Braz J Med Biol Res, 2002 Mar, 35(3), 395 - 403 Antinociceptive potency of aminoglycoside antibiotics and magnesium chloride: a comparative study on models of phasic and incisional pain in rats; Prado WA et al.; A close relationship exists between calcium concentration in the central nervous system and nociceptive processing . Aminoglycoside antibiotics and magnesium interact with N- and P/Q-type voltage-operated calcium channels . In the present study we compare the antinociceptive potency of intrathecal administration of aminoglycoside antibiotics and magnesium chloride in the tail-flick test and on incisional pain in rats, taken as models of phasic and persistent post-surgical pain, respectively . The order of potency in the tail-flick test was gentamicin (ED50 = 3.34 microg; confidence limits 2.65 and 4.2) > streptomycin (5.68 microg; 3.76 and 8.57) = neomycin (9.22 microg; 6.98 and 12.17) > magnesium (19.49 microg; 11.46 and 33.13) . The order of potency to reduce incisional pain was gentamicin (ED50 = 2.06 microg; confidence limits 1.46 and 2.9) > streptomycin (47.86 microg; 26.3 and 87.1) = neomycin (83.17 microg; 51.6 and 133.9) . The dose-response curves for each test did not deviate significantly from parallelism . We conclude that neomycin and streptomycin are more potent against phasic pain than against persistent pain, whereas gentamicin is equipotent against both types of pain . Magnesium was less potent than the antibiotics and effective in the tail-flick test only. Helicobacter, 2002 Feb, 7(1), 53 - 9 Increased primary resistance to recommended antibiotics negatively affects Helicobacter pylori eradication; Ecclissato C et al.; OBJECTIVE: To evaluate the efficacy of two commonly employed treatments for Helicobacter pylori infection and the impact of bacterial resistance to antibiotics on eradication rate . METHODS: Ninety-two consecutive H . pylori-positive patients with active peptic ulcer disease were randomly enrolled to receive a 7-day treatment with either lansoprazole 30 mg plus amoxicillin 1 g and clarithromycin 500 mg {all twice a day (b.i.d.), Group A, n = 46}; or bismuth subcitrate 125 mg four times a day (q.i.d.) plus tetracycline 500 mg q.i.d and furazolidone 200 mg b.i.d . (Group B, n = 46) H . pylori status was reassessed 30 days after completion of the therapy and bacterial resistance to the antibiotics was investigated using an in vitro assay . RESULTS: Five patients from each study group were lost to follow up . Both treatments resulted in similar H . pylori eradication rate: 66-60% (per protocol), 59-52% (intention-to-treat) in Groups A and B, respectively (non significant) . However, eradication improved to 79% in the absence of H . pylori resistance to clarithromycin or amoxicillin . CONCLUSION: Primary resistance to clarithromycin or amoxicillin may underscore a potentially serious problem for the eradication of H . pylori infection . Testing for bacterial resistance may become necessary to improve therapeutic efficacy. Ann Periodontol, 2000 Dec, 5(1), 166 - 74 The influence of preoperative antibiotics on success of endosseous implants at 36 months; Laskin DM et al.; The benefits of prophylactic antibiotics are well recognized in dentistry . However, their routine use in the placement of endosseous dental implants remains controversial . As part of the comprehensive Dental Implant Clinical Research Group (DICRG) clinical implant study, the preoperative or postoperative use of antibiotics, the type used, and the duration of coverage were left to the discretion of the surgeon . These data for 2,973 implants were recorded and correlated with failure of osseointegration during healing (Stage 1), at surgical uncovering (Stage 2), before loading the prosthesis (Stage 3), and from prosthesis loading to 36 months (Stage 4) . The results showed a significantly higher survival rate at each stage of treatment in patients who had received preoperative antibiotics. Clin Resour Manag, 2002 Feb, 3(2), 26 - 7, 17 Blood cultures, antibiotic therapy boost outcomes in septicemia. {Clinical study on the early and short -- term use of antibiotics with broad spectrum in severely burned patients} Zong G, Zhang M, Zhang G. Department of Burns and Plastic Surgery, The Eighty -- First Hospital of PLA, Nan Jing, 210002, Jiang Su Provine, P.R . ChinaOBJECTIVE: To investigate the prevention and treatment effects of early and short -- term use of antibiotics with broad spectrum on postburn severe infection in severely burned patients . METHODS: Thirty -- five burn patients with TBSA from 50% to 95% were enrolled in the study . The patients were divided into early prevention {20 cases, antibiotics were used started from 6 postburn hours (PBH)} and delayed prevention (15 cases, antibiotics were applied after 48 PBH) groups . Plasma levels of LPS, TNFa and IL -- 8 were dynamically monitored with the concomitant observation of clinical signs of postburn sepsis . RESULTS: After major burns, the plasma levels of LPS, TNFalpha and IL -- 8 increased evidently and reached the peak values on 3 similar 5 postburn days (PBD) . But the levels of all above factors in the early group were obviously lower than those in the delayed group (P < 0.05 similar 0.01) . The incidencies of sepsis and internal organ complications within 2 postburn weeks were much lower in the early group than those in the delayed group (P < 0.05) . The subeschar bacterial quantification on 4 similar 7 PBD was evidently lower in the early group than that in the delayed group (P < 0.01) . CONCLUSION: Early and short -- term use of antibiotics with broad spectrum in severely burned patients could effectively prevent postburn severe infection and lower down the incidence of internal organ complications. Biotechnol Bioeng, 2002 Apr 20, 78(2), 141 - 6 Decreasing the hyphal branching rate of Saccharopolyspora erythraea NRRL 2338 leads to increased resistance to breakage and increased antibiotic production; Wardell JN et al.; Mutation and selection for increased resistance to cell-wall synthesis inhibitors led to alterations in the hyphal branching rate of Saccharopolyspora erythraea NRRL 2338 . Mutants with decreased branching frequency exhibited increased hyphal strength (estimated by in vitro micromanipulation) . As the hyphal strength was increased, this led to a greater proportion of hyphal particles in liquid culture with a hyphal fragment diameter of greater than 88 microm . This, in turn, coincided with proportionately increased antibiotic production . Toxicol In Vitro, 2002 Apr, 16(2), 123 - 7 Effect of UV-B radiation on some common antibiotics; Ray RS et al.; Some of the commonly used antibiotics such as cephaloridine, cephalexin, cephradine, nystatin and nafcillin were tested for generation of singlet oxygen (1O(2)) under UV-B (290-320 nm) exposure and the order for 1O(2) generation was obtained: cephaloridine>cephalexin>nystatin>cephradine>nafcillin . In vitro study with deoxyguanosine (dGuo) showed that 1O(2) was responsible for drug-sensitized photodegradation of the guanine base of DNA and RNA . Sodium azide (NaN(3)) and 1,4-diazabicyclo {2.2.2} octane (DABCO) accorded significant inhibition (76-98%) in the production of (1)O(2) and photo-oxidation of dGuo . The combined effect of drug and UV-B irradiation is of paramount importance in view of cell-damaging reactions by 1O(2) . Our findings are important because of increasing UV-B radiation on the earth's surface due to depletion of the stratospheric ozone layer . The selected drugs are used routinely for the treatment of various diseases and their combined action may cause undesirable phototoxic responses . Our study suggests that exposure to sunlight should be avoided after the intake of the photosensitive drugs. Cochrane Database Syst Rev . 2002;(1):CD001860. Antibiotics for trachoma; Mabey D et al.; BACKGROUND: Trachoma is the world's leading cause of preventable blindness . In 1997 the World Health Organization launched an initiative on trachoma control based on the 'SAFE' strategy (surgery, antibiotics, facial cleanliness and environmental improvement) . OBJECTIVES: The aim of this review is to assess the evidence supporting the antibiotic arm of the SAFE strategy by assessing the effects of antibiotics on both active trachoma (primary objective) and on Chlamydia trachomatis infection of the conjunctiva (secondary objective) . SEARCH STRATEGY: We searched The Cochrane Controlled Trials Register - CENTRAL/CCTR, which contains the Cochrane Eyes and Vision Group specialised register (Cochrane Library Issue 3, 2001), MEDLINE (1966 to August 2001), and EMBASE (1980 to September 2001) . We used the Science Citation Index to look for articles that cited the included studies . We searched the reference lists of identified articles and we contacted authors and experts for details of further relevant studies . SELECTION CRITERIA: We included only randomised trials that satisfied either of two criteria: (a) trials in which topical or oral administration of an antibiotic was compared to placebo or no treatment in people with trachoma, (b) trials in which a topical antibiotic was compared with an oral antibiotic in people with trachoma . A subdivision of particular interest was of trials in which topical tetracycline/chlortetracycline was compared with oral azithromycin, as these are the two World Health Organization recommended treatments . DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data . We contacted investigators for missing data . MAIN RESULTS: We found 15 studies that randomised a total of 8678 participants . For both outcomes (active trachoma and laboratory evidence of infection) the results of the chi-square tests suggested that there was significant statistical heterogeneity among the trials . There was also marked clinical heterogeneity . No summary statistics were calculated and we therefore present a narrative summary of the results . For the comparisons of oral or topical antibiotic against placebo/no treatment, the data are consistent with there being no effect of antibiotics but are suggestive of a lowering of the point prevalence of relative risk of both active disease and laboratory evidence of infection at three and 12 months after treatment . For the comparison of oral against topical antibiotics the results suggest that oral treatment is neither more nor less effective than topical treatment . REVIEWER'S CONCLUSIONS: There is some evidence that antibiotics reduce active trachoma but results are not consistent and cannot be pooled. J Infect, 2001 Nov, 43(4), 234 - 8 Treatment of resistant mycoplasma infection in immunocompromised patients with a new pleuromutilin antibiotic; Heilmann C et al.; Patients with primary antibody deficiency (PAD) are prone to mycoplasma infection with unusual strains which may be resistant to conventional antibiotics . Mycoplasmas were isolated from the joint fluid (Ureaplasma urealyticum) of two PAD patients with arthritis and from the cerebral spinal fluid (Mycoplasma maculosum) in one with meningitis, the latter probably originating from the patient's dog . Combinations of doxycycline and quinolones or macrolides failed to clear the infections, but after demonstrating in-vitro sensitivity to the pleuromutilin, Econor, for two of the isolates, all three patients responded to oral treatment with Econor . The infection was completely eradicated in two patients, with the emergence of a resistant strain in the third.Mycoplasma infection should be considered in PAD patients with unexplained sepsis . Pleuromutilins such as Econor are powerful new anti-mycoplasmal agents which provide an additional therapeutic option when patients fail to respond to conventional antibiotics . Intensive Crit Care Nurs, 2001 Aug, 17(4), 213 - 8 Nurses' knowledge and attitudes about antibiotic therapy in critical care; Munro CL et al.; PURPOSE: To assess critical care nurses' knowledge about antibiotic use in critical care settings, and attitudes concerning the role of the nurse in monitoring response to and appropriate use of antibiotic therapy . METHOD: 90 critical care nurses from 6 adult critical care units at a 780-bed academic, health sciences centre, completed an investigator-developed survey about their knowledge of antibiotic use and their attitudes concerning the role of the nurse . RESULTS: The majority of respondents worked full time (83%) and were BSN (Bachelor of Science in Nursing) prepared (62%), with an average of 9 years' nursing experience and 7 years' experience in intensive care . Using a 100-mm visual analog scale, mean scores on knowledge and comfort with: (1) interpreting culture and sensitivity; (2) white blood cell (WBC) data; and (3) discussing results and therapy with physicians were all less than 50 mm . However, the mean score for nurses' belief of responsibility related to this collaborative role was 76 . A knowledge quiz of lab interpretation and antibiotic therapy revealed a mean score of 53.8% . Beliefs about roles were correlated with comfort in discussing therapies with physicians rather than with knowledge . Although nurses value the collaborative surveillance role, they may lack the knowledge and confidence to enact it. Otolaryngol Pol, 2001, 55(5), 489 - 96 {Therapeutic efficacy assessment of cefuroxime axetil in short 4 day course of empirical antibiotic therapy in patients with bacterial infections of upper respiratory tract and otitis media}; Olszewski J et al.; There were examined 261 patients aged 18-62 ambulatory treated and divided into five groups: I--65 patients with acute maxillary sinusitis, II--43 patients with exacerbation of chronic maxillary sinusitis, III--40 patients with angina, IV--61 patients with acute otitis media and V--52 patients with exacerbation of chronic otitis media . Cefuroxime axetil have applied 2 times a day in 500 mg oral dose by 4 days . The therapeutic efficacy of cefuroxime axetil was assessed on the basis: fever chart and self assessment chart of showed symptoms which were assessed from 0 to 4.4 days course antibiotic therapy showed that the total receding of illness symptoms stated in 90.8% patients with acute maxillary sinusitis, in 69.8% patients with exacerbation of chronic maxillary sinusitis, in 62.5% patients with angina, in 91.8% patients with acute otitis media and receding of acute symptoms of exacerbation with chronic otitis media--a ear pain in 88.5% patients and a ear leakage in 44.2% patients . The obtained results stated that the 4 days course of cefuroxime axetil can be sufficient and efficacy in treatment of acute bacterial infections of maxillary sinuses and ear media. Clin Microbiol Infect, 1996 Jun, 1 Suppl 2, S20 - S22 Non-antibiotic effect of antibiotics; Kadota Ji J; In the present study, we demonstrated the efficacy of low-dose, long-term therapy with erythromycin and an erythromycin-related compound, roxithromycin, in patients with chronic lower respiratory tract disease including diffuse panbronchiolitis (DPB), and investigated the anti-inflammatory action of such drugs . Treatment significantly improved the mean value of respiratory function tests and arterial blood gas analysis, except for PaCO2 in the erythromycin-treated group and residual volume/total lung capacity (RV/TLC) and PaCO2 in the roxithromycin-treated group . Bronchoalveolar lavage (BAL) analysis revealed that neutrophils had accumulated in the pre-treatment lavage fluid, compared with that of healthy volunteers, and the levels of neutrophil chemotactic activity (NCA), interleukin-1beta (IL-1beta), interleukin-8 (IL-8) and leukotriene B4 (LTB4) in BAL fluid of the patients were significantly higher than those in healthy volunteers . Macrolide therapy caused a significant reduction in the percentage of neutrophils, NCA and mean IL-1beta, IL-8 and LTB4 concentration in BAL fluid of the patients . The quantitative expression of Mac---1 on peripheral neutrophils significantly increased, compared with that in healthy volunteers, before therapy and significantly decreased after therapy . We also evaluated the in vitro inhibitory effects of macrolides on IL---8 production by vitamin D3-induced human monocytic cell line THP-1 cells when stimulated with lipopolysaccharide and serum . The present study has also provided evidence for T-cell activation in BAL fluid of the patients, and a significantly reduced number of activated T-cells was observed after macrolide therapy . These results indicate that macrolides may act by reducing pulmonary inflammation through reduction of neutrophil accumulation, as a consequence of reduced chemotactic gradient and cytokine production at the inflammatory sites in the lung or of reduced neutrophil adhesion molecules in the circulation . Ultimately the mechanism may involve suppression of neutrophil oxidative and proteolytic products . Lymphocytes are important cellular components of bronchial inflammation, in addition to neutrophils, in this disease, and macrolide antibiotics may also act as an immunosuppressant to inhibit T-cell activation . This is believed to be one reason why macrolides are effective in chronic lower respiratory tract disease. Zhonghua Yu Fang Yi Xue Za Zhi, 1999 Sep, 33(5), 286 - 8 {Relationship between use of antibiotics and chronic diarrhoea in infants and young children}; Xu N et al.; OBJECTIVE: To study the relationship between use of antibiotics and chronic diarrhea in infants and young children . METHODS: A matched case-control study was carried out in Fuzhou City, Fujian Province during April to October 1997, with a total of 32 cases, (aged 1 - 19 months), with chronic diarrhea (with a length > 2 months), and 128 cases of acute diarrhea (as control group I) and 94 cases of acute respiratory tract infection (as control group II), from the Department of Pediatrics, the First Affiliated Hospital of Fujian Medical University during January 1987 to December 1996 . RESULTS: Unconditional multiple logistic regression analysis showed that unreasonable use of antibiotics in treatment for acute diarrhea was the major risk factor for chronic diarrhea (OR = 5.61, 95% CI of OR = 1.15 - 27.36 with control group I, and OR = 16.92, 95% CI of OR = 2.67 - 107.32 with control group II) . Chi-square test for trend showed that odds ratio of the use of antibiotics in the cases to the controls increased with the number of antibiotics used in treatment . CONCLUSION: Unreasonable use of antibiotics in treatment for acute diarrhea was an important factor contributing to chronic diarrhea in infants and young children . Early pathogenic diagnosis for diarrhea and reasonable use of antibiotics played important roles in prevention form chronicity of diarrheal diseases. Clin Microbiol Infect, 1997 Feb, 3(6), 653 - 657 Changes in reimbursement policy for antibiotics and prescribing patterns in general practice; Steffensen FH et al.; OBJECTIVE: To study the effect of a reduction in reimbursement of the cost of antibiotics on the prescribing pattern in primary care in Denmark . METHOD: We analyzed the general practitioners' prescriptions of antibiotics during 1993--96 in relation to a reduction in reimbursement on the basis of national health service data in the county of North Jutland (population 488 000) . On 1 January 1996 the reimbursement for tetracyclines was withdrawn, and for other antibiotics reimbursement was reduced from 75% to 50% . RESULTS: The total consumption of all antibiotic groups increased steadily in the county until 1995, and in 1996 a decrease of 13% was seen . A very marked reduction was noticed immediately after 1 January 1996 for the more expensive broad-spectrum antibiotics . The use of tetracyclines dropped by 42% during the first 3 months of 1996 after withdrawal of reimbursement . CONCLUSIONS: It is reasonable to assume that the new reimbursement policy has initiated a reduction and caused a shift in general practitioners' prescribing of antibiotics . Thus a differential reimbursement policy might influence general practitioners' prescribing behavior towards antibiotics, with desirable ecological consequences. Aliment Pharmacol Ther, 2002 Feb, 16(2), 291 - 6 Primary resistance to antibiotics and its clinical impact on the efficacy of Helicobacter pylori lansoprazole-based triple therapies; Poon SK et al.; AIM: To evaluate Helicobacter pylori primary resistance and its clinical impact on the efficacy of two lansoprazole-based eradication triple therapies . METHODS: H . pylori-positive patients (n=228) were randomized to receive one of the 1-week regimens: lansoprazole 30 mg, clarithromycin 500 mg and amoxicillin 1 g (LAC), or lansoprazole 30 mg, clarithromycin 500 mg and metronidazole 500 mg (LMC), each given twice daily . H . pylori status was assessed by 13C-urea breath test and culture at diagnosis and by 13C-urea breath test 6 weeks after therapy . Antibiotic susceptibility was determined by E-test (n=98) . RESULTS: The eradication rates with per protocol/ intention-to-treat analyses were: LAC (n=95/114) 83%/69% and LMC (n=96/114) 85%/72% . Primary resistance was 11% for clarithromycin, 41% for metronidazole and 0% for amoxicillin . Eradication in metronidazole-susceptible/-resistant strains was 85%/82% in LAC and 83%/63% in LMC . Significantly lower cure rates were observed in clarithromycin-resistant patients treated with LAC (95% vs . 0%, P < 0.001) and LMC (86% vs . 0%, P < 0.001) . CONCLUSIONS: One-week LAC and LMC are similarly effective therapies . Clarithromycin resistance significantly affected H . pylori eradication in both regimens. J Pept Sci, 2002 Feb, 8(2), 45 - 55 Characterization of polypeptide antibiotics of the polymyxin series by liquid chromatography electrospray ionization ion trap tandem mass spectrometry; Govaerts C et al.; A selective reversed phase liquid chromatography/mass spectrometry (LC/MSn) method is described for the identification of related compounds in commercial polymyxin B samples . Mass spectral data for these polypeptide antibiotics were acquired on a LCQ ion trap mass spectrometer equipped with an electrospray ionization probe operated in the positive ion mode . The LCQ ion trap is ideally suited for the identification of the related substances because it provides on-line LC/MSn capability . The main advantage of this hyphenated LC/MSn technique is the characterization of novel related substances without time-consuming isolation and purifications procedures . Using this method six novel related substances were partially identified in a polymyxin B bulk sample. Arch Intern Med, 2002 Feb 11, 162(3), 256 - 64 Antibiotics for common respiratory tract infections in adults; Hirschmann JV; A thorough review of the published information indicates that antibiotics rarely benefit acute bronchitis, exacerbations of asthma and chronic bronchitis, acute pharyngitis, and acute sinusitis, although they are commonly prescribed for these illnesses . Rather than prescribing them for these conditions, practitioners should explain to their patients that antibiotics, which have numerous adverse effects, will not hasten resolution of their symptoms, which will often respond to other medications . Most patients will accept this approach if the clinician addresses their concerns, shows a personal interest in them, discusses the expected course of the ailment, and explains the treatment. J Antibiot (Tokyo), 2001 Dec, 54(12), 1072 - 9 Some biological and biochemical activities of resormycin, a novel herbicidal antibiotic; Igarashi M et al.; Biological and biochemical activities of resormycin were studied using unicellular green algae, Selenastrum capricornutum (abbreviated as Selena.), as a test organism . Resormycin inhibited the growth in vitro of Selena . more strongly in the dark than in the light . A weaker but more photo-stable derivative, (+/-)-2,3-dihydro-resormycin, showed more long-lasting activity against Selena . in the light . Resormycin started killing Selena . only after exposure for 2 days and longer, even at high concentrations . Resormycin at concentrations near IC50 rapidly inhibited incorporation of 3H-leu, but not 3H-UR or 3H-TdR, into the TCA insoluble fraction of Selena . Herbicidal activity of resormycin was confirmed using some crops and weeds. J Org Chem, 2002 Feb 8, 67(3), 668 - 73 Novel photodegradation of the antifungal antibiotic pyrrolnitrin in anhydrous and aqueous aprotic solvents; Sako M et al.; The UV irradiation of pyrrolnitrin (1a), which is an antibiotic clinically useful against dermatophytosis and possesses a unique 2-(pyrrol-3-yl)nitrobenzene moiety in the molecule, in an anhydrous aprotic solvent resulted in the exclusive formation of transient 7,4'-dichlorospiro{1,3-dihydrobenzo(c)isoxazole-3,3'-pyrrolin-2'-one} (2a) via the intramolecular oxidation of the juxtaposed pyrrole ring by the triplet-excited nitro group . The irradiation in an aqueous aprotic solvent, however, allowed the concurrent occurrence of intramolecular cyclization by the singlet-excited nitro group in 1a and the hydroxylation at the 2-position of the pyrrole ring by water to afford 3,7-dichloro-8-hydroxy-8,8a-dihydropyrrolo{2,3-b}indol-2-one (3a), accompanied by the formation of 2a . Elongation of the irradiation time in these photoreactions caused a rapid consumption of the products, 2a and 3a, to give undetermined polar polymeric products . The present results indicate that the photodegradation of 1a is significantly influenced by the presence of water in the reaction media and by the nature of its excited state . Thus, the loss of the antifungal activities by the photosensitive antibiotic 1a was chemically proved. Am J Obstet Gynecol, 2002 Feb, 186(2), 234 - 9 Chronic intrauterine infection and inflammation in the preterm rabbit, despite antibiotic therapy; Gibbs RS et al.; OBJECTIVE: In a pregnant rabbit model using intracervical inoculation of Escherichia coli with delayed antibiotic therapy, we investigated the rate of positive cultures and histologic inflammation of maternal and fetal compartments and the concentration of tumor necrosis factor-alpha in the amniotic fluid for up to 5 days . STUDY DESIGN: New Zealand White rabbits at 70% gestation were inoculated intracervically with 10(3) - 10(4) colony-forming units of E coli per uterine horn . At varying intervals after inoculation (0.5 - 4.0 hours), antibiotic therapy was initiated with ampicillin-sulbactam . Primary outcomes were positive cultures and histologic inflammation score . Tumor necrosis factor-alpha levels in the amniotic fluid were determined by bioassay . RESULTS: A total of 60 animals were inoculated with E coli . At the endpoint, uterine cultures were positive more commonly than in the fetus or amniotic fluid (41.8% vs 27.5% vs 17.3%, respectively), which was consistent with an ascending pathway of infection . Inflammation scores were similar in uterus and placenta but lower in fetal lung and absent in fetal brain (2.8 vs 3.1 vs 0.84 vs 0.0, respectively) . Comparing the durations of delay in antibiotic administration, we found a significant increase in positive uterine cultures and a significant increase in histologic inflammation score with increasing delay . The proportion of dead pups within a litter was significantly associated with the log of the tumor necrosis factor-alpha concentration in amniotic fluid and the degree of histologic inflammation in the uterus, but not with amniotic fluid or other culture positivity . CONCLUSION: The administration of therapeutic doses of antibiotic does not consistently eradicate bacteria from the rabbit uterus nor, more importantly, from the fetus and the amniotic fluid . Obtaining a negative amniotic fluid culture does not exclude either infection in the decidua or the fetus or histologic inflammation with tumor necrosis factor-alpha elaboration. Presse Med, 2002 Jan 19, 31(2), 58 - 63 {Motives for the prescription of antibiotics in the emergency department of the University Hospital Center in Nice . A prospective study}; Roger PM et al.; OBJECTIVES: Since April 1999, we have set-up an infectious disease consultation in the emergency unit of the University Hospital in Nice . Unjustified antiobiotherapy is often initiated . We therefore conducted a survey to study the motives and validity of antibiotic prescriptions . METHOD: This prospective study was conducted in two phases . The first consisted in asking the emergency physicians prescribing antibiotics to fill-in a questionnaire giving information on the diagnosis established and the antiobiotherapy proposed . In the second phase, the diagnoses and corresponding treatments were submitted to 4 experts who assessed the acceptability of the diagnoses and the antibiotics prescribed . The experts only had access to the clinical and para-clinical data available . Moreover, their therapeutic judgement was based on previously published consensuses . RESULTS: The 6-month survey collected 117 questionnaires that could be analysed . The rate of error in diagnosis was of 33% (39/117) . Thoracic x-rays could not be interpreted in 11% of cases . In single variant analysis, factors of erroneous diagnosis were due to its interpretation by an internist, the diagnostic category of "broncho-pulmonary infections" and the lack of documentation . In multi variant analysis, only the lack of documentation was related to erroneous diagnosis (OR = 5.5; IC 95% (2.03; 15.30), p < 0.0002) . The rate of antibiotherapy not adapted to the diagnosis made by the physician was of 32% (37/117) . In 24 cases the modalities of the prescription were incorrect and in 13 cases the prescription was unjustified . Only the status of the prescriber (internist) was statistically associated with an antibiotherapy not adapted to the diagnosis (OR = 2.2; IC 95% (0.93; 5.26), p < 0.05) . CONCLUSION: Unjustified antibiotherapy in an emergency unit is generally due to erroneous diagnosis of infection . The lack of documentation and inexperience of the prescribers appear to be the two elements contributing to unjustified antibiotherapy. Oncogene, 2002 Feb 14, 21(8), 1159 - 66 Ansamycin antibiotics inhibit Akt activation and cyclin D expression in breast cancer cells that overexpress HER2; Basso AD et al.; Ansamycin antibiotics, such as 17-allylaminogeldanamycin (17-AAG), bind to Hsp90 and regulate its function, resulting in the proteasomal degradation of a subset of signaling proteins that require Hsp90 for conformational maturation . HER2 is a very sensitive target of these drugs . Ansamycins cause RB-dependent G1 arrest that is associated with loss of D-cyclins via a PI3 kinase, Akt dependent pathway . Downregulation of D-cyclin was due, in part, to loss of Akt expression in response to drug . Moreover, in HER2 overexpressing breast cancer cells, 17-AAG caused rapid inhibition of Akt activity prior to any change in Akt protein . Ansamycins caused rapid degradation of HER2 and a concomitant loss in HER3 associated PI3 kinase activity . This led to a loss of Akt activity, dephosphorylation of Akt substrates, and loss of D-cyclin expression . Introduction into cells of a constitutively membrane bound form of PI3 kinase prevented the effects of the drug on Akt activity and D-cyclins . Thus, in breast cancer cells with high HER2, Akt activation by HER2/HER3 heterodimers is required for D-cyclin expression . In murine xenograft models, non-toxic doses of 17-AAG markedly reduced the expression of HER2 and phosphorylation of Akt and inhibited tumor growth . Thus, pharmacological inhibition of Akt activation is achievable with ansamycins and may be useful for the treatment of HER2 driven tumors. Am J Respir Crit Care Med, 2002 Feb 15, 165(4), 514 - 20 Particulate matter contamination of intravenous antibiotics aggravates loss of functional capillary density in postischemic striated muscle; Lehr HA et al.; Through the increased use of less expensive and counterfeit medicines, the contamination of parenteral fluids and drugs by particulate matter poses an increasing health hazard worldwide . However, the mechanism of action of such contamination has never been conclusively demonstrated . We have systemically injected the particles contained in three different 1-g preparations of the antibiotic cefotaxime into hamsters and visualized the functional capillary density in striated skin muscle, using intravital fluorescence microscopy . Injection of particles from either of the three preparations did not affect capillary perfusion in normal muscle (n = 3 hamsters, each) . However, injection of particles from two generic drug preparations, but not the original preparation or the saline control, significantly reduced capillary perfusion in muscle tissue that had previously been exposed to 4 h of pressure-induced ischemia and 2 h of reperfusion (n = 9 hamsters per group) . Histological sections demonstrated birefringent particles mechanically obliterating the microcirculation of the striated muscle . The loss of capillary perfusion due to particle injection or injection of standardized microspheres was dependent on the extent of ischemia/reperfusion-induced muscle injury, with more capillaries lost in the more severely compromised muscle areas . These findings suggest that particle contaminants may not pose a major threat in intact tissue, but may severely compromise tissue perfusion in patients with prior microvascular compromise of vital organs (i.e., after trauma, major surgery, or sepsis) and thus predispose to complications such as acute respiratory distress syndrome or multiple organ failure. J Arthroplasty, 2002 Feb, 17(2), 235 - 8 Mucoraceae infections of antibiotic-loaded cement spacers in the treatment of bacterial infections caused by knee arthroplasty; Ceffa R et al.; Two clinical cases of mycotic infections secondary to knee spacers medicated with antibiotics against bacterial infections are presented . Care must be taken between the first and second stage (when the spacer is in place), and attention must be paid to the management of the surgical wound to avoid secondary contamination. Neoplasma, 2001, 48(5), 412 - 8 Inhibition of RNA synthesis in vitro and cell growth by anthracycline antibiotics; Studzian K et al.; New derivatives of doxorubicin and daunorubicin with amidine group bonded to daunosamine at C-3' atom and bearing the morpholine ring attached to the amidine group have been recently synthesized . Their cytotoxic activities and effects on RNA synthesis in vitro were assayed . The drug concentrations inhibiting mouse leukaemia L1210 cell growth to 50% were about two- and three fold higher for the derivatives compared to doxorubicin and daunorubicin respectively . Inhibition of phage T7 RNA polymerase by the non-covalently interacting derivatives was also slightly lower than that by the parent compounds . As doxorubicin and daunorubicin, their amidine derivatives in the presence of dithiothreitol and Fe(III) ions are activated and covalently bind to DNA . The adducts formed affect RNA polymerase activity . Several bands corresponding to prematurely terminated RNA chains are observed by means of polyacrylamide gel electrophoresis . The patterns of bands are virtually identical for all the anthracyclines studied here and are similar to the terminations induced by actinomycin D . This observation is consistent with a notion that the adducts are formed at guanine in GpC sequences which are also binding sites of actinomycin D . A substantial difference between daunorubicin and its amidine derivative is shown by means of high performance liquid chromatography . The derivative undergoes rapid rearrangements in the presence of dithiothreitol and Fe(III) ions, while daunorubicin is stable for several hours under these conditions . The results presented here indicate that the amidine derivatives despite bulky morpholine substitution exhibit biological activity in the systems used here. Chem Biol, 2002 Jan, 9(1), 103 - 12 Formation of beta-hydroxy histidine in the biosynthesis of nikkomycin antibiotics; Chen H et al.; Nikkomycins, a group of peptidyl nucleoside antibiotics produced Streptomyces tendae Tu901, are potent competitive inhibitors of chitin synthase . In this study, three nikkomycin biosynthetic enzymes, NikP1, NikQ, and NikP2, were overexpressed, purified, and characterized . The NikP1 activated L-His and transferred it to the carrier protein domain to form L-His-S-NikP1, which served as the beta-hydroxylation substrate of NikQ . The beta-OH-His was then hydrolytically released from NikP1 by NikP2 . The results reported here substantiate our earlier proposal that the covalent tethering of an amino acid onto a carrier protein domain prior to downstream modification is a general strategy for diverting a fraction of the amino acid into secondary metabolism. J Am Chem Soc, 2002 Feb 20, 124(7), 1438 - 42 Binding of aminoglycoside antibiotics to the small ribosomal subunit: a continuum electrostatics investigation; Ma C et al.; The binding of paromomycin and similar antibiotics to the small (30S) ribosomal subunit has been studied using continuum electrostatics methods . Crystallographic information from a complex of paromomycin with the 30S subunit was used as a framework to develop structures of similar antibiotics in the same ribosomal binding site . Total binding energies were calculated from electrostatic properties obtained by solution of the Poisson-Boltzmann equation combined with a surface area-dependent apolar term . These computed results showed good correlation with experimental data . Additionally, calculation of the ribosomal electrostatic potential in the paromomycin binding site provided insight into the electrostatic mechanisms for aminoglycoside binding and clues for the rational design of more effective antibiotics. Org Lett, 2002 Jan 24, 4(2), 265 - 7 An aldol-based approach to the synthesis of the antibiotic anisomycin; Hulme AN et al.; {reaction: see text} A new approach to the synthesis of the antibiotic anisomycin is reported that relies upon a key aldol disconnection . The glycolate aldol coupling proceeds in 75% yield and with >95% diastereoselectivity, which allows the 13-step synthesis to proceed in 35% overall yield. Org Lett, 2002 Jan 24, 4(2), 253 - 6 Studies aimed at the total synthesis of the antitumor antibiotic cochleamycin A . An enantioselective biosynthesis-based pathway to the AB bicyclic core; Chang J et al.; {reaction: see text} A convergent, highly enantioselective synthesis of the fully functionalized AB sector of cochleamycin A is described . A pair of building blocks, crafted from L-malic and L-ascorbic acids, are conjoined in a manner that gives rise to an (E,Z,E)-1,6,8-nonatriene . On heating, the latter undergoes stereocontrolled intramolecular Diels-Alder cyclization via an endo transition state. Am J Surg, 2001 Dec, 182(6), 682 - 6 Prophylactic antibiotics are not indicated in clean general surgery cases; Knight R et al.; BACKGROUND: In assigning risk of infection, the traditional wound classification system has been replaced by the National Nosocomial Infection Surveillance (NNIS) system . NNIS classification is determined by procedure length, wound cleanliness, and ASA status . To date, no prophylactic antibiotic guidelines have been proposed for the NNIS system . METHODS: Clean general surgery cases were retrospectively reviewed in our hospital for infection and prophylactic antibiotic use . These cases were then stratified per the NNIS system . RESULTS: One thousand twenty-three clean general surgery cases had 16 (1%) surgical site infections . The infection rate in NNIS class 0, 1, and 2 cases not given prophylactic antibiotics was 1.21%, 3.03%, and 0%, respectively . The infection rate in NNIS class 0, 1, and 2 cases given prophylactic antibiotics was 0.94%, 2.44%, and 6.67%, respectively . CONCLUSIONS: No statistically significant decrease in infection rate was demonstrated by us using prophylactic antibiotics, regardless of the NNIS classification in clean general surgery cases. J Microencapsul, 2002 Mar-Apr, 19(2), 153 - 64 In vitro antibiotic release from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) rods; Gurselt I et al.; Provision and maintenance of adequate concentrations of antibiotics at infection sites is very important in treating highly resistant infections . For diseases like implant related osteomyelitis (IRO) it is best to provide this locally via implanted drug formulations, as systemic administration of the antibiotic may not be effective due to damaged vasculature . In this study, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) rods containing 7, 14 and 22% (mol) 3-hydroxyvalerate were loaded with sulbactam:cefoperazone or gentamicin, and their antibiotic release behaviours were studied under in vitro conditions in physiological phosphate buffer at room temperature . The release patterns were representative of release from monolithic devices where a rapid early release phase is followed by a slower and prolonged release . With PHBV 22 rods, the latter phase continued for approximately 2 months . This duration is critical because a proper antibiotic therapy of IRO requires the minimal effective concentration for at least 6 weeks . After in vitro release, voids with sharp edges were detected on the rods, indicating that the drug crystals dissolved but the polymer did not undergo erosion within this test period . Changing the polymer:drug ratio from 2:1 to 20:1 substantially decreased the drug release rate . A change of polymer type, however, did not lead to any detectable changes in the release patterns . Gentamicin release also followed a similar pattern, except that the concentration of the drug in the release medium exhibited a decrease after long release periods, indicating degradation (or decomposition) of the antibiotic in the release medium. Ned Tijdschr Tandheelkd, 1995 Aug, 102(8), 290 - 2 {Prescription of antibiotics for periodontitis patients by dental practitioners in the Netherlands}; Mikx FH et al.; In 1993 a representative sample of dentists in the Netherlands was questioned on the use of antibiotics in the treatment of periodontitis . It was found dat 50% of the general practitioners had a positive attitude, 15% a negative one and 35% had an indifferent attitude towards the use of antibiotics in periodontal treatment . Almost 40% of them indicated the prescription of antibiotics for periodontal reasons in the previous year . Most of the dentists (71%) prescribed a combination of metronidazole and amoxicillin . The average prescription frequency in 1992 was 18 times . The prescription frequency and the choice of a combination of metronidazole and a broad spectrum penicillin in the treatment of periodontitis is discussed, emphasizing the importance of the traditional mechanical therapy, the disturbance of the colonization resistance by means of antibiotics and the worldwide concern about the usage of antibiotics. Ned Tijdschr Tandheelkd, 1995 Sep, 102(9), 337 - 9 {Prescription of antibiotics for the prevention of bacterial endocarditis by dentists in the Netherlands}; Mikx FH et al.; In 1993 a representative sample of dental practitioners in the Netherlands was questioned on the use of antibiotics for the prevention of endocarditis in the previous year . Most of the responding dentists (67%) reported prescription of antibiotics for patients at risk . Some of them prescribed an antibiotic regimen that differed from the guidelines drawn up by the Dutch Heart Foundation . In 1992 only 47% of the responding dentists prescribed antibiotics for the prevention of endocarditis entirely according to these guidelines. J Pharm Biomed Anal, 2002 Mar 1, 27(6), 933 - 44 Thermodynamics in {Mn(II)-antibiotics-bacitracin} mixed system: a polarographic approach; Khan F et al.; Polarographic technique was used to determine the kinetic parameters, thermodynamic parameters and stability constants (log(beta)) of Mn(II) complexes with neomycin, chlortetracycline, oxytetracycline, tetracycline, penicillin V and penicillin G as primary ligands and bacitracin as the secondary ligand, at pH 7.3+/-0.01 and an ionic strength mu=1.0 M (NaClO(4)) at 25 degrees C . The study was also carried out at 35 degrees C to determine the stability constants and thermodynamic parameters viz . enthalpy change (DeltaH), entropy change (DeltaS) and free energy change (DeltaG) of complexes. J Pharm Biomed Anal, 2002 Mar 1, 27(6), 923 - 32 Spectrofluorimetric analysis of certain macrolide antibiotics in bulk and pharmaceutical formulations; Khashaba PY; The macrolides (erythromycin, erythromycin esters, azithromycin dihydrate, clarithromycin and roxithromycin) can be analyzed by a simple spectrofluorimetric method based on the oxidation by cerium(VI) in the presence of sulphuric acid and monitoring the fluorescence of cerium(III) formed at lambda(ex) 255 nm and lambda(em) 348 nm . All variables affecting the reaction conditions as cerium(VI), sulphuric acid concentrations, heating time, temperature and dilution solvents were carefully studied . Linear calibration graphs were obtained in the range of 42.6-1200 ng ml(-1) with a percentage relative standard deviation in the range of 0.014-0.058% . Quantitation and detection limits were calculated . The method was applied successfully for the assay of the studied drugs in pure and pharmaceutical dosage forms as tablets, capsules and suspension . Recovery experiments revealed recovery of 98.3-100.8% . The effect of potential interference due to common ingredients as glucose, sucrose, lactose, citric acid, and propylene glycol was investigated . Applying standard addition method shows a recovery of 97.7-100.9% macrolide antibiotics from their corresponding dosage forms. Chirality, 2002 Feb-Mar, 14(2-3), 121 - 5 Structure, conformation, and mechanism in the membrane transport of alkali metal ions by ionophoric antibiotics; Riddell FG; Recent progress in studies of the mechanism of transport of alkali metal ions by ionophoric antibiotics and the structures of alkali metal salts of the ionophores monensin and narasin is reviewed . The structures obtained from 2D NMR experiments in solution provide considerable insights into the mechanisms of transport . Teratog Carcinog Mutagen, 2002, 22(2), 147 - 58 Susceptibility to DNA damage induced by antibiotics in lymphocytes from malnourished children; Gonzalez C et al.; Infectious disease and malnutrition in children are public health problems in developing countries . Malnutrition is associated with higher levels of DNA damage, and this increased damage could be due to different factors, including the possibility that cells from malnourished children could be more susceptible to environmental damage . The aim of the present study was to evaluate the susceptibility of lymphocytes from malnourished children to DNA damage induced by antibiotics by using the comet assay . The same group of malnourished infected children were studied before and after a treatment period, and compared to a group of well-nourished infected children . Results showed that before and after drug treatment, tail length migration was two times greater in malnourished than in well-nourished children . The proportion of cells with high damage was also increased in malnourished children . Additionally in well-nourished and malnourished children, a cell subpopulation (non-damaged cells) more resistant to DNA damage induced by antibiotics was observed; this was more prevalent in the well-nourished children . Meanwhile, in malnourished children, a cell population seems to be more susceptible and reaches higher levels of DNA damage . This might help explain the impaired immune response observed in malnourished children . The increased DNA migration and the increased proportion of cells with higher levels of damage seem to indicate that malnourished children are more susceptible to DNA damage induced by drugs . Am Heart J, 2002 Feb, 143(2), 294 - 300 Antibiotics against Chlamydia pneumoniae and prognosis after acute myocardial infarction; Pilote L et al.; BACKGROUND: There is mounting pathologic and immunologic evidence that Chlamydia pneumoniae plays a role in the atherogenic pathway . However, very few clinical studies have supported these findings . METHODS: Using the administrative data of all patients > or =65 years of age who had an acute myocardial infarction (AMI) in Quebec between 1991 and 1995 (n = 26,195), we studied the relationship between the intake of antichlamydial antibiotics and post-AMI prognosis . Three groups were compared: patients exposed to (1) antichlamydial antibiotics, (2) sulfa-derivative antibiotics, to which C pneumoniae is not sensitive, and (3) neither of the above classes of antibiotics . Two periods of antibiotic exposure were explored: (1) during the first 3 months after AMI and (2) during the 6 months before AMI . RESULTS: Patients in the 3 exposure groups were similar except for a slightly lower proportion of men in the sulfa-derivative antibiotics group . Among all patients who were exposed during the 3 months after AMI and who survived at least 3 months, the 1-year mortality rate was similar across the 3 groups (10.1%, 11.1%, and 10.4% for the antichlamydial, sulfa-derivative, and nonexposed group, respectively) but favored the antichlamydial group at 2 years (15.9%, 23.0%, and 20.0%) . In adjusted survival analysis, patients in the sulfa-derivative and nonexposed groups were slightly more likely to die than patients in the antichlamydial group (relative risk {RR}, 1.38; 95% confidence interval {CI}, 1.04 to 1.82 and 1.29; 95% CI, 1.05 to 1.59, respectively) . Among individuals treated during the 6 months before AMI, the adjusted risk of dying was similar in the sulfa-derivative and nonexposed groups compared with the antichlamydial group (RR 1.03, 95% CI 0.90 to 1.18 and 1.08, 95% CI 0.99 to 1.19, respectively) . CONCLUSIONS: Exposure to antichlamydial antibiotics during the 3 months after AMI is associated with a small survival benefit, whereas exposure during the 6 months before AMI does not affect survival. Microbiology, 2002 Feb, 148(Pt 2), 405 - 12 Nuclease activities and cell death processes associated with the development of surface cultures of Streptomyces antibioticus ETH 7451; Fernandez M et al.; The presence and significance of developmentally regulated nucleases in Streptomyces antibioticus ETH 7451 has been studied in relation to the lytic processes occurring during differentiation . The cell-death processes have been followed in surface cultures by a propidium iodide viability assay . This has allowed the visualization of dead (membrane-damaged, red fluorescent) and live (membrane-intact, green fluorescent) mycelium during development, and has facilitated the analysis of the role of nucleases in these processes . A parallel activity-gel analysis showed the appearance of 20-22 kDa, 34 kDa and 44 kDa nucleases, the latter appearing only when aerial mycelium is formed . The appearance of these nucleases shows a remarkable correlation with the death process of the mycelium during differentiation and with chromosomal DNA degradation . The 20-22 kDa enzymes are possibly related to the lytic phenomena taking place in the vegetative substrate mycelium before the emergence of the reproductive aerial mycelium, whereas the function of the 44 kDa nuclease seems to be related to the sporulation step . The 20-22 kDa nucleases require Ca2+ for activity and are inhibited by Zn2+ . The nucleases are loosely bound to the cell wall from where they can be liberated by simple washing . Conceivably, these enzymes work together and co-ordinate to achieve an efficient hydrolysis of DNA from dying cells . The results show that the biochemical reactions related with the lytic DNA degradation during the programmed cell death are notably conserved in Streptomyces . Some of the features of the process and the biochemical characteristics of the enzymes involved are analogous to those taking place during the DNA fragmentation processes in eukaryotic apoptotic cells. Microbiology, 2002 Feb, 148(Pt 2), 361 - 71 'Streptomyces nanchangensis', a producer of the insecticidal polyether antibiotic nanchangmycin and the antiparasitic macrolide meilingmycin, contains multiple polyketide gene clusters; Sun Y et al.; Several independent gene clusters containing varying lengths of type I polyketide synthase genes were isolated from 'Streptomyces nanchangensis' NS3226, a producer of nanchangmycin and meilingmycin . The former is a polyether compound similar to dianemycin and the latter is a macrolide compound similar to milbemycin, which shares the same macrolide ring as avermectin but has different side groups . Clusters A-H spanned about 133, 132, 104, 174, 122, 54, 37 and 59 kb, respectively . Two systems were developed for functional analysis of the gene clusters by gene disruption or replacement . (1) Streptomyces phage phiC31 and its derived vectors can infect and lysogenize this strain . (2) pSET152, an Escherichia coli plasmid with phiC31 attP site, and pHZ1358, a Streptomyces-Escherichia coli shuttle cosmid vector, both carrying oriT from RP4, can be mobilized from E . coli into NS3226 by conjugation . pHZ1358 was shown to be generally useful for generating mutant strains by gene disruption and replacement in NS3226 as well as in several other Streptomyces strains . A region in cluster A (approximately 133 kb) seemed to be involved in nanchangmycin production because replacement of several DNA fragments in this region by an apramycin resistance gene {aac3(IV)} gave rise to nanchangmycin non-producing mutants. Appl Microbiol Biotechnol, 2002 Jan, 58(1), 46 - 57 Antifungal antibiotics; Gupte M et al.; The search for new drugs against fungal infections is a major challenge to current research in mycotic diseases . The present article reviews the current types of antifungal infections, the current scenario of antifungal antibiotics, and the need and approaches to search for newer antifungal antibiotics and antifungal drug targets. Ned Tijdschr Tandheelkd, 1994 Dec, 101(12), 489 - 91 {Antibiotics and dentistry}; Smeele LE et al.; The prescription of antibiotics in the dental office should be balanced against the possible side effects . For prophylactic use in selected cases, advice is given with regard to the choice of the antibiotics, the oral dosage and the time period. J Biol Chem, 2002 Apr 19, 277(16), 14186 - 93 Epub 2002 Feb 05. An Escherichia coli mutant lacking the cold shock-induced palmitoleoyltransferase of lipid A biosynthesis: absence of unsaturated acyl chains and antibiotic hypersensitivity at 12 degrees C; Vorachek-Warren MK et al.; An acyltransferase induced by cold shock in Escherichia coli, designated LpxP, incorporates a palmitoleoyl moiety into nascent lipid A in place of the secondary laurate chain normally added by LpxL(HtrB) (Carty, S . M., Sreekumar, K . R., and Raetz, C . R . H . (1999) J . Biol . Chem . 274, 9677-9685) . To determine whether the palmitoleoyl residue alters the properties of the outer membrane and imparts physiological benefits at low growth temperatures, we constructed a chromosomal insertion mutation in lpxP, the structural gene for the transferase . Membranes from the lpxP mutant MKV11 grown at 12 degrees C lacked the cold-induced palmitoleoyltransferase present in membranes of cold-shocked wild type cells but retained normal levels of the constitutive lauroyltransferase encoded by lpxL . When examined by mass spectrometry, about two-thirds of the lipid A molecules isolated from wild type E . coli grown at 12 degrees C contained palmitoleate in place of laurate, whereas the lipid A of cold-adapted MKV11 contained only laurate in amounts comparable with those seen in wild type cells grown at 30 degrees C or above . To probe the integrity of the outer membrane, MKV11 and an isogenic wild type strain were grown at 30 or 12 degrees C and then tested for their susceptibility to antibiotics . MKV11 exhibited a 10-fold increase in sensitivity to rifampicin and vancomycin at 12 degrees C compared with wild type cells but showed identical resistance when grown at 30 degrees C . We suggest that the palmitoleoyltransferase may confer a selective advantage upon E . coli cells growing at lower temperatures by making the outer membrane a more effective barrier to harmful chemicals. Nippon Geka Gakkai Zasshi, 2001 Dec, 102(12), 837 - 41 {A guide line for antibiotic therapy of infectious diseases of the central nervous system}; Kagawa M; The purpose of this paper is to provide assistance to clinicians in the treatment of infectious diseases of the central nervous system . Antibiotic therapy should be initiated as soon as the diagnosis is made and should not be delayed until the next scheduled dose or until investigations have been performed . The infecting organism is usually unknown when treatment is initiated and often remains so, and therefore empirical therapy should always cover the most common suspected organisms . The choice of antibiotics, dosage, and route of administration depends upon the severity of illness . Likely pathogens and the known sensitivities of pathogens of the central nervous system are discussed. J Trop Pediatr, 2001 Dec, 47(6), 369 - 71 Changing antibiotic sensitivity in enteric fever; Gupta A et al.; Emergence of drug resistance in enteric fever is a major concern for the clinician . All children hospitalized with enteric fever during the period 1 March to 31 May 2000 were studied prospectively for their clinical presentation and response to therapy, and an attempt was made to compare these results with the results of hospitalized children with enteric fever during a similar period in the years 1990 and 1995 . The results revealed that there was a significant change in the response to antibiotic therapy as evidenced by significant resistance to ciprofloxacin (55.5 per cent) and early evidence of emerging drug resistance to ceftriaxone (4.4 per cent) . Although the sample size was small and had its limitations, the results also pointed towards the re-emergence of sensitivity to chloramphenicol. Electrophoresis, 2001 Nov, 22(19), 4249 - 61 Analysis of antibiotics by capillary electrophoresis; Flurer CL; This article reviews recent developments in the characterization of antibiotics . Many capillary electrophoretic techniques have been utilized in their analyses, addressing various aspects of quantifying, profiling and monitoring . Sensitive electrochemical and laser-induced fluorescence detection systems have been utilized, demonstrating trace level determinations in clinical settings and in environmental samples . Different sample introduction methods have been explored, enhancing detection sensitivity, or reducing or eliminating sample manipulation prior to injection. Prescrire Int . 2001 Oct;10(55):151. Disopyramide: interactions with marcolide antibiotics; Virulence and potential pathogenicity of coccoid Helicobacter pylori induced by antibiotics; Department of Microbiology, Fujian Medical University, Fuzhou 350004, Fujian Province, ChinaAIM: To explore the virulence and the potential pathogenicity of coccoid Helicobacter pylori (H . pylori) transformed from spiral form by exposure to antibiotic . METHODS: Three strains of H . pylori, isolated from gastric biopsy specimens of confirmed peptic ulcer, were converted from spiral into coccoid from by exposure to metronidazole . Both spiral and coccoid form of H . pylori were tested for the urease activity, the adherence to Hep-2 cells and the vacuolating cytotoxicity to Hela cells, and the differences of the protein were analysed by SDS-PAGE and Western blot . The mutation of the genes including ureA, ureB,hpaA, vacA and cagA, related with virulence, was detected by means of PCR and PCR-SSCP . RESULTS: In the coccoid H . pylori,the urease activity, the adherence to Hep-2 cells and the vacuolating cytotoxicity to Hela cells all decreased . In strain F44, the rate and index of adherence reduced from 70.0% +/- 5.3% to 33% +/- 5.1% and from 2.6 +/- 0.4 to 0.96 +/- 0.3 (P < 0.01), respectively . The invasion of coccoid H . pylori into Hep-2 cell could be seen under electronmicroscope . SDS-PAGE showed that the content of the protein with the molecular weight over Mr 74000 decreased, and the hybriditional signal in band M(r) 125000 weakened, while the band M(r)110000 and M(r)63000 strengthened in coccoid H.pylori as shown in Western blot . The results of PCR were all positive, and PCR-SSCP indicated that there may exist the point mutation in gene hpaA or vacA . CONCLUSION: The virulence and the proteins with molecular weight over M(r)74000 in coccoid H.pylori decrease, but no deletion exists in amplification fragments from ureA, ureB, hpaA, vacA and cagA genes, suggesting that coccoid H.pylori may have potential pathogenicity. Acta Orthop Scand, 2001 Dec, 72(6), 591 - 4 Preformed acrylic bone cement spacer loaded with antibiotics: use of two-stage procedure in 10 patients because of infected hips after total replacement; Magnan B et al.; In 10 patients having deep infection after total hip replacement, we used a two-stage revision procedure involving implantation of a preformed spacer with a cylindrical rod coated with acrylic cement containing antibiotics (Spacer-G) . This device, which remained in situ for an average of 5 months, permitted healing of the infection in 8 cases and reimplantation of a new prosthesis (mean follow-up 35 months) . During treatment, 1 dislocation occurred . The spacer maintained the gap between both bone segments and allowed a certain degree of joint mobility . Use of Spacer-G improved the quality of life of the patients during treatment and accelerated recovery of function after reimplantation. Mediators Inflamm, 2001 Dec, 10(6), 323 - 32 Influence of a macrolide antibiotic, roxithromycin, on mast cell growth and activation in vitro; Shimane T et al.; BACKGROUND: Long-term administration of macrolide antibiotics is recognized to be able to favorably modify the clinical condition of inflammatory diseases, such as diffuse panbronchiolitis and cystic fibrosis . However, the precise mechanisms by which macrolide antibiotics could improve clinical conditions of the patients are not well understood . AIM: The present study was designed to examine the influence of macrolide antibiotics on effector cell functions responsible for inflammation through the choice of roxithromycin (RXM) and mast cell . METHODS: Mast cells were induced by long-term culture of splenocytes from BALB/c mice . RXM was added to the cultures at seeding and then every 4-5 days, when the culture medium was replaced with a fresh one . The influence of RXM on mast cell growth was evaluated by counting the number of cells grown on the 16th day . We also examined the influence of RXM on mast cell activation by examining histamine release and inflammatory cytokine secretion . RESULTS AND CONCLUSION: RXM could not inhibit mast cell growth, even when splenocytes were exposed to 100 microg/ml of RXM throughout the entire culture periods . RXM also could not suppress histamine release from cultured mast cells in response to non-immunological and immunological stimulations . However, RXM could suppress inflammatory cytokine, interleukin-1beta, interleukin-6, granulocyte macrophage-colony stimulating factor and tumor necrosis factor-alpha, secretions induced by concanavalin A stimulation at a concentration of as little as 0.5 microg/ml . These results may suggest that RXM modulated the ability of mast cells to secrete inflammatory cytokines and results in improvement of clinical condition of chronic inflammatory diseases. Clin Perinatol, 2001 Dec, 28(4), 807 - 18 Antibiotics and the management of preterm premature rupture of the fetal membranes; Ehrenberg HM et al.; Preterm premature rupture of membranes remains an important cause of preterm birth and neonatal morbidity and mortality . Although the underlying pathophysiology remains largely undefined, subclinical infection has been implicated both in the mechanism of membrane rupture and the resultant neonatal morbidity . The use of maternal systemic antibiotics reduces both neonatal and maternal morbidity in the expectant management of PPROM . Although concern persists over the development of resistant strains of organisms involved with neonatal sepsis, current data support the use of antibiotics in this setting . Further study is needed regarding the risks and benefits of additional tocolytic therapy or antenatal corticosteroids in the management of PPROM, and the predictors of successful and unsuccessful conservative management, and subclinical intrauterine infection . This will be helpful in the ultimate delineation of the optimal management scheme for PPROM. J Antimicrob Chemother, 2002 Feb, 49(2), 321 - 5 The use of lipid emulsions for the i.v . administration of a new water soluble polyene antibiotic, SPK-843; Mozzi G et al.; Venous tolerance of a new water soluble polyene antibiotic, SPK-843, in 5% glucose solution for infusion is low in laboratory animals . The use of Intralipid 10% emulsion was therefore proposed, in which the antibiotic remained chemically stable for at least 2 h in a mildly acid or nearly neutral environment and at concentrations of 0.1-0.5 mg/mL, producing no alterations in the emulsion structure . Tolerance was assessed through repeated infusions in the ear marginal vein of rabbits and was found much more satisfactory than the tolerance observed when the vehicle used was 5% glucose solution . The study of the effect of some variables (concentration, volume infused, dose per kg) on venous toxicity offered the possibility to plan optimal administration conditions of presumed therapeutic doses. Br J Pharmacol, 2002 Jan, 135(2), 427 - 32 The beta-lactam antibiotics, penicillin-G and cefoselis have different mechanisms and sites of action at GABA(A) receptors; Sugimoto M et al.; The action of the beta-lactam antibiotics, penicillin-G (PCG) and cefoselis (CFSL) on GABA(A) receptors (GABA(A)-R) was investigated using the two-electrode voltage clamp technique and Xenopus oocyte expressed murine GABA(A)-R . Murine GABA(A)-Rs were expressed in Xenopus oocytes by injecting cRNA that encoded for each subunit (alpha1, beta2, and gamma2) and the effects of PCG and CFSL on the alpha1beta2gamma2s subunit receptors were examined using two-electrode voltage clamp . Using the alpha1beta2gamma2s GABA(A)-R, PCG and CFSL inhibited GABA-induced currents in a concentration-dependent manner, with IC(50)s of 557.1+/-125.4 and 185.0+/-26.6 microM, respectively . The inhibitory action of PCG on GABA-induced currents was non-competitive whereas that of CFSL was competitive . Mutation of tyrosine to phenylalanine at position 256 in the beta2 subunit (beta2(Y256F)), which is reported to abolish the inhibitory effect of picrotoxin, drastically reduced the potency of PCG (IC(50)=28.4+/-1.42 mM) for the alpha1beta2(Y256F)gamma2s receptor without changing the IC(50) of CFSL (189+/-26.6 microM) . These electrophysiological data indicate that PCG and CFSL inhibit GABA(A)-R in a different manner, with PCG acting non-competitively and CFSL competitively . The mutational study indicates that PCG might act on an identical or nearby site to that of picrotoxin in the channel pore of the GABA(A)-R. Bioorg Med Chem Lett, 2002 Feb 11, 12(3), 365 - 70 Binding of aminoglycoside antibiotics with modified A-site 16S rRNA construct containing non-nucleotide linkers; Tok JB et al.; The design and synthesis of synthetically modified cyclic A-site 16S rRNA construct is reported . The binding characteristics of several members of the aminoglycoside antibiotics with this novel class of synthetically modified A-site 16S rRNA constructs were subsequently investigated. Int J Antimicrob Agents, 2002 Jan, 19(1), 53 - 9 Modulatory effect of macrolide antibiotics on the Th1- and Th2-type cytokine production; Morikawa K et al.; The effect of the macrolide antibiotics, clarithromycin, midecamycin acetate and josamycin, on the generation of Th1- and Th2-type cytokines by mitogen-stimulated human T lymphocytes was compared with that of fosfomycin . The following results were obtained . These drugs demonstrated potent inhibitory activity on the release and gene expression of TNF-alpha and IL-2 . Their inhibitory effect on IFN-alpha, IL-4, IL-5, IL-6 was less marked . The release of IL-10 was poorly suppressed . Clarithromycin had the most potent inhibitory effect of the drugs used . The present results suggested that anti-bacterial agents might modify the host's immunological response by interfering with the activity of T helper cells. FEMS Microbiol Lett, 2002 Jan 10, 206(2), 163 - 8 Cloning and characterization of a glycosyltransferase gene involved in the biosynthesis of anthracycline antibiotic beta-rhodomycin from Streptomyces violaceus; Miyamoto Y et al.; A glycosyltransferase gene, rhoG, involved in the biosynthesis of the anthracycline antibiotic beta-rhodomycin was isolated as a 4.1-kb DNA fragment containing rhoG and its flanking region from Streptomyces violaceus by degenerate and inverse PCR . Sequencing analysis showed that rhoG was located in a gene cluster involved in the biosynthesis of the constitutive deoxysugar of beta-rhodomycin . The function of rhoG was verified by gene disruption, which was generated by replacing the internal 0.9-kb region of S . violaceus chromosome with a fragment including the SacI-blunted region . The rhoG disruption resulted in complete loss of beta-rhodomycin productivity, along with the accumulation of a non-glycosyl intermediate epsilon-rhodomycinone . In addition, the complementation test demonstrated that rhoG restored beta-rhodomycin production in this gene disruptant . These results indicated that rhoG is the glycosyltransferase gene responsible for the glycosylation of epsilon-rhodomycinone in beta-rhodomycin biosynthesis. Ann Allergy Asthma Immunol, 2002 Jan, 88(1), 24 - 9 A survey of antibiotic prescribing and knowledge of penicillin allergy; Puchner TC Jr et al.; BACKGROUND: Cephalosporins can cause allergic reactions in patients with penicillin (PCN) allergy . Physicians' prescribing habits for patients with PCN allergy can vary . OBJECTIVES: 1) Survey community and academic physicians, students, residents, and allergists on their tendencies to prescribe cephalosporins and/or perform PCN skin testing in patients with different histories of PCN allergy . 2) Evaluate PCN allergy knowledge in these groups . METHODS: A questionnaire consisting of four case scenarios and five true/false questions on PCN allergy was distributed at various conferences and by mailings . RESULTS:Three hundred seventy-eight completed surveys were analyzed . Given a patient with a history of rash with PCN, an equal number of allergists and nonallergists (36%) prescribed cephalosporins, although there was a difference between pediatricians (56%) and internists (22%) . Given a history of PCN anaphylaxis, no allergists but 11% of nonallergists prescribed a cephalosporin . Skin testing was infrequently requested by nonallergists . The correct response rate for the true/false questions was 89% for allergists, community (63%) and academic (67%) physicians, pediatricians (61%), internists (67%), residents (68%), and students (68%) . Pediatric residents had the highest (74%) and community pediatricians the lowest (59%) correct response rate . CONCLUSIONS: There is marked variation in prescribing cephalosporins and in requesting PCN skin testing in patients with varied histories of PCN allergy . The survey results indicate a need for increased PCN allergy education. Hepatogastroenterology, 2001 Nov-Dec, 48(42), 1641 - 7 Duodenal ulcer healing rates in a one-year follow-up study with ranitidine bismuth citrate and antibiotics; Wurzer H et al.; BACKGROUND/AIMS: The aim of this study was to determine the one-year outcome of an eradication therapy with ranitidine bismuth citrate and antibiotics in Helicobacter pylori-positive duodenal ulcer patients in respect to ulcer and Helicobacter pylori relapse rates . METHODOLOGY: This multicenter, randomized, double-blind study involved 648 duodenal ulcer patients and had been carried out to compare the following regimens: ranitidine bismuth citrate b.i.d . co-prescribed with either clarithromycin 250 mg q.i.d . or clarithromycin 500 mg b.i.d . or clarithromycin 500 mg b.i.d . plus metronidazole 400 mg b.i.d . for 2 weeks, followed by a further 14 days of treatment with ranitidine bismuth citrate 400 mg b.i.d . to facilitate ulcer healing . H . pylori eradication was assessed by 13C-urea breath test and histology at least 4 weeks, 26 weeks and 52 weeks after the end of treatment . Ulcer relapse and H . pylori status were assessed 4 weeks, 26 weeks and 52 weeks post-treatment or if ulcer symptoms recurred . For the remainder of the follow-up period only serious adverse events were collected . RESULTS: At 12 months data of 438 (69%) patients were evaluable . The observed H . pylori eradication rates were 88-91% . H . pylori relapse rates were 2.1% after 26 weeks and 3.9% after 52 weeks . At the week 26 visit 26 patients (5.6%) and at the week 52 visit 25 patients (5.7%) had documented gastroesophageal reflux disease . CONCLUSIONS: Our data confirm the reduction of duodenal ulcer relapses after the cure of Helicobacter pylori infection. Int Immunopharmacol, 2002 Feb, 2(2-3), 367 - 80 Chemotherapeutic stress mediated by certain antitumor antibiotics induces an atypical CD69+ surface phenotype in peripheral T-lymphocytes; Morgan CD et al.; Surface antigen CD69 is a Type II integral membrane protein that is generally considered a cell activation marker expressed very early in the normal lymphocyte activation cascade . The conformation of this surface antigen suggests a putative role in transmembrane signal transduction, yet the precise function of this surface antigen has not been clearly elucidated . We had previously reported robust atypical CD69 expression in peripheral T-lymphocytes as concentration-dependent, phenotypic responses to actinomycin D-induced chemotherapeutic stress in the absence of secondary stimulation . Additional antitumor antibiotics were evaluated for inductive potential, and the incidence and respective magnitudes of this chemotherapeutic stress-induced shift in lymphocytic CD69 expression were assessed . Results indicated that atypical CD69 expression is a common response to chemotherapy drug-induced stress . Differences in the respective percentages of CD69 + T-lymphocytes, and the resulting numbers of CD69 surface antigens ultimately expressed by these cells, were documented following in vitro drug exposure . The effective drug concentrations required to mediate detectable shifts in the CD69+ phenotype differed among the selected drugs, as well, suggesting a concentration-dependent induction mechanism putatively related to drug modality . Static CD69 expression responses in CD3+ peripheral T-lymphocytes were also documented, which further suggests that the different intracellular modalities do not mediate proportional T-lymphocyte responses through elevated CD69 expression. Coll Antropol, 2001 Dec, 25(2), 459 - 65 Oral antibiotic prescription in ambulatory care in 1999--a contribution to the development of methods for drug consumption and prescription surveillance monitoring; Mandic D et al.; The aim of the study was to estimate the consumption of antibiotic in ambulatory care . Oral antibiotic consumption in 1999 was analyzed in four pharmacies in the Zagreb area . The use of oral antibiotics in comparison with total drug consumption, the share of individual subclasses of oral antibiotics and the respective shares of individual products were also analyzed . The results obtained were expressed in terms of both the defined daily doses (DDD) and US$, and were compared with available national and international data . The study demonstrated a high share of oral antibiotics in the overall drug consumption, especially of newer and more expensive agents within individual subclasses of antibiotics . Further research is required to assess the rationale of such prescribing practices, especially in view of the current financial pressure on the Croatian health care system. J Infect Chemother, 1999 Jun, 5(2), 61 - 74 Mechanisms of bacterial resistance to macrolide antibiotics; Nakajima Y; Macrolides have been used in the treatment of infectious diseases since the late 1950s . Since that time, a finding of antagonistic action between erythromycin and spiramycin in clinical isolates1 led to evidence of the biochemical mechanism and to the current understanding of inducible or constitutive resistance to macrolides mediated by erm genes containing, respectively, the functional regulation mechanism or constitutively mutated regulatory region . These resistant mechanisms to macrolides are recognized in clinically isolated bacteria . (1) A methylase encoded by the erm gene can transform an adenine residue at 2058 (Escherichia coli equivalent) position of 23S rRNA into an 6N, 6N-dimethyladenine . Position 2058 is known to reside either in peptidyltransferase or in the vicinity of the enzyme region of domain V . Dimethylation renders the ribosome resistant to macrolides (MLS) . Moreover, another finding adduced as evidence is that a mutation in the domain plays an important role in MLS resistance: one of several mutations (transition and transversion) such as A2058G, A2058C or U, and A2059G, is usually associated with MLS resistance in a few genera of bacteria . (2) M (macrolide antibiotics)- and MS (macrolide and streptogramin type B antibiotics)- or PMS (partial macrolide and streptogramin type B antibiotics)-phenotype resistant bacteria cause decreased accumulation of macrolides, occasionally including streptogramin type B antibiotics . The decreased accumulation, probably via enhanced efflux, is usually inferred from two findings: (i) the extent of the accumulated drug in a resistant cell increases as much as that in a susceptible cell in the presence of an uncoupling agent such as carbonylcyanide-m-chlorophenylhydrazone (CCCP), 2,4-dinitrophenol (DNP), and arsenate; (ii) transporter proteins, in M-type resistants, have mutual similarity to the 12-transmembrane domain present in efflux protein driven by proton-motive force, and in MS- or PMS-type resistants, transporter proteins have mutual homology to one or two ATP-binding segments in efflux protein driven by ATP . (3) Two major macrolide mechanisms based on antibiotic inactivation are dealt with here: degradation due to hydrolysis of the macrolide lactone ring by an esterase encoded by the ere gene; and modification due to macrolide phosphorylation and lincosamide nucleotidylation mediated by the mph and lin genes, respectively . But enzymatic mechanisms that hydrolyze or modify macrolide and lincosamide antibiotics appear to be relatively rare in clinically isolated bacteria at present . (4) Important developments in macrolide antibiotics are briefly featured . On the basis of information obtained from extensive references and studies of resistance mechanisms to macrolide antibiotics, the mode of action of the drugs, as effectors, and a hypothetical explanation of the regulation of the mechanism with regard to induction of macrolide resistance are discussed. Am J Gastroenterol, 2002 Jan, 97(1), 104 - 8 Antibiotics increase functional abdominal symptoms; Maxwell PR et al.; OBJECTIVES: Data suggest that subjects with irritable bowel syndrome are more likely to report a recent course of antibiotics . This study tests the hypothesis that a course of antibiotics is a risk factor for an increase in the number of functional bowel complaints over a 4-month period in a general population sample . METHODS: We initiated a prospective case-control study in three general practices in South London . Consecutive patients aged 16-49 attending their general practitioner with non-GI complaints and given a prescription for antibiotics were invited to participate . Comparison subjects who had not had antibiotics for 1 yr were identified from the practice records by age group, gender, and previous general practitioner visits . Fifty-eight antibiotic and 65 control patients agreed to participate . Questionnaires covering demographic, GI, and psychological data were sent at recruitment and at 4 months . Seventy-four percent of subjects completed the study . The number of symptoms at follow-up compared to that at recruitment . RESULTS: Twenty of 42 antibiotic subjects (48%) versus 11/49 control subjects (22%) demonstrated one or more additional functional bowel symptoms at 4 months (unadjusted odds ratio = 3.14 {1.27-7.75}) (chi2 = 6.4, p = 0.01) . Ten of 42 antibiotic subjects (24%) versus 3/49 control subjects (6%) demonstrated two or more additional functional bowel symptoms at 4 months (unadjusted odds ratio = 4.79 {1.22-18.80}) (chi2 = 5.8, p = 0.02) . CONCLUSIONS: Functional bowel symptoms come and go, but subjects who are given a course of antibiotics are more than three times as likely to report more bowel symptoms 4 months later than controls. Acta Paediatr, 2001 Nov, 90(11), 1316 - 20 Antibiotic prescription in italian children: a population-based study in Friuli Venezia Giulia, north-east Italy; Borgnolo G et al.; Comprehensive information on prescription patterns of antibiotics in Italy is scarce . This study describes the use of systemic antibiotics in children according to age and sex in Friuli Venezia Giulia, north-east Italy . A pharmacological prescription database was used to identify individual prescriptions provided to all 0-15-y-old resident children (n = 140,630) during 1998 . Overall, 124,383 prescriptions were identified . The prescription rate was highest in the 3-6 y olds, with 1491 antibiotic prescriptions per 1,000 children per year . Antibiotics were prescribed for 52% of infants, 57.2% of toddlers and 62% of preschool children . Twenty-nine percent of the prescriptions were for cephalosporins, 27% for macrolides and 24% for broad-spectrum penicillins . Prescription rates were much higher than in other countries such as Denmark, with more antibiotic courses prescribed for more children at all ages . Prescriptions from general practitioners and family paediatricians often included second-line antibiotics (e.g . cephalosporins and macrolides) or antibiotics that have not been approved for community-acquired paediatric infections (e.g . quinolones) . CONCLUSION: The development of regional guidelines for antibiotic use in children should be urgently recommended. J Chromatogr A, 2001 Dec 21, 939(1-2), 59 - 67 Non-derivatization approach to high-performance liquid chromatography-fluorescence detection for aminoglycoside antibiotics based on a ligand displacement reaction; Yang M et al.; An indirect fluorescence detection method has been developed for detecting the aminoglycoside antibiotics following chromatographic separation . This approach to detection is based on a displacement reaction between the aminoglycosides and a copper(II)-L-tryptophan (L-Trp) complex, Cu(L-Trp)2 . The aminoglycosides, which contain multiple amino groups, have strong affinities for the Cu(II) ion and displace L-Trp from the Cu(L-Trp)2 complex . The resulting increase in L-Trp fluorescence, which is quenched when coordinated to Cu(II), is indicative of the presence of the aminoglycoside . Fluorescence titration data indicate that there is a stoichiometric ratio of 1:1 between the reaction of the aminoglycosides with Cu(L-Trp)2 . This HPLC detection scheme is implemented postcolumn by mixing a buffered Cu(L-Trp)2 solution with the column eluent prior to detection . The aminoglycosides were separated with the use of a column packed with a polymeric strong cation-exchanger . Separation and detection variables were optimized and are discussed . The detection limits for the aminoglycosides tested ranged from 4.2 to 14.5 ng injected (S/N=3) . A linear working curve was achieved for amikacin in the range of 29-586 ng for a six point linearity test . The developed separation and detection scheme was further tested by analyzing commercial pharmaceutical formulations of these antibiotics. Physiol Behav, 1977 Jul, 19(1), 145 - 54 Effect of antibiotics on retention of visual discrimination training and on protein synthesis in the pigeon; Stettner LJ et al.; Forty-three pigeons were trained for one day on a visual discrimination (horizontal vs . vertical stripes) and then immediately injected with either puromycin (PM), cycloheximide (CXM), control saline, or combined PM and CXM solution . PM produced a marked amnesic effect, CXM a weaker effect . PM injected animals (but not CXM's) also took significantly more than 1 day longer than controls to reach criterion levels, indicating an effect on continued acquisition of the discrimination beyond the amnesia for Day 1 . Combination with CXM did not attenuate the PM effects . Protein inhibition profiles showed maximum PM activity of 90% inhibition, whereas CXM's maximum was 98% and was distributed more widely throughout different brain regions . In a second experiment, PM (N = 8), CXM (N = 8) or saline (N = 8) were again injected immediately after training, but the S+ was reversed on all postinjection training trials . In this case, PM animals were superior in percentage of S+ pecks on Day 2 to controls and CXM's . Further, the continued acquisition deficit was absent in the PM group, indicating that this effect is highly specific to those behavioral circuits active at the time of injection. J Allergy Clin Immunol, 2002 Jan, 109(1), 43 - 50 Early exposure to infections and antibiotics and the incidence of allergic disease: a birth cohort study with the West Midlands General Practice Research Database; McKeever TM et al.; BACKGROUND: It has been suggested that the rise in prevalence of allergic disease in westernized countries is due in part to a decrease in exposure to infections and an increase in the use of antibiotics early in life . OBJECTIVE: The purpose of this investigation was to quantify the relationships between (1) exposure to personal infections, infections in siblings, and use of antibiotics in early life and (2) the incidence of allergic disease . METHODS: Using the West Midlands section of the UK General Practice Research Database, we established a historical birth cohort of children (N = 29,238) . For each child, we identified all personal infections and infections in siblings and determined the use of antibiotics in early life; we also noted incident diagnoses of asthma, eczema, and hay fever . The data were analyzed through use of Cox regression . RESULTS: There was no clear protective effect of exposure to either personal infections or infections in siblings with respect to the incidence of allergic disease . Antibiotic exposure was associated with an increased risk of developing allergic disease in a dose-related manner: having 4 or more courses of antibiotics in the first year of life was associated with an increased incidence of asthma (hazard ratio {HR}, 3.13; 95% CI, 2.75-3.57), eczema (HR, 1.48; 95% CI, 1.31-1.68), and hay fever (HR, 2.12; 95% CI, 1.68-2.66) . However, adjusting for consulting behavior reduced these effects (adjusted HR {95% CI}: asthma, 1.99 {1.72-2.31}; eczema, 1.01 {0.88-1.17}; hay fever, 1.14 {0.88-1.47}) . CONCLUSIONS: We found no evidence that exposure to infections reduced the incidence of allergic disease, and infections did not explain the previous findings of a strong birth order effect in this cohort . The use of antibiotics might be associated with early diagnoses of allergic disease. Zhonghua Yi Xue Za Zhi, 2000 Aug, 80(8), 614 - 7 {Active efflux of antibiotics as multiple-antibiotic-resistance mechanism in clinical strains of escherichia coli}; Zhang X et al.; OBJECTIVE: To investigate multiple-antibiotic-resistance mechanism in clinical strains of Escherichia coli . METHODS: Accumulation of ciprofloxacin in clinical isolates of Escherichia coli was measured by fluorometry, and acrAB gene was identified by PCR and Southern blot . The levels of acrAB gene expression were measured by RT-PCR . DNA fragments were sequenced by automated fluorescence sequencing . RESULTS: The state concentration of ciprofloxacin in multiple-antibiotic-resistant (Mar) strains was significantly lower than that in susceptible stsains (0.73 mg/L +/- 0.04 mg/L vs 2.00 mg/L +/- 0.07 mg/L A(660), P < 0.001) . The level of acrAB gene expression in Mar strains was significantly higher than that in other strains . No deletion or point mutation in acrAB gene were found in Mar and susceptible clinical Escherichia coli isolates . CONCLUSIONS: High expression of acrAB gene leads to multiple-antibiotic-resistance in clinical strains of Escherichia coli, and Mar operon may contribute to the regulation of acrAB gene expression. Pediatr Nephrol, 2002 Jan, 17(1), 50 - 1 Antibiotic-induced recurring interstitial nephritis; Sakarcan A et al.; Acute interstitial nephritis (AIN) is often induced by drug therapy and accounts for 1%-3% of adult cases of renal failure . A 13-year-old white female with cystic fibrosis developed two episodes of biopsy proven AIN following antibiotic use over a 5-year period . The first episode resolved with pulse steroid therapy and the second resolved without intervention . Steroid therapy may play a role in aborting subsequent AIN attacks. Int J Oncol, 2002 Feb, 20(2), 261 - 6 Characteristics of mitotic cell death induced by enediyne antibiotic lidamycin in human epithelial tumor cells; He QY et al.; Mitotic cell death, a different cell death mode from apoptosis, has been focused on in tumor therapy . It may involve the mechanism of highly potent cytotoxicities of enediyne antibiotics toward tumor cells . We describe the characteristics of mitotic cell death induced by enediyne antibiotic lidamycin at low concentrations (0.01-1 nM), in the human hepatoma BEL-7402 cells and human breast carcinoma MCF-7 cells . The cells exerting mitotic cell death showed retardation at G2+M phase, enlargement of cell volume and multinucleation, some of which were positive in senescence-associate beta-galactosidase staining . The multinucleated living cells did not show apoptotic features by co-staining with mitochondria-specific dye Mitosensor and DNA-specific dye Hoechst 33342 . The DNA polyploidy rather than <apoptotic sub-G1 peak> increased with incubation time for the lidamycin-treated BEL-7402 cells . The proliferation status of BEL-7402 cells was shown by flow cytometry after the cells were labeled with PKH-67, a fluorescent dye for labeling living cells, but the fluorescent intensity of the lidamycin-treated cells was little changed . The smear DNA pattern was detected in the multinucleated cells by agarose gel electrophoresis . The results provide the first evidence for elucidating the potent cytotoxicities of lidamycin toward tumor cells and further describing characteristics of mitotic cell death. BMJ, 2002 Jan 12, 324(7329), 91 - 4 Reducing antibiotic use for acute bronchitis in primary care: blinded, randomised controlled trial of patient information leaflet; Macfarlane J et al.; OBJECTIVE: To assess whether sharing the uncertainty of the value of antibiotics for acute bronchitis in the form of written and verbal advice affects the likelihood of patients taking antibiotics . DESIGN: Nested, single blind, randomised controlled trial . SETTING: Three suburban general practices in Nottingham Participants: 259 previously well adults presenting with acute bronchitis . INTERVENTION: In group A, 212 patients were judged by their general practitioner not to need antibiotics that day but were given a prescription to use if they got worse and standard verbal reassurance . Half of them (106) were also given an information leaflet . All patients in group B (47) were judged to need antibiotics and were given a prescription and encouraged to use it . MAIN OUTCOME MEASURES: Antibiotic use in the next two weeks . Reconsultation for the same symptoms in the next month . RESULTS: In group A fewer patients who received the information leaflet took antibiotics compared with those who did not receive the leaflet (49 v 63, risk ratio 0.76, 95% confidence interval 0.59 to 0.97, P=0.04) . Numbers reconsulting were similar (11 v 14) . In group B, 44 patients took the antibiotics . CONCLUSION: Most previously well adults with acute bronchitis were judged not to need antibiotics . Reassuring these patients and sharing the uncertainty about prescribing in a information leaflet supported by verbal advice is a safe strategy and reduces antibiotic use. Org Lett, 2001 Dec 27, 3(26), 4291 - 4 Syntheses and absolute stereochemistries of UPA0043 and UPA0044, cytotoxic antibiotics having a p-quinone-methide structure; Takao KI et al.; The first syntheses of new antibiotics UPA0043 and UPA0044 were accomplished starting from commercially available 18beta-glycyrrhetinic acid and vanillin . The present syntheses involve the coupling of a sesquiterpenoid aldehyde and an aryllithium, the stereoselective formation of a p-quinone-methide system, and regioselective intramolecular cyclization via an epoxy ring opening . {reaction: see text} Adv Biochem Eng Biotechnol, 2002, 75, 209 - 42 Perspectives in liquid membrane extraction of cephalosporin antibiotics; Sahoo GC et al.; In this paper an overview of the developments in liquid membrane extraction of cephalosporin antibiotics has been presented . The principle of reactive extraction via the so-called liquid-liquid ion exchange extraction mechanism can be exploited to develop liquid membrane processes for extraction of cephalosporin antibiotics . The mathematical models that have been used to simulate experimental data have been discussed . Emulsion liquid membrane and supported liquid membrane could provide high extraction flux for cephalosporins, but stability problems need to be fully resolved for process application . Non-dispersive extraction in hollow fiber membrane is likely to offer an attractive alternative in this respect . The applicability of the liquid membrane process has been discussed from process engineering and design considerations. J Agric Food Chem, 2002 Jan 16, 50(2), 406 - 11 Screening and mass spectral confirmation of beta-lactam antibiotic residues in milk using LC-MS/MS; Holstege DM et al.; Milk is typically screened for beta-lactam antibiotics by nonspecific methods . Although these methods are rapid and sensitive, they are not quantitative and can yield false positive findings . A sensitive and specific method for the quantitation and mass spectral confirmation of five beta-lactam and two cephalosporin antibiotics commonly or potentially used in the dairy industry is described using high-performance liquid chromatography with tandem mass spectrometry . The antibiotics studied were ampicillin, amoxicillin, penicillin G, penicillin V, cloxacillin, cephapirin, and ceftiofur . The antibiotics were extracted from milk with acetonitrile, followed by reversed-phase column cleanup . The extract was analyzed by liquid chromatography coupled with a mass spectrometer, using a water/methanol gradient containing 1% acetic acid on a C-18 reversed-phase column . Determination was by positive ion electrospray ionization and ion trap tandem mass spectrometry . Quantitation was based on the most abundant product ions from fragmentation of the protonated ion for amoxicillin, cephapirin, ampicillin, and ceftiofur and on the fragmentation of the sodium adduct for penicillin G, penicillin V, and cloxacillin . The method was validated at the U.S . FDA tolerance or safe level and at 5 or 2.5 ng/mL for these compounds in bovine milk . Theoretical method detection limits in milk based on a 10:1 signal to noise ratio were 0.2 ng/mL (ampicillin), 0.4 ng/mL (ceftiofur), 0.8 ng/mL (cephapirin), 1 ng/mL (amoxicillin and penicillin G), and 2 ng/mL (cloxacillin and penicillin V) using a nominal sample size of 5 mL. J Ind Microbiol Biotechnol, 2001 Sep, 27(3), 183 - 94 Antibiotic biosynthesis: from natural to unnatural compounds; Floss HG; The evolution of the field of biosynthesis from the unravelling of the mode of formation of natural products to the use of such knowledge to create new compounds is reviewed using examples from the author's laboratory . The discussion focuses on the mode of operation of type II (spore pigment PKS) and type I (rifamycin PKS) polyketide synthases and their diversion to generate unnatural products, and on the genetics and biochemistry of deoxysugar formation in granaticin biosynthesis as a prerequisite to combinatorial enzymatic synthesis of unusual glycosides. J Ind Microbiol Biotechnol, 2001 Sep, 27(3), 157 - 62 Chemical diversity in lipopeptide antifungal antibiotics; Hino M et al.; In the course of screening for antifungal antibiotics, we have discovered a novel series of lipopeptide compounds structurally related to, but highly superior to, echinocandin B in terms of their water solubility due to the presence of a sulfate residue . These compounds, WF11899s, WF738s, WF14573s, WF16616 and WF22210, and their derivatives have diversity in their nuclear structures and acyl side chains . The producing strains were classified into two groups, the Coleomycetes group and the Hyphomycetes group . Compound FK463, a derivative of WF11899A, is currently in Phase 3 clinical development as a novel antifungal antibiotic. Am J Cardiol, 2002 Jan 1, 89(1), 18 - 21 Relation of antibiotic use to risk of myocardial infarction in the general population; Luchsinger JA et al.; There are conflicting reports of an association between Chlamydia pneumoniae (C . pneumoniae) infection and coronary artery disease (CAD); randomized trials of antibiotics for the secondary prevention of CAD are currently underway . Physicians may be tempted to believe that their choice of antibiotic class in treating any infection may alter the risk of CAD . Our objective was to determine if the use of antibiotics with antichlamydial activity in the general population reduces the risk of myocardial infarction . A healthcare claims database with 354,258 patients with continuous health and pharmacy coverage for at least 2 years between January 1, 1991 and December 31, 1997 was used for the analyses . Hazard ratios were derived from proportional hazards models with time-dependent covariates, relating antibiotic prescription to first claim related to incident first myocardial infarction during the observation period, adjusting for previous CAD, age, sex, diabetes, hypertension, hyperlipidemia, and chronic obstructive pulmonary disease . There were a total of 1,684,091 person-years of observation and 16,139 incident myocardial infarctions . The adjusted hazard ratios were 1.10 (95% confidence intervals {CI} 1.04 to 1.16) for macrolides, 1.20 (95% CI 1.13 to 1.26) for quinolones, 1.10 (95% CI 0.96 to 1.21) for cephalosporins, 1.00 (95% CI 0.96 to 1.06) for tetracyclines, 1.01 (95% CI 0.96 to 1.06) for penicillins, and 1.13 (95% CI 0.98 to 1.30) for trimetroprim-sulfamethoxazole . The hazard ratios for individual antibiotics with activity against C . pneumoniae within each group were similar . Use of antibiotics with activity against C . pneumoniae does not reduce the risk of myocardial infarction in the general population. Emerg Med J . 2002 Jan;19(1):49. Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary . Antibiotics after puncture wounds to the foot; Harrison M et al.; A short cut review was carried out to establish whether antibiotics reduce infective complications after puncture wounds to the foot . A total of 29 papers were found using the reported search, of which none answered the question posed . Further research is needed in this area. Emerg Med J, 2002 Jan, 19(1), 48 - 9 Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary . The use of antibiotics in venomous snake bite; Terry P et al.; A short cut review was carried out to establish whether antibiotics reduce the incidence of infection after venomous snake bite . Altogether 60 papers were found using the reported search, of which three 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 papers are shown in table 3 . A clinical bottom line is stated. Presse Med, 2001 Dec 8, 30(37), 1821 - 4 {Evaluation of changing antibiotic prescription habits in a general hospital center}; Chardonnet C et al.; OBJECTIVE: Two audits of antibiotic prescriptions were conducted within the framework of the fight against bacterial resistance conducted at the Valence Hospital Center (Drome, France) . The first was made between July 1st and 31st 1998 and the second between December 15th 1999 and January 15th, 2000, both based on the prospective observation scheme . PATIENTS AND METHODS: We studied prescriptions written for antibiotics, recording the compound prescribed, the therapeutic indication, the type of infection and the prescriber . Results of these two audits were compared with the chi-square test . RESULTS: The prescriber was correctly identified (name + signature) on 63.1% of the prescriptions in 1998 and on 92.9% in 1999-2000 . The patient was correctly identified (name + first name + age) in 89.9% of the prescriptions in 1998 compared with 95% in 1999-2000 . For the compounds prescribed, 30.2% of the prescriptions were complete (name + dose + frequency + duration + administration route) in 1998 compared with 44.5% in 1999-2000 . The antibiotic was prescribed for prophylactic purposes in 16.2% of the cases in 1998 and in 8.6% in 1999-2000 . Empirical curative antibiotic therapy was prescribed in 44.7% of the cases in 1998 and in 49.3% in 1999-2000 . Curative antibiotic therapy was prescribed in 16.2% in 1998 and in 9.3% in 1999-2000 for proven infection and with no mention of proof in 22.9% in 1998 and 32.8% in 2000 . DISCUSSION: We observed an improvement in the identification of the prescriber, the patient and the drugs used between the two audits . These results were generally satisfactory and reflect the impact of an information campaign conducted after the first audit . Such audits are part of the ongoing policy designed around the antibiotic booklet and within the framework of the newly instituted antibiotic committees. Shokuhin Eiseigaku Zasshi, 2001 Oct, 42(5), 335 - 8 {Survey of residual antibiotic agents in cultured fish and shellfish}; Abe N et al.; A survey of residual antibiotic agents in cultured fish and shellfish purchased from the Tokyo Central Market was carried out . Out of 240 samples tested, OTC was detected in 14 samples which consisted of flatfish, yellowtail, seriola and eel . Synthetic antibiotic agents were not detected . The highest level of OTC was 0.36 microgram/g in skin of flatfish . In the case of flatfish, the concentration of OTC was highest in skin, followed by liver, then muscle . OTC was detected in livers of all yellowtail, seriola and eel, and the concentration was higher than that in muscle or skin. J Ind Microbiol Biotechnol, 2001 Dec, 27(6), 386 - 92 Characterization of the biosynthetic gene cluster for the oligosaccharide antibiotic, Evernimicin, in Micromonospora carbonacea var . africana ATCC39149; Hosted TJ et al.; Evernimicin (EV) belongs to the orthosomycin class of antibiotics and consists of several modified L- and D-deoxysugars containing unusual orthoester and glycosyl linkages and two orsellinic acid groups, one that is halogenated . The EV biosynthetic gene cluster from Micromonospora carbonacea var . africana ATCC39149 was localized by hybridization to a dTDP-D-glucose 4,6-dehydratase probe and a 120-kb region containing the EV biosynthetic cluster and surrounding regions has been sequenced . BLAST analysis has identified a type I polyketide synthase for orsellinic acid biosynthesis as well as enzymes required for L- and D-deoxyglucose and D-deoxymannose synthesis . In addition, genes involved in glycosyltransfer and resistance were identified . Insertional mutations in several biosynthetic genes blocked EV production, indicating a role for these genes in EV biosynthesis. Acad Emerg Med, 2002 Jan, 9(1), 22 - 6 Parental use and misuse of antibiotics: are there differences in urban vs . suburban settings? Edwards DJ, Richman PB, Bradley K, Eskin B, Mandell M. OBJECTIVE: To compare the frequencies with which suburban and urban parents give their children antibiotics without first consulting a physician . METHODS: This was a prospective, comparative survey of a suburban emergency department (ED) patient population in New Jersey with an annual patient census of 60,000 visits and an urban ED in Connecticut with 58,000 annual visits . A convenience sample of parents with children <18 years of age were enrolled . Patients who were critically ill and/or not oriented were excluded . Subjects provided written answers to a series of closed questions regarding their knowledge and use of antibiotics for their children over the previous 12 months . Categorical data were analyzed by chi-square and Fisher's exact test; continuous data were analyzed by t-tests . All tests were two-tailed with alpha set at 0.05 . The primary endpoint, antibiotic "misuse," was defined as parental administration of antibiotics to a child during the previous 12 months without the consultation of a physician . RESULTS: Eight hundred one parents were enrolled; 424 at the suburban site . Parents in the suburban site were significantly different with regard to mean age (39 +/- 7.2 vs . 32 +/- 9.0, p < 0.001), percentage female sex (63% vs . 81%, p < 0.001), percentage white race (78% vs . 34%, p < 0.001), and percentage with private insurance (89% vs . 56%, p < 0.001) . A higher percentage of parents at the suburban site had misused antibiotics (12.1% vs . 4.0%; p < 0.001) . Using logistic regression, this significant difference in the rate of antibiotic misuse between the two groups remained after adjustment for demographic variables and insurance status of the parents (p < 0.001) . Parents at the suburban site were significantly less likely to have been previously discharged with their child from an office or ED setting without antibiotics only to go soon afterwards to another health facility in order to obtain such medications (5% vs . 48%; p < 0.001) . CONCLUSIONS: Parents in the suburban setting were more likely to have misused antibiotics for their childr