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