shin SS et al.; A 2-stage exchange protocol has been used widely in North America for management of infected total hip arthroplasties . Many surgeons choose to use an antibiotic-loaded cement spacer in the interval before reimplantation of the final prosthesis . We propose a simple technique for the construction of an articulating antibiotic-loaded spacer for use as part of 2-stage exchange protocol for the treatment of infected total hip arthroplasties .

Hist Philos Life Sci, 2001, 23(1), 137 - 50
The discovery of Gramicidin S: the intellectual transformation of G.F . Gause from biologist to researcher of antibiotics and on its meaning for the fate of Russian genetics; Gall YM et al.; The discovery of Gramicidin S is considered to be the outcome of the intellectual transformation of Russian biologist G.F . Gause from simply a biologist to a researcher of antibiotics . Different historical conditions of this change as well as the development of experimental biology itself at this time are analysed in detail . The meaning of Gause's occupation of a new 'niche' in soviet science for the fate of Russian post-war genetics is defined as well.

J Biomed Mater Res, 2002 Dec 5, 62(3), 378 - 86
Calcium phosphate/chitosan composite scaffolds for controlled in vitro antibiotic drug release; Zhang Y et al.; Macroporous chitosan scaffolds reinforced by beta-tricalcium phosphate (beta-TCP) and calcium phosphate invert glasses were fabricated using a thermally induced phase separation technique . These porous composite materials were specially designed as both a drug carrier for controlled drug release and a scaffold for bone regeneration . The controlled drug release of antibiotic gentamicin-sulfate (GS) loaded scaffolds and morphology of osteosarcoma MG63 cells cultured on the scaffolds were studied . In comparison with the GS loaded pure chitosan scaffolds, the initial burst release of GS was decreased through incorporating calcium phosphate crystals and glasses into the scaffolds, and the sustained release for more than 3 weeks was achieved . The possible mechanisms for the controlled drug release were investigated by SEM, FTIR, and measurements of the pH values of the PBS solution during the drug release test . SEM micrographs showed no apparent morphological differences for osteoblastic cells grown on the pure chitosan scaffolds and those grown on composite scaffolds . The cells were attached and migrated on these scaffolds, and exhibited a biological appearance, suggesting a good cellular compatibility .

Eur J Med Chem, 2002 Jun, 37(6), 443 - 60
Physicochemical properties of quinolone antibiotics in various environments; Park HR et al.; The progress and photosensitivity of quinolone antibiotics are briefly described . By the photolysis of nalidixic acid, the loss of -COOH group is observed . The photoreaction of fluoroquinolones involves heterolytic C-F bond fragmentation . The protonation and divalent cation complexation equilibria are also examined . The spectroscopic properties of these drugs are intensively investigated in biological mimetic systems such as AOT reverse micelle, and H(2)O-CH(3)OH and H(2)O-CH(3)CN mixed solvents . For ofloxacin and norfloxacin, the excited-state intramolecular charge transfer (ICT) is observed . So, fluorescence spectra exhibit reverse solvatochromism in mixed solvents . The change of radiative and non-radiative rate constant can also be explained using this ICT . The influence of dielectric effects of solvent is more significant compared with the specific hydrogen bonding interaction . Theoretical treatments support all of these results.

Cent Afr J Med, 2001 Jun, 47(6), 150 - 5
Antibiotic use in infants hospitalised with HIV-related pneumonia in Harare, Zimbabwe; Chitsike I; OBJECTIVE: To describe the clinical features of infants admitted with HIV-related pneumonia and to describe antibiotic use in relation to recommended treatment guidelines . DESIGN: Case series . SETTING: Paediatric medical wards of two University Teaching Hospitals, Parirenyatwa and Harare Central Hospitals . SUBJECTS: 100 infants aged one to 12 months admitted with HIV-related pneumonia . MAIN OUTCOME MEASURES: Mortality and antibiotic use in the two hospitals . METHODS: Records of 100 infants admitted for 48 hours or more with features of HIV-related pneumonia were analysed for clinical features and antibiotic use . RESULTS: 77% of patients were in the first six months of life with a peak age of two months and a median of four months (Q1 = 2, Q3 = 6) . The median age of children admitted to Parirenyatwa hospital was 5.5 months (Q1 = 3, Q3 = 7) and in Harare hospital it was three months (Q1 = 2, Q3 = 6) . The difference was statistically significant, p = 0.035 . Fifty four percent of cases received penicillin, aminoglycoside and cotrimoxazole and overall only 30% of prescriptions complied with Essential Drug List of Zimbabwe (EDLIZ) recommendations for treatment of severe pneumonia in children with HIV infection . The overall mortality was 27.0% . The mortality in Harare Central Hospital was 40.4% and 15.7% in Parirenyatwa . The difference was statistically significant p = 0.005 . CONCLUSION: The difficulties in establishing the cause of the pneumonia in infants with HIV infection was a contributory factor to lack of adherence to standard treatment guidelines . In countries with a high prevalence of HIV infection and with limited resources, a clinical case definition for Pneumocystis carinii pneumonia (PCP) is required as a measure to provide treatment for infants with HIV related pneumonia which is evidence based . This approach will also promote rational antibiotic prescribing and will contain cost.

J Periodontal Res, 2002 Aug, 37(4), 250 - 4
Quantitative comparison of the cytocidal effect of seven macrolide antibiotics on human periodontal ligament fibroblasts; Maizumi N et al.; The cytocidal effect of seven macrolide antibiotics on human periodontal ligament fibroblasts (Pel cells) was studied . Pel cells were exposed for 48 h to erythromycin (EM), clarithromycin (CAM), roxithromycin (RXM), azithromycin (AZM), josamycin (JM), midecamycin (MDM), and rokitamycin (RKM), and allowed to form colonies . The cytocidal effect of the macrolides was measured as a decrease in colony-forming efficiency and was found to increase with the concentration . To obtain a quantitative measure of the cytocidal effect, the LD50, i.e . the concentration that decreases colony-forming efficiency 50% relative to control cells, was extrapolated from the concentration-response curves . The rank of the macrolides according to their cytocidal effect (LD50) was RKM > RXM > CAM > AZM > JM > MDM approximately EM . RKM, RXM, CAM, AZM, and JM were at least 1.7-12.2 times more cytocidal than MDM or EM . When extrapolated from the concentration-response curves, the relative survival of the Pel cells exposed to each of the macrolides at the MIC90 concentrations for periodontopathic bacteria was estimated to be: > or = 53.8% for RKM, > or = 92.7% for RXM, > or = 94.6% for CAM, > or = 97.1% for AZM, and > or = 86.2% for EM . The effect of the antibiotics on the mRNA expression of alkaline phosphatase (ALP) and type I procollagen (COL) was examined in Pel cells exposed for 48 h to RXM, CAM, AZM, and EM, which exhibited strong, moderate, and weak cytocidal activity . The constitutive levels of both ALP and COL mRNA were retained in cells exposed to RXM at < or = 3 microM, CAM at < or = 10 microM, and AZM or EM at < or = 3 microM . The MIC90 against periodontopathic bacteria is < or = 4.8 microM for RXM, 5.3 microM for CAM, 2.7 microM for AZM, and 21.8 microM for EM . These results suggest that topical administration of CAM or AZM to the gingival crevice at their MIC90 concentration for periodontopathic bacteria would have little adverse effect on the growth and differentiation of the periodontal ligament . It is important to note, however, that these findings have yet to be extrapolated to in vivo conditions.

Acta Paediatr Suppl, 2002, 91(437), 12 - 5
ORACLE--antibiotics for preterm prelabour rupture of the membranes: short-term and long-term outcomes; Kenyon S et al.; Preterm prelabour rupture of the foetal membranes (pPROM) is the most common antecedent of preterm birth and can lead to death, neonatal disease and long-term disability . Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate, but the results were inconclusive . A large, randomized, multicentre trial was undertaken to try to resolve this issue . In total, 4826 women with pPROM were randomized to one of four treatments: 325 mg co-amoxiclav plus 250 mg erythromycin, co-amoxiclav plus erythromycin placebo, erythromycin plus co-amoxiclav placebo, or co-amoxiclav placebo plus erythromycin placebo, four times daily for 10 d or until delivery . The primary outcome measure was a composite of neonatal death, chronic lung disease or major cerebral abnormality on ultrasonography before discharge from hospital . The analysis was undertaken by intention to treat . Indications of short-term respiratory function, chronic lung disease and major neonatal cerebral abnormality were reduced with the prescription of erythromycin . In contrast, the use of co-amoxiclav was associated with a significant increase in the occurrence of neonatal necrotizing enterocolitis . CONCLUSION: Prophylactic antibiotics can play a role in preterm prelabour rupture of the membranes in reducing infant morbidity.

Appl Environ Microbiol, 2002 Sep, 68(9), 4240 - 6
A stationary-phase acyl-coenzyme A synthetase of Streptomyces coelicolor A3(2) is necessary for the normal onset of antibiotic production; Banchio C et al.; The fadD1 and macs1 genes of Streptomyces coelicolor are part of a two-gene operon . Both genes encode putative acyl coenzyme A synthetases (ACSs) . The amino acid sequence of FadD1 has high homology with those of several ACSs, while MACS1 has the closest homology with medium-chain ACSs, broadly known as SA proteins . Like FadD of Escherichia coli, FadD1 also has a broad substrate specificity, although saturated long-chain fatty acids appears to be the preferred substrate . fadD1 is a growth-phase-regulated gene, and its mRNA is detected only during the stationary phase of growth . Interestingly, a mutation in fadD1 alters the levels of another ACS or ACSs, both at the stationary phase and at the exponential phase of growth, at least when glucose is used as a main carbon source . The mutant also shows a severe deficiency in antibiotic production, and at least for Act biosynthesis, this deficiency seems to be related to delayed expression of the Act biosynthetic genes . Antibiotic production is restored by the introduction of a wt fadD1 allele into the cell, demonstrating a strict link between ACS activity and the biosynthesis of secondary metabolites . The results of this study indicate that the ACSs may be useful targets for the design of rational approaches to improving antibiotic production.

Bioorg Khim, 2002 Jul-Aug, 28(4), 379 - 84
{1H-NMR analysis of self association of an antibiotic actinocyl-bis(3-dimethylaminopropylamine) in water solutions}; Veselkov DA et al.; The self-association of the synthetic antibiotic actinocyl-bis(3-dimethylaminopropylamine) was studied in aqueous solution by one- and two-dimensional 1H NMR spectroscopy at 500 MHz . The two-dimensional homonuclear correlation NMR techniques (TOCSY and ROESY) were used to completely assign all the proton signals of the antibiotic and to quantitatively analyze the mutual arrangement of the antibiotic molecules in their aggregates . The concentration and temperature dependences of proton chemical shifts were used to determine the equilibrium constants and the thermodynamic parameters (delta H and delta S) of the self-association, as well as the limiting values of proton chemical shifts in associates . The experimental results were analyzed using both the indefinite noncooperative and cooperative models of the molecular self-association . The calculated value of the cooperativity coefficient (sigma approximately 1.1) for our synthetic antibiotic confirmed a substantially lower anticooperative effect at the aggregation of its molecules in comparison with that of the antitumor antibiotic actinomycin D (sigma approximately 1.5) . We calculated the most favorable structure of the dimeric associate of the synthetic antibiotic in aqueous solution and found that, like in the actinomycin D dimer, the antiparallel orientation of the phenoxazone chromophore planes of interacting molecules is characteristic of its dimer . The English version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol . 28, no . 4; see also http://www.maik.ru.

Chem Commun (Camb), 2002 Aug 21, (16), 1760 - 1
Biosynthesis inspired Diels-Alder route to pyridines: synthesis of the 2,3-dithiazolylpyridine core of the thiopeptide antibiotics; Moody CJ et al.; Reaction of serine derived 1-alkoxy-2-azadienes with dehydroalanine derived dienophiles results in Diels-Alder reaction and aromatisation to give 2,3,6-trisubstituted pyridines, thereby establishing the viability of the proposed biosynthetic route to the pyridine ring of the thiopeptide antibiotics originally proposed by Bycroft and Gowland.

J Antibiot (Tokyo), 2002 Jun, 55(6), 571 - 7
Arylomycins A and B, new biaryl-bridged lipopeptide antibiotics produced by Streptomyces sp . Tü 6075 . II . Structure elucidation; Holtzel A et al.; The structures of new lipopeptide antibiotics, arylomycins A and B, were elucidated by a combination of ESI-FTICR-mass spectrometry, NMR spectroscopy, Edman sequencing, and fatty acid and chiral amino acid analyses . The colourless arylomycins A share the peptide sequence of D-N-methylseryl2(D-MeSer2)-D-alanyl3-glycyl4-N-methyl- 4-hydroxyphenylglycyl5(MeHpg5)-L-alanyl6-tyrosine7 cyclised by a {3,3}biaryl bond between MeHpg5 and Tyr7 . The yellow arylomycins B differ from arylomycins A by nitro substitution of Tyr7 . The N-termini of arylomycins A and B are acylated with saturated C11-C15 fatty acids (fa1) comprising n, iso, and anteiso isomers . Arylomycins A and B represent the first examples of biaryl-bridged lipopeptides.

Scand J Infect Dis, 2002, 34(7), 512 - 9
Antibiotics differ in their tendency to cause infusion phlebitis: a prospective observational study; Lanbeck P et al.; Intravenous administration of antibiotics is a known risk factor for infusion phlebitis . We have previously demonstrated differences in cell toxicity for 4 antibiotics . Clinical experience indicates that antibiotics differ in their tendency to cause phlebitis . The present study was done prospectively on 550 patients with 1386 peripheral venous catheters . The incidence of phlebitis was 18.5% with antibiotics and 8.8% without (odds ratio 2.34) . Dicloxacillin (odds ratio 5.74) and erythromycin (odds ratio 5.33) had the greatest tendency to cause phlebitis in univariate, multivariate and Cox regression analyses . Benzylpenicillin, cefuroxime and cloxacillin were also associated with a greater risk of phlebitis, whereas ampicillin, imipenem/cilastatin, clindamycin, netilmicin and vancomycin were not . Other risk factors were the site of insertion and age 51-60 y . Medication with warfarin was found to be protective, but not with aspirin . Treatment with low molecular weight heparin reduced the risk of phlebitis, but the difference was not significant . With regard to when antibiotics were given, the day-specific risk increased between Days 1 and 2, but no further on subsequent days . The hypothesis that antibiotics differ in their tendency to cause phlebitis was confirmed.

J Pharm Pharmacol, 2002 Aug, 54(8), 1019 - 31
RNA-acting antibiotics: in-vitro selection of RNA aptamers for the design of new bioactive molecules less susceptible to bacterial resistance; Maurel MC et al.; During the last few years, antibiotic multiresistance has been increasing, not only in hospitals, but also, more worryingly, in general medicine . Different ways are being explored to bypass this problem . RNA-acting antibiotics such as aminosides (aminoglycosides) bind to bacterial RNA causing premature termination of proteins and mistranslation in bacteria . It is now possible to study the interactions of such antibiotics with their target by in-vitro selection of RNA molecules that recognize these antibiotics (RNA aptamers, SELEX method) . The knowledge of the antibiotic-RNA interactions represents a promising way for the rational design of new bioactive compounds less susceptible to bacterial resistance.

Redox Rep, 2002, 7(2), 85 - 94
Oxygen consumption and electron spin resonance studies of free radical production by alveolar cells exposed to anoxia: inhibiting effects of the antibiotic ceftazidime; Mouithys-Mickalad A et al.; By EPR spectroscopy, we investigated free radical production by cultured human alveolar cells subjected to anoxia/re-oxygenation (A/R), and tested the effects of ceftazidime, an antibiotic previously demonstrated to possess antioxidant properties . Two A/R models were performed on type II pneumocytes (A549 cell line), either on cells attached to culture dishes (monolayer A/R model; 3.5 h of anoxia, 30 min of re-oxygenation) or after cell detachment (suspension A/R model; 1 h of anoxia, 10 min of re-oxygenation) . Ceftazidime and selective inhibitors (SOD, Tiron, L-NMMA) were added before anoxia . Free radical production was assessed by the EPR spin trapping technique . Oxygen consumption was monitored, in parallel with EPR studies, in the suspension A/R model . The production of free radical species was demonstrated by the generation of PBN-radical adducts: (a(N) = 15.2 G) in the monolayer A/R model and a six-line EPR spectrum (a(N) = 15.7 G and a(H) = 2.7 G) in the suspension A/R model . A kinetic study performed by oximetry, in parallel with EPR spectroscopy, demonstrated marked alterations of the cell respiratory function and that the free radical production started during anoxia and increased during re-oxygenation . In the suspension A/R model, the amplitude of EPR spectra were decreased upon the addition of 200 U/ml SOD (37% inhibition), 0.1 mM Tiron (67% inhibition) and 1 mM L-NMMA (43% inhibition) . Addition of 1 mM ceftazidime decreased the amplitude of EPR spectra (37% inhibition) in both A/R models . Complementary in vitro EPR studies demonstrated that CAZ scavenged the hydroxyl radical (produced by the Fenton reaction) . The protective effect of ceftazidime in the cell model could thus be linked to its ability to scavenge superoxide anions, nitrogen-derived species and hydroxyl radicals.

Science, 2002 Aug 16, 297(5584), 1170 - 3
Biosynthesis of the enediyne antitumor antibiotic C-1027; Liu W et al.; C-1027 is a potent antitumor agent with a previously undescribed molecular architecture and mode of action . Cloning and characterization of the 85-kilobase C-1027 biosynthesis gene cluster from Streptomyces globisporus revealed (i) an iterative type I polyketide synthase that is distinct from any bacterial polyketide synthases known to date, (ii) a general polyketide pathway for the biosynthesis of both the 9- and 10-membered enediyne antibiotics, and (iii) a convergent biosynthetic strategy for the C-1027 chromophore from four building blocks . Manipulation of genes governing C-1027 biosynthesis allowed us to produce an enediyne compound in a predicted manner.

Antimicrob Agents Chemother, 2002 Sep, 46(9), 3065 - 7
Antibiotic susceptibilities of Parachlamydia acanthamoeba in amoebae; Maurin M et al.; Parachlamydia acanthamoeba are intracellular bacteria of amoebae and are considered potential etiological agents of human pneumonia . We have determined the in vitro antibiotic susceptibilities of two strains (strain Bn(9) and Hall's coccus) in Acanthamoeba polyphaga . The two strains were susceptible to tetracyclines, macrolides, and rifampin, but resistant to fluoroquinolones.

Antimicrob Agents Chemother, 2002 Sep, 46(9), 3026 - 30
Antibiotic pharmacodynamics in surgical prophylaxis: an association between intraoperative antibiotic concentrations and efficacy; Zelenitsky SA et al.; The objective of this study was to characterize the relationship between gentamicin concentrations during surgery and the development of wound infection following colorectal operations . Despite decades of research in surgical prophylaxis, the relationship between intraoperative antibiotic concentrations and postoperative infection and the concentrations required for effective prophylaxis have not been established . A pharmacodynamic analysis was conducted using data from a previous prospective, randomized, double-blind clinical study which compared two dosage regimens of gentamicin plus metronidazole for prophylaxis in connection with elective colorectal surgery . Univariate and multivariate analyses of risk factors for postoperative wound infection were conducted, and the relationship between intraoperative gentamicin concentrations and surgical outcome was characterized . The gentamicin concentration at the time of surgical closure was one of the strongest independent risk factors for infection (P = 0.02), along with the presence of diabetes mellitus (P = 0.02), stoma (P = 0.04), and advanced age (P = 0.05) . Gentamicin concentrations at closure of less than 0.5 mg/liter were associated with an infection rate of 80% (representing 8 of 10 patients with concentrations below that level) (P = 0.003) . Receiver operating characteristic curve analysis identified a critical closure concentration of 1.6 mg/liter for effective surgical prophylaxis (P = 0.002; sensitivity, 70.8%; specificity, 65.9%) . This study provides new and important information on antibiotic pharmacodynamics in surgical prophylaxis . It demonstrates the critical effect of the antibiotic concentration at closure on wound infection and suggests a significant association between the concentration and other well-established risk factors, like the timing of preoperative antibiotic administration and surgery duration.

Antimicrob Agents Chemother, 2002 Sep, 46(9), 2747 - 51
Evaluation of antibiotic susceptibilities of three rickettsial species including Rickettsia felis by a quantitative PCR DNA assay; Rolain JM et al.; Rickettsiae grow only intracellularly, and the antibiotic susceptibilities of these bacteria have been assessed by either plaque, dye uptake, or immunofluorescence assays, which are time-consuming . We used a quantitative PCR (with the LightCycler instrument) to assess the levels of inhibition of Rickettisa felis, R . conorii, and R . typhi DNA synthesis in the presence of various antibiotics . We established the kinetics of rickettsial DNA during growth and showed that R . conorii grows more quickly than R . typhi in cell culture, with maximum replication occurring after 5 and 7 days, respectively . The MICs of the antibiotics tested for R . conorii and R . typhi by the quantitative PCR assay were similar to those previously obtained by plaque and dye uptake assays . We found that R . felis is susceptible to doxycycline, rifampin, thiamphenicol, and fluoroquinolones but not to gentamicin, erythromycin, amoxicillin, or trimethoprim-sulfamethoxazole . The resistance of this new species to erythromycin is consistent with its current taxonomic position within the spotted fever group . We believe that quantitative PCR could be used in the future to simplify and shorten antibiotic susceptibility assays of other rickettsiae and other strict intracellular pathogens.

Lung, 2002, 180(2), 73 - 89
Inhibitory effects of 14-membered ring macrolide antibiotics on bleomycin-induced acute lung injury; Kawashima M et al.; 14-membered ring macrolides have been reported to have anti-inflammatory effects and to decrease neutrophil infiltration into the airways in chronic lower respiratory tract diseases . This study investigated the potential inhibitory effects of macrolide antibiotics on bleomycin-induced acute lung injury . Four drugs were studied: two 14-membered ring macrolides, clarithromycin (CAM) and roxithromycin (RXM); a 15-membered ring macrolide, azithromycin (AZM); and a 16-membered ring macrolide, josamycin (JM) . Their effects were compared with macrolide untreated, pretreated, and post-treated groups . An acute lung injury was inhibited by pretreatment with CAM or RXM, which significantly ameliorated the bleomycin-induced increases in the total cell and neutrophil counts in bronchoalveolar lavage (BAL) fluids and the wet lung weight . The pretreatment with CAM or RXM also suppressed inflammatory cell infiltration and interstitial lung edema in the histopathological study . These inhibitory effects were associated with a decreased KC concentration in the BAL fluid and a decreased number of apoptotic cells in the lungs . Posttreatment with CAM or RXM had no marked inhibitory effects . Pretreatment with AZM was much less effective, and JM showed no inhibitory effects . These findings suggest that 14-membered ring macrolides have different effects on inflammatory lung disease than 15- and 16-membered ring macrolides and may be therapeutic agents for acute lung injury and pulmonary fibrosis.

J AOAC Int, 2002 Jul-Aug, 85(4), 853 - 60
Quantitative LC/MS-MS determination of sulfonamides and some other antibiotics in honey; Kaufmann A et al.; A simple and rapid method was developed for the determination of 20 antibiotics (sulfonamides, tetacyclines, and flumequine) in honey by liquid chromatography tandem mass spectrometry . The proposed method is sensitive (limit of detection 0.5 to 10 ppb for the various antibiotics) and selective . A hydrolysis step ensures the liberation of sugar-bound sulfonamides . The approach has been used to analyze some 300 honey samples . A number of them were found to have exceeded the Swiss limit of 50 ppb.

Am J Orthop, 2002 Jul, 31(7), 425 - 7
Technique for fabrication of an antibiotic-loaded cement hemiarthroplasty (ANTILOCH) prosthesis for infected total hip arthroplasty; Pearle AD et al.; In North America, staged reimplantation is the preferred treatment for infected total hip arthroplasty . A simple technique for implantation of an antibiotic-loaded cement spacer molded in the shape of a hemiarthroplasty prosthesis is described . A Teflon mold was cast in the shape of an Austin Moore hip hemiarthroplasty prosthesis . This mold allows for fabrication of a solid antibiotic-loaded cement spacer that accurately reproduces the shape of a hemiarthroplasty prosthesis . This technique allows for easy insertion, patient comfort, between-stage mobility, and local concentric delivery of antibiotic.

Br Dent J, 2002 Jul 13, 193(1), 46 - 9
General dental practitioners' experiences of a collaborative clinical audit on antibiotic prescribing: a qualitative study; Palmer NA et al.; OBJECTIVE: To evaluate general dental practitioners' experiences of a multi-collaborative antibiotic prescribing audit . DESIGN: Qualitative analysis of compulsory post-audit group report data collection forms and individual practitioners' post-audit evaluation forms . SUBJECTS: Information was collected from 175 general dental practitioners in the North West of England who participated in the audit . METHOD: The general dental practitioners were divided into groups of 8-10 to undertake the audit . Information from compulsory post-audit group reports was transcribed and analysed . The information was categorised into a number of areas including changes in practice, patients' expectations, training and quality of service . On completion of the audit individual practitioners were asked to complete an evaluation form on the audit process . RESULTS: 141 (80.5%) individual evaluation forms were returned . Over 90% of GDPs felt that the audit process was easily understood and the majority of the practitioners thought the audit was worthwhile . Approximately 69% of participants felt that the audit had helped to change their antibiotic prescribing practices . Analysis of the post-audit group report data collection forms revealed more than 100 statements . The most common areas were changes required in practice, patients' expectations, increased training and quality of service . CONCLUSION: The collaborative clinical audit project was seen to be a worthwhile learning experience by the participating general dental practitioners . The audit encouraged GDPs to change their antibiotic prescribing practices and thereby improve patient care . GDPs also highlighted the need for continuing education in the prescribing of antibiotics.

Clin Otolaryngol, 2002 Aug, 27(4), 260 - 2
Are topical antibiotics necessary in the management of otitis externa?
Tsikoudas A, Jasser P, England RJ.
Otitis externa is an inflammatory disorder of the skin of the outer ear canal frequently associated with bacterial or fungal infection . It is normally treated with aural toilet and topical preparations containing antibiotic/antifungal and steroid preparations . A group of 39 patients presenting with otitis externa were randomized in a double-blind manner into those receiving drops containing an aminoglycoside and steroid preparation and those receiving the same preparation without the aminoglycoside . All patients were reviewed on days 0, 3, 7 and 11 of a 14-day course of drops and their response to medication monitored . Patients documented their symptoms at each appointment and clinical response was also measured by a blinded observer . The study suggests that an aminoglycoside antibiotic conveys no significant benefit in this condition.

J Orthop Res, 2002 Jul, 20(4), 654 - 61
In vivo study of hot compressing molded 50:50 poly (DL-lactide-co-glycolide) antibiotic beads in rabbits; Ueng SW et al.; The authors investigated poly (DL-lactide-co-glycolide) beads as an antibiotic delivery system in vivo for the treatment of various surgical infections . In this study, the copolymer 50:50 poly (DL-lactide):co-glycolide was mixed with vancomycin powder and hot compressing molded at 55 degrees C to form 8 mm in diameter biodegradable antibiotic beads . The antibiotic beads were implanted in the distal femoral cavities of rabbits for in vivo investigation . The local concentration of vancomycin was well above the breakpoint sensitivity concentration (the antibiotic concentration at the transition point between bacterial killing and resistance to the antibiotic) for 56 days . The release was most marked during the first day . The diameters of the sample inhibition zone ranged from 8 to 18 mm, and the relative activity of vancomycin ranged from 9.1% to 100% . Only low systemic blood levels of vancomycin were measured after beads implantation . There was no increase in the concentration of blood urea nitrogen and serum creatinine after the implantation . Histological observations showed that the bead materials were biodegradable, resorbed slowly, and did not cause a significant host reaction . This study offers a biodegradable delivery system of antibiotics to treat various surgical infections.

J Arthroplasty, 2002 Aug, 17(5), 600 - 3
Rush pin technique for temporary antibiotic-impregnated cement prosthesis for infected total hip arthroplasty; Barrack RL; A technique is described for intraoperative fabrication of an antibiotic-impregnated temporary prosthesis using a rod pin as an endoskeleton . The technique has the advantage of the availability of numerous rod lengths and diameters, which allows the surgeon to produce a custom component with a wide range of lengths and offsets . The technique has been used successfully in many cases over a 5-year period .

Nature, 2002 Aug 8, 418(6898), 658 - 61
Biomimetic synthesis and optimization of cyclic peptide antibiotics; Kohli RM et al.; Molecules in nature are often brought to a bioactive conformation by ring formation (macrocyclization) . A recurrent theme in the enzymatic synthesis of macrocyclic compounds by non-ribosomal and polyketide synthetases is the tethering of activated linear intermediates through thioester linkages to carrier proteins, in a natural analogy to solid-phase synthesis . A terminal thioesterase domain of the synthetase catalyses release from the tether and cyclization . Here we show that an isolated thioesterase can catalyse the cyclization of linear peptides immobilized on a solid-phase support modified with a biomimetic linker, offering the possibility of merging natural-product biosynthesis with combinatorial solid-phase chemistry . Starting from the cyclic decapeptide antibiotic tyrocidine A, this chemoenzymatic approach allows us to diversify the linear peptide both to probe the enzymology of the macrocyclizing enzyme, TycC thioesterase, and to create a library of cyclic peptide antibiotic products . We have used this method to reveal natural-product analogues of potential therapeutic utility; these compounds have an increased preference for bacterial over eukaryotic membranes and an improved spectrum of activity against some common bacterial pathogens.

Farmaco, 2002 Jul, 57(7), 513 - 29
Optimization strategies for HPLC enantioseparation of racemic drugs using polysaccharides and macrocyclic glycopeptide antibiotic chiral stationary phases; Aboul-Enein HY et al.; The chiral resolution by high performance liquid chromatography (HPLC) is controlled by a number of parameters . The optimization of HPLC parameters is an important issue in chiral resolution . This review discusses the optimization of HPLC conditions for the chiral resolution of racemic drugs on polysaccharides and macrocyclic glycopeptide antibiotic chiral stationary phases (CSPs) . The most important parameters discussed are composition of mobile phase, pH of mobile phase, flow rate, temperature and effect of other parameters.

Clin Rev Allergy Immunol, 2002 Aug, 23(1), 123 - 41
Antibiotic hypersensitivity in patients with CF; Ramesh S; Antibiotic hypersensitivity reactions are relatively common in patients with cystic fibrosis (CF) . The nature of the reactions and the mechanisms are no different in CF than the general population . Beta-lactam agents are the most common cause of these reactions . The risk depends on the specific beta-lactam agent used with Penicillins having a higher frequency of allergic reactions . There are several risk factors for developing these allergic responses, especially the increased usage . Since the available choices for antibiotic therapy is limited by the sensitivity of the organisms, management becomes a challenge . It is essential to classify the nature of the hypersensitivity reactions and determine the risks of repeat administration of the drug . Unfortunately, reliable skin tests are not available for all the antibiotics . RAST is of limited value . Recent data on cross-reactions between beta-lactam antibiotics and the option of newer agents offer useful alternative choices . Knowledge of the chemical structures of the antibiotics is useful for selecting suitable substitutes . Desensitization is a viable option in many of the reactions unless otherwise contradicted.

Arch Intern Med, 2002 Aug 12-26, 162(15), 1746 - 52
Sixty-three cases of Mycobacterium marinum infection: clinical features, treatment, and antibiotic susceptibility of causative isolates; Aubry A et al.; BACKGROUND: Mycobacterium marinum is a nontuberculous mycobacterium responsible for skin infections . Although cases have been seldom reported, no series of M marinum infection has been recently reported and the treatment is not standardized . METHODS: A national survey was conducted on culture-confirmed M marinum infections that occurred in France from January 1, 1996, to December 31, 1998 . Clinical characteristics and therapeutic data were analyzed, and the minimum inhibitory concentrations of 11 antibiotics were determined against the causative isolates . RESULTS: Sixty-three cases of M marinum infection were studied . In 53 (84%) of the patients, inoculation was related to fish tank exposure . The site of infection was mainly the upper limb (in 60 {95%} of the 63 patients), and infection was spread to deeper structures in 18 (29%) of the patients . All patients were treated with antibiotics (median time, 3(1/2) months), and 30 (48%) underwent surgery . Various antibiotic regimens were prescribed, and the initial regimen was modified in 22 (35%) of the patients . Clarithromycin, cyclines, and rifampin were the most commonly prescribed antibiotics . Cure was observed for 55 (87%) of the patients . Failure was related to deep structure involvement (3 of 45 vs 5 of 18 patients; P =.04) but not to any antibiotic regimen . All strains showed the same susceptibility pattern without acquired resistance . The 90% minimum inhibitory concentrations of rifampin and rifabutin were far lower (0.5 and 0.06 micro g/mL, respectively) than the 90% minimum inhibitory concentrations of clarithromycin (2 micro g/mL) and the cyclines (minocycline, 4 micro g/mL; and doxycycline, 8 micro g/mL) . CONCLUSIONS: Mycobacterium marinum infections are emerging infections related to fish tank hobby . Because of the severity of the cases with spread of infection, clinical awareness of M marinum infection and its associated risk factors is important so that the diagnosis can be made and therapy can be initiated promptly.

Bull Exp Biol Med, 2001 Dec, 132(6), 1163 - 5
Effects of antibiotics on reactive oxygen species generation by neutrophils; Abdrashitova NF et al.; Antibiotic therapy of patients with exacerbation of chronic obstructive bronchitis exposed and not exposed to ozone did not improve oxidative metabolism in neutrophils . Cefazolin, ceftizoxime, and gentamicin normalized functional biocidal reserves of neutrophils, which correlated with pronounced therapeutic effects.

Mol Cell, 2002 Jul, 10(1), 117 - 28
The structures of four macrolide antibiotics bound to the large ribosomal subunit; Hansen JL et al.; Crystal structures of the Haloarcula marismortui large ribosomal subunit complexed with the 16-membered macrolide antibiotics carbomycin A, spiramycin, and tylosin and a 15-membered macrolide, azithromycin, show that they bind in the polypeptide exit tunnel adjacent to the peptidyl transferase center . Their location suggests that they inhibit protein synthesis by blocking the egress of nascent polypeptides . The saccharide branch attached to C5 of the lactone rings extends toward the peptidyl transferase center, and the isobutyrate extension of the carbomycin A disaccharide overlaps the A-site . Unexpectedly, a reversible covalent bond forms between the ethylaldehyde substituent at the C6 position of the 16-membered macrolides and the N6 of A2103 (A2062, E . coli) . Mutations in 23S rRNA that result in clinical resistance render the binding site less complementary to macrolides.

Presse Med, 2002 May 25, 31(18), 838 - 40
{Hepatic inflammatory pseudotumor regressing with antibiotic therapy}; Casassus-Builhe D et al.; INTRODUCTION: Inflammatory hepatic pseudo-tumors are rare, non-neoplastic lesions, and their diagnosis is usually made on hepatectomy samples . OBSERVATION: The general health of a 77 year-old patient was suddenly altered and clinical examination (and scan) revealed a hepatic tumor . Diagnosis of inflammatory hepatic pseudo-tumor was evoked by analysis of a biopsy . In view of the age and the general state of the patient we chose prolonged antibiotic therapy rather than hepatic surgery . Nine months later, the tumor had regressed . COMMENTS: Because they are rare (100 cases described), hepatic pseudo-tumors raise two questions: can diagnosis be made simply by biopsy or should one always analyze the complete sample and, if hepatectomy is contraindicated, is non-surgical treatment effective? The progression of our patient permits us to reply positively to both questions.

Protein Pept Lett, 2002 Aug, 9(4), 275 - 82
CRAMP analog having potent antibiotic activity without hemolytic activity; Kang SW et al.; CRAMP-18 is an 18-residue functional region, corresponding to residues 16-33 of a mouse-derived antibiotic peptide CRAMP . To develop novel antibiotic peptides possessing strong antibiotic activity against bacterial, fungal and tumor cells without hemolytic activity, three analogs of CRAMP-18 were synthesized containing either Leu- or Lys-substitution . Leu-substitution ({L(1, 8)}-CRAMP-18) in the hydrophobic helix face of CRAMP-18 induced a dramatic increase in antibiotic activity without a significant increase in hemolytic activity . Lys-substitution ({K(2, 13)}-CRAMP-18 or {K(9, 16)}-CRAMP-18) in the hydrophilic helix face produced a smaller response . Therefore, {L(1, 8)}-CRAMP-18 may be an attractive candidate for developing novel peptide antibiotics.

Zh Mikrobiol Epidemiol Immunobiol, 2002 May-Jun, (3), 68 - 70
{Evaluation of the influence of deep geomagnetic impacting on growth rate and sensitivity to antibiotics in Escherichia coli}; Kolmakov VM et al.; The short-term (1-7 days) and prolonged (30-90 days) adaptation of bacteria to hypomagnetic conditions was studied by observing changes in growth rate and resistance to antibiotics in E . coli used as an experimental model . The decrease of the growth rate of bacterial cells in the exponential phase was found to occur . The effect disappeared when the screened culture was placed under normal geomagnetic conditions for 1 hour daily . After prolonged screening an increase in the resistance of these bacteria to kanamycin and carbenicillin was registered . These changes were not hereditary: after the cessation of screening the sensitivity of the bacteria to antibiotics was restored.

Cochrane Database Syst Rev . 2002;(3):CD003427.
Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease; Riddington C et al.; BACKGROUND: People with sickle cell disease are particularly susceptible to infection . Infants and very young children are especially vulnerable, and the Cooperative Study of Sickle Cell Disease observed an incidence rate of 10 per 100 patient years of pneumococcal septicaemia in children under the age of three . Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group . Therefore, prophylactic penicillin regimes may be advisable for this population . OBJECTIVES: To assess the effects of prophylactic antibiotic regimes for preventing pneumococcal infection in children with sickle cell disease . SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, hand searching relevant journals and hand searching abstract books of conference proceedings . Date of the most recent search: December 2001 . SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with sickle cell disease with placebo, no treatment or a comparator drug . DATA COLLECTION AND ANALYSIS: Both reviewers independently extracted data and assessed trial quality . MAIN RESULTS: Five trials were identified by the initial search, of which three trials met the inclusion criteria . All of the included trials showed a reduced risk of infection in children with sickle cell disease (SS or Sb0Thal) receiving prophylactic penicillin . For initiation of treatment the odds ratio was 0.37 (95% CI 0.16, 0.86), and for withdrawal OR= 0.49 (95% CI 0.09, 2.71) . Adverse drug effects were rare and minor . Rates of pneumococcal infection were found to be relatively low in children over the age of five . REVIEWER'S CONCLUSIONS: Prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous sickle cell disease, and is associated with minimal adverse reactions . Further research may help to determine the ideal age to safely withdraw penicillin.

FEBS Lett, 2002 Jul 31, 524(1-3), 92 - 6
Polyene antibiotic amphotericin B in monomolecular layers: spectrophotometric and scanning force microscopic analysis; Gruszecki WI et al.; Monolayers of amphotericin B (AmB) and monolayers composed of AmB and dipalmitoylphosphatidylcholine (DPPC) were formed at the argon-water interface and deposited on a solid support by means of the Langmuir-Blodgett technique . The hypsochromic shift observed in the absorption spectra of monolayers is indicative of aggregated structures of AmB . The exciton splitting theory allowed us to calculate the distance between neighboring molecules in the aggregates as 7.8 A . Scanning force microscopy of the AmB monolayers revealed the formation of a homogeneous monolayer composed of molecules separated by a distance of 6-8 A . Microscopy also reveals the formation of cylindrical structures of AmB with a diameter close to 17 A (internal diameter close to 6 A) in the monolayers containing additionally 10 mol% DPPC.

Boll Chim Farm, 2002 Mar-Apr, 141(2), 143 - 9
Pharmaco-economical analysis of the treatment with antibiotics in a surgery department; Dimitrov D et al.; The fulfillment of a pharmaco-economical analysis of the treatment with antibiotics is an important task in the conditions of a transition period, that is currently in Bulgaria . The great problem with the insufficient financial sources prevents the supply with drugs, medical supply and technology . This analysis is a kind of an auxiliary source in the process of managing in the sphere of the health policy and in particular--in the sphere of the pharmacy.

Mol Pharmacol, 2002 Aug, 62(2), 289 - 96
Inhibition of branched-chain alpha-keto acid dehydrogenase kinase and Sln1 yeast histidine kinase by the antifungal antibiotic radicicol; Besant PG et al.; The 90-kDa heat shock family (HSP90) of protein and two-component histidine kinases, although quite distinct at the primary amino acid sequence level, share a common structural ATP-binding domain known as the Bergerat fold . The Bergerat fold is important for the ATPase activity and associated chaperone function of HSP90 . Two-component histidine kinases occur in bacteria, yeast, and plants but have yet to be identified in mammalian cells . The antifungal antibiotic radicicol (Monorden) has been shown to bind to the Bergerat fold of HSP90 and to inhibit its ATPase activity . The structural similarity between the Bergerat fold of HSP90 and bacterial two-component histidine kinases prompted our inquiry into whether radicicol could be a potential inhibitor of histidine kinase-like proteins . Structural homology searches suggest that the ATP-binding domains of the yeast histidine kinase Sln1 and the mammalian, branched-chain alpha-keto acid dehydrogenase kinase are very similar to that of other Bergerat fold family members . On the basis of structural homology, we tested radicicol as a potential inhibitor of Sln1 and branched-chain alpha-keto acid dehydrogenase kinase (BCKDHK) and propose a mechanism of inhibition of these kinases . Although BCKDHK has been shown to have serine autophosphorylation activity, we speculate, based on the results from this study and other supporting evidence, that BCKDHK may also have intrinsic histidine kinase activity.

Bioorg Med Chem Lett, 2002 Aug 19, 12(16), 2241 - 4
Decoding region bubble size and aminoglycoside antibiotic binding; Ryu do H et al.; Aminoglycoside antibiotics promiscuously bind to structurally diverse RNA molecules containing internal bubbles and bulges with affinities in the microM range . An interesting exception is found in the human 12S mitochondrial decoding region where aminoglycoside binding, unlike in the case of its bacterial and human cytoplasmic counterparts, is absent . Mutations that reduce the size of the bubble in the 12S decoding region immediately restore aminoglycoside binding, giving the system chemical switch like behavior.

Pancreatology, 2001, 1(6), 668 - 73
Benefit of continuous regional arterial infusion of protease inhibitor and antibiotic in the management of acute necrotizing pancreatitis; Takeda K et al.; Although we have reported the beneficial effect of continuous regional arterial infusion (CRAI) of protease inhibitor and antibiotic on acute necrotizing pancreatitis (ANP), the optimal timing of the initiation of CRAI therapy has not been clarified . The present study was conducted to evaluate whether the difference of the timing of CRAI therapy may affect the clinical course and outcome in ANP . 73 patients with ANP were stratified into three groups according to the interval between the onset and initiation of CRAI therapy as follows: group I (32 patients in whom CRAI therapy was initiated within 48 h after the onset); group II (22 patients in whom CRAI therapy was initiated between 48 and 72 h after the onset), and group III (19 patients in whom CRAI was initiated more than 72 h after the onset) . The mortality rate was 3.2% in group I, 9.1% in group II, and 26.3% in group III . The mortality rate was significantly low in group I compared with that in group III . The frequency of respiratory failure in group I was also significantly low compared with that in group III . CRP and APACHE II score were reduced rapidly in both groups I and II after the initiation of CRAI therapy . These results suggested that the optimal timing of CRAI therapy in ANP should be considered to be within 72 h after the onset.

Proc Natl Acad Sci U S A, 2002 Jul 23, 99(15), 9789 - 94 Epub 2002 Jul 15.
Designed to penetrate: time-resolved interaction of single antibiotic molecules with bacterial pores; Nestorovich EM et al.; Membrane permeability barriers are among the factors contributing to the intrinsic resistance of bacteria to antibiotics . We have been able to resolve single ampicillin molecules moving through a channel of the general bacterial porin, OmpF (outer membrane protein F), believed to be the principal pathway for the beta-lactam antibiotics . With ion channel reconstitution and high-resolution conductance recording, we find that ampicillin and several other efficient penicillins and cephalosporins strongly interact with the residues of the constriction zone of the OmpF channel . Therefore, we hypothesize that, in analogy to substrate-specific channels that evolved to bind certain metabolite molecules, antibiotics have "evolved" to be channel-specific . Molecular modeling suggests that the charge distribution of the ampicillin molecule complements the charge distribution at the narrowest part of the bacterial porin . Interaction of these charges creates a region of attraction inside the channel that facilitates drug translocation through the constriction zone and results in higher permeability rates.

Arch Microbiol, 2002 Aug, 178(2), 102 - 14 Epub 2002 May 14.
Cloning and analysis of the simocyclinone biosynthetic gene cluster of Streptomyces antibioticus Tü 6040; Galm U et al.; The biosynthetic gene cluster of the aminocoumarin antibiotic simocyclinone D8 was cloned by screening a cosmid library of Streptomyces antibioticusTu 6040 with a heterologous probe from a gene encoding a cytochrome P450 enzyme involved in the biosynthesis of the aminocoumarin antibiotic novobiocin . Sequence analysis of a 39.4-kb region revealed the presence of 38 ORFs . Six of the identified ORFs showed striking similarity to genes from the biosynthetic gene clusters of the aminocoumarin antibiotics novobiocin and coumermycin A(1) . Simocyclinone also contains an angucyclinone moiety, and 12 of the ORFs showed high sequence similarity to biosynthetic genes of other angucyclinone antibiotics . Possible functions within the biosynthesis of simocyclinone D8 could be assigned to 23 ORFs by comparison with sequences in GenBank . Experimental proof for the function of the identified gene cluster was provided by a gene inactivation experiment, which resulted in the abolishment of the formation of the aminocoumarin moiety of simocyclinone . Feeding of the mutant with the aminocoumarin moiety of novobiocin led to a new, artificial simocyclinone derivative.

Rapid Commun Mass Spectrom, 2002, 16(14), 1365 - 76
An original approach to determining traces of tetracycline antibiotics in milk and eggs by solid-phase extraction and liquid chromatography/mass spectrometry; Bruno F et al.; An original and highly specific method able to identify and quantify traces of five tetracycline antibiotics (TCAs) in milk and eggs is presented . This method uses a single solid-phase extraction (SPE) cartridge for simultaneous extraction and purification of TCAs in the above matrices . After diluting 5 mL of intact whole milk or 2 g egg samples with Na(2)EDTA-containing water, samples are passed through a 0.5-g Carbograph 4 extraction cartridge . After analyte elution from the SPE cartridge, an aliquot of the final extract is injected into a liquid chromatography/mass spectrometry (LC/MS) instrument equipped with an electrospray ion source and a single quadrupole . MS data acquisition is performed in the positive-ion mode and by a time-scheduled multiple-ion selected ion-monitoring program . With methanol as organic modifier, the in-source collision-induced dissociation (CID) process generated fragment ions able to pick up one methanol molecule . In several cases, these methanol-adduct fragment ions have m/z values higher than those of the protonated molecules . This event is rarely encountered in MS, thus making the analysis of TCAs by this method extremely specific . Compared with a conventional published method, the present protocol extracted larger amounts of TCAs from both milk and egg and decreased the analysis time by a factor of 3 . Recovery of TCAs in milk at the 25-ppb level ranged between 81 and 96% with relative standard deviation (RSD) no larger than 9% . Recovery of TCAs in egg at the 50-ppb level ranged between 72 and 92% with RSD no larger than 7% . Estimated limits of quantification(S/N = 10) of the method were 2-9 ppb TCAs in whole milk and 2-19 ppb TCAs in eggs.

Biochem Pharmacol, 2002 Jul 1, 64(1), 151 - 8
Inhibition of transport across the hepatocyte canalicular membrane by the antibiotic fusidate; Bode KA et al.; Hyperbilirubinemia is a frequent side effect induced by long-term therapy with the antibiotic fusidate . The aim of this study was to elucidate the molecular mechanisms of fusidate-induced hyperbilirubinemia by investigating its influence on hepatic transport systems in the canalicular membrane . Using canalicular membrane vesicles from rat liver, we determined the effect of fusidate on the adenosine 5'-triphosphate (ATP)-dependent transport of substrates of the apical conjugate export pump, multi-drug resistance protein 2 (Mrp2, symbol Abcc2) and the bile salt export pump (Bsep, symbol Abcb11) . Fusidate inhibited the ATP-dependent transport of the Mrp2 substrates 17beta-glucuronosyl estradiol and leukotriene C4, and the transport of cholyltaurine by Bsep with Ki values of 2.2+/-0.3, 7.6+/-1.3, and 5.5+/-0.8 microM, respectively . To elucidate the in vivo implication of these findings, the effect of fusidate treatment on the elimination of intravenously administered tracer doses of 17beta-glucuronosyl estradiol and cholyltaurine into bile was studied in rats . Treatment with fusidate (100 micromol/kg body weight) reduced the biliary excretion rate of 17beta-glucuronosyl {3H}estradiol and {3H}cholyltaurine by 75 and 80%, respectively . Extended treatment of rats with fusidate (100 micromol/kg body weight, three times daily i.p . for 3 days) reduced hepatic Mrp2 protein levels by 61% (P<0.001) . Our data suggest that there are at least two different mechanisms involved in the impairment of transport processes and hepatobiliary elimination by fusidate, direct inhibition of transport of Mrp2 and Bsep substrates by competitive interaction and impairment by a decreased level of hepatic Mrp2.

Gastroenterology, 2002 Jul, 123(1), 33 - 40
Combined budesonide and antibiotic therapy for active Crohn's disease: a randomized controlled trial; Steinhart AH et al.; BACKGROUND & AIMS: Although antibiotics are frequently used to treat Crohn's disease, this practice is not supported by strong evidence from randomized trials . METHODS: We conducted a double-blind multicenter study of patients with active Crohn's disease of the ileum, right colon, or both . Patients were randomized to receive oral ciprofloxacin and metronidazole, both 500 mg twice daily, or placebo for 8 weeks . All patients received oral budesonide 9 mg once daily . The primary efficacy measure was the proportion of patients in remission at week 8 . RESULTS: Of the 134 patients who were randomized, 130 were evaluated for efficacy; 66 received placebo, and 64 received antibiotics . At week 8, 21 patients (33%) assigned to antibiotics were in remission as compared with 25 patients (38%) in the placebo group (P = 0.55; absolute difference, -5%; 95% confidence interval, -21% to 11%) . An interaction (P = 0.025) between treatment allocation and disease location on treatment response was identified . Among patients with disease of the colon, 9 of 17 (53%) were in remission after treatment with antibiotics, compared with 4 of 16 (25%) of those who received placebo (P = 0.10) . Discontinuation of therapy because of adverse events occurred in 13 of 66 (20%) patients treated with antibiotics, compared with 0 of 68 in the group who received placebo (P < 0.001) . CONCLUSIONS: In patients with active Crohn's disease of the ileum, the addition of ciprofloxacin and metronidazole to budesonide is an ineffective intervention, but this antibiotic combination may improve outcome when there is involvement of the colon.

Emerg Med J . 2002 Jul;19(4):325.
Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary . Topical antibiotics in acute bacterial conjunctivitis; Crawford I et al.; A short cut review was carried out to establish whether there is any evidence to show if topical antibiotic therapy reduces time to remission in acute bacterial conjunctivitis . Altogether 1231 papers were found using the reported search, of which one presented the best evidence to answer the clinical question . The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this paper are tabulated . A clinical bottom line is stated.

Obstet Gynecol, 2002 Jul, 100(1), 101 - 6
Prenatal prescription of macrolide antibiotics and infantile hypertrophic pyloric stenosis; Cooper WO et al.; OBJECTIVE: To assess the association between prenatal antibiotics, including erythromycin, and infantile hypertrophic pyloric stenosis in a large cohort of infants . METHODS: This was a retrospective cohort study of births to women enrolled in Tennessee Medicaid/TennCare, 1985-1997 . Prescriptions for erythromycin, nonerythromycin macrolides, and other antibiotics were identified from pharmacy files linked with birth certificate files . The primary study outcome was development of pyloric stenosis in the infant, identified from linked hospital discharge diagnosis and surgical procedure codes . RESULTS: The cohort included 260,799 mother/infant pairs . Among these women, 13,146 filled prescriptions for erythromycin (50.4 per 1000), and 621 filled prescriptions for nonerythromycin macrolides (2.4 per 1000) . There was no association with prenatal erythromycin prescription and infantile hypertrophic pyloric stenosis either after 32 weeks' gestation (adjusted odds ratio 1.17, 95% confidence interval, 0.84, 1.64, P =.33) or at any time during pregnancy (adjusted odds ratio 1.15, 95% confidence interval 0.84, 1.56, P =.36) . There was an association between maternal prescriptions for nonerythromycin macrolides and infantile hypertrophic pyloric stenosis (adjusted odds ratio 2.77, 95% confidence interval 1.22, 6.30, P =.01) . CONCLUSION: The hypothesized association between erythromycin and infantile pyloric stenosis was not seen . Causal inference from the association between prenatal nonerythromycin macrolides and infantile hypertrophic pyloric stenosis is limited by the small number of affected children and the evidence of other differences between users of nonerythromycin macrolides and controls.

J Parasitol, 2002 Jun, 88(3), 605 - 11
In vitro effects of antibiotics on Brugia malayi worm survival and reproduction; Rao R et al.; Recent studies have suggested that intracellular Wolbachia spp . endobacteria are necessary for the reproduction and survival of filarial nematodes . The effects of antibiotics that are active against related bacteria on adult worms and microfilariae (Mf) of Brugia malayi in vitro were investigated . Antibiotics tested were doxycycline (Doxy), tetracycline (Tet), rifampicin (Rif), azithromycin (Azith), and chloramphenicol (Chlor) . Doxy, Tet, Rif, and Azith reduced release of Mf by adult female worms . The minimum effective concentrations that reduced Mf release by 50% were 5 microg/ml for Doxy, 20 microg/ml for Tet, 40 microg/ml for Rif, and 100 microg/ml for Azith . The same drugs (at higher concentrations) killed adult worms and Mf . Embryograms showed that Tets blocked embryogenesis in female worms . Electron microscopy (EM) showed that the Tets, Rif, and Azith cleared Wolbachia spp . from adult worms and damaged developing embryos . These studies show that antibiotics active against Rickettsiaceae affect adult B . malayi worms and Mf in vitro . Additional studies will be needed to elucidate the mechanisms of action of these antibiotics on Wolbachia and filarial worms.

J Org Chem, 2002 Jul 12, 67(14), 4771 - 6
Efficient one-pot synthesis of the 2-aminocarbonylpyrrolidin-4-ylthio-containing side chain of the new broad-spectrum carbapenem antibiotic ertapenem; Brands KM et al.; An efficient synthesis of the 2-aminocarbonylpyrrolidin-4-ylthio containing side chain of ertapenem (MK-0826) is described . Starting material N-(O,O-diisopropyl phosphoryl)-trans-4-hydroxy-L-proline is converted in a one-pot process to (2S)-cis-3-{{(4-mercapto-2-pyrrolidinyl)carbonyl}amino}benzoic acid monohydrochloride in 70-75% overall yield via a series of six reactions . The development of each of these reactions and the isolation of the product is discussed in detail.

J Pharm Biomed Anal, 2002 Jul 20, 29(4), 669 - 79
Comparative study of the micellar enhanced spectrophotometric determination of beta-lactamic antibiotics by batch and flow injection analysis using a multisimplex design; Fernandez-Gonzalez A et al.; A study has been made on the spectrophotometric determination of the beta-lactamic antibiotics, amoxicillin and ampicillin, in micellar media using Cu ions as catalyst . Batch and flow injection approaches were compared . Multisimplex design was used to determine the optimal values of the flow injection analysis (FIA) system . Chemical (buffer, pH and Cu(II) concentrations) and physical (flow rate, temperature and reaction coil length) variables were considered . The analytical performance characteristics were as follows: the detection limits for batch and flow-through systems were 2.5 x 10(-7) and 2 x 10(-6) M, respectively, and a relative standard deviation less than 1% was found for both methods . The proposed FIA methodology was satisfactorily applied to the determination of the antibiotics in pharmaceutical formulations.

Am J Respir Crit Care Med, 2002 Jul 1, 166(1), 72 - 5
Lack of association between antibiotic use in the first year of life and asthma, allergic rhinitis, or eczema at age 5 years; Celedon JC et al.; Five retrospective studies have reported an association between antibiotic use in early life and asthma in childhood . We studied the relationship between the use of oral antibiotics in the first year of life and asthma, allergic rhinitis, and eczema at age 5 years among 448 children with a parental history of atopy monitored from birth . After adjustment for potential confounders, we found no significant association between antibiotic use in the first year of life and asthma (odds ratio {OR} for one versus no courses of antibiotics, 0.5; 95% confidence interval {CI} for OR, 0.2 to 1.5; OR for two or more versus no courses of antibiotics, 1.0; 95% CI for OR, 0.5 to 2.2), recurrent wheezing, allergic rhinitis, or eczema at age 5 years . There was no significant association between antibiotic use in the first year of life and having at least one of three atopic diseases (asthma, allergic rhinitis, or eczema) at age 5 years (OR for one versus no courses of antibiotics, 0.7; 95% CI, 0.4 to 1.4; OR for two or more versus no courses of antibiotics, 0.9; 95% CI, 0.5 to 1.4) . Our findings do not support the hypothesis that antibiotic use in early life is associated with the subsequent development of asthma and atopy in childhood.

Curr Opin Investig Drugs, 2002 Apr, 3(4), 533 - 7
Antibiotics for the treatment of onchocerciasis and other filarial infections; Hoerauf A et al.; More effective drugs are needed for the treatment of human filarial diseases and the elimination of these infections as a public health problem . The drugs must either kill or sterilize adult worms . The relevant filariae, Onchocerca volvulus, Wuchereria bancofti and Brugia species, harbor rickettsial endoboacteria of the genus Wolbachia as symbionts . Animal experiments have shown that the elimination of these endobacteria causes inhibition of embryogenesis, and with Onchocerca ochengi a macrofilaricidal effect . Trials with human onchocerciasis patients using doxycydine demonstrated a long-term sterilizing activity, opening up a new strategy for the control of filarial infections . Indications of antiwolbachial therapy against onchocerciasis are discussed.

Therapie, 2002 Jan-Feb, 57(1), 39 - 47
{Evaluation of the impact of individual antibiotic order forms on consumption of antibiotics}; Labarere J et al.; The aim of the study was to assess the impact of an individual patient order form which concerned the 21 most costly antibiotics in a university hospital . Antibiotics expenditures were monitored from 1995 to 1999 and were expressed in 1999 French Francs per 100 patient days (p.d.) . The time series were analyzed by auto-regressive models . The trend of antibiotics expenditures which were concerned by the individual patient order form was a yearly increase of 50 FF/100 p.d . (p < 0.01) . The individual patient order form had no significant impact on global antibiotics expenditures but there were some differences across departments: antibiotics costs decreased 1.293 FF/100 p.d . (p = 0.02) in intensive care departments . Monitoring antibiotics consumption should be continued in order to increase power of analysis and to assess the impact of the implementation of guidelines.

Rev Med Chir Soc Med Nat Iasi, 2000 Jul-Sep, 104(3), 123 - 6
{Hemorrhagic risk factors during beta-lactam antibiotics therapy}; Ambarus V et al.; Any type hemorrhagic manifestation may occur 12 hours to 5 weeks after the administration of beta-lactam antibiotics . The mechanisms of blood losses proved to be by: 1) immunologic thrombocytopenia (penicillins); 2) alteration of platelet functions (semisynthetic penicillins); 3) hypoprothrombinemia (cephalosporins) . The risk factors for the occurrence of hemorrhage under beta-lactam antibiotics therapy are: concomitant administration of cytostatics for a neoplastic malignancy; b) acute or chronic renal failure; c) concomitant treatment for duodenal and gastric ulcer; d) malnutrition; e) dosage and duration of antibiotic administration . The frequency of bleeding under beta-lactams is not determined as yet . A severe case diagnosed at the IIIrd Medical Clinic of Iasi presenting spontaneous daily nasal bleedings that occurred 24 hours after the initiation of the treatment with cephalosporins (Kefurox) is presented . In this patient the risk factor was chronic renal failure.

Scand J Prim Health Care, 2002 Mar, 20(1), 35 - 9
Parents' perspectives on otitis media and antibiotics . A qualitative study; Jonsson H et al.; BACKGROUND: Judicious use of antibiotics is an important factor in decreasing the current increase in bacterial resistance . Discussion with patients and their guardians on whether to use antibiotics or not can be expected to increase in the future . OBJECTIVE: To explore the views and feelings of parents of children with acute otitis media towards the disease and its treatment . DESIGN: A qualitative study with semi-structured interviews . SUBJECTS: Twenty-one parents of pre-school children with newly diagnosed acute otitis media who had attended a primary care centre in Reykjavik . RESULTS: The parents did not consider the disease a threat . They generally thought the disease was caused by environmental factors or by a disturbance in body mechanism . The majority thought that treatment with antibiotics could harm their children . CONCLUSION: The parents of young children hold views on acute otitis media and antibiotics which are markedly different from the medical model.

Clin Pediatr (Phila), 2002 Jun, 41(5), 285 - 99
Patient, physician, and nurse satisfaction with antibiotics; Steele RW et al.; To prospectively evaluate patient (parent), physician, and nurse satisfaction with antibiotics, 12,102 children in 661 pediatric study centers throughout the United States with infections to be treated on an outpatient basis were followed with questionnaires completed by parents and with interviews of patients and their parents . Comprehensive surveys were also completed by participating pediatricians and their nursing staffs of which 11,913 (98.4%) contained adequate information for inclusion in an analysis . Data were combined and analyzed using standard statistical methods . Loracarbef was perceived as being superior to other antibiotics based on cost, palatability, and dosing intervals . Few differences were seen among most antibiotics based on treatment outcome or adverse events . All antibiotics studied offered acceptable efficacy and were well tolerated as judged by physicians, nurses, parents, and children . Slight differences might result in increased compliance for some patients.

Infez Med, 2001 Sep, 9(3), 137 - 46
{Potential antibiotic pharmaceutical cost reduction in an operative unit of infectious diseases . Projects for making savings and improvements}; Sabbatani S et al.; The authors intend to evaluate the results obtained from a pharmaco-economic project included in the 1999 and 2000 budgets . The objectives of the study are: 1) to establish whether there has been a saving in expenses for antibiotic therapy (T.A.) during the first half-year of 1999 and during the first half-year of 2000 and to ascertain the reasons for any positive result; 2) to evaluate the average hospital stay in the first half-year of 2000 and to observe how many times patients were been discharged early with shift therapy . Of the 286 patients (1999) and 309 (2000) considered, we focused attention on 187 (1999) and 190 patients (2000) who were treated with antibiotic therapy . A substantial cost saving was found in antibiotic use (-31%) in the first half-year of 2000 due to the early discharge and the continuation of home therapy for a fair number of patients and due to increased attention in the choice of medicine for less serious diseases . The second objective was not achieved with the reduction of average hospital stay even if the average length of antibiotic therapies (D.M.T.) fell from 13.1 days at 1st September to 9.8 days in the first half-year of 2000 (P:NS) . These results suggest that projects designed to achieve financial savings and improvements require more cooperation between clinical U.O . and services that enable hospital stay to be shortened.

Eur J Pharm Biopharm, 2002 Jul, 54(1), 25 - 32
Dry powder inhalation of antibiotics in cystic fibrosis therapy: part 2 . Inhalation of a novel colistin dry powder formulation: a feasibility study in healthy volunteers and patients; Le Brun PP et al.; The aim of the present study was to perform a proof of principle study with a new colistin dry powder inhalation system in six healthy volunteers and five patients with cystic fibrosis . All subjects were asked to inhale 25 mg colistin sulfate dry powder . The patients were also asked to nebulize 160 mg colistin sulfomethate as a solution . Colistin serum concentrations were determined as an indirect parameter to compare both forms of administration . Pulmonary function tests were performed . Peak serum colistin concentrations ranged from 14 to 59 microg/l in volunteers after inhalation of 25 mg as dry powder . In patients, peak concentrations ranged from 18 to 64 microg/l after nebulization of 160 mg colistin sulfomethate solution and from 77 to 159 microg/l after inhalation of 25 mg colistin sulfate dry powder . Pulmonary function tests were not significantly different after inhalation of the dry powder by the volunteers nor after nebulization of the solution by the patients . In some patients a decrease in pulmonary function and moderate to severe cough was observed after inhalation of the dry powder . The new colistin inhaler provides an attractive alternative for nebulized colistin and was highly appreciated by the patients . The decrease in pulmonary function and cough in patients is a drawback, which may be overcome by dose reduction and a further improvement of the new dosage form.

Eur J Pharm Biopharm, 2002 Jul, 54(1), 17 - 24
Dry powder inhalation of antibiotics in cystic fibrosis therapy, part 1: development of a powder formulation with colistin sulfate for a special test inhaler with an air classifier as de-agglomeration principle; de Boer AH et al.; The aim of this study was to investigate the pulmonary administration of antibiotics as dry powder to patients with cystic fibrosis (CF), as an alternative for nebulization . This part of the study describes the development of a powder formulation with colistin sulfate as model substance . The aim of the new dosage form was to increase pulmonary deposition, therapeutic efficiency and, by that, compliance by the CF patients . A physical powder mixture of colistin and a size fraction of lactose (106-150 microm) was prepared and the mixture was optimized with respect to colistin content (83.3%) for use in a special test inhaler . A laser diffraction apparatus with special inhaler adapter was applied for analysis of the size distribution of the aerosol cloud from the inhaler . The size distributions of the aerosol clouds from the test inhaler at flow rates between 30 and 60 l/min for the optimized formulation showed nearly the same median diameter as that for the primary drug particles . But the X(100)-value was much lower, because of an effective large particle separation from the inspiratory air by an air classifier in the test inhaler . The results suggest that dry powder inhalation might be a suitable and highly efficient alternative for nebulization of antibiotic drugs in CF therapy.

J Bacteriol, 2002 Jul, 184(14), 3984 - 91
Activation of antibiotic biosynthesis by specified mutations in the rpoB gene (encoding the RNA polymerase beta subunit) of Streptomyces lividans; Hu H et al.; We found that the biosynthesis of actinorhodin (Act), undecylprodigiosin (Red), and calcium-dependent antibiotic (CDA) are dramatically activated by introducing certain mutations into the rpoB gene that confer resistance to rifampin to Streptomyces lividans 66, which produces less or no antibiotics under normal growth conditions . Activation of Act and/or Red biosynthesis by inducing mutations in the rpoB gene was shown to be dependent on the mutation's position and the amino acid species substituted in the beta-subunit of the RNA polymerase . Mutation analysis identified 15 different kinds of point mutations, which are located in region I, II, or III of the rpoB gene and, in addition, two novel mutations (deletion of nucleotides 1287 to 1289 and a double substitution at nucleotides 1309 and 1310) were also found . Western blot analyses and S1 mapping analyses demonstrated that the expression of actII-ORF4 and redD, which are pathway-specific regulatory genes for Act and Red, respectively, was activated in the mutants able to produce Act and Red . The ActIV-ORF1 protein (an enzyme for Act biosynthesis) and the RedD protein were produced just after the upregulation of ActII-ORF4 and RedZ, respectively . These results indicate that the mutation in the rpoB gene of S . lividans, resulting in the activation of Act and/or Red biosynthesis, functions at the transcription level by activating directly or indirectly the key regulatory genes, actII-ORF4 and redD . We propose that the mutated RNA polymerase may function by mimicking the ppGpp-bound form in activating the onset of secondary metabolism in STREPTOMYCES:

Br J Dermatol, 2002 Jun, 146(6), 1047 - 51
Comparative frequency of patch test reactions to topical antibiotics; Morris SD et al.; BACKGROUND: Neomycin, clioquinol and fusidic acid are all topical antibiotics widely used in dermatological practice in the U.K., either as a single agent or in combination with topical corticosteroids . However, an adverse effect of topical antibiotics is contact sensitization . OBJECTIVES: To examine the frequency of positive patch test reactions to fusidic acid, clioquinol and neomycin . METHODS: To compare the frequency of allergic patch test reactions over 1 year, we patch tested all patients attending the St John's Institute of Dermatology contact dermatitis clinic for one calendar year with fusidic acid, neomycin and clioquinol . RESULTS: We patch tested 1119 patients . Positive patch test reactions to neomycin were noted in 40 patients (3.6%), compared with eight patients (0.7%) to clioquinol and three patients (0.3%) to fusidic acid . The frequency of medicament allergy to neomycin was thus five times more common than to clioquinol and ten times more common than to fusidic acid . Although fusidic acid is not part of our extended standard series, it is in our medicaments series . Therefore, in the second part of our study, we reviewed all cases of positive patch test reactions to fusidic acid over the last 20 years . We found that the frequency of hypersensitivity has decreased since the early 1980s despite increasing usage; the current average frequency being 1.62 patch-tested patients per year (1.45%) of those patch tested to the medicaments series) . The most common diagnosis in such patients was stasis dermatitis (54.2%) . CONCLUSIONS: The frequency of fusidic acid allergy in an eczema population is low and is comparable with published data from over 10 years ago.

Saudi Med J, 2002 Jun, 23(6), 705 - 7
Do antibiotics decrease post-tonsillectomy morbidity?
Al-Kindy SA.
OBJECTIVE: A tonsillectomy audit was carried out and compared with other studies, to emphasize the role of antibiotics . METHODS: This study was carried out at North West Armed Forces Hospital, Tabuk, Kingdom of Saudi Arabia, during the year January 1999 through to December 1999 . This is a retrospective study of patients who had tonsillectomy with or with adenoidectomy, the topics audited included indication for surgery, grade of surgeon, method of surgery, length of hospital stay, complications and the use of postoperative antibiotics . RESULTS: A total of 185 patients underwent tonsillectomy with or without adenoidectomy . The patients age ranged between 2 years to 53 years and the majority were children . In our audit we found no difference with regard to grade of surgeons, method of hemostasis in the outcome of surgery . Moreover, postoperative antibiotics had no role in pain control, postoperative fever, secondary hemorrhage or reduction in hospital stay . The administration of analgesics on the basis of, as required, had poor pain control . CONCLUSION: Post tonsillectomy antibiotics did not prove to have a role in minimizing postoperative morbidity . Moreover, analgesics given on the basis of as required had a limited value.

Scand J Infect Dis, 2002, 34(5), 366 - 71
Antibiotic prescription rates vary markedly between 13 European countries; Molstad S et al.; There is a lack of data on antibiotic utilization in most European countries . In this study, information about the number of antibiotic prescriptions was obtained for Austria, Belgium, Finland, France, Germany, Greece, Italy, The Netherlands, Portugal, Spain and the UK from the Institute for Medical Statistics Health Global Services in the UK . For Denmark and Sweden the information was obtained from the Danish Medicines Agency (Laegemiddelstyrelsen) and the National Corporation of Swedish Pharmacies (Apoteket AB), respectively . Between 1994 and 1997 the number of prescriptions per 1,000 inhabitants increased in France and Greece whilst Portugal, Spain and Sweden reported a decrease . In 1997, Greece (1,350), Spain (1,320) and Belgium (1,070) had the highest numbers of antibiotic prescriptions per 1,000 inhabitants in the Anatomical Therapeutic Chemical classification system for drugs group J01 while The Netherlands (390), Sweden (460) and Austria (480) had the lowest . The most common antibiotic drug was extended-spectrum penicillin in 6/13 countries, macrolides in Austria, Finland, Germany and Italy, phenoxymethylpenicillin in Denmark and Sweden and cephalosporins in Greece . The variation in the number of antibiotic prescriptions per 1,000 inhabitants between the 13 European countries was substantial in terms of both total use and use of different antibiotics.

Mol Microbiol, 2002 Jun, 44(5), 1199 - 1211
A signal transduction system in Streptomyces coelicolor that activates the expression of a putative cell wall glycan operon in response to vancomycin and other cell wall-specific antibiotics; Hong HJ et al.; We have investigated a signal transduction system proposed to allow Streptomyces coelicolor to sense and respond to changes in the integrity of its cell envelope . The system consists of four proteins, encoded in an operon: sigmaE, an RNA polymerase factor; CseA (formerly ORF202), a protein of unknown function; CseB, a response regulator; and CseC, a sensor histidine protein kinase with two predicted transmembrane helices (Cse stands for control of sigma E) . To develop a sensitive bioassay for inducers of the sigE system, the promoter of the sigE operon (sigEp) was fused to a reporter gene conferring resistance to kanamycin . Antibiotics that acted as inducers of the sigE signal transduction system were all inhibitors of intermediate and late steps in peptidoglycan biosynthesis, including ramoplanin, moenomycin A, bacitracin, several glycopeptides and some beta-lactams . The cell wall hydrolytic enzyme lysozyme also acted as an inducer . These data suggest that the CseB-CseC signal transduction system may be activated by the accumulation of an intermediate in peptidoglycan biosynthesis or degradationa . A computer-based searching method was used to identify a sigmaE target operon of 12 genes (the cwg operon), predicted to specify the biosynthesis of a cell wall glycan . In low-Mg(2+) medium, transcription of the cwg operon was induced by vancomycin in a sigE-dependent manner but, in high-Mg(2+) medium, there was substantial cwg transcription in a sigE null mutant, and this sigE-independent activity was also induced by vancomycin . Based on these data, we propose a model for the regulation and function of the sigmaE signal transduction system.

AAPS PharmSci . 2001;3(4):E34.
Delivery of antibiotics to the eye using a positively charged polysaccharide as vehicle; Felt O et al.; The positively charged polysaccharide chitosan is able to increase precorneal residence time of ophthalmic formulations containing active compounds when compared with simple aqueous solutions . The purpose of the study was to evaluate tear concentration of tobramycin and ofloxacin after topical application of chitosan-based formulations containing 0.3% wt/vol of antibiotic and to compare them with 2 commercial solutions: Tobrex and Floxal, respectively . The influence of the molecular weight, deacetylation degree, and concentration of 4 different samples of chitosan on pharmacokinetic parameters (area under the curve values {AUC(eff)} and time of efficacy {t(eff)}) of tobramycin and ofloxacin in tears was investigated over time . It was demonstrated that the 2 chitosan products of high molecular weight (1350 and 1930 kd) and low deacetylation degree (50%) significantly increased antibiotic availability when compared to the controls, with AUC(eff) showing a 2- to 3-fold improvement . The time of efficacy of ofloxacin was significantly increased from about 25 minutes to 46 minutes by the chitosan of higher Mw (1930 kd) at a concentration of 0.5% wt/vol, whereas a similar performance was achieved by a chitosan of low Mw (580 kd) at a concentration of 1.5% wt/vol in the case of tobramycin.

J Pharmacol Exp Ther, 2002 Jul, 302(1), 320 - 7
Blockade of human cardiac potassium channel human ether-a-go-go-related gene (HERG) by macrolide antibiotics; Volberg WA et al.; Several macrolides have been reported to cause QT prolongation and ventricular arrhythmias such as torsades de pointes . To clarify the underlying ionic mechanisms, we examined the effects of six macrolides on the human ether-a-go-go-related gene (HERG)-encoded potassium current stably expressed in human embryonic kidney-293 cells . All six drugs showed a concentration-dependent inhibition of the current with the following IC(50) values: clarithromycin, 32.9 microM; roxithromycin, 36.5 microM; erythromycin, 72.2 microM; josamycin, 102.4 microM; erythromycylamine, 273.9 microM; and oleandomycin, 339.6 microM . A metabolite of erythromycin, des-methyl erythromycin, was also found to inhibit HERG current with an IC(50) of 147.1 microM . These findings imply that the blockade of HERG may be a common feature of macrolides and may contribute to the QT prolongation observed clinically with some of these compounds . Mechanistic studies showed that inhibition of HERG current by clarithromycin did not require activation of the channel and was both voltage- and time-dependent . The blocking time course could be described by a first-order reaction between the drug and the channel . Both binding and unbinding processes appeared to speed up as the membrane was more depolarized, indicating that the drug-channel interaction may be affected by electrostatic responses.

J Chromatogr A, 2002 Apr 5, 952(1-2), 121 - 9
Multiresidue determination of (fluoro)quinolone antibiotics in swine kidney using liquid chromatography-tandem mass spectrometry; van Vyncht G et al.; New antibiotics were recently developed, among which are the (fluoro)quinolones . This paper presents an analytical method which allows the determination of 11 (fluoro)quinolones in swine kidneys: norfloxacin, ofloxacin, cinoxacin, oxolinic acid, nalidixic acid, flumequine, enrofloxacin, enoxacin, ciprofloxacin, danofloxacin and marbofloxacin . The procedure involves a rapid and efficient pre-treatment by solid-phase extraction (recoveries 83-98%), followed by the sensitive and selective determination of all compounds in a single run using LC-ESI-MS-MS . Multiple reaction monitoring (MRM) was used for selective detection of each (fluoro)quinolone . Quinine was selected as internal standard . The accuracy of the method, expressed as recovery, was between 89 and 109%; the repeatability had a maximum RSD lower than 15% . The limits of detection (LOD) were much lower than the respective Maximum Residue Limits (MRL)/4.

J Am Acad Dermatol, 2002 Jun, 46(6), 917 - 23
Oral contraceptive efficacy and antibiotic interaction: a myth debunked; Archer JS et al.; The purpose of this study was to review the pharmacokinetic and clinical literature regarding the efficacy of oral contraceptives when used concomitantly with antibiotic therapy . Relevant literature was identified by searching MEDLINE and EMBASE . Other sources were located by consulting the bibliographies of the material collected from MEDLINE and EMBASE . Pharmacokinetic evidence demonstrates that plasma levels of oral contraceptive steroids are unchanged with the concomitant administration of antibiotics, including ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline . However, reduced steroid levels have been reported in women taking rifampin with oral contraceptives . Clinical reports of contraceptive failure with antibiotic use are retrospective, have multiple potential biases, and are not supported by pharmacokinetic data . Available scientific and pharmacokinetic data do not support the hypothesis that antibiotics (with the exception of rifampin) lower the contraceptive efficacy of oral contraceptives.

J Antibiot (Tokyo), 2002 Apr, 55(4), 417 - 22
PPARgamma activation and adipocyte differentiation induced by AS-6, a prenyl-phenol antidiabetic antibiotic; Togashi M et al.; The prenyl-phenol antibiotics ascochlorin-related compounds, are known to reduce serum cholesterol and triglyceride, suppress hypertension, and ameliorate types-I and II diabetes . However, little is known about the molecular mechanism for these physiological effects . Here we report that the ascochlorin derivative, 4-O-carboxymethyl ascochlorin (AS-6) acts as a potent activator of the nuclear hormone receptor, PPARgamma, although it does not activate the related receptors, PPARalpha, PPARdelta or RARalpha . AS-6 interacts directly with the PPARgamma molecule in vitro, and induces differentiation of the mouse preadipocyte cell line 3T3-L1 . Our results suggest that AS-6 is a partial agonist for PPARgamma with a novel chemical structure.

Clin Infect Dis, 2002 Jul 1, 35(1), 26 - 31 Epub 2002 Jun 05.
Practical aspects of choosing an antibiotic for patients with a reported allergy to an antibiotic; Robinson JL et al.; Physicians often must select antibiotics for patients who are reported to have an antibiotic allergy . For penicillins, the sensitivity of penicillin skin testing for predicting serious allergic reactions is excellent . For other beta-lactam antibiotics, penicillin skin testing is useful for excluding the possibility of sensitivity to the beta-lactam ring . For other antibiotics, the patient history remains the most useful tool for determining whether a serious reaction is likely to occur with further drug exposure . The cross-reactivity between penicillins and second- or third-generation cephalosporins (excluding cefamandole) is probably no higher than is the cross-reactivity between penicillins and other classes of antibiotics . When a patient has a suspected immunoglobulin E-mediated antibiotic allergy, desensitization therapy should be considered, if the efficacy of alternate antibiotics is in doubt . For the treatment of serious infections, it is usually possible to safely administer the antibiotic of choice despite a history of possible antibiotic allergy.

J Mol Neurosci, 2002 Jun, 18(3), 271 - 81
Effects of the polyene antibiotic derivative MS-8209 on the astrocyte lysosomal system of scrapie-infected hamsters; Grigoriev VB et al.; Amphotericine B (AmB), a macrolide polyene antibiotic, is one of a few drugs that has shown therapeutic properties in scrapie-infected hamster . Its beneficial effect on survival time is mostly marked when animals are treated with its derivative MS-8209 . To explore the MS-8209 effect at the cellular level, we investigated at the light and electron microscopy levels, the sequential appearance and distribution of PrP concurrently with histopathological changes in hamsters that were infected intracerebrally with the 263 K scrapie strain and treated or not with the drug . The first histopathological modifications and PrP immunostaining were observed in the thalamus and at the inoculation site where the drug caused a delay in the appearance of lesions and PrP accumulation . Using immunoelectron microscopy, at 70 d postinfection, the inoculation site of untreated animals showed an accumulation of PrP in plaque areas constitued by filaments mixed with alterated membrane structures and in developed lysosomal system of reactive astrocytes . Most of the numerous lysosomes containing PrP showed intra-organelle filaments . In contrast, in MS-8209 treated animals, the number of lysosomes was significantly lower (p < 0.0038), with very few organelles harboring PrP . Our results suggest that in this scrapie model, MS-8209 treatment delays the disease by preventing the replication of the scrapie agent at the inoculation site where the astrocytes appear to be the first cells producing abnormal PrP . The lysosomal system of these astrocytes could constitute a privileged target for MS-8209.

Clin Nutr, 2002 Apr, 21(2), 141 - 4
Resting energy expenditure in young patients with cystic fibrosis receiving antibiotic therapy for acute respiratory exacerbations; Castro M et al.; BACKGROUND: patients with cystic fibrosis commonly have severe malnutrition and growth retardation . Among possible causes of these manifestations are low caloric intake, loss of nutrients and increased resting energy expenditure . This study was designed to assess the influence of antibiotic therapy for infectious exacerbations on resting energy expenditure in young patients with cystic fibrosis . METHODS: We studied 17 patients with cystic fibrosis (mean age, 13.6 years) . All were hospitalized to receive intravenous antibiotic therapy (mean duration, 2 weeks) for acute respiratory exacerbations . At the beginning of therapy and after it ended, all patients underwent blood chemical tests, anthropometrical measures, determination of body composition by bioelectrical impedance, spirometry, and indirect calorimetry . RESULTS: Antibiotic therapy led to a significant improvement in biochemical, spirometric variables and in estimated calorimetry measurements expressed in relation to fat-free mass . These findings suggest that infective exacerbations are among the causes of increased resting energy expenditure in young patients with cystic fibrosis . CONCLUSIONS: Indirect calorimetry may prove useful in the diagnosis of infective exacerbations and in monitoring the effect of antibiotic therapy in patients with cystic fibrosis .

J Org Chem, 2002 Jun 14, 67(12), 3979 - 84
Importance of specific hydrogen-bond donor-acceptor interactions for the key carbocycle-forming reaction catalyzed by 2-deoxy-scyllo-inosose synthase in the biosynthesis of 2-deoxystreptamine-containing aminocyclitol antibiotics; Eguchi T et al.; A crucial enzyme in the biosynthesis of the 2-deoxystreptamine aglycon of clinically important aminocyclitol antibiotics is 2-deoxy-scyllo-inosose synthase (DOIS), which converts ubiquitous D-glucose 6-phosphate (G-6-P) into the specific carbocycle 2-deoxy-scyllo-inosose . Among all the oxygenated carbons of the substrate, C-1, -4, -5, and -6 are directly involved in the chemical transformation . To get insight into the roles of C-2 and C-3 hydroxy groups, 2-deoxy-2-fluoro-, 3-deoxy-3-fluoro-, 2-amino-2-deoxy-, and 3-amino-3-deoxy-D-glucose 6-phosphates (2-F-G-6-P, 3-F-G-6-P, 2-NH(2)-G-6-P, and 3-NH(2)-G-6-P, respectively) were subjected to the DOIS reaction as probe, since a fluorine substituent generally acts as a hydrogen-bond acceptor, and an ammonium functionality derived physiologically from an amino group as a hydrogen-bond donor . Among those tested, 2-F-G-6-P and 3-NH(2)-G-6-P were used as substrates by DOIS and were converted into the corresponding deoxyfluoro- and aminodeoxy-scyllo-inososes, respectively . In contrast, 3-F-G-6-P and 2-NH(2)-G-6-P were inactive in the cyclization reaction . Clearly, DOIS recognizes the G-6-P substrate through specific hydrogen-bonding interactions, i.e., through a hydrogen-donating group for C-2 and an accepting group for C-3 of the substrate . Modeling of DOIS based on the structure of evolutionary-related dehydroquinate synthase is also described.

J Mol Biol, 2002 May 3, 318(3), 723 - 32
Structures of glycopeptide antibiotics with peptides that model bacterial cell-wall precursors; Lehmann C et al.; The vancomycin-related antibiotics balhimycin and degluco-balhimycin have been crystallized in complexes with di-, tri- and pentapeptides that emulate bacterial cell-wall precursors, and four structures determined at atomic resolution (<1 A) . In addition to the features expected from previous structural and spectroscopic studies, two new motifs were observed that may prove important in the design of antibiotics modified to overcome bacterial resistance . A changed binding mode was found in two dipeptide complexes, and a new type of face-to-face oligomerization (in addition to the well-established back-to-back dimerization) was seen when the model peptide reaches a critical fraction of the size of the cell-wall precursor pentapeptide . The extensive interactions involving both antibiotic and peptide molecules in this interface should appreciably enhance the kinetic and thermodynamic stability of the complexes . In the pentapeptide complex, the relative positions of the peptides are close to those required for d-Ala elimination, so this structure may provide a realistic model for the prevention of the enzyme-catalyzed cell-wall crosslinking by antibiotic binding . (c) 2002 Elsevier Science Ltd.

Curr Med Chem, 2002 Jun, 9(12), 1145 - 65
Resistance to beta-lactam antibiotics: structure and mechanism based design of beta-lactamase inhibitors; Sandanayaka VP et al.; Resistance to antibiotics is currently a major health concern in treating infectious diseases . The most common mechanism of resistance to beta-lactam antibiotics is the production of beta-lactamases, which destroy beta-lactam antibiotics before they reach the bacterial target . Combination therapy, which involves treatment with a beta-lactam antibiotic and a beta-lactamase inhibitor, has been successfully used to control resistance during last two decades . Due to the lack of effectiveness of the currently available beta-lactamase inhibitors against class C enzymes and new variants of beta-lactamases, there is a need to develop an inhibitor with broad-spectrum activity . Since the discovery of clavulanic acid, there has been an enormous research effort in this area to identify better antibiotic/inhibitor combinations and to understand the molecular bases for interactions between beta-lactam antibiotics, beta-lactamases, and beta-lactamase inhibitors . This review describes some of the structure- and mechanism-based approaches to design of new beta-lactamase inhibitors and the study of probable mechanisms of inhibition using X-ray, electrospray ionization mass spectrometry, and molecular modeling techniques.

J Pharm Biomed Anal, 2002 Jun 15, 28(6), 1205 - 13
Selective spectrophotometric determination of phenolic beta-lactam antibiotics; Salem H et al.; Two simple and selective spectrophotometric methods were developed for the quantitative determination of cefoperazone sodium, cefadroxil monohydrate, cefprozil anhydrous and amoxicillin trihydrate in pure forms as well as in their pharmaceutical formulations . The methods are based on the selective oxidation of these drugs with either Ce (IV) or Fe (III) in acid medium to give an intense yellow coloured product (lambda(max)=397 nm) . The reaction conditions were studied and optimized . Beer's plots were obeyed in a general concentration range of 5-30 microg ml(-1) with correlation coefficients not less than 0.9979 for the four drugs with the two reagents . The methods are successfully applied to the analysis of pharmaceutical formulations containing amoxicillin, either alone or in combination with potassium clavulanate, flucloxacillin or dicloxacillin . They were also applied to the analysis of the other three studied drugs in vials, capsules, tablets and suspensions with good recovery; percent ranged from 99.7 (+/-0.46) to 100.32 (+/-1.05) in the Ce (IV) method and 99.6 (+/-0.50) to 100.3 (+/-1.32) in the Fe (III) method . Interferences from other antibiotics and additives products were investigated.

Anticancer Drug Des, 2001 Aug-Oct, 16(4-5), 247 - 53
Spin-labeled 1-alkyl-1-nitrosourea synergists of antitumor antibiotics; Gadjeva V et al.; A new method for synthesis of four spin-labeled structural analogues of the antitumor drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), using ethyl nitrite for nitrosation of the intermediate spin-labeled ureas has been described . In vitro synergistic effects of 1-ethyl-3-{4-(2,2,6,6-tetramethylpiperidine-1-oxyl)}-1-nitrosourea (3b) on the cytotoxicity of bleomycin and farmorubicin were found in human lymphoid leukemia tumor cells . We measured the tissue distribution of 3b in organ homogenates of C57BL mice by an electron paramagnetic resonance method . The spin-labeled nitrosourea was mainly localized in the lungs . Our results strongly support the development and validation of a new approach for synthesis of less toxic nitrosourea derivatives as potential synergists of antitumor drugs.

J Biol Chem, 2002 Aug 23, 277(34), 30436 - 44 Epub 2002 Jun 04.
Structural basis and mechanism of the inhibition of the type-3 copper protein tyrosinase from Streptomyces antibioticus by halide ions; Tepper AW et al.; The inhibition of the type-3 copper enzyme tyrosinase by halide ions was studied by kinetic and paramagnetic (1)H NMR methods . All halides are inhibitors in the conversion of l-3,4-dihydroxyphenylalanine (l-DOPA) with apparent inhibition constants that follow the order I(-) < F(-) << Cl(-) < Br(-) at pH 6.80 . The results show that the inhibition arises from the interaction of halide with both the oxidized (affinity F(-) > Cl(-) > Br(-) >> I(-)) and reduced (affinity I(-) > Br(-) > Cl(-) >> F(-)) enzyme . The paramagnetic (1)H NMR of the oxidized enzyme complexed with the halides is consistent with a direct interaction of halide with the type-3 site and shows that the (Cu-His(3))(2) coordination occurs in all halide-bound species . It is surmised that halides bridge both of the copper ions in the active site . Fluoride and chloride are shown to bind only to the low pH form of oxidized tyrosinase, explaining the strong pH dependence of the inhibition by these ions . We further show that p-toluic acid and the bidentate transition state analogue, Kojic acid, displace chloride from the oxidized active site, whereas the monodentate substrate analogue, p-nitrophenol, forms a ternary complex with the enzyme and the chloride ion . On the basis of the experimental results, a model is formulated for the inhibitor action and for the reaction of diphenols with the oxidized enzyme.

Int J Infect Dis, 2002 Mar, 6(1), 74 - 7
Epidemiological observations of the judicious use of antibiotics in a pediatric teaching hospital; Mora Y et al.; OBJECTIVE: This study in a tertiary care teaching center with 361 beds was conducted to assess use, misuse, and abuse of antibiotics . MATERIALS AND METHODS: Every day of the study, a computer program was used to compile a list of patients' bedside records . On a specific day, the bedside charts of selected patients were reviewed to determine whether: (1) a justification for antibiotic prescription was recorded; (2) duration of antibiotic therapy had been defined; (3) suitable cultures had been obtained; and (4) treatment was appropriate for the infection to be treated . For 6 months, charts were evaluated 3 days per week . RESULTS: Of 750 bedside charts 500 (67%) were selected for review . Of the 500 patients, 175 (35%) did not receive antibiotics . The abuses or misuses of antibiotics most frequently observed among the 325 treated patients were no record of justification for the antibiotic prescribed (130/325, 40%); no appropriate blood or fluid samples obtained for culture (45/325, 14%); no subsequent control cultures or cultures obtained before modifying therapy (80/175, 46%); no indication of a planned duration of therapy (180/325, 55%); and improper dosage prescribed in relation to weight (25/325, 8%) . Abuse or misuse of antibiotics was more frequently observed among surgical patients than among nonsurgical patients (P<0.05) . CONCLUSION: Rational use of antibiotics should be emphasized in every training program as a main strategy to control the increase in drug resistance and to prolong the usefulness of antibiotics.

Curr Allergy Asthma Rep, 2002 Jul, 2(4), 297 - 303
Otitis media: diagnosis, management, and judicious use of antibiotics; Stool S et al.; Otitis media continues to present a major challenge to practitioners in the clinical setting . With the ever-increasing trend toward the use of a sound research-structured approach to health care and the use of evidence-based guidelines, it is important to have an understanding of these findings related to otitis media . A review of research-supported literature regarding the diagnosis and management of this disease, and suggestions for the judicious use of antibiotics, are presented in this paper.

J Nutr, 2002 Jun, 132(6), 1214 - 8
Rice expressing lactoferrin and lysozyme has antibiotic-like properties when fed to chicks; Humphrey BD et al.; Two experiments were conducted to determine whether rice that has been genetically produced to express human lactoferrin (LF) or lysozyme (LZ) protects the intestinal tract similarly to subtherapeutic antibiotics (bacitracin + roxarsone; Antibiotics) . Experiment 1 compared 10 corn-soy diets containing 20% of various proportions of LF, LZ or conventional rice (CONV) . Chicks fed 5% LF + 10% LZ + 5% CONV had significantly better feed efficiency and thinner lamina propria in the duodenum than those fed 20% CONV . Experiment 2 compared five corn-soy diets containing experimental rice combinations totaling 15% rice . Chicks fed 10% LZ + 5% CONV or 5% LF + 10% LZ had significantly lower feed intake and significantly better feed efficiency than those fed 15% CONV . Chicks fed 10% LZ + 5% CONV, 5% LF + 10% LZ or Antibiotics had significantly greater villous height in the duodenum compared with chicks fed 15% CONV . The lamina propria of the ileum was thinner and contained fewer leukocytes in chicks fed 10% LZ + 5% CONV or Antibiotics compared with those fed 15% CONV . The results from these experiments demonstrate a potential of genetically produced LF and LZ rice to be used as a substitute for antibiotics in broiler diets.

J Chemother, 1991 Jan, 3 Suppl 1, 112 - 5
Antibiotics and their interaction with the host defense system in vivo; Grassi GG et al.; The Authors review their own data on the in-vitro effect of a wide number of chemotherapeutic agents on phagocyte functions (chemotaxis, phagocytosis, phagocytosis-dependent metabolic activation, microbicidal activity) . Aminoglycosides affected some leukocyte functions only at concentrations higher than those achieved in therapy . Macrolides, glycopeptides and fluoroquinolones showed no toxic effect on phagocytic activities . Beta-lactams, generally, did not influence phagocytic activities . However, ceftriaxone and cefoperazone irreversibly inhibited neutrophil chemotaxis . Cefodizime, on the other hand, enhanced phagocytosis of both neutrophils and monocytes, when non-opsonized particles were used as phagocytic challenge . Rifamycins inhibited neutrophil chemotaxis and enhanced the intracellular killing of S . aureus . These interactions with phagocyte function were tested ex vivo on cells of normal volunteers treated with these antibiotics . While no effect on chemotaxis in subjects treated with ceftriaxone and cefoperazone could be demonstrated, both cefodizime and rifampicin maintained their in-vitro activity in ex-vivo experiences . These findings seem to indicate that, so far, no definite conclusion can be drawn on the in-vivo significance of in-vitro findings.

Am J Orthop . 2002 May;31(5):250, 294.
A simple method of intra-articular antibiotic delivery in infected hip arthroplasty; McGrory BJ et al.; Intra-articular delivery of antibiotics is known to be important in the treatment of infected hip arthroplasty . We describe a simple, inexpensive, and convenient method of obtaining high levels of local antibiotics when the femoral component is not removed or when an articulating spacer is utilized . A case example is given in which this type of treatment resulted in a good outcome.

Arch Pediatr Adolesc Med, 2002 Jun, 156(6), 621 - 4
Antibiotic use for upper respiratory tract infections: how well do pediatric residents do?
Nambiar S, Schwartz RH, Sheridan MJ.
BACKGROUND: Antibiotics are often used inappropriately for the treatment of upper respiratory tract infections in children, and the emergence of resistant bacteria is a growing public health concern . OBJECTIVE: To assess awareness and compliance with the Centers for Disease Control and Prevention (Atlanta, Ga) and American Academy of Pediatrics (Elk Grove Village, Ill) principles for judicious antibiotic use for upper respiratory tract infections among residents from a sample of pediatric residency programs in the mid-Atlantic region of the United States . PARTICIPANTS AND METHODS: Residents at the participating programs were requested to complete a survey questionnaire . RESULTS: Of the 524 pediatric residents surveyed, 74% (388 participants) completed the questionnaire . Familiarity with the principles increased with a year of training; 16%, 36%, and 50% of first-year (PL1), second-year (PL2), and third- or fourth-year (PL3/PL4) residents, respectively, had heard or read about the principles (chi(2)(trend); P<.001) . In response to a direct question about the use of antibiotics for an otherwise well, afebrile 18-month-old child with purulent rhinorrhea, 29%, 25%, and 15% of PL1, PL2, and PL3/PL4 residents, respectively, would prescribe antibiotics within 10 days of onset of illness (chi(2)(trend); P =.008) . A significant difference was found between PL1 vs PL3/PL4 participants (difference = 20%; 95% CI = 3%-26%) . If the same infant had a temperature of 38.8 degrees C, then 63%, 45%, and 47% of PL1, PL2, and PL3/PL4 residents, respectively, would prescribe antibiotics (chi(2)(trend); P =.008) . CONCLUSIONS: Awareness among pediatric residents about the judicious use of antibiotics for upper respiratory tract infections is often lacking, and inappropriate use of antibiotics for this condition continues to be prevalent . This was especially noted among PL1 residents, with an improving trend noted with increasing years of training.

Biosci Biotechnol Biochem, 2002 Apr, 66(4), 808 - 19
Growth-phase dependent expression of the mevalonate pathway in a terpenoid antibiotic-producing Streptomyces strain; Hamano Y et al.; Streptomyces griseolosporeus MF730-N6, a terpenoid antibiotic-terpentecin (Tp) producer, has both the nonmevalonate and mevalonate pathways for the formation of IPP . The Tp biosynthetic gene (ter) and the mevalonate pathway gene cluster (mev) including an HMG-CoA reductase gene (hmgr) had previously been cloned from strain MF730-N6 . In this study, two distinct dxs genes (dxs 1 and dxs 2) and a dxr gene, which encode DXP synthases and DXP reductoisomerase, and participate in the initial and the second step of the nonmevalonate pathway, respectively, were cloned . These gene products were expressed in E . coli and confirmed to have the expected activities . The dxs 1, dxs 2, dxr, mev, and ter genes were used for Northern blot and primer extension analyses to examine temporal expression of these genes together with a gap gene coding for GAP dehydrogenase, which was also cloned in this study and used as an internal control . Transcripts of the dxs 1, dxs 2, dxr, and gap genes were detected throughout the cultivation . On the other hand, messages of the mev and ter genes were not detected at early growth phase but appeared when Tp production started . These results suggested that the nonmevalonate pathway and the mevalonate pathway were mainly used for the primary metabolism and the secondary metabolism, respectively, and that both of the two dxs genes were actually transcribed in this strain.

Pharm Res, 2002 Apr, 19(4), 457 - 62
Can the enhanced renal clearance of antibiotics in cystic fibrosis patients be explained by P-glycoprotein transport?
Susanto M, Benet LZ.
PURPOSE: To investigate in vitro if P-glycoprotein (P-gp) transport can differentiate between antibiotic drugs exhibiting increased active renal clearance (CL(r)) in cystic fibrosis (CF) patients (i.e., dicloxacillin, trimethoprim) and drugs that do not exhibit this phenomenon (i.e. . cefsulodin, sulfamethoxazole) . METHODS: Transport studies were carried out in MDCK (wild type) and MDR1-MDCK (P-gp overexpressing) cells that were grown to confluence on Transwell inserts . {14C}-mannitol transport and transepithelial electrical resistance (TEER) were measured to validate the integrity of the cells . Drug concentrations were analyzed using HPLC . RESULTS: Dicloxacillin and trimethoprim are substrates of P-gp (B-->A/A-->B ratios in MDR1-MDCK cells are 32 and 50, respectively) . P-gp inhibitors (i.e., GG918, cyclosporine, ketoconazole, vinblastine) decreased the B-->A transport of dicloxacillin and trimethoprim and increased the A-->B transport of trimethoprim while non-P-gp inhibitors (e.g., PAH) had no effect . In contrast, cefsulodin and sulfamethoxazole are not substrates of P-gp (B-->sA/A-->B values in MDCK and MDR1-MDCK cells are -1) . CONCLUSIONS: Our in vitro studies suggest that P-glycoprotein may play a role in increasing renal clearance of drug substrates in CF patients . Dicloxacillin and trimethoprim . which are both substrates of P-gp, show increased active renal clearance in CF patients while cefsulodin and sulfamethoxazole, which are not P-gp substrates, do not show increased active renal clearance in CF patients.

J Chromatogr B Analyt Technol Biomed Life Sci, 2002 Jun 25, 773(2), 159 - 66
Study of different off-line sample processing procedures and the measurement of antibiotic and antiviral levels in human serum by high-performance liquid chromatography; Metz P et al.; We attempted to devise a preparation method for clinical samples that could be used for all antibiotics and antivirals . We studied thirteen antibiotics, including five penicillins, four cephalosporins, metronidazole, ofloxacin, and sulfamethoxazole and four protease inhibitors including indinavir, retonavir, nelfinavir, and sequinavir . We compared four sample preparation techniques including solvent precipitation, filtration and resin column . We employ HPLC methods based on a minimal number of columns and mobile phases . We were unable to find one sample preparation method that could be used for all antibiotics and antivirals . But, we did develop an algorithm for determining optimal processing procedures for all drugs.

Eur Respir J, 2002 May, 19(5), 966 - 75
Acute exacerbation of chronic obstructive pulmonary disease and antibiotics: what studies are still needed?
Sohy C, Pilette C, Niederman MS, Sibille Y.
The use of antibiotics in acute exacerbations of chronic bronchitis (AECBs) remains the subject of controversy despite considerable medical and socioeconomic implications . First, the contribution of bacterial infection to AECBs is difficult to assess in patients with chronic obstructive pulmonary disease (COPD) who are chronically colonized with respiratory pathogens . In addition, several studies suggest a major role of viral infections in AECBs . Secondly, it is unlikely that all COPD patients will benefit from antibiotics during AECBs . In particular, the benefit in mild COPD remains uncertain . Unfortunately, the number of studies complying with evidence-based medicine requirements is too small for definite recommendations in AECBs to be drawn up . Considering the impact of acute exacerbations of chronic bronchitis on chronic obstructive pulmonary disease patients, as well as the community, and the impact of antibiotic therapy on the development of bacterial resistance, there is an urgent need for the design of appropriate multicentric studies to define the usefulness of this type of treatment in acute exacerbations of chronic bronchitis.

J Am Pharm Assoc (Wash), 2002 May-Jun, 42(3), 428 - 31
Stability of three cephalosporin antibiotics in AutoDose Infusion System bags; Xu QA et al.; OBJECTIVE: To evaluate the physical and chemical stability of three commonly used cephalosporin antibiotic solutions packaged in AutoDose Infusion System bags stored and evaluated at appropriate intervals for up to 7 days at 23 degrees C and up to 30 days at 4 degrees C . SETTING: Laboratory . INTERVENTIONS: The test samples were prepared by adding the required amount of the cephalosporin antibiotic to the AutoDose Infusion System bags and diluting to the target concentration with 0.9% sodium chloride injection . MAIN OUTCOME MEASURES: Physical stability and chemical stability based on drug concentrations initially and at appropriate intervals over periods of up to 7 days at 23 degrees C and up to 30 days at 4 degrees C . RESULTS: All of the cephalosporin admixtures were clear when viewed in normal fluorescent room light and with a Tyndall beam . Measured turbidity and particulate content were low and exhibited little change . The cefazolin sodium-containing samples were colorless throughout the study . The admixtures with ceftazidime and ceftriaxone sodium had a slight yellow tinge initially, and the room temperature samples turned a frank yellow color after 5 days . The refrigerated samples did not change color . High-performance liquid chromatography analysis showed that cefazolin sodium and ceftriaxone sodium remained stable for 30 days and ceftazidime remained stable for 7 days at 4 degrees C . At room temperature, losses were much more rapid . Cefazolin sodium and ceftriaxone sodium retained at least 90% of their initial concentrations through 7 days and 5 days, respectively, when stored at 23 degrees C . Ceftazidime remained stable for only 1 day at 23 degrees C . CONCLUSION: Cefazolin sodium, ceftazidime, and ceftriaxone sodium exhibited physical and chemical stabilities consistent with those found in previous studies of these drugs . The AutoDose Infusion System bags did not adversely affect the physical and chemical stabilities of these three cephalosporin antibiotics.

J Nat Prod, 2002 May, 65(5), 779 - 82
Oviedomycin, an unusual angucyclinone encoded by genes of the oleandomycin-producer Streptomyces antibioticus ATCC11891; Mendez C et al.; Our investigations on the discovery of novel natural metabolites using type II polyketide synthase gene probes (actI/III) yielded an unusual angucyclinone, oviedomycin (2), when applied to the oleandomycin (1) producer Streptomyces antibioticus ATCC11891 . The novel natural product was produced using S . albus R(-)M(-) as a host strain, into which a cosmid containing the oviedomycin gene cluster was transformed . Its structure was elucidated by NMR spectroscopy and mass spectrometry.

J Endod, 2002 May, 28(5), 396 - 404
Antibiotic use by members of the American Association of Endodontists in the year 2000: report of a national survey; Yingling NM et al.; The purpose of this study was to determine the prescribing habits of active members of the American Association of Endodontists (AAE) with regard to antibiotics . A one-page, double-sided questionnaire was sent to the active members of the AAE living in the United States . The 1999 mailing list of 3203 members was obtained from the AAE, and the return rate was 50.1% (1606 surveys) . With a sample size over 1000, the study was able to distinguish differences to within 0.5% with power = 80% (at alpha = 5%) . The data were analyzed using descriptive statistics and chi-square tests of independence . Penicillin VK, 500 mg, 4 times a day, was the first choice antibiotic prescribed by 61.48% of respondents . Clindamycin (Cleocin), 150 mg, 4 times a day, was selected by 29.59% . For those patients with a penicillin allergy, 57.03% prescribed clindamycin and various erythromycin preparations were prescribed by 26.65% . A loading dose was used by 85.14% . The average duration of antibiotic therapy was 7.58 days . Those respondents involved in academics, either part-time or full-time, were significantly more likely to prescribe penicillin VK, 500 mg, 4 times a day at a rate of 85% versus those in part-time or full-time private practice at a rate of 67% . For cases of irreversible pulpitis, 16.76% of responding endodontists prescribed antibiotics . For the scenario of a necrotic pulp, acute apical periodontitis, and no swelling, 53.93% prescribed antibiotics . Almost 12% prescribed antibiotics for necrotic pulps with chronic apical periodontitis and a sinus tract . For the most part, the majority of the members of the AAE were selecting the appropriate antibiotic for use in orofacial infections, but there are still many who are prescribing antibiotics inappropriately . Although there were trends of improvement in some areas with regards to prescribing antibiotics, there were other areas where there had been no improvement in 25 years . Unless these trends change, our generation and those to come may not have effective antibiotics for use in the management of true orofacial infections.

Cancer Invest, 2002, 20(3), 420 - 33
Empirical oral antibiotic therapy for low risk febrile cancer patients with neutropenia; Koh A et al.; For over 30 years, fever and neutropenia in cancer patients has been treated with the utmost urgency, necessitating inpatient evaluation and immediate initiation of empirical broad-spectrum parenteral (i.v.) antibiotics . This practice is based on the recognition that delays in starting antibiotic therapy in febrile neutropenic patients have been associated with life-threatening infections and sometimes fatal consequences . Over the past decade, it has become evident that neutropenic cancer patients are not a homogeneous group and that practice guidelines may vary on their risk status . In fact, attempts have been made to stratify patients into high-risk and low-risk groups and differentiate treatment options respectively . Recent studies suggest that those neutropenic cancer patients who are at low risk may even be successfully treated with oral therapy, thus opening the possibility for ambulatory or home-based management . Oral antibiotic therapy, especially if safely delivered at home, offers a number of advantages including lower cost, improved quality of life (although the impact of shifting the burden of care from the hospital to the home setting on the patient, parent or care provider needs careful assessment) and a decreased risk for nosocomial infection.

J Infect Dis, 2002 Jun 1, 185(11), 1631 - 6 Epub 2002 May 17.
Effect of macrolide antibiotics on human endothelial cells activated by Chlamydia pneumoniae infection and tumor necrosis factor-alpha; Uriarte SM et al.; This study investigated the potential anti-inflammatory activity of 3 macrolide antibiotics, clarithromycin, roxithromycin, and azithromycin, in an in vitro model of transendothelial migration (TEM) . Human umbilical vein endothelial cells (HUVECs) were seeded in Transwell inserts, treated with serial dilutions of the antibiotics, and infected with Chlamydia pneumoniae or stimulated with tumor necrosis factor (TNF)-alpha . In HUVECs infected with C . pneumoniae or stimulated with TNF-alpha, both azithromycin and roxithromycin caused significant decreases in neutrophil and monocyte TEM, compared with antibiotic-free controls . Clarithromycin had no detectable effect in either group . Azithromycin caused significant decreases in interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1, whereas roxithromycin significantly decreased IL-8 . This study indicates heterogeneity in the anti-inflammatory activity of these antibiotics . Mechanisms of monocyte and neutrophil TEM inhibition by azithromycin and roxithromycin are unclear but may be partially due to inhibition of IL-8 and MCP-1 production.

J Dairy Sci, 2002 Apr, 85(4), 782 - 9
Trends in somatic cell counts, bacterial counts, and antibiotic residue violations in New York State during 1999-2000; van Schaik G et al.; Milk quality data on a month-by-month basis from March 1999 to December 2000 were studied from five of the largest milk plants operating in New York State . The analyses focused on bulk tank somatic cell count (SCC), bacterial counts in the form of plate loop count (PLC), and antibiotic residue violations in the pool of milk of New York State, their mutual relation, and the influence of farm size . The average SCC was 363,000 cells/ml, the average PLC was 24,400 bacteria/ml, and the average number of antibiotic residue violations in the pool of milk was 3.9 per 1000 producers . Each month between 72 and 88% of the milk pool had SCC levels in compliance with the European Union (EU) requirements (SCC < 400,000 cells/ml) . The findings in this study suggest that larger farms had lower SCC and PLC but more antibiotic violations . However, the larger farms contribute most to the SCC and PLC of the total pool of milk . Farms with high SCC also had higher PLC and more antibiotic violations . Measurable improvements in overall quality of the pool of milk in New York state would most likely occur by targeting incentives, education, and training programs for any farms with very high SCC and for larger farms with SCC between 400,000 and 750,000 cells/ml.

Med Clin (Barc), 2002 Apr 27, 118(15), 561 - 8
{Trends in antibiotic consumption in Spain, 1985-2000}; Lazaro Bengoa E et al.; BACKGROUND: The purpose of this study was to analyse the trend in antibiotics consumption to draw on the National Health System (NHS) over the last 16 years in Spain and its different Autonomous Communities (AC) . MATERIAL AND METHOD: Consumption data for all antibiotics used in Spain, either alone or in fixed-dose combinations, were obtained using the database ECOM . This database includes all the packages sold through retail pharmacies and reimbursed by the NHS . Data are expressed as defined dairy doses per 1,000 inhabitants per day (DHD), in accordance with the methodology recommended by the World Health Organization . Demographic data were provided by the National Institute of Statistics . RESULTS: In 1985 the overall consumption of antibiotics was 21.9 DHD, while in 2000 it was 20.4 DHD . It was possible to distinguish three phases over the study period . The first phase lasts until 1989, where a mild decreasing trend was observed (1.1 DHD; 5.0%), mainly due to the fall of fixed-dose combinations of antibiotics and the association of sulfamethoxazole-trimethoprim . The second phase, lasting until 1996, was characterized by a generalized increase in the consumption in all AC, with an average of 2.3 DHD (+ 11.1%), ranging from 0.4 to 4.6 DHD; this increase was mainly due to the marketing of new macrolides, cephalosporins and quinolones . Finally, there was a third phase beginning in 1996, where the consumption of antibiotics came into a sustained and generalized decline, ranging from 0.5 to 5.1 DHD, and depending on the AC (national average 2.7 DHD, 11.7% lower than that in 1996) . This latter trend was mainly due to the fall of wide-spectrum penicillins . Differences between AC regarding the level of consumption were huge over the study period, although the pattern of use was quite similar . There was, for instance, a difference of 10.4 DHD between Region de Murcia and Islas Baleares in 2000, or 9.9 DHD between the former and Madrid in the same year . CONCLUSIONS: The consumption of antibiotics in Spain and all its AC has declined since 1996, probably related to the campaigns launched by public administrations to promote the rational use of these agents . The main subgroup involved in this trend is wide-spectrum penicillins . Differences in antibiotics use between AC are too big to be accounted for by different epidemic patterns and, therefore, should be analysed further.

Mol Pharmacol, 2002 Jun, 61(6), 1348 - 58
A novel beta-lactam antibiotic activates tumor cell apoptotic program by inducing DNA damage; Smith DM et al.; Many of the anticancer drugs in current use are toxic and thus limited in their efficacy . It therefore becomes essential to develop novel chemotherapeutic agents with lower levels of toxicity . The beta-lactam antibiotics have been used for many years to treat bacterial infections with limited or no toxicity . Until now, it has never been shown that beta-lactams could kill tumor cells . Here, for the first time, we have discovered and characterized the apoptosis-inducing properties of a family of novel beta-lactam antibiotics against human leukemia, breast, prostate, and head-and-neck cancer cells . We found that one particular lead compound (lactam 1) with an N-methylthio group was able to induce DNA damage and inhibit DNA replication in Jurkat T cells within a 2-h treatment . This was followed by p38 mitogen-activated protein kinase activation, S phase arrest, and apoptotic cell death . p38 was found to be a central player in beta-lactam-induced apoptosis and resided downstream of DNA damage but upstream of caspase activation . Accompanying caspase-8 activation was cleavage of the pro-apoptotic Bcl-2 family protein Bid, and release of the mitochondrial cytochrome c . This was also associated with activation of caspase-9 and -3 . Analogs of lactam 1 in which the N-methylthio group was replaced with other organothio chains exhibited progressive decreased potencies to induce DNA damage, p38 kinase activation, S phase arrest, and apoptosis, demonstrating requirement of the N-methylthio group . Because of the ease of synthesis and structural manipulation, we believe these beta-lactams may have the potential to be developed into anticancer agents.

J Antibiot (Tokyo), 2002 Mar, 55(3), 301 - 7
Simocyclinones, novel cytostatic angucyclinone antibiotics produced by Streptomyces antibioticus Tü 6040 II . Structure elucidation and biosynthesis; Holzenkampfer M et al.; The simocyclinones D4 (1) and D8 (2), members of a novel class of antibiotics, were isolated from the mycelial extract of Streptomyces antibioticus Tu 6040 and consist of angucyclinone, deoxysugar, octatetraene dicarboxylate and aminocoumarin structural elements . The structure elucidation was done by one and two dimensional NMR experiments, and other spectroscopic methods in combination with incorporation experiments using 13C labelled precursors.

Pharmacotherapy, 2002 May, 22(5), 630 - 6
Risk of clinical blood dyscrasia in a cohort of antibiotic users; Huerta C et al.; Blood dyscrasias, although rare, can be fatal . Many drugs, including antibiotics, are associated with these dyscrasias . We conducted a cohort study with a nested case-control analysis using data from the General Practice Research Database to estimate incidence rates of clinical blood dyscrasias in the general population and to examine their association with use of antibiotic drugs . The study population consisted of patients aged 5-69 years receiving at least one antibiotic prescription from January 1994-September 1998 . The final cohort consisted of 822,048 persons who received 1,507,307 antibiotic prescriptions during the study period . The main outcome measure was a diagnosis of neutropenia, agranulocytosis, hemolytic anemia, thrombocytopenia, bicytopenia, pancytopenia, or aplastic anemia . We confirmed 122 patients who developed clinical blood dyscrasias . The incidence was 3.3/100,000 person-years in the general population . Patients older than 60 years (relative risk {RR} 2.8, 95% confidence interval {CI} 1.6-5.0) and those who took phenothiazines (RR 49.0, 95% CI 4.9-488.2) had an increased risk of blood dyscrasia . Users of antibiotics had an RR of 4.4 (95% CI 2.6-7.5), and patients taking more than one class of antibiotics had an RR of 29.1 (95% CI 9.1-92.8) . Among individual antibiotic classes, the greatest risk was with cephalosporins (RR 13.8, 95% CI 3.6-52.6) . Although uncommon, our study supports an association between blood dyscrasias and antibiotics.

Metab Eng, 2002 Apr, 4(2), 138 - 50
Carbon flux distribution in antibiotic-producing chemostat cultures of Streptomyces lividans; Avignone Rossa C et al.; The carbon metabolism of derivatives of Streptomyces lividans growing under phosphate limitation in chemostat cultures and producing the antibiotics actinorhodin and undecylprodigiosin was investigated . By applying metabolic flux analysis to a stoichiometric model, the relationship between antibiotic production, biomass accumulation, and carbon flux through the major carbon metabolic pathways (the Embden Meyerhoff Parnas and pentose-phosphate pathways) was analyzed . Distribution of carbon flux through the catabolic pathways was shown to be dependent on growth rate, as well as on the carbon and energy source (glucose or gluconate) used . Increasing growth rates promoted an increase in the flux of carbon through glycolysis and the pentose-phosphate pathway . The synthesis of both actinorhodin and undecylprodigiosin was found to be inversely related to flux through the pentose-phosphate pathway.

Structure (Camb), 2002 Mar, 10(3), 301 - 10
Structural basis for the cyclization of the lipopeptide antibiotic surfactin by the thioesterase domain SrfTE; Bruner SD et al.; Many biologically active natural peptides are synthesized by nonribosomal peptide synthetases (NRPS) . Product release is accomplished by dedicated thioesterase (TE) domains, some of which catalyze an intramolecular cyclization to form macrolactone or macrolactam cyclic peptides . The excised 28 kDa SrfTE domain, a member of the alpha/beta hydrolase enzyme family, exhibits a distinctive bowl-shaped hydrophobic cavity that hosts the acylpeptide substrate and tolerates its folding to form a cyclic structure . A substrate analog confirms the substrate binding site and suggests a mechanism for substrate acylation/deacylation . Docking of the peptidyl carrier protein domain immediately preceding SrfTE positions the 4'-phosphopantheinyl prosthetic group that transfers the nascent acyl-peptide chain to SrfTE . The structure provides a basis for understanding the mechanism of acyl-PCP substrate recognition and for the cyclization reaction that results in release of the macrolactone cyclic heptapeptide.

Bioresour Technol, 2002 Apr, 82(2), 205 - 8
The effects of certain antibiotics on biogas production in the anaerobic digestion of pig waste slurry; Lallai A et al.; Antibiotics commonly used in the treatment of pigs - amoxicillin trihydrate, oxytetracycline hydrochloride and thiamphenicol were added at different concentrations to aliquots of pig waste slurry plus anaerobic sludge in serum bottles . The biogas production and methane concentration in the headspace were monitored to determine the effect of the antibiotics on the anaerobic process . With thiamphenicol significant differences in methane production were found for concentrations of 80 and 160 mg l(-1) slurry . Compared to the control, only minor differences in methane production were noted in the bottles to which amoxicillin (60 and 120 mg l(-1)) had been added . Methane production was about the same for the bottles with different oxytetracycline concentrations (125 and 250 mg l(-1)) and for the control.

J Antibiot (Tokyo), 2002 Feb, 55(2), 191 - 203
Total synthesis of novel antibiotics pyloricidin A, B and C and their application in the study of pyloricidin derivatives; Hasuoka A et al.; The novel natural antibiotics pyloricidin A, B and C, which possess potent and highly selective anti-Helicobacter pylori activity, were synthesized from D-galactosamine as a chiral template for the common (2S,3R,4R,5S)-5-amino-2,3,4,6-tetrahydroxyhexanoic acid moiety . The synthetic strategy, using 2-amino-2-deoxyuronic acid derivatives as key intermediates, was also useful to prepare a series of derivatives modified at the beta-D-phenylalanine and with altered stereochemistry on the 5-amino-2,3,4,6-tetrahydroxyhexanoic acid moiety . From the drastic decrease of their anti-H . pylori activity, it was clear that the beta-D-phenylalanine part and the stereochemistry of the 5-amino-2,3,4,6-tetrahydroxyhexanoic acid moiety were significant for the activity.

J Antibiot (Tokyo), 2002 Feb, 55(2), 134 - 40
NMR analysis of quinocycline antibiotics: structure determination of kosinostatin, an antitumor substance from Micromonospora sp . TP-A0468; Igarashi Y et al.; A quinocycline antibiotic, kosinostatin, was isolated from the culture broth of Micromonospora sp . TP-A0468 along with isoquinocycline B . Structure of kosinostatin was determined to be the stereoisomer of isoquinocycline B regarding to the stereochemistry at the C-2' spiro carbon by NMR analysis . Kosinostatin isomerizes to isoquinocycline B through the inversion of the stereocenter at C-2' . Comparison of physico-chemical properties indicated that kosinostatin is presumably identical with quinocycline B isolated by CELMER et al . from Streptomyces aureofaciens.

J Palliat Care, 2002 Spring, 18(1), 25 - 8
Antibiotic use in the last week of life in three different palliative care settings; Oneschuk D et al.; The purpose of this study was to examine the frequency and types of antibiotics prescribed in the last week of life in three different palliative care settings, including an acute care hospital, tertiary palliative care unit, and three hospice units . A total of 150 consecutive patients were evaluated, 50 in each of the three settings . Twenty-nine patients (58%) in the acute hospital setting, 26 (52%) in the tertiary palliative care unit, and 11(22%) in the hospice settings were prescribed antibiotics . In the acute care and tertiary palliative care settings, the most frequent route of antibiotic administration was intravenous and, in the hospice setting, oral . We conclude that there is marked variability in the numbers and types of antibiotics prescribed in these different palliative care settings in the last week of life . The high use of intravenous antibiotics and the large number of patients who were still receiving antibiotics at the time of death indicate the need for further prospective studies.

J Biomed Mater Res, 2002 Jul, 61(1), 66 - 74
Self-curing acrylic formulations containing PMMA/PCL composites: properties and antibiotic release behavior; Mendez JA et al.; Partially biodegradable acrylic composites containing poly(methyl methacrylate)-poly(epsilon-caprolactone) (PMMA/PCL) systems were prepared by mixing the corresponding PMMA/PCL beads (89:11, 86:14, 83:17, and 77:23 weight ratio) used as solid phase with methyl methacrylate (MMA) (liquid phase) in a solid/liquid ratio of 1.5:1 . The physical and chemical microheterogeneity of these beads influenced significantly the curing parameters, because several aspects involved in the polymerization reaction are closely related to both morphology and size distribution of the particles . In vitro behavior was studied by immersion in simulated body fluid at pH = 7.4 and 37 degrees C for more than 8 weeks and the composition was followed by 1H-nuclear magnetic resonance spectroscopy . Approximately 2% wt/wt weight loss was observed after a period of 8 weeks for the composites richest in PCL . Mechanical properties of the dry and wet specimens were evaluated by compressive and tensile tests . In all cases, the presence of PCL in the composites provided a significant decrease in both compressive strength and elastic modulus compared with plain PMMA . Tensile and compressive strength also decreased significantly after 2 weeks of immersion in simulated body fluid compared with dry specimens . The self-curing composites based on PMMA/PCL beads and loaded with 3% wt/wt vancomycin were evaluated as carriers for local release of antibiotics . The composite prepared with beads of PMMA/PCL ratio 86:14 was the most effective . It eluted 64% of the initial drug within the first 5 h, allowing progressive release of nearly the total amount of the initial drug (90%) in approximately 2 months . The results obtained suggest that the described composites can be suitable for antibiotic release in non-load bearing graft applications .

Arch Pediatr, 2002 Apr, 9(4), 358 - 64
{Procalcitonin and viral meningitis: reduction of unnecessary antibiotics by measurement during an outbreak}; Marc E et al.; OBJECTIVE: Viral meningitis are often treated with antibiotics in emergency because routine analysis of CSF is not always efficient for distinguishing between viral and bacterial infection . The aim of the study was to evaluate the usefulness of procalcitonin (PCT) to reduce antibiotic treatments . METHODS AND RESULTS: A blood PCT level < 0.5 ng/mL was prospectively used for the diagnosis of viral origin of meningitis in 58 patients (two months-14 years), in which enterovirus was isolated by culture or PCR during an outbreak (May-June 2000) . CSF cells range was 10 to 2800/mL (m: 244), PMN 5 to 2464/mL and CSF proteins range was 0.19 to 0.92 mg/dL (m: 0.37) . Seventeen patients received antibiotic therapy in admission . In nine patients, PCT (dosage was routinely measured 3/week) result < 0.5 ng/mL was obtained in 24 h and in 48 h in six: treatment was then stopped and children led hospital . In two patients, PCT was > 1 ng/mL because of bacterial coinfection . CSF and PCT values were similar to those of an already published control group . CONCLUSION: PCT dosage allowed to shorten hospitalization of 4.47 (controls) to 2.06 (patients) days in patients receiving unnecessary antibiotic treatments . During this outbreak, PCT dosage allowed to reduce 40 days of hospitalization.

Int Surg, 2001 Jul-Sep, 86(3), 176 - 83
Prophylactic antibiotics after severe trauma: more is not better; Velmahos GC et al.; After severe trauma, physicians frequently use multiple antibiotics for prolonged periods of time to prevent sepsis, based on intuition rather than scientific evidence . Over a 1-year period (January-December 1999) we included prospectively 112 critically injured patients who required an operation and/or chest tube insertion and stayed for more than 2 days in the intensive care unit (ICU) . Of these patients, 46 received a single prophylactic antibiotic for 24 hours (group SING+SHORT), and 66 received one or more prophylactic antibiotics for more than 24 hours (group MULT+LONG), based on physician discretion . Twenty-seven outcome parameters were collected to compare the effect of the different prophylactic antibiotic regimens . The two groups were similar in regard to overall injury severity, age, gender, mechanism of injury, and physiologic condition on admission . However, more SING+SHORT patients had an abdominal operation (83% versus 62%, P = 0.02), and more MULT+LONG patients had an orthopedic operation (35% versus 15%, P = 0.03) . There was no difference in sepsis (41% versus 42%, P = 1.0), organ failures (37% versus 50%, P = 0.18), mortality (7% versus 12%, P = 0.52), ICU stay (14 +/- 2.5 versus 16 +/- 2 days, P = 0.57), hospital stay (26 +/- 3 versus 28 +/- 2 days, P = 0.53), or any other outcome parameter . Independent risk factors for sepsis were blunt mechanism of trauma, Injury Severity Score > or = 25, and more than two units of blood transfused over the first 24 hours, but not the amount of prophylactic antibiotics given . In conclusion, we found that 24-hour prophylaxis with a single broad-antibiotic is as effective as prophylaxis for longer periods of time with multiple spectrum antibiotics for critically injured patients at high risk for sepsis.

Hepatogastroenterology, 2002 Mar-Apr, 49(44), 330 - 4
The effect of biliary decompression on antibiotic biliary excretion; Yamamoto S et al.; BACKGROUND/AIMS: Raised biliary pressure may affect antibiotic biliary excretion . We evaluated whether biliary decompression for patients with biliary obstruction could improve antibiotic biliary excretion . METHODOLOGY: Eight patients with common bile duct obstruction undergoing endoscopic nasobiliary drainage were evaluated . During endoscopic cannulation, biliary pressure above the obstruction and antibiotic concentrations in the bile and peripheral blood were determined 60 min after the intravenous antibiotic (panipenem) administration . RESULTS: Biliary pressure was initially elevated above normal in all the patients, but normalized after biliary drainage for 5 to 7 days . At the initial endoscopic retrograde cholangiopancreatography, the aspirated bile contained low or undetectable levels of the antibiotic, but the mean bile panipenem concentration and the mean bile/plasma ratio of panipenem concentrations significantly improved after biliary decompression . CONCLUSIONS: The results suggest an important role of biliary pressure in determining antibiotic transfer into the bile.

Clin Microbiol Infect, 2001, 7 Suppl 6, 22 - 6
Minimum antibiotic stewardship measures; Gould LM; European Study Group on Antibiotic Policies; An ESCMID study group on antibiotic policies (ESGAP) was formed in 1998 . Several subgroups have been formed to develop key strategy in various aspects of antibiotic stewardship . Sub group III was formed to lead on antibiotic stewardship in European hospitals . This article is a final version of guidelines that have been developed by the group through internet discussion . A provisional version has been posted on the ESGAP section of ESCMID's website . Some important aspects of community antibiotic use have also been included.

J Fam Pract, 2002 Apr, 51(4), 324 - 8
Do delayed prescriptions reduce the use of antibiotics for the common cold? A single-blind controlled trial; Arroll B et al.; OBJECTIVE: To test the use of a delayed prescription compared with instructions to take antibiotics immediately in patients presenting to family physicians with upper respiratory tract infections (common colds) . STUDY DESIGN: Randomized controlled single-blind study . POPULATION: Subjects were 129 patients presenting with the common cold who requested antibiotics or whose physicians thought they wanted them . All patients were in a family practice in Auckland, New Zealand, consisting of 15 physicians (9 male, 6 female) who had completed medical school between 1973 and 1992 . OUTCOMES MEASURED: Outcomes were antibiotic use (taking at least 1 dose of the antibiotic), symptom scores, and responses to the satisfaction questions asked at the end of the study . RESULTS: Patients in the delayed-prescription group were less likely to use antibiotics (48%, 95% CI, 35%-60%) than were those instructed to take antibiotics immediately (89%, 95% CI, 76%-94%) . Daily body temperature was higher in the immediate-prescription group . The lack of difference in the symptom score between the 2 groups suggests that there is no danger in delaying antibiotic prescriptions for the common cold . CONCLUSIONS: Delayed prescriptions are a safe and effective means of reducing antibiotic consumption in patients with the common cold . Clarification of patient expectations for antibiotics may result in a lower prescription rate . When the patient demands a prescription, delaying its delivery has the potential to provide gentle education.

J Fam Pract . 2002 Mar;51(3):265.
Do primary care physicians underprescribe antibiotics for peptic ulcer disease? Report from an Italian research network; Palombi L et al.; OBJECTIVE: To determine how often primary care physicians prescribe eradication therapy for peptic ulcer disease (PUD) and nonulcer dyspepsia (NUD) . STUDY DESIGN: During a 2-year period (1998-2000) we analyzed data concerning patients with PUD or NUD seen by 80 Italian primary care physicians uniformly distributed throughout the country . We classified patients as having a definitive or a presumptive diagnosis on the basis of the completeness of the diagnostic workup and interpreted the prescription of antibiotics for dyspepsia as evidence of attempted eradication of Helicobacter pylori . POPULATION: Consecutive ambulatory patients . OUTCOMES MEASURED: The frequency with which predefined groups of patients received eradication therapy . RESULTS: Of 6866 patients, 690 (10%) received eradication therapy . Of 2162 patients with PUD, 596 (27.6%) received eradication therapy; of 4704 patients with NUD, however, only 94 (2%) received this treatment (P =.0001) . A total of 341 (37.7%) of 904 PUD patients with a definitive diagnosis were given eradication therapy and 255 (20.3%) of 1258 PUD patients with a presumptive diagnosis were given therapy (P &lt.0001) . In NUD patients, 7 of 743 (0.9%) with a definitive diagnosis received eradication therapy, while 87 (2.2%) of 3961 of those with a presumptive diagnosis were given the same therapy (P =.025) . CONCLUSIONS: While Italian primary care physicians appropriately target eradication therapy for H pylori infection in patients with peptic ulcer disease rather than nonulcer disease, the intervention was still underused in these patients . Improvements in this prescribing behavior are needed.

Acta Pharmacol Sin, 2002 May, 23(5), 430 - 8
Interactions between quinolone antibiotics and phospholipid membrane for prediction of alveolar macrophage uptake in vitro; Sun J et al.; AIM: To compare the effectiveness of the different parameters for predicting alveolar macrophage (AM) uptake, interactions between quinolones, including two amphipathic bases, and phospholipid membrane were evaluated by three different membrane-like systems . METHODS: AM cells were isolated, cultured as confluent monolayers, then incubated with drug solution at 37 degrees C . At designated time points, uptake was terminated by aspirating solution, followed by rinsing, cell lysis, a nd analysis of drug and protein concentrations . Immobilized artificial membrane (IAM) chromatography and liposome/buffer system were used to determine interactions with phospholipid membrane, expressed as lipophilicity indices, lg k(IAM) and lg D(L/B,7.4), respectively . An n-octano l/buffer system was also employed as the reference hydrophobicity, lg D(O/B,7.4)4 . RESULTS: For the tested set, lg k(IAM) correlated more significantly with lg D(L/B,7.4) (r2 = 0.93) than with lgD(O/B,7.4) (r2 = 0.65) . There were better correlations between either lg k(IAM) or lg D(L/B,7.4) and the extent of accumulation in AM than did lg DO/B,7.4 (r2 = 0.89, 0.92, and 0.67, respectively) . Correlations obtained using lg k(IAM), lg D(L/B,7.4), and lg D(O/B,7.4) were comparable when regressed against the logarithm of influx rate into AM f or a set consisting of five amphoteric quinolones and quinidine . CONCLUSION: Liposome/buffer system and IAM chromatography could provide nearly similar scale of lipophilicity measurement, both distinct from n-octanol/buffer system . Accumulation by AM was better described by lg k(IAM) or lg D(L/B,7.4) than lg D(O/B,7.4), and the passive diffusion was principal form during drugs transported across AM membrane.

Appl Environ Microbiol, 2002 May, 68(5), 2404 - 10
Enzymatic synthesis of aminoglycoside antibiotics: novel adenosylmethionine:2-deoxystreptamine N-methyltransferase activities in hygromycin B- and spectinomycin-producing Streptomyces spp . and uses of the methylated products; Walker JB; Aminocyclitols structurally related to streptamine, a 1,3-diaminocyclitol, are common components of the RNA-binding aminoglycoside antibiotics . The respective aminocyclitol cores of hygromycin B and spectinomycin are N(3)-methyl-2-deoxy-D-streptamine and N(1),N(3)-dimethyl-2-epi-streptamine . Adenosyl{methyl-(14)C}methionine:2-deoxystreptamine N-methyltransferase activities were detected in extracts of early-stationary-phase mycelia of the hygromycin B producer Streptomyces hygroscopicus subsp . hygroscopicus ATCC 27438 and the spectinomycin producer Streptomyces flavopersicus ATCC 19756 . Extracts of both strains methylated the N(1)- and N(3)-amino groups of 2-deoxystreptamine, streptamine, and 2-epi-streptamine; the N(1)-amino group of N(3)-methyl-2-deoxy-D-streptamine, and the N(3)-amino group of N(1)-ethyl-2-deoxy-D-streptamine, the semisynthetic aminocyclitol of netilmicin . The mono{(14)C}methyl derivatives of 2-deoxystreptamine, streptamine, and 2-epi-streptamine were excellent substrates for L-glutamine:aminocyclitol aminotransferase and thereby provided a sensitive assay for derepression of this key enzyme, a generic biosynthetic marker that we have shown to be the only enzyme common to the biosyntheses of all major aminoglycoside antibiotics . Other prospective uses for these methyl-labeled 2-deoxystreptamine analogs are also described.

J Org Chem, 2002 May 3, 67(9), 2934 - 41
Studies on the formation and incorporation of streptolidine in the biosynthesis of the peptidyl nucleoside antibiotic streptothricin F; Jackson MD et al.; Streptothricin F (STF, 1) is a peptidyl nucleoside antibiotic produced by Streptomyces lavendulae . Studies were conducted to address the formation and timing of incorporation of the arginine-derived base streptolidine (4) during the biosynthesis of 1 . {guanidino-(13)C}Streptolidine (10) was prepared by modification of an established method and used in whole-cell incorporation experiments . Analysis of the purified STF by (13)C NMR revealed a 1.9% enrichment of the guanidino carbon, confirming 4 as an advanced precursor to 1 and supporting proposals that 1 is assembled via a convergent biosynthetic pathway . To identify advanced intermediates in the conversion of L-arginine to 4, (2S,3R)-{guanidino-(13)C}capreomycidine (32) was prepared from oxazolidine aldehyde (18) via 1,1-dimethylethyl (4R,1'S)-4-(1',3'-diaminopropyl)-2,2-dimethyl-3-oxazolidinecarboxylate (30) . Treatment of 30 with Br(13)CN yielded the corresponding diprotected amino alcohol, which was readily converted to 32 . The STF isolated from whole-cell incorporation experiments with 32 showed no significant (13)C enrichment at the guanidino carbon . These results suggest that 32 may be an enzyme-bound intermediate, unable to enter the cell, or is not a precursor to STF.

Biochemistry, 2002 Apr 30, 41(17), 5383 - 96
Effect of magnesium ions on the tertiary structure of the hepatitis C virus IRES and its affinity for the cyclic peptide antibiotic viomycin; Vos S et al.; A key ion-dependent folding unit within the hepatitis C IRES comprises the IIIef junction and pseudoknot . This region is also important in recruitment of the 40S ribosomal subunit . Here, circular dichroism is used to study the influence of metal ions on the structure and stability of this region . Comparison of the thermal stability of an IRES fragment encompassing subdomains IIIe/f and IV (named 3EF4) with that of a larger fragment also possessing subdomain IIId (3DEF4) indicates an additional stabilizing effect of Mg(2+) ions on the latter fragment . Magnesium and potassium ions stabilize both fragments through nonspecific counterion effects . The additional effect of magnesium on 3DEF4, observed in the absence or presence of 100 mM KCl, is attributed to a nonspecific but high-affinity site for metal ions created by a region of unusual high charge density . Subdomain IIId presumably participates in tertiary packing interactions that provide such a site . Viomycin binds to the full-length IRES and RNA fragments with K(d) values of 25-55 microM . Interestingly, viomycin binding to the two fragments is affected differently by Mg(2+); noncompetitive inhibition of binding to 3DEF4 is observed, whereas binding to 3EF4 is not impaired . Formation of a Mg(2+)-stabilized tertiary fold, involving subdomain IIId, may thereby hinder viomycin binding to 3DEF4 indirectly . Mutational and deletion studies locate viomycin binding within subdomains IIIe/f rather than within the pseudoknot . In pseudoknot mutants, Mg(2+) ions have different effects on viomycin binding and thermal stability, suggesting altered tertiary interactions involving subdomain IIId.

Curr Opin Infect Dis, 2000 Jun, 13(3), 233 - 240
Phagocytosis and killing of intracellular pathogens: interaction between cytokines and antibiotics; Ouadrhiri Y et al.; Phagocytosis and bacterial killing are the primary functions of macrophages . Among the mechanisms involved in the phagocytic process, cytokines, especially those of T-helper 1 profile, appear to influence considerably the internalization and the intracellular fate of the pathogen within the macrophage . In particular, the evidence for a cooperation of cytokines with antibiotics in intracellular infection could provide new therapeutic approaches to intracellular infectious diseases in the future.

Anticancer Drug Des, 2001 Apr-Jun, 16(2-3), 143 - 53
The role of ring D in the antitumour antibiotic streptonigrin: metal complexation, DNA binding and topoisomerase inhibition by ABC ring analogues of streptonigrin; Anderberg PI et al.; interaction of 7-amino-2-(6'-carboxy-2'-pyridyl)-6-methoxy-5,8-quinolinedione, an ABC ring analogue of the antitumour antibiotic streptonigrin, with zinc(II), oligonucleotides and DNA in the presence of zinc(II), and on the relaxation of DNA by topoisomerase II, has been studied . This ligand contains the key functional groups present in streptonigrin required for biological activity, but lacks the phenolic ring D which confers optical activity on streptonigrin . Variable temperature NMR experiments showed that in the presence of zinc(II) triflate, the methyl ester of the ligand forms a mixture of 1:1 and 1:2 metal:ligand bipyridyl complexes, whose relative stabilities are temperature dependent . Titrations of the water-soluble ligand with zinc(II) nitrate at room temperature showed that the predominant species present in aqueous solution at physiological pH is the 1:1 bipyridyl complex . The interaction of the ligand with the hexanucleotides d(GCATGC)2 and d(ATGCAT)2 was studied by 1H- and 31P-NMR spectroscopy . In the presence of 1 equiv of zinc(II) nitrate and 1 equiv of the ligand, small changes in chemical shifts of the proton resonances associated with the purine resonances were detected consistent with a weak interaction of the zinc(II) complex of the ligand with the oligonucleotides, possibly via a groove binding mechanism . UV-VIS titrations showed a weak interaction of the ligand with calf thymus DNA and poly(dG-dC)2 in the presence of zinc(II) but negligible interaction with poly(dA-dT)2 . Gel electrophoresis experiments showed that, in contrast to streptonigrin, the ligand did not inhibit the relaxation of plasmid DNA by human topoisomerase II . These results show that the interaction of the ABC ligand with zinc(II), oligonucleotides, DNA and topoisomerase II is different to streptonigrin and hence the design of biologically active ABC ring analogues of streptongrin that operate via different mechanisms should be possible.

Antimicrob Agents Chemother, 2002 May, 46(5), 1174 - 82
Biosynthetic gene cluster of simocyclinone, a natural multihybrid antibiotic; Trefzer A et al.; The entire simocyclinone biosynthetic cluster (sim gene cluster) from the producer Streptomyces antibioticus Tu6040 was identified on six overlapping cosmids (1N1, 5J10, 2L16, 2P6, 4G22, and 1K3) . In total, 80.7 kb of DNA from these cosmids was sequenced, and the analysis revealed 49 complete open reading frames (ORFs) . These ORFs include genes responsible for the formation and attachment of four different moieties originating from at least three different pools of primary metabolites . Also in the sim gene cluster, four ORFs were detected that resemble putative regulatory and export functions . Based on the putative function of the gene products, a model for simocyclinone D8 biosynthesis was proposed . Biosynthetic mutants were generated by insertional gene inactivation experiments, and culture extracts of these mutants were analyzed by high-performance liquid chromatography . Production of simocyclinone D8 was clearly detectable in the wild-type strain but was not detectable in the mutant strains . This indicated that indeed the sim gene cluster had been cloned.

AORN J, 1999 Mar, 69(3), 542 - 5, 548-50
The millennium bug--do we have the right antibiotics?
Remmert KW.
This article introduces readers to the scope of the Year 2000 (Y2K) issue . In addition to describing how this problem came to be, the author examines the extent of the problem as defined by professionals in information technology . The author also explores what the cost of fixing the problem may be and what industry is doing to mitigate the effects the Y2K bug will have on patient care, supplies, and financial operations . The author expresses the need for caregivers to have a greater interest in the problem and to ask questions about what is being done at individual institutions.

Curr Opin Hematol, 2002 May, 9(3), 215 - 21
Antibiotics and growth factors in the management of fever and neutropenia in cancer patients; Garcia-Carbonero R et al.; The association of neutropenia and infection continues to be a major cause of morbidity and mortality in cancer patients receiving myelosuppressive chemotherapy . Prompt hospitalization and initiation of empirical intravenous broad-spectrum antibiotics has been the standard of care during the past three decades . Recently, risk-assessment models have been developed that allow the identification of febrile neutropenic patients that are at low risk for medical complications and mortality . New treatment strategies are being evaluated in this low-risk patient population to safely reduce toxicity, decrease costs, and improve quality of life . These include early shift from intravenous therapy to oral antibiotics, immediate initiation of oral empiric treatment, early hospital discharge, or outpatient care . A risk-based approach should also be applied to the use of colony-stimulating factors in this setting . Growth factors should not be routinely administered to neutropenic patients with uncomplicated febrile episodes . However, recent data support their use in populations with high-risk neutropenic fever.

Zhonghua Fu Chan Ke Za Zhi, 2002 Jan, 37(1), 25 - 6
{Analysis of prophylactic antibiotics for cesarean section}; Li C et al.; OBJECTIVE: To study the appropriate antibiotic for prophylactic use in cesarean section . METHODS: The effects and side effects of prophylatic antibiotics in 1 266 cesarean section were studied retrospectively . Six regiems were engaged: (1) Penicillin and Ampicillin; (2) Mezlocillin sodium; (3) Sulbactam and Ampicillin; (4) Ciprofloxacin; (5) Clindamycin; (6) Cefacidal . RESULTS: The duration of postoperative body temperature return to normal of 1 - 6 group is (54.0 +/- 28.4) hours, (48.9 +/- 27.8) hours, (49.9 +/- 23.9) hours, (58.6 +/- 33.7) hours, (52.5 +/- 25.2) hours, (63.1 +/- 51.1) hours respectively . It was longer in cefazolin group than the others . There were less puerperal morbidity and side effects of Mezlocillin . CONCLUSIONS: Penicillin and Ampicillin are still the most common choices as prophylatic antibiotic in cesarean section . Mezlocillin is appropriate as well.

Photochem Photobiol, 2002 Mar, 75(3), 237 - 48
Spectroscopic properties of fluoroquinolone antibiotics in water-methanol and water-acetonitrile mixed solvents; Park HR et al.; The fluorescence properties of ofloxacin (OFL), norfloxacin (NOR) and flumequine (FLU) were studied in H2O-CH3OH and H2O-CH3CN mixed solvents because these solvents were thought to behave as a biological mimetic system . The emission spectra of OFL and NOR were very sensitive to the composition of the solvents . In the Lippert-Mataga analysis of the steady-state fluorescence data of OFL and NOR, clear reverse solvatochromism was exhibited in both mixed solvents . This observation can be explained by the twisted excited-state intramolecular charge transfer, which is accelerated by water . Theoretical treatments further support these results . The radiative and nonradiative rate constants were analyzed as a function of solvent dipolarity-polarizability (pi*) and hydrogen-bond donor acidity (alpha) . These results were well consistent with the suggested mechanism of the excited-state chemical process of OFL and NOR, which depended upon the solvent-solute interactions such as bulk dielectric effects and specific hydrogen-bonding interactions . However, the influence of dielectric effects was more significant . The solvent structures of H2O-CH3CN and the preferential solvation by water were also examined . The emission spectra of FLU do not exhibit any characteristic responses to the properties of the environment.

Rapid Commun Mass Spectrom, 2002, 16(9), 823 - 33
Mass spectrometric fragmentation of cyclic peptides belonging to the polymyxin and colistin antibiotics studied by ion trap and quadrupole/orthogonal-acceleration time-of-flight technology; Govaerts C et al.; Electrospray ionization linked to quadrupole/orthogonal-acceleration time-of-flight (Q/oaTOF) and ion trap equipment was used to study the fragmentation behavior of the linear side-chain cyclized peptides of the polymyxin B and E antibiotics . This study exemplifies both the benefits and the drawbacks of mass spectrometric techniques for the determination of the sequence of such complex linear side-chain cyclized peptides . Q/oaTOF accurate mass measurements did not help sufficiently to assign the product ions observed in the product ion spectra . An ion trap mass spectrometer providing MS(n) capability was used to eliminate ambiguities encountered with a single MS/MS approach . The complex fragmentation behavior of these compounds of well-established structure is described which could be useful for structural characterization of unknown substances related to polymyxin B and E in the future .

FEBS Lett, 1971 Feb 12, 13(1), 65 - 67
Peptidyl puromycin synthesis; effect of several antibiotics which act on 50 S ribosomal subunits; Tanaka K et al.; The effects of several antibiotics which are know to bind with 50 S ribosomal subunits, on the formation of several di- and tri-peptidyl puromycins have been examined . Tylosin and spiramycin inhibited the formation of phenylalanyl-(14)C-phenylalanyl-puromycin, glycyl-(14)C-phenyllalanyl-puromycin, leucyl-(14)C-phenylalanyl-puromycin, N(epsilon)-carbobenzoxylysyl-(14)C-phenylalanyl-puromycin, and valyl-glycyl-(14)C-phenylalanyl-puromycin as well as N-acetyl-(14)C-phenylalanyl-puromycin . Of these compounds, erythromycin and oleandomycin selectively inhibited the formation of phenylalanyl-(14)C-phenylalanyl-puromycin . Although chloramphenicol and lincomycin inhibited the formation of most of these peptidyl puromycins, the formation of phenylalanyl-(14)C-phenylalanyl-puromycin and leucyl-(14)C-phenylalanyl-puromycin was found to be resistant to these antibiotics . So far, no significant effect of siomycin has been observed on pepetidyl puromycin formation in the absence of G factor.

FEBS Lett, 1970 Oct, 10(5), 339 - 342
Optical rotatory dispersion properties of nucleic acid complexes with the oligopeptide antibiotics distamycin A and netropsin; Zimmer C et al.; ORD measurements of nucleic acids in the presence of the oligopeptides netropsin and distamycin A have indicated association of the antibiotics with DNA and strong conformational changes of the DNA structure with specificity to AT-rich helical regions . The RNA conformation is relatively unaffected by these antibiotics . The results are explained in terms of a perturbation of the DNA secondary structure as well as of the chromophore system of the oligopeptides.

Cell Mol Biol Lett, 2002, 7(1), 31 - 48
The mechanism of the hemolytic activity of polyene antibiotics; Knopik-Skrocka A et al.; The kinetics of the filipin-, amphotericin B- and nystatin-induced hemolysis of human erythrocytes were investigated . Filipin-induced hemolysis is of the damage type . It is an all-or-none process, partly inhibited by Ca2+ or Ba2+ but not by Mg2+, Na+ or SO42- . The hemolytic activity of filipin is explained by the formation of large aggregates within the erythrocyte membrane in the form of large perforations, permeable to substances of low molecular weight as well as to macromolecules, including hemoglobin . In isotonic KCl solution, both amphotericin B and nystatin, at low concentrations, form smaller aggregates within the membranes . As a result, the permeability of the membranes to KCl increases and hemolysis occurs . However, the kinetics of the hemolysis induced by the two polyenes is complex . The process shows some features of the permeability type and some of the damage type . It is suggested that amphotericin B and nystatin may simultaneously form a number of transport systems, differing in their molecular organisation and hemolytic activity . Their participation in erythrocyte membrane permeability can be modified by small changes in membrane organisation and the chemical composition of the incubation medium . In isotonic solutions of divalent cation chlorides, and at higher antibiotic concentration, additional aggregates, allowing divalent cations to permeate, appear . These structures do not permit SO4(2-) to permeate.

J Am Chem Soc, 2002 Apr 17, 124(15), 3914 - 9
Cooperative binding interactions of glycopeptide antibiotics; Shiozawa H et al.; Glycopeptide antibiotics of the vancomycin group bind to bacterial cell wall analogue precursors, and typically also form dimers . We have studied the interplay between these two sets of noncovalent bonds formed at separate interfaces . Indole-2-carboxylic acid (L) forms a set of hydrogen bonds to the glycopeptide antibiotic chloroeremomycin (CE) that are analogous to those formed by N-Ac-D-Ala . The ligand/CE dimer interactions (in L/CE/CE/L) are shown to occur with positive cooperativity and structural tightening at the dimer interface . From theoretical considerations and from other data, it is inferred, but not proven, that in the exercise of positive cooperativity, the interface that will be tightened to the greatest degree is the one that lies in the shallowest free energy well.

J Biol Chem, 2002 Jul 5, 277(27), 24744 - 52 Epub 2002 Apr 08.
Characterization of monomeric L1 metallo-beta -lactamase and the role of the N-terminal extension in negative cooperativity and antibiotic hydrolysis; Simm AM et al.; The L1 metallo-beta-lactamase from Stenotrophomonas maltophilia is unique among this class of enzymes because it is tetrameric . Previous work predicted that the two regions of important intersubunit interaction were the residue Met-140 and the N-terminal extensions of each subunit . The N-terminal extension was also implicated in beta-lactam binding . Mutation of methionine 140 to aspartic acid results in a monomeric L1 beta-lactamase with a greatly altered substrate specificity profile . A 20-amino acid N-terminal deletion mutant enzyme (N-Del) could be isolated in a tetrameric form but demonstrated greatly reduced rates of beta-lactam hydrolysis and different substrate profiles compared with that of the parent enzyme . Specific site-directed mutations of individual N terminus residues were made (Y11S, W17S, and a double mutant L5A/L8A) . All N-terminal mutant enzymes were tetramers and all showed higher K(m) values for ampicillin and nitrocefin, hydrolyzed ceftazidime poorly, and hydrolyzed imipenem more efficiently than ampicillin in contrast to wild-type L1 . Nitrocefin turnover was significantly increased, probably because of an increased rate of breakdown of the intermediate species due to a lack of stabilizing forces . K(m) values for monomeric L1 were greatly increased for all antibiotics tested . A model of a highly mobile N-terminal extension in the monomeric enzyme is proposed to explain these findings . Tetrameric L1 shows negative cooperativity, which is not present in either the monomer or N-terminal deletion enzymes, suggesting that the cooperative effect is mediated via N-terminal intersubunit interactions . These data indicate that while the N terminus of L1 is not essential for beta-lactam hydrolysis, it is clearly important to its activity and substrate specificity.

Crit Care, 2002 Feb, 6(1), 45 - 51 Epub 2001 Jan 11.
Clinical review: non-antibiotic strategies for preventing ventilator-associated pneumonia; Ferrer R et al.; Prevention of nosocomial pneumonia (NP) is the most important step towards reducing hospitalisation costs . The non-antibiotic prevention strategies include measures related to the correct care of the artificial airway, strategies related directly to the maintenance of the mechanical ventilator and the equipment, strategies focused in the gastrointestinal tract, and strategies related to the position of the intubated patients . While simple methods should be part of routine practice, the use of more invasive and expensive preventive measures should be used only in patients who are at high risk of NP . The appropriate use of these techniques can reduce the incidence of NP in intensive care unit patients.

Nucleic Acids Res, 2002 Apr 15, 30(8), 1774 - 81
DNA sequence recognition by the indolocarbazole antitumor antibiotic AT2433-B1 and its diastereoisomer; Carrasco C et al.; The antibiotic AT2433-B1 belongs to a therapeutically important class of antitumor agents . This natural product contains an indolocarbazole aglycone connected to a unique disaccharide consisting of a methoxyglucose and an amino sugar subunit, 2,4-dideoxy-4-methylamino-L-xylose . The configuration of the amino sugar distinguishes AT2433-B1 from its diastereoisomer iso-AT2433-B1 . Here we have investigated the interaction of these two disaccharide indolocarbazole derivatives with different DNA sequences by means of DNase I footprinting and surface plasmon resonance (SPR) . Accurate binding measurements performed at 4 and 25 degrees C using the BIAcore SPR method revealed that AT2433-B1 binds considerably more tightly to a hairpin oligomer containing a {CG}(4) block than to an oligomer with a central {AT}(4) tract . The kinetic analysis shows that the antibiotic dissociates much more slowly from the GC sequence compared to the AT one . Preferential binding of AT2433-B1 to GC-rich sequences in DNA was independently confirmed by DNase I footprinting experiments performed with a 117 bp DNA restriction fragment . The specific binding sequence 5'-AACGCCAG identified from the footprints was then converted into a biotin-labeled DNA hairpin duplex and compound interactions with this specific sequence were characterized by high resolution BIAcore SPR experiments . Such a combined approach provided a detailed understanding of the molecular basis of DNA recognition . The discovery that the glycosyl antibiotic AT2433-B1 preferentially recognizes defined sequences offers novel opportunities for the future design of sequence-specific DNA-reading small molecules.

J Chemother, 2001 Nov, 13 Spec No 1(1), 66 - 72
Gentamicin PMMA beads and other local antibiotic carriers in two-stage revision of total knee infection: a review; Walenkamp GH; Local antibiotic carriers are available as resorbable carriers (e.g . gentamicin-loaded collagen) and non resorbable carriers, mostly gentamicin-loaded bone cement in the form of beads or spacers . The release of the antibiotic may differ largely, depending on the properties of the carrier . In the use of spacers the release may remain too low, resulting in subinhibitory gentamicin concentrations . Revision of late deep infection of a knee prosthesis includes extraction, debridement and the use of local and systemic antibiotics . Reimplantation can be performed if healing is appropriate and the bone stock reaches . Otherwise arthrodesis is necessary.

Curr Opin Microbiol, 2002 Apr, 5(2), 194 - 201
Active transport of iron and siderophore antibiotics; Braun V et al.; Bacteria solubilize iron (Fe(3+)) with secreted siderophores, which are then taken up as Fe(3+)-siderophore complexes . Some bacteria also use iron in heme, hemoglobin, hemopexin, transferrin and lactoferrin of eukaryotic hosts . Crystal structures of two outer membrane transport proteins, FhuA and FepA, and biochemical data reveal strong long-range conformational changes of the proteins upon binding of Fe(3+)-siderophore complexes and in response to energy transfer from the cytoplasmic membrane into the outer membrane via the TonB-ExbB-ExbD protein complex . The crystal structure of the periplasmic binding protein FhuD strongly deviates from the uniform overall structure of binding proteins hitherto determined . Sideromycins, antibiotics that contain Fe(3+)-siderophore complexes as carriers, are highly effective, as they enter cells via Fe(3+)-siderophore transport systems . In this review, recently published data is discussed to demonstrate the state of understanding of iron transport across the outer membrane and the cytoplasmic membrane.

J Protein Chem, 2002 Feb, 21(2), 97 - 104
Aminoglycosides as substrates and inhibitors of peroxidases: a possible role of these antibiotics against myeloperoxidase-dependent cytotoxicity; Lorrai A et al.; The kinetics of the catalytic cycle of myeloperoxidase and of horseradish peroxidase reacting with aminoglycosides have been studied by conventional and stopped-flow spectrophotometry . Aminoglycosides acted as one-electron reducing substrates converting compound I, formed when stoichiometric amounts of hydrogen peroxide were added to the enzyme, to compound II, and compound II to the resting, ferric enzyme . The latter gradually decayed into a further spectroscopic derivative (lambda(max) = 540 and 403 nm) tentatively identified as a complex of ferric heme with the antibiotic oxidation product(s), and the resulting enzyme was fully inactivated . Since myeloperoxidase is the only human enzyme known to convert chloride ions into the cytotoxic hypochlorous acid, the data presented in this paper bear relevance to the pharmacological effects of aminoglycoside antibiotics, which, while inhibiting bacterial growth, also prevent oxidative cellular damage caused by hypochlorous acid aging as substrates and inhibitors of myeloperoxidase.

Ned Tijdschr Tandheelkd, 1998 Dec, 105(12), 437 - 9
{Oro-antral perforations . Desirability of antibiotic support in surgical closure within 24 hours}; Gortzak RA et al.; OBJECTIVE: The routine use of antibiotics in oro-antral perforations is advocated by a number of authors, in order to prevent post-operative complications such as sinusitis . Our aim was to establish wether the preventive use of antibiotics seams to be indicated in the closure of this perforations . DESIGN: A retrospective investigation . SETTING: The department of Oral and Maxillofacial Surgery and Oral Pathology of the Academic Center for Dentistry Amsterdam (ACTA) and the Free University Hospital Amsterdam . METHODS: In a retrospective study 46 patients have been investigated, 32 males and 14 females, who underwent a surgical closure of an oro-antral perforation in 1995, within 24 hours after its occurrence, in a department of oral and maxillofacial surgery . Twenty-two patients received preoperative antibiotics and 24 patients were treated without the use of antibiotics . RESULTS: Three (6.5%) patients had a post-operative sinusitis . In the other 43 patients there were no postoperative complications . CONCLUSION: The preventive use of antibiotics in oro-antral perforations in order to prevent post-operative complications such as sinusitis seams not to be indicated in the closure of this perforations . However, before a final conclusion on this matter can be drawn, a prospective randomized study should be undertaken.

Plast Reconstr Surg, 2002 Apr 15, 109(5), 1685 - 93; discussion 1694-5
Antibiotic use in aesthetic surgery: a national survey and literature review; Perrotti JA et al.; Although much has been written regarding the use of antibiotics in surgery, no clear guidelines exist in the literature regarding the use of antibiotics in aesthetic surgery . To determine the pattern of antibiotic use in aesthetic surgery, a comprehensive survey was mailed to 6000 American Society of Plastic and Reconstructive Surgeons members and candidates . A total of 1767 completed responses were returned, which represents a response rate of 30 percent . The type, route, and duration of antibiotic administration are reported for 10 common cosmetic surgical procedures . The results of the survey confirmed that there is widespread use of antibiotics in aesthetic surgery . To provide guidelines for proper antibiotic use, the current literature was extensively reviewed . The authors found little or no correlation between reported clinical practice and the literature . It is hoped that this study will stimulate further investigation into this area of aesthetic surgeryPublication Types:

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