Antibiotics

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 children . On the other hand, parents in the urban setting were more likely to have been discharged by a physician at one health facility and gone to another physician's office or ED in order to obtain antibiotics for their children.

Acta Pharm Hung, 2001, 71(1), 108 - 13
{Analysis of antibiotic usage}; Balpataki R et al.; Economic analysis is founded on the assumption that resources are limited and that should be used in a way that maximizes the benefits gained . Pharmacoeconomics extends these assumptions to drug treatment . Therefore, a full pharmacoeconomic analysis must consider two or more alternative treatments and should be founded on measurement of incremental cost, incremental efficacy, and the value of successful outcome . Antibiotic policy based only on administrative restrictions is failed, instead of it disease formularies and infectologist consultation system are needed . Equally important are various programmes that encourage the cost-conscious use of the antibiotics chosen . Some of the methods evaluated in the literature include: streamlining from combination therapy to a single agent, early switching from parenteral to oral therapy, initiating treatment with oral agents, administering parenteral antibiotic at home from outset of therapy, and antibiotic streamlining programmes that are partnered with infectious disease physicians . The solution is the rational and adequate use of antibiotics, based on the modern theory and practice of antibiotic policy and infection control, that cannot be carried out without the activities of experts in this field.

Drug Resist Updat, 2001 Jun, 4(3), 178 - 86
Resistance of Helicobacter pylori to antibiotics and its impact on treatment options; Megraud F; The treatment of Helicobacter pylori infection is jeopardized by resistance to the antibiotics used, which turns out to be the main risk factor for failure . Resistance is due to point mutations . For clarithromycin only two sites in the 23S rRNA sequence are concerned and can be easily detected by molecular methods, while for metronidazole several mutations on rdxA and other genes can be responsible and so do not allow such detection . The situation for the rare cases of amoxicillin resistance is not fully determined . The impact of resistance on the clinical outcome is dramatic for clarithromycin while it only decreases the success by 20% for metronidazole.

Cell Mol Life Sci, 2001 Nov, 58(12-13), 1897 - 906
Towards new beta-lactam antibiotics; Andersson I et al.; Antibiotics have had a profound impact on human health and belong to one of the largest-selling classes of drugs worldwide . Introduced into industrial production only some half century ago, these miracle drugs have been the main contributors to the recent increase in human life expectancy . However, the accelerated emergence of bacteria that are resistant to multiple antibiotic types now appears as the most serious threat to continuing success in the treatment of infectious diseases . Recent advances in our knowledge of the structures and mechanisms of enzymes in the biosynthetic pathways of penicillins and cephalosporins, amongst the most important antibiotics in current use, have identified a common structural core together with common iron- and cosubstrate-binding motifs . The diversity in the catalytic specificities of these oxygenases using very similar structural platforms suggests that altering the substrate and product specificities of these enzymes should be possible in the laboratory . This opens up new avenues for industrial production and medical utilisation.

Yakugaku Zasshi, 2001 Dec, 121(12), 915 - 27
{New orally active penem antibiotic: Farom}; Ishiguro M et al.; An orally active penem antibiotic, Farom (generic name: faropenem), was designed by the conformational analysis of active and inactive penem derivatives . Faropenem showed potent activity against a wide variety of bacteria including extended-spectrum beta-lactamase (ESBL)-producing ones . The mechanism of the stability against ESBL was elucidated by modeling the Michaelis complex of faropenem and Toho-1, an ESBL . Modeling of a complex of faropenem at the active site of a penicillin-binding protein 2 (PBP2) model suggested the characteristic affinity for faropenem with PBP2 of Escherichia coli . Faropenem has been totally synthesized from (R)-1,3-butanediol . The synthetic intermediate, a 3-hydroxyethyl-4-acetoxyazetidinone derivative, was efficiently prepared by the 2 + 2 coupling of a optically active vinylsulfide derivative and chlorosulfonyl isocyanate, followed by the substitution of the acetoxy group for the thiophenyl group at the C-4 position.

Analyst, 2001 Nov, 126(11), 1990 - 5
Efficient and sensitive screening and confirmation of residues of selected polyether ionophore antibiotics in liver and eggs by liquid chromatography-electrospray tandem mass spectrometry; Rosen J; A method using liquid chromatography tandem mass spectrometry (LC-MS-MS) with electrospray (ES) for the determination of traces of narasin, monensin and salinomycin in chicken liver and eggs was developed, validated and used for routine surveillance . The essence of this paper is to demonstrate that one single method can serve very well for two entirely different purposes, i.e., screening and confirmation . Highly reliable confirmation of the identity at low concentrations was demonstrated when residues of narasin were detected and quantified (0.2 to 11 ng g(-1)) in 50% of the Swedish eggs analysed in 1999 . Four daughter ions were detected with ion ratios meeting suggested confirmation criteria for the European Union, even at 0.2 ng g(-1) . The method was found to be highly cost-effective since both screening and confirmation of 98 liver samples were performed in only two analytical runs (the Swedish national surveillance scheme of 1999, report level 5 ng g(-1)) . The high performance of the method for the different applications was possible due to a combination of the power of ES-LC-MS-MS, a procedure involving screening of pooled samples, and method optimisation of the work-up (automated solid phase extraction), LC and MS parameters . Validation data for narasin (0.5 to 20 ng g(-1)) in eggs are presented (accuracy 94 to 108%, relative standard deviation 4 to 10%, limit of detection 0.026 ng g(-1)) . The time for an LC-MS-MS run was 4 min, corresponding to 48 s per sample in a pool.

Analyst, 2001 Nov, 126(11), 1942 - 6
A new electrochemical enzyme-linked immunosorbent assay for the screening of macrolide antibiotic residues in bovine meat; Draisci R et al.; A new sensitive electrochemical enzyme-linked immunosorbent assay (ELISA) for the detection of two macrolides (erythromycin and tylosin) in bovine muscle was developed, using the mouse monoclonal antibodies anti-erythromycin and anti-tylosin . The competitive indirect assay was performed using an erythromycin (or tylosin)-BSA conjugate as a coating molecule; after competition between free and coated analytes for the antibodies, the activity of the horseradish peroxidase-labelled antiglobulins was measured electrochemically using 3,3',5,5'-tetramethylbenzidine (TMB) as substrate . The detection limit of the assay was 0.4 ng ml(-1) for erythromycin and 4.0 ng ml(-1) for tylosin, while the sensitivity (25% inhibition concentration) was 1.4 ng ml(-1) for erythromycin and 13.0 ng ml(-1) for tylosin . The specificity of the assay was assessed by studying the cross-reactivity of various macrolides other than erythromycin and tylosin . The results indicate that the monoclonal antibodies anti-erythromycin and anti-tylosin can readily distinguish the target compound from other macrolides, with the exception of roxithromycin, a semisynthetic macrolide antibiotic derived from erythromycin . Fortified and real samples were analysed by the developed ELISA method and results confirmed by micro-LC-MS-MS using an atmospheric pressure ionisation (API) source and an ionspray (IS) interface . The latter provides unequivocal identification and quantification of the analytes at the level of interest . The ELISA assay showed precision (RSD) values ranging from 6.3 to 11.4% for erythromycin and from 7.5 to 12.6% for tylosin; the accuracy (relative error, RE) ranged from -16.0 to -9.8% and from -9.5 to 8.0% for erythromycin and tylosin, respectively . All results obtained demonstrate that the electrochemical ELISA is a suitable method for a sensitive, simple, rapid and reliable screening of the two macrolides in animal tissues.

Support Care Cancer, 2001 Nov, 9(8), 619 - 24
Outpatient parenteral antibiotic therapy in patients with haematological malignancies . A pilot study of an early discharge strategy; Johansson E et al.; The objectives of this study were to estimate the feasibility of a self-administration outpatient parenteral antibiotic therapy (OPAT) model . to record the complication rate and to estimate patient acceptance during the OPAT period in patients with acute leukaemia (AL) or aggressive non-Hodgkin lymphoma (NHL) . Patients were trained to administer the antibiotic infusions themselves, via their central venous access device, according to a checklist and step-by-step instructions . Study-specific questionnaires were used to evaluate patient acceptance . Eleven patients {AL (n=8) and NHL (n=3), median age 51 years, range 29-661 participated in the education programme and subsequent OPAT during ten episodes of documented infection and six episodes of fever of unknown aetiology . All patients had assessment of the infectious episode and initial parenteral antibiotic therapy in the hospital before they continued self-administration at home . The median education time was 3 h (range 0.75-4.5) . The patients could stay at home for 4 days (median, range; 1-12) with ongoing intravenous antibiotic therapy instead of being hospitalised . None of the patients developed recurrent fever . All patients reported that OPAT was of great value and they would favour OPAT again during subsequent antibiotic therapy . In conclusion, the results of this pilot series suggest that OPAT, in this setting, is a safe alternative during the last days of an episode of fever / infection . All patients were satisfied overall, and none was readmitted.

Vet Rec, 2001 Nov 17, 149(20), 611 - 3
In vitro antibiotic sensitivity of strains of Ornithobacterium rhinotracheale isolated in The Netherlands between 1996 and 1999; van Veen L et al.; All the strains of Ornithobacterium rhinotracheale isolated in the Netherlands between 1996 and 1999 were tested in the agar gel diffusion test for their sensitivity to amoxycillin, tetracycline, enrofloxacin and trimethoprim/sulphonamide (TMP/S) . The percentages of strains sensitive to amoxycillin and tetracycline decreased in successive years from approximately 62 per cent to 14 per cent, and four strains were resistant to enrofloxacin or TMP/S . Twelve multiresistant strains were tested against seven alternative antibiotics; they were resistant to all of them except clavulanic acid-potentiated amoxycillin.

Pharmacoepidemiol Drug Saf, 2001 Jun-Jul, 10(4), 309 - 14
Trends in primary care antibiotic prescribing in England 1994-1998; Unsworth L et al.; PURPOSE: To investigate the changing decisions to prescribe antibiotics as manifest in the patterns of prescriptions dispensed in England, and to investigate antibiotic prescribing in different types of practice . METHODS: Antibiotic prescribing data and practice characteristics collected for every practice in England for the years 1994/5-1997/8 . Morbidity data for common infections was also obtained from published sources . RESULTS: Antibiotic prescribing was related to practice characteristics, with high prescribing in deprived and single-handed practices in particular . There was a fall in antibiotic prescribing in all types of practice of practice over the period of the study . Morbidity data from other sources shows a fall in diagnosed morbidity from some infectious diseases over the same period . There were no differences in choice of antibiotic in different types of practice . CONCLUSIONS: The fall in antibiotic prescribing is universal across all kinds of practices and is possibly related to the fall in diagnoses . It is uncertain whether this reflects true morbidity.

J Am Board Fam Pract, 2001 Nov-Dec, 14(6), 457 - 61
Mycobacterium chelonae: nonhealing leg ulcers treated successfully with an oral antibiotic; Terry S et al.; BACKGROUND: Mycobacterium chelonae is an important human pathogen and should be considered when a physician is faced with nonhealing cutaneous wounds, including ulcers of the lower leg . METHODS: The medical literature was searched from 1965 to the present using the key words "Mycobacterium chelonae" and "leg ulcers." A case of Mycobacterium chelonae infection is reported . RESULTS AND CONCLUSION: Clarithromycin as single-agent oral therapy has been effective in treating these infections once the proper diagnosis is established . Diagnosis of M . chelonae infection requires being alert to this infectious agent and obtaining cultures for mycobacteria . Aggressive surgical debridement with direct excision of the wound might now be unnecessary because of the effectiveness of oral clarithromycin administered as a single oral agent.

Med Dosw Mikrobiol, 2001, 53(1), 39 - 43
{Susceptibility to macrolide antibiotics of Bordetella pertussis and Bordetella parapertussis strains isolated from whooping cough patients in 1968 and in 1997-99}; Chodorowska M et al.; The activity of erythromycin, azithromycin, clarithromycin, dirithromycin, oleandomycin, roxithromycin, spiramycin and josamycin against 21 and 34 B . pertussis strains and against 6 and 8 B . parapertussis strains isolated respectively in the years 1968 and 1997-99 was examined . The antibiotic agar dilution method was used . The minimum concentration of macrolides which inhibited growth of B . pertussis and B . parapertussis was calculated for 50% (MIC50) and 90% (MIC90) of isolates . The susceptibility to macrolides of B . pertussis and B . parapertussis strains isolated in the years 1968 and 1997-99 did not differ significantly . The MIC90 values of erythromycin were the same for B . pertussis (MIC90 = 0.125 mg/l) and B . parapertussis strains (MIC90 = 0.25 mg/l) recovered in 1968 as for those recovered in the years 1997-99 . The most active antibiotic against all strains was azithromycin (MIC90 = 0.06 mg/l) . The least active antibiotics were oleandomycin (MIC90 = 2-4 mg/l) and spiramycin (MIC90 = 8 mg/l) . The study showed that erythromycin remains the antibiotic of choice for treatment of whooping cough and in case of emergence of B . pertussis and/or B . parapertussis strains erythromycin resistant, can be replaced by azithromycin.

Chem Biol, 2001 Dec, 8(12), 1239 - 52
Elucidation of the function of two glycosyltransferase genes (lanGT1 and lanGT4) involved in landomycin biosynthesis and generation of new oligosaccharide antibiotics; Trefzer A et al.; BACKGROUND: The genetic engineering of antibiotic-producing Streptomyces strains is an approach that became a successful methodology in developing new natural polyketide derivatives . Glycosyltransferases are important biosynthetic enzymes that link sugar moieties to aglycones, which often derive from polyketides . Biological activity is frequently generated along with this process . Here we report the use of glycosyltransferase genes isolated from the landomycin biosynthetic gene cluster to create hybrid landomycin/urdamycin oligosaccharide antibiotics . RESULTS: Production of several novel urdamycin derivatives by a mutant of Streptomyces fradiae Tu2717 has been achieved in a combinatorial biosynthetic approach using glycosyltransferase genes from the landomycin producer Streptomyces cyanogenus S136 . For the generation of gene cassettes useful for combinatorial biosynthesis experiments new vectors named pMUNI, pMUNII and pMUNIII were constructed . These vectors facilitate the construction of gene combinations taking advantage of the compatible MunI and EcoRI restriction sites . CONCLUSIONS: The high-yielding production of novel oligosaccharide antibiotics using glycosyltransferase gene cassettes generated in a very convenient way proves that glycosyltransferases can be flexible towards the alcohol substrate . In addition, our results indicate that LanGT1 from S . cyanogenus S136 is a D-olivosyltransferase, whereas LanGT4 is a L-rhodinosyltransferase.

Rev Esp Quimioter, 2001 Sep, 14(3), 254 - 63
{Knowledge, attitude and experience of the Spanish population with respect to antibiotics}; Ripoll MA et al.; Infectious diseases of the upper respiratory tract are one of the most common health problems and antibiotics are used to treat them . The correct use of these drugs depends on a variety of factors: the doctor, the patient and the pharmaceutical industry . The objective of this study was to examine the knowledge, attitude and perception of patients with regard to antibiotics . The study was conducted by carrying out personal interviews with 600 adults and 200 childcare workers who had had a mild to moderate respiratory infection in the two previous months for which an antibiotic was prescribed . In general, the infections had little impact on the everyday lives of the patients, and were mostly categorized as coughing, flu or sore throat . Almost half of the patients waited for the doctor to prescribe an antibiotic when they had an appointment (42% adults and 47% caregivers) . A total of 85% of the adults and 71% of the children were treated with penicillin . The majority improved in three days and felt they had recovered in six, a time period which was in accordance with the patients' expectations of the efficacy of the drug . The perception of efficacy was related to a faster initiation of symptomatic improvement or recovery, to short-term treatments, to the information received, and to a better attitude toward their doctor . In general, the patients felt satisfied with the attention they received and related this satisfaction to their trust in their doctor, the efficacy of treatment and the duration of their appointment . The use of antibiotics in mild to moderate respiratory infections is common, and they are often used to treat disease processes that seemingly do not require their use . To improve the use of antibiotics attention needs to be placed on the prescribers and on the consumers.

Acta Crystallogr D Biol Crystallogr, 2002 Jan, 58(Pt 1), 173 - 5 Epub 2001 Dec 21.
Crystallization and preliminary X-ray crystallographic studies of a macromolecular antitumour antibiotic, C1027; Chen Y et al.; C1027 is a macromolecular antitumour antibiotic produced by Streptomyces globispourus C1027 and consists of an apoprotein and a non-protein labile chromophore . Little is known about how the thermally unstable chromophore is stabilized by the apoprotein . The purified C1027 was monodisperse according to dynamic light-scattering measurements and crystallized in two different crystal forms from two different starting conditions using the vapour-diffusion method . Condition I yielded hexagonal prism crystals having space group P3(1)/P3(2) and unit-cell parameters a = b = 66.8, c = 55.4 A . Diffraction data were collected to 2.1 A resolution using an in-house Rigaku rotating Cu anode X-ray generator . Another condition produced rod-like crystals with space group P3(1)21/P3(2)21 and unit-cell parameters a = b = 55.15, c = 55.87 A . A data set to 1.8 A resolution was collected from a rod-like crystal using a MAR CCD detector at the SRS synchrotron source.

Proc Natl Acad Sci U S A, 2001 Dec 18, 98(26), 14901 - 6
Glycopeptide antibiotic biosynthesis: enzymatic assembly of the dedicated amino acid monomer (S)-3,5-dihydroxyphenylglycine; Chen H et al.; Four proteins, DpgA-D, required for the biosynthesis by actinomycetes of the nonproteinogenic amino acid monomer (S)-3,5-dihydroxyphenylglycine (Dpg), that is a crosslinking site in the maturation of vancomycin and teicoplanin antibiotic scaffolds, were expressed in Escherichia coli, purified in soluble form, and assayed for enzymatic activity . DpgA is a type III polyketide synthase, converting four molecules of malonyl-CoA to 3,5-dihydroxyphenylacetyl-CoA (DPA-CoA) and three free coenzyme A (CoASH) products . Almost no turnover was observed for DpgA until DpgB was added, producing a net k(cat) of 1-2 min(-1) at a 3:1 ratio of DpgB:DpgA . Addition of DpgD gave a further 2-fold rate increase . DpgC had the unusual catalytic capacity to convert DPA-CoA to 3,5-dihydroxyphenylglyoxylate, which is a transamination away from Dpg . DpgC performed a net CH(2) to C=O four-electron oxidation on the Calpha of DPA-CoA and hydrolyzed the thioester linkage with a k(cat) of 10 min(-1) . Phenylacetyl-CoA was also processed, to phenylglyoxylate, but with about 500-fold lower k(cat)/K(M) . DpgC showed no activity in anaerobic incubations, suggesting an oxygenase function, but had no detectable bound organic cofactors or metals . A weak enoyl-CoA hydratase activity was detected for both DpgB and DpgD.

Antimicrob Agents Chemother, 2002 Jan, 46(1), 225 - 8
In vitro potentiation of antibiotic activities by a catecholate iron chelator against chloroquine-resistant Plasmodium falciparum; Pradines B et al.; FR160, a catechol iron chelator, and tetracyclines or norfloxacin exert in vitro additive or synergistic activity against a chloroquine-resistant Plasmodium falciparum clone . FR160 shows antagonistic effects in association with macrolides, ofloxacin, and rifampin.

Arch Surg, 2001 Dec, 136(12), 1391 - 5
Results of a pilot trial comparing prolonged intravenous antibiotics with sequential intravenous/oral antibiotics for children with perforated appendicitis; Rice HE et al.; HYPOTHESIS: For children with perforated appendicitis, the use of a prolonged course of intravenous (i.v.) antibiotics is equivalent to a short course of i.v . antibiotics followed by sequential conversion to oral (PO) antibiotics . DESIGN: Prospective, randomized, clinical trial . SETTING: Multicenter study in tertiary children's hospitals . PATIENTS: Children (aged 5-18 years) with perforated appendicitis found at laparotomy . INTERVENTION: Children were randomized after appendectomy either to a 10-day course of a combination of i.v . ampicillin, gentamicin sulfate, and clindamycin (n = 10); or to a short course of a combination of i.v . ampicillin, gentamicin, and clindamycin, followed by conversion to a combination of p.o . amoxicillin and clavulanate potassium plus metronidazole (n = 16) . MAIN OUTCOME MEASURES: The primary outcome measure was clinical success, which was rated as complete, partial, or failure . Secondary outcome measures included return of oral intake, duration of fever, return of normal white blood cell count, and patient charges . Treatment equivalence was determined using confidence interval analysis . RESULTS: We found treatment equivalence between the i.v . and i.v./p.o . groups, with 6 (60%) complete and 4 (40%) partial successes for the 10 patients in the i.v . group and 15 (94%) complete and 1 (6%) partial successes for the 16 patients in the i.v./p.o . group (P< or =.05) . There was no difference in return of oral intake, duration of fever, or return of normal white blood cell count between the groups . Conversion to oral therapy results in savings of approximately $1500 per case . CONCLUSION: There is treatment equivalence between prolonged i.v . therapy and i.v . therapy followed by conversion to oral antibiotic therapy in children with perforated appendicitis.

J Nutr, 2001 Dec, 131(12), 3247 - 50
Administration of the oral antibiotic frenolicin-B selectively alters copper nutriture in male rats; Kossor DC et al.; The polyketide antibiotic Frenolicin-B (FB) produces anorexia and esophageal epithelial hyperplasia (EH) in rats, findings that are characteristic of zinc deficiency . Because FB also chelates divalent cations in vitro, we conducted studies to determine whether FB modifies blood and organ concentrations of zinc and other essential metals (calcium, copper, iron and magnesium) . Groups of male Sprague-Dawley rats ( approximately 250g; n = 20/group) consumed diets with adequate (40 microg/g), deficient (<2 microg/g) or fortified (100 microg/g) zinc concentrations ad libitum for 28 d . Two groups fed either Zn-adequate or Zn-fortified diets also were given 100 mg/(kg . d) of FB in diet, and 2 groups were pair-fed controls . Histopathology or metal analyses were performed on tissues from 10 rats/group . FB caused EH of the nonglandular stomach but not of other tissues . Of the metals evaluated, only copper concentrations were significantly reduced in all tissues examined except kidney . A broad range of kidney copper concentrations was found; these concentrations were associated with plasma copper and proteinaceous deposits within tubules . In rats, FB substantially and selectively depletes Cu in vivo, suggesting that drugs with structures that permit metal chelation should be evaluated for their potential to alter trace metal nutriture.

Trop Med Int Health, 2001 Dec, 6(12), 1016 - 22
Phenothiazines: potential alternatives for the management of antibiotic resistant infections of tuberculosis and malaria in developing countries; Amaral L et al.; The in vitro and in vivo activity of phenothiazines against antibiotic susceptible and antibiotic resistant Mycobacterium tuberculosis and malaria-causing Plasmodia is reviewed . Given the facts that pulmonary tuberculosis and malaria are the major causes of death in developing countries, that both of these infections continue to escalate in their resistance to antibiotics, that the cost for the management of these infections is beyond that afforded by most developing nations, and lastly, that new and effective agents are not forthcoming from the pharmaceutical industry, the scientific rationale for the potential use of select phenothiazines for the management of these infections is presented.

Org Lett, 2001 Dec 13, 3(25), 4015 - 8
Enantiodivergent synthesis of either enantiomer of ABCDE-ring analogue of antitumor antibiotic fredericamycin A via intramolecular {4 + 2} cycloaddition approach; Akai S et al.; {reaction: see text} An intramolecular enantiodivergent synthesis of both enantiomers of the ABCDE-ring analogue 22 of fredericamycin A is reported . Key steps involve an intramolecular {4 + 2} cycloaddition of 17 and an aromatic Pummerer-type reaction of 19 . A lipase-catalyzed enantioselective desymmetrization of prochiral diol 2 using 1-ethoxyvinyl 2-furoate 3 led to the pivotal intermediate (R)-4.

Plasmid, 2001 Nov, 46(3), 223 - 8
Sequence and gene expression analyses of plasmid pHPM8 from Helicobacter pylori reveal the presence of two operons with putative roles in plasmid replication and antibiotic activity; Quinones M et al.; The DNA sequence of a 7.8-kb Helicobacter pylori plasmid, pHPM8, was determined . Six open reading frames (ORFs) were present . Ribonuclease protection studies showed that ORF1/ORF2 and ORF3/ORF4 genes are organized in operons possibly involved in plasmid replication and in production of a peptide with antibiotic activity, respectively . Finding areas of pHPM8 with a high level of identity to H . pylori chromosomal DNA supported the hypothesis that recombination occurs between plasmids and the chromosome of H . pylori .

Pediatr Infect Dis J, 2001 Aug, 20(8), 751 - 8
Appropriateness of antibiotic prescriptions in community-acquired acute pediatric respiratory infections in Spanish emergency rooms; Ochoa C et al.; OBJECTIVE: To describe the variability and appropriateness of antibiotic prescriptions in community-acquired acute respiratory infections (ARI) during childhood in Spain . METHODS: A descriptive, multicenter study of variability in clinical practice was conducted by evaluating a prospective series of pediatric patients attending the emergency rooms of 11 Spanish hospitals and diagnosed with community-acquired ARI . The appropriateness of the antibiotic prescriptions was assessed by comparing our clinical practice with consensus guidelines developed for this study . RESULTS: We collected data from 6,249 ARI emergencies studied on 30 separate days . Antibiotics were prescribed in 58.7% of the ARI (bronchiolitis, 11.5%; bronchitis, 40.2%; pharyngotonsillitis, 80.9%; nonspecified ARI, 34.8%; pneumonia, 92.4%; otitis, 93.4%; sinusitis, 92.6%) . The most commonly used antibiotics were amoxicillin/clavulanate (33.2%), amoxicillin (30.2%), cefuroxime axetil (8.5%) and azithromycin (6%) . According to the consensus guidelines developed for this study, therapy was considered to be appropriate in 63.1% of the ARI (first choice, 52.1%; alternative choice, 11.0%) and inappropriate in 36.9% . The percentages of inappropriate prescription according to ARI groups were: bronchiolitis, 11.5%; bronchitis, 31.5%; pharyngotonsillitis, 54.8%; nonspecified ARI, 34.7%; pneumonia, 13.9%; otitis, 25.6%; and sinusitis, 22.2% . CONCLUSIONS: There is excessive use of antibiotics in acute respiratory infections that are presumably viral in origin . An important number of ARI of potentially bacterial origin are treated with antibiotics that are not sufficiently efficacious or that have a broader spectrum than necessary.

Am J Rhinol, 2001 Sep-Oct, 15(5), 315 - 20
Postoperative antibiotic use of septoplasty: a survey of practice habits of the membership of the American Rhinologic Society; Rechtweg JS et al.; Prophylactic antibiotics are used routinely in otolaryngology . Little objective data exist concerning their use in sinonasal procedures . We wished to determine the practice patterns of otolaryngologists regarding prophylactic antibiotics for septoplasty patients . A survey of 743 (60.3% responded) members of the American Rhinologic Society was used to get information about their practice habits and rationale for using antibiotics after septoplasty . Sixty-six percent of respondents routinely used antibiotics . Postoperative infection and toxic shock syndrome (TSS) were the primary indications . Forty-four percent of respondents used some form of packing and 38% used a splint . There was no relationship between the annual number of procedures and the reasons for using antibiotics . Doctors who performed more than 50 cases a year were less likely to use packing or splints (p < 0.001) . Older surgeons used less younger surgeons a packing/splints (p < 0.001) . Respondents who used packing/ splints were more likely to use antibiotics (p = 0.008) . Older respondents used packing whereas younger respondents used splints (p = 0.002) . The rationale for antibiotics varied by age; re more concerned with TSS and older physicians were more concerned with infection (p = 0.005) . This survey shows great variability in the usage and rationale for antibiotics after septoplasty.

Infect Control Hosp Epidemiol, 2001 Sep, 22(9), 565 - 71
Correlates of antibiotic use in Taiwan hospitals; McDonald LC et al.; OBJECTIVE: To determine factors that correlate with increased antibiotic use among adult inpatients in Taiwan . DESIGN: Retrospective survey of medical records . SETTING: 14 acute-care hospitals (8 regional hospitals, 6 medical centers) in Taiwan . PARTICIPANTS: A systematic probability sample from each hospital, totaling 663 adult inpatients who were discharged or had died in early 1999 . MEASUREMENTS: Infectious disease physicians at the 14 hospitals collected data from medical records regarding patient demographics, hospitalization, discharge diagnosis, and antibiotics received . RESULTS: A total of 447 (67%) patients received antibiotics for an overall rate of 813 antibiotic-days (number of days patients received each antibiotic)/1,000 patient-days . Both the proportion of beds in intensive care units ({ICUs} Pearson correlation coefficient {r}, 0.67; 95% confidence interval {CI 95}, 0.36-0.89; P<.01) and the proportion of patients admitted to surgical services (r, 0.66; CI 95, 0.20-0.88; P=.01) correlated with the mean patient rate of antibiotic-days/hospital-day (MPAUD) . In contrast, we found no correlation between the proportion of patients who received antibiotics and the MPAUD . Using multiple linear regression, medical center status was the only independent predictor for increased MPAUD (regression coefficient {b}, 0.15; CI 95, 0.05-0.24; P<.01) . There was no correlation between pooled rates of antibiotic-days/hospital-day and any hospital demographic factors . First-generation cephalosporin (39%) and aminoglycoside (24%) use accounted for the majority of antibiotic-days . CONCLUSIONS: Antibiotic use is greater in medical centers than in regional hospitals and appears to be independent of surgical case mix or the proportion of ICU beds . Determination of multiple, independent measures of antibiotic use may be necessary to understand the relation between antibiotic use and resistance in hospital.

Clin Infect Dis, 2002 Jan 1, 34(1), 55 - 64 Epub 2001 Nov 27.
Effect of changes in antibiotic prescribing on patient outcomes in a community setting: a natural experiment in Australia; Beilby J et al.; This study examined whether a significant change in antibiotic use caused by an Australian government directive targeted at amoxicillin with clavulanic acid (AC) was associated with changes in prescription share, health care costs, and patient outcomes . We used an integrated database of computerized general practice medical records, which included data regarding 34,242 patients and 318,234 recorded patient visits . There were 15,303 antibiotic prescriptions provided to 9921 patients during a 4-year period, with AC prescribed for 1453 (14.6%) of these patients . A total of 5125 patient outcomes were identified . There was a shift away from best-practice antibiotic prescribing, and a significant association was identified between the rate and cost of process-of-care and patient outcomes and the decrease in AC-prescription share . This policy initiative created unintended changes in prescribing behavior, increased costs to the government, and a trend toward poorer patient outcomes . Detailed analyses are required before instigating initiatives aimed at changing clinicians' prescribing behavior.

J Matern Fetal Med, 2001 Oct, 10(5), 312 - 7
Appropriateness of antibiotic use in the postpartum period; Smulian JC et al.; OBJECTIVE: To determine the appropriateness of current postpartum antibiotic use in clinical practice . METHODS: Medical records were reviewed for all patients delivering in a 3-month period who received postpartum antibiotics during the delivery hospitalization . Subjects were excluded if they received a single postpartum antibiotic dose as part of a mitral valve prolapse prophylaxis protocol, or if they received no more than one postpartum antibiotic dose for surgical prophylaxis . Characteristics of postpartum antibiotic use were abstracted . RESULTS: Two hundred and eleven of 1537 (14%) delivering patients met the inclusion criteria . Seventy-four (35%) delivered vaginally and 137 (65%) delivered by Cesarean section . Postpartum fevers were found in 40 (54%) of vaginal delivery cases and 80 (58%) of women delivering by Cesarean section who received postpartum antibiotics (p = 0.54) . For vaginal deliveries there were no differences in the duration of antibiotic use or number of antibiotic doses based on fever status . For Cesarean deliveries, a fever was associated with more antibiotic doses and a longer duration of antibiotic use . Physician justification for antibiotic use was documented in only 116 cases (55%) . CONCLUSIONS: The high proportion of women receiving postpartum antibiotics having no evidence for infection or documented indication for therapy suggests that antibiotics may not be appropriately used in the postpartum period.

J Biol Chem, 2002 Feb 8, 277(6), 4368 - 73 Epub 2001 Nov 29.
Inactivation of the amidotransferase activity of carbamoyl phosphate synthetase by the antibiotic acivicin; Miles BW et al.; Carbamoyl phosphate synthetase (CPS) from Escherichia coli catalyzes the formation of carbamoyl phosphate from 2 mol of ATP, bicarbonate, and glutamine . CPS was inactivated by the glutamine analog, acivicin . In the presence of ATP and bicarbonate the second-order rate constant for the inactivation of the glutamine-dependent activities was 4.0 x 10(4) m(-1) s(-1) . In the absence of ATP and bicarbonate the second-order rate constant for inactivation of CPS was reduced by a factor of 200 . The enzyme was protected against inactivation by the inclusion of glutamine in the reaction mixture . The ammonia-dependent activities were unaffected by the incubation of CPS with acivicin . These results are consistent with the covalent labeling of the glutamine-binding site located within the small amidotransferase subunit . The binding of ATP and bicarbonate to the large subunit of CPS must also induce a conformational change within the amidotransferase domain of the small subunit that enhances the nucleophilic character of the thiol group required for glutamine hydrolysis . The acivicin-inhibited enzyme was crystallized, and the three-dimensional structure was determined by x-ray diffraction techniques . The thiol group of Cys-269 was covalently attached to the dihydroisoxazole ring of acivicin with the displacement of a chloride ion.

J Emerg Med, 2001 Nov, 21(4), 387 - 92
Presentation, time to antibiotics, and mortality of patients with bacterial meningitis at an urban county medical center; Miner JR et al.; Our objective was to analyze the presentation, time to antibiotics, treatment, and mortality of patients with bacterial meningitis at a large urban county hospital over a 10-year period . A retrospective chart review of all patients with the diagnosis of bacterial meningitis was done . Information concerning presentation, etiologic organisms, treatment (including time to antibiotics), and outcomes were collected and analyzed . There were 165 charts reviewed with 171 total cases of bacterial meningitis . For adults with community-acquired meningitis, the mortality rate was 14%, for children it was 1.6% . Seventy-six percent of patients received antibiotics in the Emergency Department (ED) with a mean time to antibiotics of 1:08 h +/- 13 min . The rest received them as inpatients with a mean time to antibiotics of 6 +/- 9 h . The mortality rate for patients with community-acquired disease who received an Emergency Department antibiotic was 7.9%; for patients who received their antibiotics as inpatients the mortality rate was 29% . Our results indicate that the mortality rates from bacterial meningitis at our institution are lower than previously published results . Furthermore, our study supports the concept that the early administration of antibiotics in the ED may reduce mortality and may be an explanation of the lower mortality rates seen here.

Can J Gastroenterol, 2001 Nov, 15(11), 751 - 6
Management of fistulas in patients with Crohn's disease: antibiotic to antibody; Pare P; Fistulas are common in patients with Crohn's disease and, when associated with inflammatory disease and established for several weeks, tend to be chronic . Perianal fistulas are the most frequent complication of, and are most often associated with, colonic disease . Perianal fistulas commonly require surgical resection and permanent ileostomy . Antibiotics, cyclosporine, methotrexate and thalidomide have been used in uncontrolled trials; only azathioprine, 6-mercaptopurine and infliximab have been assessed in double-blind, placebo controlled studies . Relapse of the fistula occurs with all drugs, unless treatment is continued long term . Each drug differs in its onset of action and long term tolerability . An approach to fistulizing disease in Crohn's disease is suggested.

J Food Prot, 2001 Nov, 64(11), 1844 - 7
Detection limits of beta-lactam antibiotics in ewe milk by penzym enzymatic test; Althaus RL et al.; The Penzym is an enzymatic test widely used for the detection of beta-lactam antibiotic residuals in milk . It is a specific method with good sensitivity to this group of antibiotics and enables results to be obtained within a short time . In the present work, the detection limits of 10 beta-lactam antibiotics were determined in ewe milk, given the lack of previous studies of the Penzym test in ovine milk . For each antibiotic, eight concentrations were tested on 20 ewe milk samples proceeding from individual ewes (160 analyses per drug) . The limits of the Penzym test were determined by means of logistic regression models, as follows: 5 microg/kg amoxicillin, 4 microg/kg ampicillin, 33 microg/kg cloxacillin, 3 microg/kg penicillin "G," 43 microg/kg cephadroxil . 10 microg/kg cephalosporin "C," 16 microg/kg cephalexin, 900 microg/kg cephoperazone, 120 microg/kg Ceftiofur, and 77 microg/kg cephuroxime . The percentages of positive results for those antibiotics at the maximum residue limit (MRL) concentration established by the European Union (EU) were: 100% (penicillin "G"), 93.3% (ampicillin), 93.3% (cloxacillin), 56.7% (Ceftiofur), and 56.7% (amoxicillin).

Proc Natl Acad Sci U S A, 2001 Dec 4, 98(25), 14212 - 7 Epub 2001 Nov 27.
The anticancer drug-DNA complex: femtosecond primary dynamics for anthracycline antibiotics function; Qu X et al.; The anthracycline-DNA complex, which is a potent agent for cancer chemotherapy, has a unique intercalating molecular structure with preference to the GC bases of DNA, as shown by Rich's group in studies of single-crystal x-ray diffraction . Understanding cytotoxicity and its photoenhancement requires the unraveling of the dynamics under the solution-phase, physiological condition . Here we report our first study of the primary processes of drug function . In a series of experiments involving the drug (daunomycin and adriamycin) in water, the drug-DNA complexes, the complexes with the four nucleotides (dGTP, dATP, dCTP, and dTTP), and the drug-apo riboflavin-binding protein, we show the direct involvement of molecular oxygen and DNA base-drug charge-separation-the rates for the reduction of the drug and dioxygen indicate the crucial role of drug/base/O(2) in the efficient and catalytic redox cycling . These dynamical steps, and the subsequent reactions of the superoxide product(s), can account for the photoenhanced function of the drug in cells, and potentially for the cell death.

J Biol Chem, 2002 Feb 8, 277(6), 3965 - 72 Epub 2001 Nov 27.
Mutations in subunit C of the vacuolar ATPase confer resistance to bafilomycin and identify a conserved antibiotic binding site; Bowman BJ et al.; Bafilomycin A1, a potent inhibitor of vacuolar H(+)-ATPases (V-ATPase), inhibited growth of Neurospora crassa in medium adjusted to alkaline pH . Ninety-eight mutant strains were selected for growth on medium (pH 7.2) containing 0.3 or 1.0 microm bafilomycin . Three criteria suggested that 11 mutant strains were altered in the V-ATPase: 1) these strains accumulated high amounts of arginine when grown at pH 5.8 in the presence of bafilomycin, 2) the mutation mapped to the locus of vma-3, which encodes the proteolipid subunit c of the V-ATPase, and 3) V-ATPase activity in purified vacuolar membranes was resistant to bafilomycin . Sequencing of the genomic DNA encoding vma-3 identified the following mutations: T32I (two strains), F136L (two strains), Y143H (two strains), and Y143N (five strains) . Characterization of V-ATPase activity in the four kinds of mutant strains showed that the enzyme was resistant to bafilomycin in vitro, with half-maximal inhibition obtained at 80-400 nm compared with 6.3 nm for the wild-type enzyme . Surprisingly, the mutant enzymes showed only weak resistance to concanamycin . Interestingly, the positions of two mutations corresponded to positions of oligomycin-resistant mutations in the c subunit of F(1)F(0)-ATP synthases (F-ATPases), suggesting that bafilomycin and oligomycin utilize a similar binding site and mechanism of inhibition in the related F- and V-ATPases.

J Anim Sci, 2001 Oct, 79(10), 2542 - 9
Evaluation of conjugated linoleic acid and dietary antibiotics as growth promotants in weanling pigs; Weber TE et al.; An experiment was conducted to determine the efficacy of dietary conjugated linoleic acid (CLA) as a growth promotant in weanling swine . Weanling pigs (n = 192; 7.6 kg and 29 d of age) were randomly assigned to four treatments that were arranged as a 2 x 2 factorial . Concentrations of dietary CLA (0 or 0.6%) and antibiotics (+/-) constituted the main effect variables . Dietary CLA treatments consisted of a 1% addition of an oil containing 60% CLA isomers or 1% soybean oil, and dietary antibiotic treatments were antibiotics or no antibiotics . The experimental diets were fed for 9 wk in four phases (1, wk 1; 2, wk 2 and 3; 3, wk 4 through 6; and 4, wk 7 through 9), after which all pigs were fed identical medicated diets for the duration of the finishing phase . Live weights were recorded at wk 17 postweaning and at marketing to determine any residual effects of dietary treatments on finisher ADG and days to market . Medicated diets fed during phases 1 and 2 contained 55 mg carbadox/kg; during phase 3 contained 299 mg tilmicosin/kg; and during phase 4 contained 110 mg tylosin and 110 mg sulfamethazine/kg . Pigs fed medicated diets had higher overall ADG than pigs fed unmedicated diets for wk 0 through 9 (P < 0.03) . Gain:feed (G:F) was greater for pigs fed medicated diets than for pigs fed unmedicated diets during phase 1 (P < 0.03) and for the duration of the nursery phase (P < 0.03) . There were no effects of CLA on ADG, ADFI, or G:F . There were no residual effects of nursery CLA or antibiotics on finisher ADG and days to market . Blood samples collected from a subset of pigs (n = 72) at the completion of phases 2, 3, and 4 were assayed for serum IGF-I and antibody concentrations to porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae . There was a tendency for pigs fed medicated diets to have greater IGF-I concentrations than pigs fed unmedicated diets at the completion of phase 4 (P < 0.06) . Pigs fed CLA had greater antibody titers (P < 0.02) to Mycoplasma hyopneumoniae at d 63 than pigs fed diets without CLA . These results indicate that feeding 0.6% dietary CLA did not enhance growth performance in weanling swine and that the use of dietary antibiotics can increase production efficiency in nursery pigs . Furthermore, there were no interactions between CLA and dietary antibiotics on the variables addressed in this study.

Presse Med, 2001 Oct 27, 30(31 Pt 1), 1549 - 51
{Whipple disease associated with pulmonary arterial hypertension . Jarisch-Herxheimer reaction after antibiotic therapy}; Peschard S et al.; BACKGROUND: Pulmonary hypertension is an uncommon feature of Whipple's disease and the underlying pathophysiological mechanism remains a subject of debate . CASE REPORT: A 57-year-old woman was hospitalized for exploration of migrating joint pain that had developed for 5 years . Histologically proven Whipple's disease was diagnosed on duodenal biopsies . The lung angiogram performed to explore signs of right heart failure demonstrated pulmonary hypertension and ruled out pulmonary embolism . Abundant pericardial effusion developed progressively . Antibiotic therapy using sulfamethoxazole-trimethoprime led to a systemic Jarisch Herxheilmer reaction . The pulmonary hypertension resolved rapidly, the pericardial effusion more slowly . DISCUSSION: The pulmonary hypertension in this patient appeared to be directly related to Whipple's disease, probably via vascular infiltration by Tropheryma whippeli.

Presse Med, 2001 Oct 27, 30(31 Pt 2), 17 - 22
{Objectives for antibiotic therapy in acute exacerbations of chronic bronchitis}; Gaillat J; ANTIBIOTIC EFFICACY: According to early studies, antibiotics have moderate efficacy in acute exacerbation of chronic bronchitis . The lack of efficacy is particularly clear for patent exacerbation with marked alteration of respiratory function . Recent studies have shown that newer compounds exhibit an efficacy similar (no proven superiority) to comparison compounds (75 to 95% favorable outcome with treatment) . The recommendations of the IVth Consensus Conference on Anti-infectious Therapy thus propose first line antibiotic therapy for patients with a forced expiratory volume in 1 second (FEV1) between 80 and 35% and broader spectrum and new antibiotics in case of failure of the first line treatment for patients with severe obstruction or frequently recurrent exacerbation . EVALUATION CRITERIA: Using exacerbation-free interval, reduction in the number of exacerbations, duration of treatment and/or hospital stay as evaluation criteria, interesting results are obtained with amoxicillin/clavulanic acid, azithromycin, and ciprofloxacin . Independent factors predictive of therapeutic failure are, according to one study, FEV1 less than 35%, ambulatory administration of oxygen, more than 4 acute exacerbations within 24 months, history of pneumonia or sinusitis, and requirement for long-term corticosteroid therapy . Factors predictive of recurrence are, according to another study, dependence on oxygen therapy, prolonged corticosteroid therapy, smoking, and/or heart disease . Cost effectiveness is particularly interesting with ciprofloxacin, especially in more severe patients . PERSPECTIVES: It is important to target antibiotic therapy for acute exacerbation of chronic bronchitis specifically for patients who will truly benefit, adapting the prescribed compound to the bacterial target.

Br J Cancer, 2001 Nov 16, 85(10), 1444 - 51
A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics; Sculier JP et al.; The European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC) . Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m(-2), vindesine 3 mg m(-2), ifosfamide 5 g m(-2); all drugs given on day 1 repeated every three weeks . (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support . (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole) . Primary endpoint was survival . 233 eligible patients were randomised . Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity . Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70% . The response rate was significantly higher in arm B in comparison to arm A (P = 0.04) . There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C . Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding . Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C . Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support.

J Antibiot (Tokyo), 2001 Sep, 54(9), 718 - 29
Pluraflavins, potent antitumor antibiotics from Saccharothrix sp . DSM 12931; Vertesy L et al.; The new pluramycin-type antibiotics pluraflavin A, C43H54N2O14, pluraflavin B, C43H56N2O15, and pluraflavin E, C36H41NO14 were isolated from cultures of the Saccharothrix species DSM 12931 . The structures of the novel compounds were elucidated with the aid of 2D NMR and mass spectrometric investigations . The characteristic structural element of pluraflavins A and B is an additional 4-epi-vancosamine unit at position 13 of the anthraquinone-gamma-pyrone ring system . Pluraflavin E has a carboxyl group in this position . Pluraflavin A has a reactive dimethyl epoxide side chain at position 2 of the anthraquinone-gamma-pyrone aglycon, which may explain the high activity of the antibiotic . The outstanding biological characteristic of pluraflavin A is its powerful, organ-dependent cytostatic action: the IC50 in the colon carcinoma proliferation assay is in the subnanomolar range.

J Bone Joint Surg Am, 2001, 83-A Suppl 2 Pt 2, 92 - 7
Temporary articulating methylmethacrylate antibiotic spacer (TAMMAS) . A new method of intraoperative manufacturing of a custom articulating spacer; Goldstein WM et al.; A temporary articulating antibiotic-impregnated cement spacer for use during the first stage of a two-stage revision of a total knee replacement that had failed because of infection was developed by one of us (W.M.G.) . It is simply a knee prosthesis made of methylmethacrylate and antibiotics that is manufactured intraoperatively with use of instruments, medications, and supplies that are already available at most hospitals . This construct allows for motion of the knee during treatment of the infection, thereby reducing the risk of loss of motion after subsequent revision . The technique has been successfully utilized in five patients since 1999 and has now become our standard treatment method.

Int J Antimicrob Agents, 2001 Nov, 18(5), 471 - 6
Effects of the quantity of water and milk ingested concomitantly with AS-924, a novel ester-type cephem antibiotic, on its pharmacokinetics; Matsumoto F et al.; The effect of the quantity of water ingested concomitantly with drugs, on the absorption of AS-924, a novel prodrug-type cephem antibiotic, was studied in five healthy adult volunteers by a cross-over method, using cefteram-pivoxil (CTER-PI) as the control drug . In addition, the effect of milk on the absorption of AS-924 was also investigated . The absorption of CTER-PI was significantly reduced when administered together with 30 ml of water compared with its absorption when administered together with 150 ml of water, whereas no such reduction was found in the case of AS-924 . Ingestion of milk did not significantly affect the absorption of AS-924 . These results confirm that absorption of AS-924 after oral administration is not likely to be affected by the quantity of water taken concomitantly with the drug, nor by milk.

Int J Antimicrob Agents, 2001 Nov, 18(5), 463 - 9
Effects of food intake and age on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic . Comparison with cefpodoxime proxetil; Totsuka K et al.; The effects of food intake and age on intestinal absorption of AS-924, a novel prodrug-type cephem antibiotic, were examined in 16 healthy adult volunteers (eight young volunteers and eight elderly volunteers) by the cross-over method, using cefpodoxime proxetil (CPOD-PR) as the control drug . The gastrointestinal absorption of AS-924 and CPOD-PR was increased slightly by food intake and the extent of increase was slightly greater after administration of CPOD-PR . The absorption of AS-924 was not affected by age, whereas intestinal absorption of CPOD-PR increased with age . In conclusion, these results confirmed that AS-924 has the unique characteristics as a novel prodrug and that its absorption is less likely to be affected by food intake and age.

Obstet Gynecol, 2001 Nov, 98(5 Pt 1), 853 - 60
Drug interactions between oral contraceptives and antibiotics; Dickinson BD et al.; OBJECTIVE: To evaluate the evidence on possible drug interactions between antibiotics and oral contraceptives (OCs) that may lead to OC failure . DATA SOURCES: MEDLINE and Lexis/Nexis Medical Library searches for 1966-1999 using the key word "oral contraceptives," cross-indexed with the terms "antibiotics," "adverse effects," and "pregnancy," and MEDLINE search using the additional MeSH term "drug interactions." No language restrictions were used . METHODS OF STUDY SELECTION: A total of 167 articles were retrieved for analysis . Another 32 articles were identified by review of the references cited in these publications . Articles were selected based on their ability to provide information on the relationship between antibiotic therapy and OC efficacy in otherwise compliant users (defined as women with unplanned pregnancies who reported compliance with their OC regimen) . Additionally, studies that either directly measured the effects of antibiotics on the pharmacokinetics of OC components, or that analyzed the effects of antibiotics on measures of ovulation in OC users were accepted . TABULATION, INTEGRATION, AND RESULTS: At least 30 cases have been reported of pregnancies occurring in women taking OCs and antibiotics, particularly rifampin . Approximately 20% of pregnant women reporting to family planning or abortion clinics reported concomitant OC and antibiotic use . Information from adverse event reporting databases generally mirrors the types of information gleaned from these case reports and clinical surveys and accounts for approximately one-third of reported cases . Retrospective surveys, primarily from dermatology-based practices, also have reported 24 pregnancies in OC users who concomitantly received therapy with antibiotics, most commonly tetracyclines and penicillins . Apparent OC failure rates in clinical surveys were within the usual range expected for patterns of typical use . In pooled results obtained from relatively small populations, oral antibiotics, with the exception of rifampin, have not significantly affected the pharmacokinetics of ethinyl estradiol, levonorgestrel, and norethindrone or reduced the serum concentrations of gonadotropins . However, individual patients have been identified who experienced significant decreases in the plasma concentration of these components of OCs and who appeared to ovulate . CONCLUSION: Rifampin impairs the effectiveness of OCs . Pharmacokinetic studies of other antibiotics have not shown any systematic interaction between antibiotics and OC steroids . However, individual patients do show large decreases in the plasma concentrations of ethinyl estradiol when they take certain other antibiotics, notably tetracycline and penicillin derivatives . Because it is not possible to identify these women in advance, a cautious approach is advised.

Microbiology, 2001 Nov, 147(Pt 11), 3083 - 92
A polyketide biosynthetic gene cluster from Streptomyces antibioticus includes a LysR-type transcriptional regulator; Colombo V et al.; In the search for Type II polyketide synthases (PKSs) a DNA fragment was isolated from Streptomyces antibioticus ATCC 11891 (a producer of oleandomycin) . DNA sequencing of the cloned fragment revealed six complete ORFs whose deduced products showed similarities to those of other genes known to be involved in polyketide biosynthesis . Several S . coelicolor strains mutated in different steps of actinorhodin biosynthesis (actI, actIII, actV(A) and actVII) were complemented by the cloned genes, suggesting that the isolated genes encode an aromatic polyketide of unknown structure and function . The cluster also contains a putative LysR-type transcriptional regulator (ORF0), which controls PKS gene expression in a heterologous host . DNA binding assays and transcriptional analysis suggest that the pathway-specific regulator for actinorhodin biosynthesis (actII-ORF4) is also involved in the expression of the cloned PKS in the host strain.

Eur J Clin Pharmacol, 2001 Sep, 57(6-7), 529 - 34
The effect of formulary restriction in the use of antibiotics in an Italian hospital; Bassetti M et al.; OBJECTIVE: To compare the expenditure and usage of antibiotics at the San Martino Teaching Hospital, a 2500-bed hospital in Genoa, Italy, before and after the implementation of an antibiotic control program that streamlined the hospital formulary and the creation of a restricted group of antibiotics requiring approval before use . METHODS: Usage and expenditure data for all antibiotics were collected from 1996 to 1998 . Antibiotic usage was standardised by defined daily doses (DDDs) per 100/patient-days . Cost data were expressed in Euros . Changes in antibiotic usage was determined by comparing the mean usage during 1996 and 1997, the period before the implementation of the antibiotic control program, to 1998 when the streamlined formulary and restricted group of antibiotics, controlled by the Infectious Disease Team (IDT) . were initiated . The Wilcoxon rank sign test was used to determine statistical significance of the changes in overall antibiotic use; a P value of less than 0.05 was considered significant . RESULTS: After the implementation of the antibiotic control program, overall antibiotic usage decreased by 8.5%, 28.00 DDD/100 patient-days during 1996-1997 to 25.62 DDD/100 patient-days during 1998 . The control program resulted in overall savings of 342,927 Euros after the first year of implementation . The usage and expenditure in the restricted group of antibiotics decreased by 78.5% and 53.5%, respectively, (P=0.03) . Restricting the use of ceftazidime and imipenem accounted for the majority of the decreased usage and savings . In the non-restricted group of antibiotics, usage increased only by 32.6% resulting in a net reduction of 46.3% in all antibiotic use . CONCLUSION: Although antibiotic control programs have been successful in other countries, this represents the first attempt at successful antibiotic control in a large Italian teaching hospital . Streamlining the formulary to control antibiotic choices and the creation of a restriction program using the expertise of infectious disease physicians resulted in significant reductions in the use of and expenditure for antibiotics.

J Bacteriol, 2001 Dec, 183(23), 6898 - 907
Binding site of macrolide antibiotics on the ribosome: new resistance mutation identifies a specific interaction of ketolides with rRNA; Garza-Ramos G et al.; Macrolides represent a clinically important class of antibiotics that block protein synthesis by interacting with the large ribosomal subunit . The macrolide binding site is composed primarily of rRNA . However, the mode of interaction of macrolides with rRNA and the exact location of the drug binding site have yet to be described . A new class of macrolide antibiotics, known as ketolides, show improved activity against organisms that have developed resistance to previously used macrolides . The biochemical reasons for increased potency of ketolides remain unknown . Here we describe the first mutation that confers resistance to ketolide antibiotics while leaving cells sensitive to other types of macrolides . A transition of U to C at position 2609 of 23S rRNA rendered E . coli cells resistant to two different types of ketolides, telithromycin and ABT-773, but increased slightly the sensitivity to erythromycin, azithromycin, and a cladinose-containing derivative of telithromycin . Ribosomes isolated from the mutant cells had reduced affinity for ketolides, while their affinity for erythromycin was not diminished . Possible direct interaction of ketolides with position 2609 in 23S rRNA was further confirmed by RNA footprinting . The newly isolated ketolide-resistance mutation, as well as 23S rRNA positions shown previously to be involved in interaction with macrolide antibiotics, have been modeled in the crystallographic structure of the large ribosomal subunit . The location of the macrolide binding site in the nascent peptide exit tunnel at some distance from the peptidyl transferase center agrees with the proposed model of macrolide inhibitory action and explains the dominant nature of macrolide resistance mutations . Spatial separation of the rRNA residues involved in universal contacts with macrolides from those believed to participate in structure-specific interactions with ketolides provides the structural basis for the improved activity of the broader spectrum group of macrolide antibiotics.

Br Dent J, 2001 Oct 13, 191(7), 391 - 3
Are antibiotics being used appropriately for emergency dental treatment?
Dailey YM, Martin MV.
AIM: To investigate the therapeutic prescribing of antibiotics to patients presenting for emergency dental treatment . DESIGN: A prospective clinical study . METHOD: Information was collected via a questionnaire concerning the patient's reason for attendance and treatment undertaken at emergency dental clinics in North and South Cheshire . RESULTS: Over an 11-week period 1,069 patients attended the five clinics, 1,011 questionnaires were analyzed . The majority of the attendees had pain (879/1011) . 35% (311/879) of these patient had pulpitis and 74% (230/311) had been issued a prescription for antibiotics, without any active surgical intervention . Th principal antibiotic prescribed for both adult and child patients was amoxicillin . CONCLUSION: The majority of patients attending the emergency dental clinics had pain, with a large proportion having localised infections either as pulpitis or localised dental abscess . Three quarters of these patients had no surgical intervention and were inappropriately prescribed antibiotics.

BMC Psychiatry . 2001;1(1):5 . Epub 2001 Oct 10.
Aminoglycoside antibiotics and autism: a speculative hypothesis; Manev R et al.; BACKGROUND: Recently, it has been suspected that there is a relationship between therapy with some antibiotics and the onset of autism; but even more curious, some children benefited transiently from a subsequent treatment with a different antibiotic . Here, we speculate how aminoglycoside antibiotics might be associated with autism . PRESENTATION: We hypothesize that aminoglycoside antibiotics could a)trigger the autism syndrome in susceptible infants by causing the stop codon readthrough, i.e., a misreading of the genetic code of a hypothetical critical gene, and/or b) improve autism symptoms by correcting the premature stop codon mutation in a hypothetical polymorphic gene linked to autism . TESTING: Investigate, retrospectively, whether a link exists between aminoglycoside use (which is not extensive in children) and the onset of autism symptoms (hypothesis "a"), or between aminoglycoside use and improvement of these symptoms (hypothesis "b") . Whereas a prospective study to test hypothesis "a" is not ethically justifiable, a study could be designed to test hypothesis "b" . IMPLICATIONS: It should be stressed that at this stage no direct evidence supports our speculative hypothesis and that its main purpose is to initiate development of new ideas that, eventually, would improve our understanding of the pathobiology of autism.

Am J Respir Cell Mol Biol, 2001 Oct, 25(4), 492 - 9
Inhibition of human neutrophil elastase by erythromycin and flurythromycin, two macrolide antibiotics; Gorrini M et al.; Fourteen-member-ring macrolides are antibiotics with a variety of anti-inflammatory activities, and have repeatedly been reported to reduce mucus hypersecretion in conditions such as cystic fibrosis and bronchiectasis . Their structure is characterized by a macrocyclic lactone ring . Because human neutrophil elastase (HNE) plays a crucial role in the vicious circle leading to mucus hypersecretion, and lactones are known to be elastase inhibitors, we hypothesized that macrolides might directly inhibit elastase . To investigate this hypothesis we designed a series of spectrophotometric experiments using a chromogenic substrate with two macrolides, erythromycin (Er) and flurythromycin (FE) . We determined the 1st order rate constant (k(obs)) by inhibition and competitive substrate assays, the latter allowing us to calculate the substrate binding constant or inhibition constant and the acylation rate constant (k(a)) . A proflavine displacement assay was used to determine the deacylation rate constant (k(d)) . Both Er and FE are good HNE inhibitors, showing a high k(a) and a low k(d) . Because the number of turnovers per inactivation of Er was congruent with 20-fold higher than that of FE, we supposed that the lower reactivation of HNE-FE was due to the formation of a more stable inactivated enzyme . This hypothesis was confirmed by the hydrazine reactivation of the acyl enzyme . For Er we identified a k(d) only, whereas for FE, in addition to the k(d), an alkylation constant (k(2)) was calculated, correlated to a fully inactivated enzyme . From our kinetics data, we therefore conclude that Er acts as an alternate substrate HNE inhibitor, whereas FE acts as an inactivator.

Mikrobiol Z, 2001 Jul-Aug, 63(4), 53 - 61
{Characteristics of mutants of Streptomyces peucetius subsp . caesius ATCC 27952 resistant to anthracycline antibiotics}; Dubyts'ka LP et al.; Daunorubicine (DNR) and doxorubicine (DXR) resistance to anthracycline antibiotics and antibiotical activity of the strain Streptomyces peucetius subsp . caesius ATCC 27952-2 and its daunorubicine- and doxorubicine-resistant (DNRr and DXRr) mutants have been studied . It has been found that strain S . peucetius subsp . caesius ATCC 27952-2 is much more resistant to DXR than to DNR . It has been shown that frequency of appearance of spontaneous mutants of the strain S . peucetius subsp . caesius ATCC 27952-2, resistant to DNR (10-30 micrograms/ml) makes 1.1 x 10(-6)-1.0 x 10(-8) and DXR (10-30 micrograms/ml) 7.7 x 10(-4)-3.0 x 10(-4) . Treatment of spores of the initial strain by N-methyl-N'-nitro-N-nitrosoguanidin resulted in the 60-700-fold increase of arising frequency of DNRr-mutants while frequency of arising of DXRr-mutants did not change essentially . The majority of DNRr-mutants (76.9%) were characterised by high resistance to DXR, while there are such mutants among DXRr-mutants which possess the cross-resistance to DNR (below 30%) . The mean value of antibiotic activity was the highest among DXRr-mutants induced by NG and sampled in the medium with 30 micrograms/ml of DXR . The majority of the tested DNRr- and DXRr-mutants (13 of 15) synthesized 1.8-10.9 times more of anthracycline compounds as compared with the initial strain . All the mutants synthesized 2.6-28.3 and 1.6-20.7 times more of DNR and DXR, respectively, than the initial strain . The results obtained prove that it is expedient to search for the strains with high production of DXR among DNR1-mutants, while DXRr-mutants are promising for choosing the producers of the both antibiotics.

J Med Chem, 2001 Nov 8, 44(23), 3915 - 24
Preparation and evaluation of sulfide derivatives of the antibiotic brefeldin a as potential prodrug candidates with enhanced aqueous solubilities; Fox BM et al.; Several sulfide (+)-brefeldin A (BFA) analogues were prepared through the Michael addition of various thiols . Many of the sulfides were also oxidized to the corresponding sulfoxide with m-CPBA . The sulfides were designed to act as BFA prodrugs via the metabolic oxidation to the sulfoxide and subsequent syn elimination . Kinetic experiments were used to prove that the syn elimination of the sulfoxides prepared did in fact take place . Five selenide BFA prodrugs were also prepared that are envisioned to act in the same manner as the sulfides . As expected, when oxidation of the selenide to selenoxide was attempted, in situ syn elimination was observed . All of the compounds prepared were evaluated for antiproliferative activity against human cancer cell lines in the National Cancer Institute screen . The sulfoxides were much more potent than either the sulfides or selenides . Especially notable were sulfoxide 21, which possessed a cytotoxicity mean graph midpoint value (MGM) value lower than BFA itself, and sulfoxide 22, which possessed an MGM value slightly less potent than that of BFA . The sulfide analogues were shown to possess increased aqueous solubilty with respect to BFA.

Infection, 2001 Oct, 29(5), 251 - 6
Influence of macrolide antibiotics on promotion of resistance in the oral flora of children; Kastner U et al.; BACKGROUND: The long elimination half-life of azithromycin allows subinhibitory serum and epithelial lining fluid (ELF) concentrations over a period of several weeks post treatment, which may have an impact on the emergence of macrolide resistance . In this prospective, open-label, randomized study, four macrolides and the azalide azithromycin were studied for their likelihood to promote resistance in the oral flora of children with respiratory tract infections . PATIENTS AND METHODS: Children were randomly assigned to receive azithromycin, clarithromycin, erythromycin, roxithromycin and josamycin . Throat swabs were obtained prior to treatment and weekly for 6 weeks . Minimum inhibitory concentrations (MICs) for resistant strains were assessed by E-test and National Committee for Clinical laboratory Standards (NCClS) broth microdilution . RESULTS: One week post treatment, up to 90% of children harbored macrolide-resistant strains in their oral flora . Except for azithromycin, the percentage of patients colonized by resistant organisms decreased to a rate of 17% for clarithromycin (10/60), erythromycin (2/12) and josamycin (2/12) and 33% for roxithromycin (4/12) after 6 weeks . In the azithromycin group, 85% (51/60) of patients were colonized by macrolide-resistant organisms after 6 weeks, 11.6% (7/60) of children suffered from reinfection . CONCLUSION: Azithromycin therapy appears to put selective pressure on the infective and native flora of children, promoting the carriage of macrolide-resistant strains.

Orthopedics, 2001 Oct, 24(10), 971 - 5
Management of infected bulk allografts with antibiotic-impregnated polymethylmethacrylate spacers; Quinn RH et al.; Twenty-seven patients developed infection following bulk allograft transplantation and were treated with resection of the allograft, placement of an antibiotic-impregnated polymethylmethacrylate (PMMA) spacer, and intravenous antibiotics . Overall, the infection was eradicated in 14 (52%) of 27 patients . Of the 11 patients who did not undergo allograft reimplantation, 5 underwent amputations for persistent infection in the presence of the spacer and 4 had a retained spacer at most recent follow-up . No significant correlation was noted between successful eradication of the infection and age, sex, diagnosis, adjuvant therapy, acute or chronic infection, number of operative procedures, type of allograft procedure, duration of antibiotics, or type of organism . Although deep infection of allograft transplantations continues to result in a high rate of failure, this method of management results in successful limb salvage in almost half of the patients.

Klin Khir, 2001 Jul, (7), 48 - 51
{Application of computer thermography in diagnosis of chronic focus of inflammation and the definition of indications to the use of antibiotics before operation in patients with post-operative hernia of anterior abdominal wall}; Il'chenko FN et al.; We studied the informative value of computer thermography in diagnostics of inflammatory changes in hernia region in 53 patients with post-operative hernia of anterior abdominal wall . Four variants of thermogram were obtained depending from temperature gradient in symmetric points of hernia hilus . This was used to substantiate preventive antibiotics prescription according to general scheme in pre-operation period in 25 patients and administration of electrophoresis of cefazoline in further 28 patients . The method was effective to reduce inflammatory changes in hernia hilus region in 88.9% of patients, which was defined based on temperature gradient decrease in symmetric regions of hernia . Post-operative complications rate decreased from 15.7 to 12.3% . The suppuration of post-operative wound was not observed.

Cochrane Database Syst Rev . 2001;(4):CD001058.
Antibiotics for preterm premature rupture of membranes; Kenyon S et al.; BACKGROUND: The consequences of prematurity continue to result in neonatal morbidity and mortality . One of the causes of prematurity is preterm prelabour rupture of membranes in which there is evidence that subclinical infection plays a role . OBJECTIVES: The aim of the review was to evaluate the effectiveness and the immediate and long-term safety of the effects of administering antibiotics to women with preterm prelabour rupture of membranes on maternal infectious morbidity, fetal and neonatal morbidity and mortality, and longer term childhood development . SEARCH STRATEGY: All randomized trials identified using the search strategy described by the Cochrane Pregnancy and Childbirth Group . Date of last search: 31 May 2001 . SELECTION CRITERIA: All trials which reported clinically relevant outcomes (as opposed to laboratory data) were included . DATA COLLECTION AND ANALYSIS: Data were extracted from each report without any blinding of either the results or the treatments which women received . Unpublished data were sought from a number of authors . MAIN RESULTS: There were 13 trials included in the review which randomised over 6,000 women and their babies . The use of antibiotics following preterm prelabour rupture of membranes (pPROM) is associated with a statistically significant reduction in maternal infection after delivery prior to discharge (relative risk (RR) 0.85, 95% confidence interval (CI) 0.76,0.96) and morbidity (including chlorination) (RR 0.62, 95% CI 0.51,0.75) There was a statistically significant reduction in the numbers of babies born within 48 hours (RR 0.77, 95% CI 0.72,0.83) and seven days RR 0.88, 95% CI 0.84,0.92) of randomisation . Neonatal infection (including pneumonia) (RR 0.67, 95% CI 0.52,0.85) and positive blood culture (RR 0.75, 95% CI 0.60,0.93) were statistically significantly reduced in the babies whose mothers received antibiotics as was the numbers of babies requiring oxygen therapy overall (RR 0.88, 95% CI 0.81,0.96) and at 28 days of age or older (RR 0.81, 95% CI 0.68,0.97) . One trial (ORACLE) found a statistically significant reduction in the use of surfactant (RR 0.83, 95% CI 0.72,0.96) . There was also a statistically significant reduction in the number of babies diagnosed with abnormal cerebral ultrasound (RR 0.82, 95% CI 0.68,0.99) scans prior to discharge from hospital . Overall, there was no evidence of adverse effect . Intrinsically there are fewer data relating to specific antibiotics . When looking at the effect of beta lactum antibiotics (augmentin) where two trials were included, there was a statistically significant reduction in the number of babies born within 48 hours (RR 0.75, 95% CI 0.67,0.84) and seven days (RR 0.91, 95% CI 0.85,0.97) of randomisation . However, there was a highly significant increase in the numbers of babies with necrotising enterocolitis (RR 4.60, 95% CI 1.98,10.72) in the augmentin treatment group . The effect of macrolide antibiotics (erythromycin), included four trials and found statistically significant reductions in the number of babes born within 48 hours (RR 0.84, 95% CI 0.76,0.93) of randomisation but delivery < 7 days did not exclude unity . There was statistically significant reductions in those requiring oxygen therapy (RR 0.87, 95% CI 0.78,0.98) and those with a positive blood culture (RR 0.70, 95% CI 0.52,0.94) . REVIEWER'S CONCLUSIONS: There are sufficient data to recommend routine prescription of macrolide antibiotics in this clinical situation . The routine prescription of macrolide antibiotic (erythromycin) is recommended as beta lactum antibiotics (augmentin) is associated with a statistically significant increase in neonatal necrotising enterocolitis.

Cochrane Database Syst Rev . 2001;(3):CD002741.
Antibiotics for acute asthma; Graham V et al.; BACKGROUND: Antibiotics are often prescribed to patients who are admitted to hospital with acute asthma . Their exacerbation is often precipitated by a viral upper respiratory infection (URTI), but in some instances antibiotics are prescribed in spite of questionable efficacy . A lack of strong evidence either to support or to refute the use of treatments in acute asthma leaves room for discussion and debate as to how effective antibiotics are in an acute setting . This review assesses what evidence is available . OBJECTIVES: To determine the efficacy of antibiotics prescribed in the treatment of acute asthma SEARCH STRATEGY: Electronic databases (MEDLINE, EMBASE and CINAHL) were searched to identify all possible randomised control trials . SELECTION CRITERIA: Only RCTs or quasi RCTs were eligible for inclusion . Studies were included if patients were treated for acute asthma in the ED or its equivalent with antibiotics or placebo . Two reviewers independently assessed articles for potential relevance, final inclusion, and methodological quality . DATA COLLECTION AND ANALYSIS: Two reviewers completed trial quality assessment and data extraction independently . MAIN RESULTS: From 128 potential studies, two trials were identified for inclusion in the review . Both trials reported numbers of exacerbations and not patient numbers due to re admissions over the course of the trials . The total number of patients in this review was 97, but values were recorded for 115 exacerbations . REVIEWER'S CONCLUSIONS: The role of antibiotics in the treatment of acute asthma is difficult to assess from the current literature . Recommendations regarding antibiotic use in acute asthma will remain consensus driven until more research is conducted which includes larger numbers of patients.

Acta Paediatr, 2001 Sep, 90(9), 1025 - 32
Interleukin-8: a valuable tool to restrict antibiotic therapy in newborn infants; Franz AR et al.; This study was conducted to evaluate the accuracy and kinetics of interleukin 8 (IL-8) as a test for early-onset bacterial infections (EOBI) in neonates and to examine whether IL-8 would allow "unnecessary" antibiotic therapy to be reduced . First, IL-8 was measured 378 times on admission, along with C-reactive protein (CRP), immature to total neutrophil ratio (IT ratio) and blood cultures, in full-term and preterm neonates with suspected EOBI . Combined culture-proven and clinical EOBI were detected on admission by the combination of IL-8 > or = 70 pg ml(-1) and/or CRP > 10 mg l(-1) with 92% sensitivity and 74% specificity . An increased IL-8 was found in 62% of the infected infants, while CRP was still normal . In a second study period, IL-8 was determined prospectively in 331 infants who presented clinical signs of EOBI or had a birth history of amniotic infection . Antibiotic therapy was restricted to those infants with suspected infection who also had an increased IL-8 and/or CRP (n = 158) . Another 39 infants received antibiotics on the basis of clinical signs despite negative IL-8 and CRP . Of 150 non-infected infants in whom IT ratio, IL-8 and CRP were available, treatment would have been indicated for 93 infants based on IT ratio and/or CRP (n = 77) or clinical signs (n = 16), but was only initiated in 55 infants based on IL-8 and/or CRP (n = 28) or clinical signs (n = 27), an apparent reduction in "unnecessary" antibiotic therapy of 40% . Conclusion: The combination of IL-8 and CRP is a reliable test for the diagnosis of EOBI and may be helpful in enabling antibiotic therapy to be reduced in newborn infants.

Rev Med Brux, 2001 Sep, 22(4), A260 - 3
{Antibiotics and pregnancy}; Bossens M; Antibiotherapy during pregnancy has to be adapted according two factors: pregnancy related pharmacodynamic changes and potentially negative side effects for the developing foetus of some antibiotics . Pregnancy induce a weight gain, an increase of intravascular volume, of glomerular filtration, and of hepatic metabolism . The foetoplacental unit create a new volume in which antibiotics penetrates increasingly during gestation . As a consequence, during pregnancy, maternal plasmatic levels of antibiotics reaches values 10-50% under the ranges observed with the same dosages administered to non pregnant women . Tobramycin of which clearance diminish during pregnancy is the only exception for this rule . In term pregnancy, placental transfer of antibiotics is very high, except for macrolides . Thalidomide, a well-known responsible of phocomely, is still used in the treatment of leprae . No other antibiotic as a well demonstrated teratogenic effect in human foetuses . Nevertheless, tetracyclin use in pregnancy must be avoided according a high risk of enamel dysplasia, with brownish discoloration of deciduous teeth . No teratogenic effect has been recorded for betalactams and for erythromycin, the first choice antibiotics during pregnancy . Some antibiotherapy are specific of obstetrical conditions . Antibiotics interferes with estrogens metabolism, inducing a fall in circulating level of estriol.

Ned Tijdschr Geneeskd, 2001 Oct 13, 145(41), 1982 - 5
{Reduced risk of complications associated with severe acute (necrotizing) pancreatitis by administration of antibiotics; results from a literature review}; Bosscha K et al.; OBJECTIVE: To determine the role of antibiotics in patients with acute pancreatitis . DESIGN: Literature review . METHOD: A Medline search for randomised clinical trials (RCTs) during the period 1990-1999 was carried out using the key words 'pancreatitis', 'acute' and 'antibiotics' . Outcome measures were pancreas-related infection, sepsis and death . RESULTS: Four RCTs were identified . Control groups were not given antibiotics . Based on the pooled data, the differences in risk in favour of the groups treated with various antibiotics were as follows: -14% (95% CI: -26(-)-1; p = 0.04) for pancreas infections, -25% (95% CI: -39(-)-12; p = 0.0002) for sepsis and -13% (95%-BI: -22(-)-3; p = 0.007) for death . CONCLUSION: Administration of antibiotics to patients with severe acute (necrotising) pancreatitis reduces the risk of serious complications.

J Antimicrob Chemother, 2001 Nov, 48(5), 691 - 703
Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for lower respiratory tract infections; Contopoulos-Ioannidis DG et al.; We carried out a meta-analysis of randomized controlled trials of azithromycin compared with other antibiotics in the treatment of lower respiratory tract infections, including acute bronchitis (five comparisons including 1372 patients), acute exacerbations of chronic bronchitis (13 comparisons including 1342 patients) and community-acquired pneumonia (18 comparisons with 1664 patients) . For the first two indications, azithromycin did not offer any statistically significant reduction in clinical failures {random effects odds ratios 0.84, 95% confidence interval (CI) 0.54-1.31 and 0.64, 95% CI 0.31-1.32, respectively} and absolute risk differences were small . For community-acquired pneumonia, azithromycin significantly reduced clinical failures by about one-third (random effects odds ratio 0.63, 95% CI 0.41-0.95) . The absolute incremental benefit was approximately one clinical failure prevented per 50 treated patients with community-acquired pneumonia . There was no significant heterogeneity for different comparators and for bacterial versus atypical pneumonias . Azithromycin was discontinued because of adverse events in only 23 of 3487 patients (0.7%) . Although results should be interpreted cautiously as most trials were open-label and susceptible to bias, the meta-analysis indicates that, compared with antibiotics with traditional pharmacokinetics that require more prolonged courses, azithromycin offers no significant advantage for bronchitis, but may be more effective in community-acquired pneumonia.

J Antimicrob Chemother, 2001 Nov, 48(5), 597 - 603
Use of antibiotic locks to treat colonized central venous catheters; Berrington A et al.; Infections that result from bacterial colonization of central venous catheters are a significant problem in modern healthcare . The most effective means of eradication of such infections is the removal of colonized lines, but line removal carries drawbacks of its own and in many cases the balance of risks favours treatment in situ . Systemic antibiotics are usually administered but these frequently fail to achieve sterilization, and accordingly attention has turned to intraluminal therapy using antibiotic locks, in which 1-2 mL of a concentrated antibiotic solution is instilled to fill the lumen, left for a predetermined period, and removed . The evidence in favour of this technique is anecdotal and should not be allowed to influence any decision about line removal, but is sufficiently encouraging to justify the use of locks when in situ treatment is deemed acceptable . Indications, agents and appropriate administration regimes are discussed.

Metab Eng, 2001 Oct, 3(4), 380 - 92
Biosynthetic pathway of cephabacins in Lysobacter lactamgenus: molecular and biochemical characterization of the upstream region of the gene clusters for engineering of novel antibiotics; Sohn YS et al.; The cephabacins, one of the beta-lactam antibiotics, are produced by Lysobacter lactamgenus . The previous studies the cephabacin biosynthesis were limited to a gene cluster that encodes the gene products responsible for the biosynthesis of the cephem nucleus . The long-term goal of this research is to elucidate the metabolic diversity and biosynthetic pathway of cephabacins and to design and/or discover new pharmacologically active compounds by engineering the cephabacin biosynthetic pathway in L . lactamgenus . In this study, we have cloned and sequenced a 24-kb fragment of a DNA locus upstream of the previously reported but incomplete putative ORF9 of L . lactamgenus . This contains three putative ORFs (the complete ORF9, ORF10, and ORF11) transcribed in the same direction and one putative ORF (ORF12) in the opposite direction . The isolated DNA locus extends the previously cloned part of the DNA locus containing the genes responsible for biosynthesis of the cephem nucleus up to 45 kb . The 42-kb fragment of the 45-kb gene cluster is located between a potential TATA box just upstream of the ORF11 and a termination loop just downstream of the previously reported bla gene . The complete ORF9 contains three nonribosomal peptide synthetase (NRPS) modules and one polyketide synthase (PKS) module and the ORF11 contains one NRPS module . The complete ORF9 also contains a putative thioesterase domain at the C-terminal end . We predicted the amino acid specificity of the four NRPSs by generating specificity binding pockets and expressed one of the NRPSs to confirm the amino acid specificity . The adenylation domain of the NRPS1, which is the last module of the NRPSs, showed significant amino acid specificity for L-arginine . These findings are in perfect agreement with the composition that was expected for the structure of cephabacins which contain an acetate residue, an L-arginine, and one to three L-alanines at the C-3' position of the cephem nucleus of cephabacins . The ORF10, encoding a putative ABC transporter which might be involved in conferring resistance against cephabacins, was identified between the complete ORF9 and the ORF11 . Therefore, the complete ORF9, ORF10, ORF11 reported here and the other genes previously reported constitute an operon for the biosynthesis of cephabacins in L . lactamgenus . Based on our results, the biosynthetic pathways of acetate and elongated peptide moieties and a mechanism by which cephabacins are assembled by connecting the peptide moiety synthesized by the gene products of the complete ORF9 and the ORF11 to the C-3' position of the cephem nucleus synthesized by the gene products of pcbAB, pcbC, cefE, cefF, and cefD have been elucidated .

J Surg Res, 2001 Nov, 101(1), 52 - 5
The effectiveness of systemic antibiotics in preventing postoperative, intraabdominal adhesions in an animal model; Oncel M et al.; OBJECTIVE: Postoperative intraabdominal adhesions can be prevented by antibiotic lavage . We assessed whether systemic antibiotics could prevent adhesion formation in a rat model . METHODS: Cecal abrasion was performed in the peritoneal cavities of 40 Wistar albino rats . Twenty rats were treated with a 5-day course of cefepim and metronidazole; the remaining animals were given saline injections . The animals were sacrificed 14 days after surgery . Adhesion severity scores and histopathologic findings were compared . RESULTS: The median adhesion severity score was 2 (0-3) in the antibiotic group and 2.5 (1-4) in the controls (P = 0.03) . In tissue specimens from controls, the adhesions were marked by mature collagen bundles . In treated rats, the adhesions were immature, characterized by early inflammatory cells, less collagen formation, and no collagen bundles . CONCLUSIONS: Postoperative systemic antibiotics slow adhesion formation and reduce the severity of the adhesions .

Arch Bronconeumol, 2001 Oct, 37(9), 366 - 70
{Community-acquired pneumonia: influence of the duration of intravenous antibiotic therapy on hospital stay and the cost-benefit ratio}; Fernandez Alvarez R et al.; Intravenous antibiotic therapy (IVAT) is usually prescribed for patients hospitalized with community-acquired pneumonia (CAP) . Studies have associated prolonged IVAT with longer hospital stays and higher costs . The aim of this study was to determine the factors that influence the expense generated by and mean stay of patients hospitalized for pneumonia, with special attention to the influence of IVAT duration . MATERIAL AND METHODS: One hundred twenty-five CAP patients admitted to the respiratory medicine wards of our hospital were randomly assigned to five different staff physicians . IVAT was prescribed following the norms of the Spanish Society of Respiratory Medicine and Chest Surgery (SEPAR) . IVAT was withdrawn when the attending physician considered it appropriate.We collected epidemiological, comorbidity, clinical and analytical data . Complications were recorded and severity of CAP was classified using the model proposed by Fine . Follow-up care was given at an outpatient clinic until symptoms disappeared and chest films resolved . Multivariate analysis determined the factors predicting mean hospital stay and high cost . Costs were calculated based on data issued by the billing department . RESULTS: The mean cost of care was 307,274 pesetas, mean duration of IVAT was 5.8 days and mean hospital stay was 9.4 days . Multivariate analysis showed that cost was related to mean hospital stay and IVAT . Mean hospital stay was associated with IVAT, the presence of respiratory insufficiency and the day of the week when admission took place (with weekend admission leading to longer stays) . CONCLUSIONS: The duration of IVAT in CAP influences mean hospital stay and cost, without adding any evident therapeutic benefit (in the group of patients selected) . Recommendations for diagnosing and treating CAP may be advisable.

J Fam Pract, 2001 Oct, 50(10), 853 - 8
Antibiotic use in acute respiratory infections and the ways patients pressure physicians for a prescription; Scott JG et al.; OBJECTIVE: We identified those aspects of physician-patient communication that influence physicians to prescribe antibiotics for respiratory infections . STUDY DESIGN: A multimethod comparative case study was performed including descriptive field notes of outpatient visits . POPULATION: We included patients (children and adults) and clinicians in 18 purposefully selected family practices in a midwestern state . A total of 298 outpatient visits for acute respiratory tract (ART) infections were selected for analysis from more than 1600 encounters observed . OUTCOMES MEASURED: Unnecessary antibiotic use and patterns of physician-patient communication were measured . RESULTS: Antibiotics were prescribed in 68% of the ART infection visits, and of those, 79% were determined to be unnecessary according to Centers for Disease Control and Prevention guidelines . Patients were observed to pressure physicians for medication . The types of patterns identified were direct request, candidate diagnosis (a diagnosis suggested by the patient), implied candidate diagnosis (a set of symptoms specifically indexing a particular diagnosis), portraying severity of illness, appealing to life-world circumstances, and previous use of antibiotics . Also, clinicians were observed to rationalize their antibiotic prescriptions by reporting medically acceptable reasons and diagnoses to patients . CONCLUSIONS: Patients strongly influence the antibiotic prescribing of physicians by using a number of different behaviors . To decrease antibiotic use for ART infections, patients should be educated about the dangers and limited benefits of such use, and clinicians should consider appropriate responses to these different patient pressures to prescribe antibiotics.

J Org Chem, 1999 Jul 23, 64(15), 5371 - 5376
Unique Solvent-Dependent Atropisomerism of a Novel Cytotoxic Naphthoxanthene Antibiotic FD-594; Eguchi T et al.; The absolute stereochemistry of FD-594 1, a new cytotoxic antibiotic, was determined by X-ray diffraction, and its conformation was studied by CD and NMR spectroscopy . The aglycon part of 1 was found to have (3R,6S,7S) configuration . Particularly interesting was the solvent-dependent atropisomerism of 1 and related compounds . The CD spectra of 1 exhibited in two solvent systems almost opposite mirror-image curves depending on the solvent . While a large negative Cotton effect (Deltaepsilon = -33.9, 279 nm) was observed in CHCl(3), a similar positive Cotton effect (Deltaepsilon = 38.9, 279 nm) appeared in methanol most probably due to dramatic conformational changes . Similar chiroptical reversal was observed in aglycon 2 and aglycon methyl ether 4 . These results can be best described in terms of solvent-dependent atropisomerism . This constitutes the first observation of solvent-dependent atropisomerism of a natural product . The crucial factor that perturbs the stable conformation in different solvents is discussed on the basis of molecular mechanics calculations.

J Org Chem, 1999 Feb 5, 64(3), 736 - 746
Studies of Acyl Nitrene Insertions . A Stereocontrolled Route toward Lankacidin Antibiotics; Williams DR et al.; Photochemically generated acyl nitrenes undergo facile addition to 4,5-dihydrofurans 20 and 24b to yield the novel 2-ethoxyoxazolines 21 and 25 . The regiocontrolled C=C insertion has provided for introduction of the sterically hindered C-3 amido appendage of the lankacidins 1-4 with high stereoselectivity . High chemoselectivity for the C=C insertion pathway was demonstrated upon production of the acyl nitrene intermediate from azide 33b . Intramolecular competition for allylic C(3)-H insertion versus C=C addition yielded exclusive formation of seven-membered N-acyl aziridines 34a,b . The latent aldehydic functionality of oxazolines such as 21 and 25 is exposed upon a brief hydrolysis, permitting further chemical elaboration . Wittig condensation of the lactol from 25 has led to the synthesis of the lactone fragment 5, containing all of the necessary stereochemistry and functionality for incorporation into the lankacidin antibiotics . The acyl nitrene insertion into 4,5-dihydrofurans affords a route toward unusual beta-amido acids and amino sugar derivatives as shown via stereocontrolled formation of the amidofuranose derivatives 31 and 32 . The three-step process of acyl nitrene addition, hydrolysis of the resulting 2,5-dialkoxy oxazoline intermediates, and Wittig carbon chain elongation provides the stereocontrolled formation of novel beta-amido esters.

Int J Antimicrob Agents, 2001 Sep, 18(3), 299 - 303
How to organise antibiotic prescription; Dellamonica P et al.; In recent years, efforts have been made in hospitals to improve antibiotic prescription . Most universities organise courses on the subject, which lead to a local university diploma . However, possessing such a diploma does not give entitlement to prescribe . In fact, most doctors prescribe antibiotics and such courses are only of interest to volunteer physicians . While some are very careful, the majority prescribe the drugs as they are rarely toxic . Others are refractory to any information and particularly to any training . Two methods are typically proposed to reduce unjustified prescription . As a result of imposed restrictions, only trained doctors having met the training standards are allowed to prescribe and have to keep to a limited budget . The persuasive method, on the other hand, opens the way for a wide scope of training courses, which are provided by industry; some are said to be biased as they encourage prescription and the risk of selecting resistant mutant bacteria is scarcely documented . This method does not always coincide with the training curricula . The industry is torn between declared objectives such as judicious drug use and prevailing commercial aims . As a result, prescription is not restrained by any objective limit . It should be noted that prescription varies greatly from one hospital to another and within a given hospital between one department and another . Certain departments prescribe much more than others and these (emergency, medical and surgical intensive care, respiratory disease) should be targeted first.

J Org Chem, 1998 Aug 21, 63(17), 5838 - 5846
Practical Synthesis of alpha-Amino Acid N-Carboxy Anhydrides of Polyhydroxylated alpha-Amino Acids from beta-Lactam Frameworks . Model Studies toward the Synthesis of Directly Linked Peptidyl Nucleoside Antibiotics; Palomo C et al.; A straightforward method for the synthesis of polyhydroxylated alpha-amino acid N-carboxy anhydrides (NCAs) is described as the means by which short peptide segments comprised of a polyhydroxylated chain are easily affordable . The entire sequence lies in the preparation of nonracemic 3-hydroxy beta-lactams through the highly diastereoselective Staudinger reaction of hydroxyketene equivalents with chiral alpha-oxyaldehyde-derived imines, followed by TEMPO radical assisted cycloexpansion to the corresponding NCA and subsequent peptide coupling with alpha-amino acid esters . The method has been applied to the synthesis of short peptide segments derived from carbamoylpolyoxamic acid, some glycoglycines, as well as C(2) symmetric hydroxy amino acids.

J Org Chem, 1997 Jun 27, 62(13), 4364 - 4369
Synthetic Studies on the Kinamycin Family of Antibiotics: Synthesis of 2-(Diazobenzyl)-p-naphthoquinone, 1,7-Dideoxy-3-demethylprekinamycin, and 1-Deoxy-3-demethylprekinamycin; Williams W et al.; 2-(Diazobenzyl)-p-naphthoquinone was synthesized from 2-benzyl-1,4-dimethoxynaphthalene by cerric ammonium nitrate oxidation to 2-benzyl-p-naphthoquinone followed by diazo transfer with tosyl azide . 1,7-Dideoxy-3-demethylprekinamycin was prepared from 1,4-dimethoxynaphthalene by bromination, lithiation, and condensation with acetanthranil to give 2-(2'-N-acetaminobenzoyl)-1,4-dimethoxynaphthalene, which, following deacylation, was subjected to Pschorr cyclization to give 1,3,7-trihydro-O,O-dimethylkinafluorenone . This was then demethylated, subjected to hydrazinolysis, and then oxidized with Fetizon's reagent to complete the synthesis . 1-Deoxy-3-demethylprekinamycin was synthesized from 3-bromo-1,5-dimethoxy-4-naphthol by an identical route.

Inorg Chem, 1998 May 4, 37(9), 2255 - 2262
Comprehensive 2D (1)H NMR Studies of Paramagnetic Lanthanide(III) Complexes of Anthracycline Antitumor Antibiotics; Wei X et al.; The binding of several lanthanide(III) ions to anthracycline antitumor antibiotics daunomycin and adriamycin in methanol and aqueous solutions has been studied by means of optical and 2D NMR (COSY, TOCSY, and EXSY) techniques . These results indicate that a 1:1 Yb(3+)-drug complex (1) is the predominant complex at a metal-to-ligand ratio <10 with slightly higher proton activities, e.g., approximately pH 4-5 in an aqueous solution . In the presence of a base, a 1:2 (2) or 1:3 (3) Yb(3+)-drug complex can be formed . In addition, a 2:1 complex (4) is formed when the metal-to-drug ratio is >25 . These Yb(3+)-drug complexes undergo slow chemical exchange with each other relative to the NMR time scale . Therefore, 1D and 2D magnetization transfer experiments can be utilized for the assignment of the isotropically shifted signals arising from the drug nuclei in the various paramagnetic complexes . The spin-lattice (T(1)) relaxation times and solution magnetic susceptibilities of these Yb(3+)-drug complexes confirmed the binding of the metal ion to 11,12-beta-ketophenolate in all the complexes (except the second Yb(3+) in the 2:1 complex which binds to the 5,6-beta-ketophenolate) . Several other lanthanide(III) ions Pr(3+), Eu(3+), and Dy(3+) show similar binding properties to daunomycin based on optical and NMR studies . The binding of Yb(3+) to daunomycin has a profound effect on the reduction potential of the drug, showing a decrease in the potential by 150 mV upon addition of 1 equiv of Yb(3+) to the drug solution . This observation indicates that metal ions must play a significant role in the action of these family of drugs in vivo.

J Org Chem, 1996 Sep 6, 61(18), 6268 - 6272
Kinetics and Thermodynamics of Binding of a Model Tripeptide to Teicoplanin and Analogous Semisynthetic Antibiotics; Scrimin P et al.; The thermodynamics and kinetics of binding of model tripeptides epsilon-N-acetyl-alpha-N-dansyl-L-Lys-D-Ala-D-Ala (ADLAA) or alpha-N,epsilon-N-diacetyl-L-Lys-D-Ala-D-Ala (AALAA) to teicoplanin (1a) and a series of semisynthetic derivatives with (1b-f) or devoid of (2a-g) the glycidic side arms and modified at the terminal amino acids of the peptide backbone have been studied by fluorescence or UV spectroscopy . The binding process is suggested to occur via a two-step mechanism . The first, fast process is likely governed by an electrostatic interaction between the C- and N-termini of the peptide chain of the substrate and of the antibiotic, respectively, while the second slower one, accounts for the formation of the hydrogen bonds responsible of the major contribution to the overall binding energy . The binding constants with all modified derivatives are smaller than that with native teicoplanin . Larger modification of the overall binding constant are observed when the sugar residues are removed and, to a lower extent, when the N-terminus of the peptide chain is acylated . The kinetic process is very little affected by the modifications introduced.

J Org Chem, 1996 Jun 26, 61(13), 4427 - 4433
Complete Diastereocontrol in Intramolecular 1,3-Dipolar Cycloadditions of 2-Substituted 5-Hexenyl and 5-Heptenyl Nitrones: Application to the Synthesis of the beta-Lactam Antibiotic 1beta-Methylthienamycin; Jung ME et al.; The diastereoselectivity of intramolecular 1,3-dipolar cycloadditions of 2-substituted 5-hexenyl and 5-heptenyl nitrones to give 6-substituted and 3,6-disubstituted perhydrocyclopenta{c}isoxazoles has been investigated . An alkyl or aryl substituent at C2 completely controls the stereochemistry of the ring juncture and, in the case of the 5-heptenyl systems, also the stereochemistry of the 3-methyl group . Thus one stereocenter controls the formation of the other three to give a product with four contiguous stereocenters . The use of an ethylene ketal substituent in these systems allows the reaction to be carried out at much lower temperatures, an example of the gem-dialkoxy effect . This cycloaddition process has been used in an efficient formal total synthesis of the potent beta-lactam antibiotic, 1beta-methylthienamycin.

Histol Histopathol, 2001 Oct, 16(4), 1143 - 8
Vestibular histofluorescence could be due to accumulation of both the antibiotic and its derivative, streptidine, after acute streptomycin treatment in the guinea pig; Meza G et al.; Acute treatment with 300 mg/kg of pigmented guinea pigs with streptomycin sulfate induces an elevation of endogenous fluorescence in vestibular ampullary cristae . Fluorescence accumulates in all compartments of the epithelium, i.e., vestibular sensory and supporting cells and nerve fibers of the stroma and it was very intense 1 and 12 hours after its administration . Fluorescence decreased to control levels 24 hours following streptomycin injection . Fluorescence levels were very low either in untreated animals or in animals injected with saline physiological solution . To investigate whether this fluorescence was an intrinsic property of the antibiotic or whether it was due to a derivative of it, or both, an in vitro fluorescence spectrum was performed with 100 microM solutions of streptomycin or streptidine, or both, dissolved in various buffer solutions at 488 nm of excitation . A discrete level of fluorescence was observed in the spectrum regardless of media when separate solutions of both streptomycin or streptidine were studied . Fluorescence notably increased at 522-532 nm when the solutions contained both streptomycin and streptidine together . These results suggest that streptidine putatively derived from streptomycin may contribute to the observed fluorescence accumulation in vestibular preparations after acute treatment . Thus, these metabolic properties of the inner ear which transform streptomycin into streptidine, something never considered earlier, could be claimed as partially responsible for converting a therapeutic agent into a compound which could be as harmful as STP to the inner ear.

Int Immunopharmacol, 2001 Oct, 1(11), 1913 - 21
Modulation of Th2 type cytokine production from human peripheral blood leukocytes by a macrolide antibiotic, roxithromycin, in vitro; Asano K et al.; The influence of a macrolide antibiotic, roxithromycin (RXM), on Th1 and Th2 cytokine productions from human peripheral blood T cells was examined under stimulation with co-stimulatory molecules . Peripheral blood T cells prepared from both healthy and allergic rhinitis donors were cultured in the presence of RXM on anti-CD3 mAb and anti-CD26 mAb-coated wells, anti-CD3 mAb and anti-CD28 mAb-coated wells, and anti-CD3 and PMA . T-cell proliferation, along with the concentration of interleukin (IL)-2, interferon (IFN)-gamma, IL-4 and IL-5 were measured . RXM did not affect T-cell proliferation induced by several ways of co-stimulatory activation as assessed by 3H-thymidine incorporation into DNA . RXM also had no effect on IL-2 and IFN-gamma secretion by T cells prepared from both healthy and allergic rhinitis donors . On the other hand, RXM markedly inhibited both IL-4 and IL-5 secretions under each of the co-stimulatory conditions in a dose-dependent manner . These results indicate that RXM inhibits specifically Th2 cytokine secretion from T cells induced by co-stimulatory molecule stimulations . This inhibitory action of RXM may be partially responsible for attenuating effect of the agent on the inflammatory diseases.

Aten Primaria, 2001 Oct 15, 28(6), 386 - 90
{Do patients understand their prescribed antibiotic treatments?}; Lopez Diaz J et al.; OBJECTIVE: To assess to what degree patients who had been prescribed an antibiotic understand the dose and duration of the prescription . DESIGN: Descriptive, cross-sectional . SETTING: Primary care in Toledo . PARTICIPANTS: People over 18 who attended 10 pharmacies in Toledo with an antibiotic prescription in April and May 2000 . MAIN MEASUREMENTS: The prescriptions were dispensed by a pharmacist in charge at each establishment . After receipt of the prescription, the patient was asked about the dose of the drug prescribed . This was then compared with the instructions on the drug . RESULTS: 155 women and 163 men made up the sample, with an average age of 46.42 (SD, 17.2) . The most commonly prescribed antibiotics were: a) amoxycillin (24.2%), 2) amoxycillin-clavulanic acid (18.2%), and c) ciprofloxacin (10.6%) . 63.2% of those interviewed remembered correctly the dosage prescribed without having to consult any kind of instruction, whereas 17.6% did need to consult instructions . 33% brought instructions written by the doctor . The average age of those who answered incorrectly was 52.8; and of those who answered correctly, 44.9 (p < 0.01) . There were no significant differences between men and women . CONCLUSIONS: There is an important number of patients, especially older ones, who have not received or have not understood the instructions received from their doctor.

Antimicrob Agents Chemother, 2001 Nov, 45(11), 3128 - 31
ATP synthase is necessary for microcin H47 antibiotic action; Trujillo M et al.; Microcin H47 is a gene-encoded peptide antibiotic produced by a natural Escherichia coli strain isolated in Uruguay . In order to identify cellular components necessary for its antibiotic action, microcin H47-resistant mutants isolated in this work, as well as previously described mutants affected in membrane proteins, were analyzed . These studies indicated that (i) receptor outer membrane proteins for ferric-catechol siderophores would be involved in microcin-specific binding to the cell surface, (ii) the TonB pathway is needed for microcin H47 uptake, and (iii) the presence of the ATP synthase complex is necessary for microcin action . The possibility that this last structure contains the antibiotic target is discussed.

J Pharm Biomed Anal, 2001 Dec, 26(5-6), 883 - 9
Characterization of micellar solubilization of antibiotics using micellar electrokinetic chromatography; Mrestani Y et al.; Micellar electrokinetic chromatography (nMEKC) method was applied to the determination of the partition behaviour between water and micelle for a group of antibiotics using sodium dodecyl sulphate (SDS) as an anionic model surfactant . In the method, the running buffer contains both the micelles and the drug, and the injected solution contains the same concentration of the micelles as the running buffer but no drug . The mobility of the drug can be measured from a negative peak recorded in the chromatogram . The required parameters for the determination of the capacity factor were measured by the MEKC technique . Thermodynamic properties such as enthalpy and entropy changes of micellar solubilization were calculated from the temperature dependence of the partition coefficients . The critical micellar concentrations (CMC) of the SDS salt were determined in phosphate solutions at pH 7 at different temperatures using the MEKC . The method described in this article based on MEKC is efficient and very fast in order to determine parameters for characterizing micellar solubilization of drugs.

J Pediatr, 2001 Oct, 139(4), 578 - 82
Randomized clinical trial of soy formula with and without added fiber in antibiotic-induced diarrhea; Burks AW et al.; OBJECTIVE: The objective of this study was to examine the effects of soy formulas with and without added soy fiber in children who developed diarrhea while receiving antibiotics . DESIGN: In a masked, randomized parallel study, older infants and toddlers were fed commercial soy formulas with or without added soy fiber for 10 days on occurrence of diarrhea during the administration of antibiotics . Subjects were stratified by feeding (formula versus cow's milk) . The primary variables were duration of diarrhea, stool characteristics, and intake . Secondary variables were weight and spit-up . RESULTS: All 45 children who completed the 10-day study received >30% of their caloric intake from formula . Fiber intake from other foods did not differ between groups and averaged 0.5 g/day . Total median fiber intake of the group fed the formula with added fiber was 6.53 g/day . The mean duration of diarrhea was 25.1 +/- 5.2 hours for children fed the formula with added fiber and 51.6 +/- 10.7 hours for those fed the regular formula (P =.0013) . CONCLUSION: The duration of antibiotic-induced diarrhea in children fed the soy formula with added soy fiber was significantly reduced.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2001 Oct, 92(4), 435 - 9
Intracanal use of a corticosteroid-antibiotic compound for the management of posttreatment endodontic pain; Negm MM; OBJECTIVE: The purpose of this randomized, double-blind study was to determine the effect of a corticosteroid-antibiotic combination when used as an intracanal medicament for the treatment of posttreatment pain in endodontically involved teeth with vital pulp-test readings . STUDY DESIGN: Out of 988 patients, 480 experienced intratreatment pain . Endodontic treatment was completed in 3 visits . Patients who experienced pain after the first or second visit (postextirpation or postinstrumentation) were given an emergency visit during which no local anesthetic was used . The patients randomly received either intracanal corticosteroid-antibiotic compound or a placebo . Patients subjectively rated their pain on a scale of 1 to 4 as none, mild, moderate, and severe . The ratings were done at 1, 2, 4, 8, 12, and 24 hours postmedication . RESULTS: Intracanal use of the corticosteroid-antibiotic medication significantly reduced (P < .001) the mean pain score quite rapidly and was significantly superior to the placebo until the end of the study (P < .001) . Furthermore, there were no reoccurrences of pain, and no side effects from use of the drug were noted . CONCLUSION: These results support the intracanal use of corticosteroid-antibiotic combination for controlling posttreatment endodontic pain.

Pharmacology, 2001, 63(3), 142 - 6
Neuromuscular blocking effects of the aminoglycoside antibiotics arbekacin, astromicin, isepamicin and netilmicin on the diaphragm and limb muscles in the rabbit; Liu M et al.; Aminoglycoside antibiotics are known to produce a depression of neuromuscular function which may cause prolonged paralysis of respiratory muscles . However, differences in the effects of aminoglycoside antibiotics on diaphragm and limb muscles have not been investigated . We determined the neuromuscular blocking effects of the aminoglycoside antibiotics arbekacin sulfate, astromicin sulfate, isepamicin sulfate and netilmicin sulfate on the diaphragm, tibialis anterior and soleus muscles in anesthetized rabbit nerve-muscle preparations . Neuromuscular block was assessed by mechanical response with single twitch stimulation . Cumulative drug dose-response curves were obtained for three different muscles in 24 rabbits . The mean ED(50) and ED(95) of the antibiotics in diaphragm, tibialis anterior and soleus muscles were calculated . The neuromuscular blocking effects of all the aminoglycosides on ED(50) and ED(95) values were in the order of soleus > tibialis anterior > diaphragm, and soleus > diaphragm > tibialis anterior, respectively . The ED(50) ratios for the tibialis anterior and soleus muscles were approximately 1.5 and 2.7 times greater than that for the diaphragm .

Biopolymers, 2000-2001, 56(2), 85 - 95
Structural basis of DNA recognition by anticancer antibiotics, chromomycin A(3), and mithramycin: roles of minor groove width and ligand flexibility; Chakrabarti S et al.; Anticancer antibiotics, chromomycin A(3) (CHR) and mithramycin (MTR), inhibit cellular processes like transcription and replication, by binding reversibly to double-stranded DNA via minor groove, in the presence of bivalent metal ions like Mg(2+) with GC base specificity . Here, we have attempted to assess the roles of two parameters-namely DNA groove dimension and flexibility of the ligand-in the structural recognition between the ligands, (drug)(2)Mg(2+) and DNA . For the purpose we have employed three synthetic oligonucleotides with minor groove width lying between B- and A-type structures as model DNA sequences: d(GCGCGCGC)(2) in B-form, d(CCGGCGCCGG)(2) in B-form with unusual wide minor groove, and (GGGGCCCC)(2) in A-form . Association of the (drug)(2)Mg(2+) with the oligomers have been probed using spectroscopic techniques like absorbance, fluorescence, and CD . The binding and thermodynamic parameters for the different association processes have also been characterized . Major conclusions from the above studies are as follows . Groove size of the oligomers influences the conformation of the bound ligand . A saccharide dependent variation in structural rigidity of the ligands, (MTR)(2)Mg(2+) and (CHR)(2)Mg(2+), has been observed that leads to differences in the energetics of recognition of the same DNA sequence by the two ligands . In contrast to (CHR)(2)Mg(2+), higher flexibility in (MTR)(2)Mg(2+) makes its conformation in the DNA bound form less sensitive to the groove dimension of DNA .

Eksp Klin Farmakol, 2001 Jul-Aug, 64(4), 68 - 72
{Biological evaluation of the effect of beta-lactam antibiotics on apoptosis in human lymphoid cells in vitro}; Reshetnikov SI et al.; Models are developed that allow the effect of beta-lactam antibiotics on the level of apoptosis in human lymphoid cells to be evaluated in vitro . The antibiotics produced a dose-dependent decrease in apoptosis of mature lymphocytes both under normal conditions and in the state of dexamethasone-induced immunodepression . The beta-lactam antibiotics also affect the apoptosis in a pre-B-lymphoblast model . The dexamethasone-induced apoptosis is inhibited by beta-lactam antibiotics only in high doses.

Curr Opin Microbiol, 2001 Oct, 4(5), 520 - 5
The role of combichem in antibiotic discovery; Trias J; Combinatorial chemistry (combichem) has had a significant impact on the discovery of new antibiotics . Most of the successes have come from the use of small libraries to explore a specific pharmacophore . However, large diverse libraries are more appropriate when identifying hits by screening specific bacterial or fungal targets . Combichem has been used to optimize new azole and oxazolidinone leads . An entirely new class of antibiotics, inhibitors of bacterial peptidyl-deformylase, has been discovered by combining mechanism-based drug design and combichem . These compounds are active in vivo . The impact of combichem on discovery projects that aim to develop new antibiotics for the treatment of infectious diseases is discussed.

Peptides, 2001 Oct, 22(10), 1661 - 8
Short peptides conferring resistance to macrolide antibiotics; Tenson T et al.; Translation of specific short peptides can render the ribosome resistant to macrolide antibiotics such as erythromycin . Peptides act in cis upon the ribosome on which they have been translated . Amino acid sequence and size are critical for peptide activity . Pentapeptides with different consensus sequences confer resistance to structurally different macrolide antibiotics, suggesting direct interaction between the peptide and the drug on the ribosome . Translation of resistance peptides may result in expulsion of the macrolide antibiotics from the ribosome . The consensus sequence of peptides conferring erythromycin resistance is similar to the sequence of the leader peptide involved in translational attenuation of erythromycin resistance genes, indicating that a similar type of interaction between the nascent peptide and antibiotics can occur in both cases.

Structure (Camb), 2001 Aug, 9(8), 707 - 16
Active transport of an antibiotic rifamycin derivative by the outer-membrane protein FhuA; Ferguson AD et al.; BACKGROUND: FhuA, an integral membrane protein of Escherichia coli, actively transports ferrichrome and the structurally related antibiotic albomycin across the outer membrane . The transport is coupled to the proton motive force, which energizes FhuA through the inner-membrane protein TonB . FhuA also transports the semisynthetic rifamycin derivative CGP 4832, although the chemical structure of this antibiotic differs markedly from that of ferric hydroxamates . RESULTS: X-ray crystallography revealed that rifamycin CGP 4832 occupies the same ligand binding site as ferrichrome and albomycin, thus demonstrating a surprising lack of selectivity . However, the binding of rifamycin CGP 4832 is deviant from the complexes of FhuA with hydroxamate-type ligands in that it does not result in the unwinding of the switch helix but only in its destabilization, as reflected by increased B factors . Unwinding of the switch helix is proposed to be required for efficient binding of TonB to FhuA and for coupling the proton motive force of the cytoplasmic membrane with energy-dependent ligand transport . The transport data from cells expressing mutant FhuA proteins indicated conserved structural and mechanistic requirements for the transport of both types of compounds . CONCLUSIONS: We conclude that the binding of rifamycin CGP 4832 destabilizes the switch helix and promotes the formation of a transport-competent FhuA-TonB complex, albeit with lower efficiency than ferrichrome . Active transport of this rifamycin derivative explains the 200-fold increase in potency as compared to rifamycin, which is not a FhuA-specific ligand and permeates across the cell envelope by passive diffusion only.

Eur J Emerg Med, 2001 Sep, 8(3), 181 - 8
Adherence to antibiotics prescribed in an accident and emergency department: the influence of consultation factors; Lam F et al.; The objective of this study was to investigate the extent of non-adherence to prescribed antibiotics and the relationship of non-adherence to consultation and attitudinal factors . Self-completion postal questionnaires were sent to 202 consecutive adult attenders to an accident and emergency (A&E) department who had been given antibiotics to take home, within a week of the A&E attendance . The questionnaire included a detailed log of dosing, two sections of eight questions each on the patients' perceptions of the consultation and of their attitudes to medicines in general, which were marked on Likert scales; and questions inviting free text answers . Efforts were made to maximize the response rate, and to contact a random sample of 10 non-responders to assess any non-response bias . The response rate was 56% . The non-responders sampled reported similar non-adherence to that of the responders . Of the 113 responders, 10 (9%) indicated that they had taken none of their prescribed medicines, and 25 (22%) that they had taken less than 80% . The most common pattern of non-adherence was early cessation . Two aspects of the consultation (expectations about a prescription, and that there were too many tablets) were related to adherence . In conclusion, this study suggests that the effectiveness of some A&E consultations is reduced by inadequate exploration of patients' concerns and expectations.

J Biomed Mater Res, 2001 Dec 5, 57(3), 321 - 6
Silica sol-gel for the controlled release of antibiotics . II . The effect of synthesis parameters on the in vitro release kinetics of vanomycin; Aughenbaugh W et al.; Room temperature-processed silica sol-gel (xerogel) was investigated as a novel controlled release carrier of vancomycin for the treatment of osteomyelitis . Vancomycin-loaded xerogels were fabricated with varying water/alkoxysilane molar ratios and vancomycin concentrations . The goal of this study was to determine the effect of varying the aforementioned synthesis parameters on the daily in vitro release kinetics of vancomycin from the xerogel disks . A controlled, load-dependent, long-term release of vancomycin was observed for all of the molar ratios that were used in the study (4, 6, and 10) . Variations in the water/alkoxysilane molar ratio affected the release process extensively . A cumulative release of about 90% of the original amount of vancomycin was found for molar ratios 6 and 10 by 21 and 14 days, respectively . Only about 30% was released from xerogels with a molar ratio of 4 after 21 days of immersion . A first-order release stage was followed by a steady release stage for xerogels with molar ratios of 6 and 10, whereas zero-order release was observed for xerogels with a molar ratio of 4 . The findings of this study indicate that the release kinetics of vancomycin from xerogel can be tailored by varying the xerogel synthesis parameters.

Artif Intell Med, 2001 Oct, 23(2), 171 - 86
Case-based reasoning for antibiotics therapy advice: an investigation of retrieval algorithms and prototypes; Schmidt R et al.; We have developed an antibiotics therapy advice system called ICONS for patients in an intensive care unit (ICU) who have caught an infection as additional complication . Since advice for such critically ill patients is needed very quickly and as the actual pathogen still has to be identified by the laboratory, we use an expected pathogen spectrum based on medical background knowledge and known resistances . The expected pathogen spectra and the resistance information are periodically updated from laboratory results . To speed up the process of finding suitable therapy recommendations, we have applied case-based reasoning (CBR) techniques . As all required information should always be up to date in medical expert systems, new cases should be incrementally incorporated into the case base and outdated ones should be updated or erased . For reasons of space limitations and of retrieval time an indefinite growth of the case base should be avoided . To fulfill these requirements we propose that specific single cases should be generalised to more general prototypical ones and that subsequent redundant cases should be erased . In this paper, we present evaluation results of different generation strategies for generalised cases (prototypes) . Additionally, we compare measured retrieval times for two indexing retrieval algorithms: simple indexing, which is appropriate for small and medium case bases, and tree-hash retrieval, which is advantageous for large case bases.

FEMS Microbiol Lett, 2001 Sep 25, 203(2), 191 - 7
An unusual beta-ketoacyl:acyl carrier protein synthase and acyltransferase motifs in TaK, a putative protein required for biosynthesis of the antibiotic TA in Myxococcus xanthus; Paitan Y et al.; The antibiotic TA of Myxococcus xanthus is produced by a type-I polyketide synthase mechanism . Previous studies have indicated that TA genes are clustered within a 36-kb region . The chemical structure of TA indicates the need for several post-modification steps, which are introduced to form the final bioactive molecule . These include three C-methylations, an O-methylation and a specific hydroxylation . In this study, we describe the genetic analysis of taK, encoding a specific polyketide beta-ketoacyl:acyl carrier protein synthase, which contains an unusual beta-ketoacyl synthase and acyltransferase motifs and is likely to be involved in antibiotic TA post-modification . Functional analysis of this beta-ketoacyl:acyl carrier protein synthase by specific gene disruption suggests that it is essential for the production of an active TA molecule.

Am J Med, 2001 Oct 1, 111(5), 361 - 6
Antibiotic use and risk of ischemic stroke in the elderly; Luchsinger JA et al.; PURPOSE: To determine whether treating infections with antibiotics that have antichlamydial activity decreases the risk of ischemic stroke in the elderly . SUBJECTS: We analyzed data from 199 553 subjects 65 years and older in a health care claims database who had continuous health and pharmacy coverage for at least 2 years between January 1, 1991, and September 30, 1997 . Using proportional hazards models with time-dependent covariates for prior antibiotic prescription and adjusting for cardiovascular risk factors, we determined the associations between antibiotic use and first claim for ischemic stroke (n = 7,335) during the observation period . RESULTS: Rates of stroke (per 1,000 person-years) were 6.64 for macrolides, 9.27 for quinolones, 7.49 for tetracyclines, 6.88 for penicillins, 7.97 for cephalosporins, 8.58 for trimethoprim-sulfamethoxazole, and 7.29 for subjects with no antibiotic claims . The adjusted hazard ratios (HR) were 0.94 (95% confidence interval {CI}: 0.87 to 1.01) for macrolides, 1.04 (95% CI: 0.91 to 1.18) for tetracyclines, 1.02 (95% CI: 0.95 to 1.08) for penicillins, and 1.00 (95% CI: 0.82 to 1.22) for trimethoprim-sulfamethoxazole . Subjects with claims for quinolone antibiotics (HR = 1.17; 95% CI: 1.09 to 1.26) and cephalosporins (HR = 1.09; 95% CI: 1.02 to 1.16) had a slightly higher risk of stroke . CONCLUSION: Exposures to short courses of antibiotics are not associated with lower risk of ischemic stroke in patients aged 65 years and older.

Eur Arch Otorhinolaryngol, 2001 Aug, 258(6), 287 - 91
A topical steroid without an antibiotic cures external otitis efficiently: a study in an animal model; Emgard P et al.; In an animal external otitis model, inflammatory reactions were evoked by mechanical stimulation of the rat ear canal skin . The rats were in four groups: group A treated with a group III steroid, betamethasone dipropionate; group B treated with hydrocortisone combined with oxytetracycline; group C treated with hydrocortisone with oxytetracycline and polymyxin B added; Group D, the controls, treated with saline . All rats were observed otomicroscopically daily during the first 7 days after treatment and then on days 10 and 20 . A standardized scoring system was used to evaluate colour, swelling and effusion of the ear canal . Histological specimens were collected on days 3, 7, 10 and 20 . The most rapid improvement in the ear canal status occurred in the animals treated with betamethasone dipropionate . The inflammatory reaction of the ear canal skin caused by mechanical stimulation was characterized by oedema of the stroma but few inflammatory cells were present . The surface of the epithelium towards the connective tissue layer was smooth in the group III-treated animals (group A) whereas other groups had irregularities of the basal membrane . From this study it is inferred that the group III steroid betamethasone dipropionate alone heals experimentally induced external otitis more rapidly than hydrocortisone with oxytetracycline, with or without polymyxin B . These findings should be considered in future clinical trials of external otitis.

Swiss Med Wkly, 2001 Jul 28, 131(29-30), 438 - 41
Use of broad spectrum antibiotics in six non-university Swiss hospitals; von Gunten V et al.; PRINCIPLES: Broad-spectrum antibiotics (BSAs) are costly and prone to misuse . Their use is associated with the emergence of resistant bacteria . This article describes the first step of an interhospital programme for the appropriate use of BSAs . METHODS: BSAs were defined as the i.v . antibiotics present in the formulary shared by the six participating institutions and considered to be antipseudomonal agents (i.e . cefepime, ceftazidime, ciprofloxacin, imipenem, meropenem, piperacillin/tazobactam) plus trovafloxacin . Annual utilisation rates and interhospital comparisons were provided to each institution using the "defined daily dosages" (DDDs) of the World Health Organization . RESULTS: From 1997 to 1999, the overall utilisation rate of BSAs increased from 20.6 treatment days (TD)/1000 patient days (PD) to 36.5 TD/1000 PD . Significant interhospital differences were detected (range: 12.1 TD/1000 PD in 1997-66.5 TD/1000 PD in 1999) . The highest relative risk for treatment with any BSA for each individual hospital in comparison to the others was determined for 1999 (RR = 2.92; 95% confidence interval: 2.81-3.04) . In 1999, the most frequently used BSAs were cefepime, imipenem, and piperacillin/tazobactam respectively . CONCLUSIONS: Although this programme does not provide information on the indications for using BSAs in various hospitals, it helps to identify those institutions where the selection pressure for resistant bacteria is highest, and that could particularly benefit from specific interventions aiming at decreasing this pressure and controlling drug expenditure . Moreover, the feedback of utilisation rates and interhospital comparisons to the prescribing physicians might have a positive impact on BSA use.

Eur J Public Health, 2001 Sep, 11(3), 280 - 3
Socioeconomic differences in use of medical care and antibiotics among schoolchildren in Sweden; Hjern A et al.; BACKGROUND: Studies of mortality among children and adults in Sweden have demonstrated considerable socioeconomic differences . This paper describes socioeconomic patterns of physical morbidity and use of medical care and antibiotics in schoolchildren in Sweden . METHODS: A cross-sectional study based on parent interviews from the Swedish Survey of Living Conditions in 1996-1997 was used . The study population consisted of 3,557 children aged 6-15 years . RESULTS: Forty-five percent of the schoolchildren in the study were reported to have been absent from school because of illness at least once during the previous three months, 8% were taking regular medication and 10% had ever suffered from a chronic disorder . There were no indications of socioeconomic differences according to the education of the responding parent in morbidity or use of consultations with a physician . However, children in families where the responding parents had primary education only consumed antibiotics less often (OR 0.7 and CI: 0.5-0.9) when compared to children in families with post-secondary education . Children in rural areas used consultations with a physician less often and consumed less antibiotics (adjusted OR 0.7 and CI: 0.4-0.9 and 0.7 and CI: 0.5-0.9 respectively) . CONCLUSION: No obvious patterns of socioeconomic inequality in physical morbidity or use of medical care were identified among schoolchildren in Sweden . Further studies are needed in order to explain the social inequality in consumption of antibiotics among schoolchildren in Sweden and to describe social and regional patterns of psychiatric, behavioural and psychosomatic morbidity.

Eur J Public Health, 2001 Sep, 11(3), 260 - 3
Telephone prescribing of antibiotics . General practitioners' views and reflections; Bjornsdottir I et al.; BACKGROUND: In this era of increasing problems with resistance, rational prescribing of antibiotics is extremely important . Therefore, rationales for prescribing require analyses . The objective of this study was to explore general practitioners' (GPs') reasons for prescribing antibiotics by telephone . METHODS: Qualitative analysis of semistructured interviews with and observations of GPs in Iceland enquiring about the rationale for prescribing antibiotics was used . Ten GPs were interviewed for 45 min to 2 h each including three who were observed between 3 and 10 h . RESULTS: The GPs generally indicated a restrictive attitude to telephone prescribing, although they all gave examples of their prescribing by telephone . The prescribing was mostly but not always based on some kind of diagnosis . The factors influencing diagnosis and prescribing were largely non-clinical: knowledge of the patients as persons, including their complaint threshold, confidence in their descriptions, the GPs' communication strategies and the travelling distance between patients and GPs . The clinical factors were the patients' description of signs and symptoms and knowledge of their history . Prescriptions not based on diagnosis were 'therapeutic trial' or GP-approved self-medication . Sometimes, the GPs requested to see a patient even though the diagnosis was based on history, signs and symptoms . CONCLUSIONS: Multiple factors affected the decision-making process when antibiotics were prescribed by telephone, most of which were non-clinical . The diagnosis, if there was one, was generally presumptive . GPs' general attitudes correlated well with current knowledge but were contrasted by the reality of their daily work conditions.

Pediatrics, 2001 Oct, 108(4), 845 - 50
Improving parent knowledge about antibiotics: a video intervention; Bauchner H et al.; OBJECTIVE: To determine whether an educational video could improve parent knowledge, beliefs, and behaviors about the appropriate use of oral antibiotics . STUDY DESIGN: A randomized, controlled trial was conducted in an urban primary care clinic and a suburban pediatric practice . Parents were randomly assigned to the intervention or control groups . Parents in the intervention group were asked to view a 20-minute video, specifically developed for this project, over a 2-month period, and given a brochure about antibiotics . Parent knowledge, beliefs, and behaviors were assessed at the time of enrollment and then by telephone 2 months later . RESULTS: A total of 193 (94%) of 206 parents completed the study . The groups were equivalent with respect to all important baseline characteristics . No differences were found for adjusted posttest means between the intervention and control groups for knowledge, beliefs, or behavior . For example, the intervention group scored 8.04 on the knowledge questionnaire (11 true-false questions), compared with 7.82 for the control group . Subgroup analysis, based on site of enrollment, indicated that families in the intervention group from the primary care urban clinic improved their knowledge score (6.03 to 6.92) and were more likely to report that there were problems with children receiving too many antibiotics (intervention 67% vs control 34%) . CONCLUSION: Overall, this video had only a modest effect on parent knowledge, beliefs, and self-reported behaviors regarding oral antibiotics . We believe that any campaign promoting the judicious use of oral antibiotics must use a multifaceted approach and target both parents and physicians.

J Neurochem, 2001 Sep, 78(6), 1409 - 14
Tetracycline derivatives and ceftriaxone, a cephalosporin antibiotic, protect neurons against apoptosis induced by ionizing radiation; Tikka T et al.; DNA damage induced by low doses of ionizing radiation causes apoptosis, which is partially mediated via the generation of free radicals . Both free radicals and apoptosis are involved in the majority of brain diseases, including stroke, Alzheimer's disease and amyotrophic lateral sclerosis . Because previous studies have shown that tetracycline derivatives doxycycline and minocycline have anti-inflammatory effects and are protective against brain ischemia, we studied whether minocycline and doxycycline or ceftriaxone, a cephalosporin antibiotic with the potential to inhibit excitotoxicity, protect neurons against ionizing radiation in primary cortical cultures . A single dose of 1 Gy significantly increased lactate dehydrogenase release, induced DNA fragmentation in neurons and triggered microglial proliferation . Treatment with minocycline (20 nM), doxycycline (20 nM) and ceftriaxone (1 microM) significantly reduced irradiation-induced lactate dehydrogenase release and DNA fragmentation . The most efficient protection was achieved by minocycline treatment, which also inhibited the irradiation-induced increase in microglial cell number . Our results suggest that some tetracycline derivatives, such as doxycycline and minocycline, and ceftriaxone, a cephalosporin derivative, protect neurons against apoptotic death.

Altern Med Rev, 2001 Aug, 6(4), 355 - 66
Helicobacter pylori eradication: are there alternatives to antibiotics?
Gaby AR.
It is now generally accepted that infection with Helicobacter pylori is an important cause of peptic ulcer disease and that eradication of this organism greatly reduces the recurrence rate of ulcers . H . pylori also can cause chronic gastritis and hypochlorhydria and is a risk factor for gastric cancer . Conventional eradication therapies, which consist of two antibiotics plus either a proton-pump inhibitor or a bismuth compound, are highly effective, but can cause significant side effects in some cases . Alternative methods of eradicating H . pylori are therefore being investigated . To date, the research in this area is still preliminary, and no treatment has emerged as a clear alternative to the conventional triple-therapy regimens.

Br Dent J, 2001 Sep 8, 191(5), 253 - 5
Can audit improve antibiotic prescribing in general dental practice?
Palmer NA, Dailey YM, Martin MV.
OBJECTIVE: To investigate whether clinical audit can improve general dental practitioners' prescribing of antibiotics . DESIGN: An intervention study carried out in general dental practice in the North West of England . METHOD: Information was collected over an initial six-week period from 175 general dental practitioners on their current antibiotic prescribing practices . The information collected was the antibiotic prescribed including dose, frequency and duration, the clinically presenting signs and conditions, the medical history (if for prophylaxis), and any other reasons for prescribing . This was compared to the practitioners' antibiotic prescribing for a further six-week period following an audit, which included an educational component and the issuing of guidelines . RESULTS: During the initial period practitioners issued 2316 prescriptions for antibiotics . This was reduced by 42.5% to 1330 during the audit . The majority of the antibiotics (81%) for both periods were prescribed for therapeutic reasons . The most commonly prescribed antibiotics were amoxycillin (57.6%), metronidazole (23.8%), penicillin (9.3%), erythromycin (4.8%) and a combination of amoxycillin and metronidazole (1.7%) . The antibiotic regimens used by practitioners were significantly changed by the audit (P<0.001) and there was a significant reduction in the number of prescriptions (P<0.05) which did not conform to national guidelines . CONCLUSIONS: The results from this investigation support the conclusion that clinical audit, with the issuing of guidelines and an educational component, can change prescribing practices leading to a more rational and appropriate use of antibiotics in general dental practice.

Int J Antimicrob Agents, 2001, 18 Suppl 1, S93 - 7
New perspectives on macrolide antibiotics; Pechere JC; Macrolides are not used exclusively for the treatment of community-acquired respiratory tract infections . Their ability to penetrate cells makes them highly suitable for the treatment of diseases caused by intracellular pathogens, such as non-gonococcal urethritis and trachoma . Azithromycin is approved for these indications . Clinical studies have also been conducted, or are currently being carried out, to assess the use of macrolides in the treatment of atherosclerosis, eradication of Helicobacter pylori and the management of life-threatening gastrointestinal diseases, cystic fibrosis and malaria.

Int J Antimicrob Agents, 2001, 18 Suppl 1, S49 - 55
The place of antibiotic therapy in the management of chronic acute exacerbations of chronic bronchitis; Akalin HE; In the USA, more than 16 million adults are affected by chronic obstructive pulmonary disease, and chronic bronchitis has been estimated to affect up to 13 million individuals or approximately 4-6% of adults . Chronic bronchitis is an increasing cause of significant morbidity and mortality . During acute exacerbations of chronic bronchitis, subjects experience a worsening of bronchitic symptoms, with an increase from baseline in one or more or the following; dyspnoea, cough and/or sputum volume, purulence or viscosity . The severity of an exacerbation can be graded by how many of these symptoms are present . Antibiotic therapy should be initiated based on patient history and severity of the exacerbation.

J Bacteriol, 2001 Oct, 183(20), 6009 - 16
Molecular and functional analyses of the gene (eshA) encoding the 52-kilodalton protein of Streptomyces coelicolor A3(2) required for antibiotic production; Kawamoto S et al.; Analysis of proteins recovered in the S100 precipitate fraction of Streptomyces griseus after ultracentrifugation led to the identification of a 52-kDa protein which is produced during the late growth phase . The gene (eshA) which codes for this protein was cloned from S . griseus, and then its homologue was cloned from Streptomyces coelicolor A3(2) . The protein was deduced to be 471 amino acids in length . The protein EshA is characterized by a central region that shows homology to the eukaryotic-type cyclic nucleotide-binding domains . Significant homology was also found to MMPI in Mycobacterium leprae, a major antigenic protein to humans . The eshA gene mapped near the chromosome end and was not essential for viability, as demonstrated by gene disruption experiments, but its disruption resulted in the abolishment of an antibiotic (actinorhodin but not undecylprodigiosin) production . Aerial mycelium was produced as abundantly as by the parent strain . Expression analysis of the EshA protein by Western blotting revealed that EshA is present only in late-growth-phase cells . The eshA gene was transcribed just preceding intracellular accumulation of the EshA protein, as determined by S1 nuclease protection, indicating that EshA expression is regulated at the transcription level . The expression of EshA was unaffected by introduction of the relA mutation, which blocks ppGpp synthesis.

J Pediatr, 2001 Sep, 139(3), 380 - 4
Maternal and infant use of erythromycin and other macrolide antibiotics as risk factors for infantile hypertrophic pyloric stenosis; Mahon BE et al.; OBJECTIVES: To evaluate the risk for infantile hypertrophic pyloric stenosis (IHPS) among infants prescribed systemic erythromycin, infants prescribed a course of erythromycin ophthalmic ointment, and infants whose mothers were prescribed a macrolide antibiotic during pregnancy . STUDY DESIGN: Retrospective cohort study of infants born at an urban hospital from June 1993 through December 1999 . RESULTS: Of 14,876 eligible infants, 43 (0.29%) developed IHPS . Infants prescribed systemic erythromycin had increased risk of IHPS, with the highest risk in the first 2 weeks of age (relative risk = 10.51 for erythromycin in first 2 weeks, 95% CI 4.48, 24.66) . Erythromycin ophthalmic ointment for conjunctivitis was not associated with increased risk of IHPS . Maternal macrolide antibiotics within 10 weeks of delivery may have been associated with higher risk of IHPS but the data were not conclusive . CONCLUSIONS: This study confirms an association between systemic erythromycin in infants and subsequent IHPS, with the highest risk in the first 2 weeks of age . No association was found with erythromycin ophthalmic ointment . A possible association with maternal macrolide therapy in late pregnancy requires further study . Systemic erythromycin should be used with prudence in early infancy.

J Microbiol Immunol Infect, 1999 Mar, 32(1), 1 - 8
A multicenter study on eradication of Helicobacter pylori infection in patients with duodenal ulcer by lansoprazole-antibiotics combined therapy; Yang JC et al.; The aim of this prospective randomized multicenter study was to find out if there is one or several promising regimens containing lansoprazole with various combinations of antibiotics which have a high eradication rate of Helicobacter pylori, few side-effects, good patient compliance, and relative low cost if possible . Two hundred and ninety-seven patients with H . pylori positive duodenal ulcer were enrolled and randomly allocated into one of the five treatment groups: 1) group A: received lansoprazole 30 mg once daily for 2 weeks plus amoxicillin (AM) 500 mg and metronidazole (MZ) 500 mg twice daily for one week in the first week; 2) group B: the AM in group A was replaced by clarithromycin (CM) 250 mg; 3) group C: the MZ in group A was replaced by CM 250 mg; 4) group D: the AM and CM in group C was used for 2 wk; 5) group E: the CM in group D was doubled to 500 mg twice daily . All patients received endoscopies pre- and 4-6 weeks post termination of treatment . H . pylori was detected by culture, histology and rapid urease test (CLO test) . 13C-urea breath test was performed if the patients refused the second endoscopy . The E-test was adopted to evaluate the MZ and CM resistance of H . pylori . Totally, 253 patients completed the study . The eradication rate of groups A, B, C, D and E were 75%, 80%, 78%, 92%, and 96%, respectively . The eradication rate of group E was significantly higher than that of groups A, B, or C . There were no significant differences of eradication rates between the groups D and E . Sixty-seven cases (28.8%) were MZ-resistant . The difference of eradication rates between MZ-S and MZ-R patients was significant in group A (85.3% vs . 42.9%) and in the combination of groups A and B (83.8% vs . 59.4%) . Good compliance (defined as taking > 90% of medications) was seen in more than 90% of cases in each group . Triple therapy containing lansoprazole 30 mg once daily, AM 500 mg and CM 250 mg twice daily for two weeks is a promising regimen which reaches a high eradication rate, avoids MZ resistance, and has very good patient compliance at an acceptable cost.

Biochemistry, 2001 Sep 25, 40(38), 11578 - 85
Association of the anticancer antibiotic chromomycin A(3) with the nucleosome: role of core histone tail domains in the binding process; Mir MA et al.; The anticancer antibiotic chromomycin A(3) is a transcription inhibitor which forms two types of complexes with Mg(2+): complex I (1:1 in terms of chromomycin A(3)-Mg(2+)) and complex II (2:1 in terms of chromomycin A(3)-Mg(2+)) . These complexes are the DNA-binding ligands . With the broad objective of elucidation of the mechanism for action of this group of transcription inhibitors in eukaryotic systems, we have studied the interaction of the antibiotic with nucleosome core particles under different conditions . We have demonstrated and characterized the role of core histone proteins, particularly the N-terminal tail domains, in the association of nucleosome with both complexes of chromomycin . From a scrutiny of the spectroscopic features of the two bound complexes and comparison of the binding and associated thermodynamic parameters, we have shown the following . Core histone(s) stand(s) in the way of access of the ligand(s) to nucleosomal DNA . N-Terminal intact and chopped core particles interact differentially with the same complex . The modes of interaction of the two complexes, I and II, with the same system are different . Tryptic removal of N-terminal tail domains of core histones enhances the binding potential and access of both complexes of chromomycin to the nucleosomal DNA . Agarose gel electrophoresis of an equilibrium mixture containing either complex I or complex II and a saturating concentration of the core particle has demonstrated that both complexes have a tendency to disrupt the nucleosome structure, leading to a release of nucleosomal DNA . Compared to the N-terminal intact nucleosome, the N-terminal chopped nucleosome is more susceptible to disruption . Therefore, we suggest from the above results that the N-terminal tail domains, which have an important role in eukaryotic gene expression, stand in the way of a free access of external agents such as anticancer drugs to the eukaryotic genome . The significance of the results to understand the molecular basis of the transcription inhibitory capacity of chromomycin is discussed.

J Antibiot (Tokyo), 2001 Jul, 54(7), 588 - 94
FR901469, a novel antifungal antibiotic from an unidentified fungus No . 11243 . III . Structure determination; Fujie A et al.; A novel antifungal antibiotic, FR901469, was isolated from an unidentified fungus No . 11243 . It is a water-soluble 40-membered macrocyclic lipopeptidolactone, consisting of D-Ala, L-Tyr, L-Val, trans-4OH-L-Pro, trans-3OH-L-Pro, threo-3OH-L-Gln, Gly, L-Orn, L-Thr, three residues of D-alloThr and a (3R)-hydroxypalmitic acid . Its structure, including absolute configurations, was unequivocally determined as 1 based on chemical and spectroscopic evidence.

J Biol Chem, 2001 Nov 23, 276(47), 44297 - 306 Epub 2001 Sep 13.
Pleiotropic functions of a Streptomyces pristinaespiralis autoregulator receptor in development, antibiotic biosynthesis, and expression of a superoxide dismutase; Folcher M et al.; In Streptomyces, a family of related butyrolactones and their corresponding receptor proteins serve as quorum-sensing systems that can activate morphological development and antibiotic biosynthesis . Streptomyces pristinaespiralis contains a gene cluster encoding enzymes and regulatory proteins for the biosynthesis of pristinamycin, a clinically important streptogramin antibiotic complex . One of these proteins, PapR1, belongs to a well known family of Streptomyces antibiotic regulatory proteins . Gel shift assays using crude cytoplasmic extracts detected SpbR, a developmentally regulated protein that bound to the papR1 promoter . SpbR was purified, and its gene was cloned using reverse genetics . spbR encoded a 25-kDa protein similar to Streptomyces autoregulatory proteins of the butyrolactone receptor family, including scbR from Streptomyces coelicolor . In Escherichia coli, purified SpbR and ScbR produced bound sequences immediately upstream of papR1, spbR, and scbR . SpbR DNA-binding activity was inhibited by an extracellular metabolite with chromatographic properties similar to those of the well known gamma-butyrolactone signaling compounds . DNase I protection assays mapped the SpbR-binding site in the papR1 promoter to a sequence homologous to other known butyrolactone autoregulatory elements . A nucleotide data base search showed that these binding motifs were primarily located upstream of genes encoding Streptomyces antibiotic regulatory proteins and butyrolactone receptors in various Streptomyces species . Disruption of the spbR gene in S . pristinaespiralis resulted in severe defects in growth, morphological differentiation, pristinamycin biosynthesis, and expression of a secreted superoxide dismutase.

Antimicrob Agents Chemother, 2001 Oct, 45(10), 2958 - 60
Two new point mutations at A2062 associated with resistance to 16-membered macrolide antibiotics in mutant strains of Mycoplasma hominis; Furneri PM et al.; We describe two mutants of Mycoplasma hominis PG-21 which show resistance to 16-membered macrolides but susceptibility to lincosamides, obtained by in vitro exposure to increasing doses of josamycin . The 23S rRNA gene showed that each had a mutation (A2062G and A2062T) corresponding to nucleotide 2062 in Escherichia coli, which was associated with the acquired phenotype.

Antimicrob Agents Chemother, 2001 Oct, 45(10), 2939 - 42
Antioxidant functions required for insusceptibility of Saccharomyces cerevisiae to tetracycline antibiotics; Angrave FE et al.; Cu,Zn superoxide dismutase (Sod1) is required for insusceptibility of Saccharomyces cerevisiae to oxytetracycline (OTC) . Here we report that Sod1 is also required for insusceptibility to doxycycline (DOX) . Furthermore, among a range of antioxidant and redox balance mutants, mac1 and ctr1 deletion strains exhibited marked sensitization to OTC and DOX . Certain mutants exhibited a slight sensitivity to methacycline and minocycline . Addition of copper suppressed antibiotic sensitivity . Thus, intracellular copper as well as superoxide dismutase can be critical for eukaryotic tolerance of several tetracycline antibiotics.

Bioorg Med Chem, 2001 Oct, 9(10), 2557 - 63
Aptamers that bind to the antibiotic moenomycin A; Schurer H et al.; Nuclease-resistant moenomycin-binding aptamers with dissociation constants in the range of 300 to 400 nM have been selected . Competition experiments have demonstrated that these aptamers recognize a disaccharide analogue of moenomycin . The results offer the opportunity of setting up a selective and sensitive assay for identifying moenomycin biosynthetic precursors.

J Gen Intern Med, 2001 Sep, 16(9), 599 - 605
What factors influence physicians' decisions to switch from intravenous to oral antibiotics for community-acquired pneumonia?
Halm EA, Switzer GE, Mittman BS, Walsh MB, Chang CC, Fine MJ.
OBJECTIVE: One of the major factors influencing length of stay for patients with community-acquired pneumonia is the timing of conversion from intravenous to oral antibiotics . We measured physician attitudes and beliefs about the antibiotic switch decision and assessed physician characteristics associated with practice beliefs . DESIGN: Written survey assessing attitudes about the antibiotic conversion decision . SETTING: Seven teaching and non-teaching hospitals in Pittsburgh, Pa . PARTICIPANTS: Three hundred forty-five generalist and specialist attending physicians who manage pneumonia in 7 hospitals . MEASUREMENTS AND RESULTS: Factors rated as "very important" to the antibiotic conversion decision were: absence of suppurative infection (93%), ability to maintain oral intake (79%), respiratory rate at baseline (64%), no positive blood cultures (63%), normal temperature (62%), oxygenation at baseline (55%), and mental status at baseline (50%) . The median thresholds at which physicians believed a typical patient could be converted to oral therapy were: temperature < or =100 degrees F (37.8 degrees C), respiratory rate < or =20 breaths/minute, heart rate < or =100 beats/minute, systolic blood pressure > or =100 mm Hg, and room air oxygen saturation > or =90% . Fifty-eight percent of physicians felt that "patients should be afebrile for 24 hours before conversion to oral antibiotics," and 19% said, "patients should receive a standard duration of intravenous antibiotics." In univariate analyses, pulmonary and infectious diseases physicians were the most predisposed towards early conversion to oral antibiotics, and other medical specialists were the least predisposed, with generalists being intermediate (P <.019) . In multivariate analyses, practice beliefs were associated with age, inpatient care activities, attitudes about guidelines, and agreeableness on a personality inventory scale . CONCLUSIONS: Physicians believed that patients could be switched to oral antibiotics once vital signs and mental status had stabilized and oral intake was possible . However, there was considerable variation in several antibiotic practice beliefs . Guidelines and pathways to streamline antibiotic therapy should include educational strategies to address some of these differences in attitudes.

Arch Otolaryngol Head Neck Surg, 2001 Sep, 127(9), 1093 - 8
Efficacy of a stepwise protocol that includes intravenous antibiotic therapy for the management of chronic sinusitis in children and adolescents; Don DM et al.; BACKGROUND: Recent concern regarding interference with facial skeletal growth and the risk of complications after endoscopic sinus surgery (ESS) has led to interest in exploring other treatment options for the management of chronic sinusitis in children . OBJECTIVE: To present the use of a stepwise protocol that includes intravenous (IV) antibiotic therapy as a therapeutic alternative to pediatric ESS . DESIGN: Retrospective analysis of pediatric patients with chronic sinusitis treated from January 1, 1993, to July 1, 1998, with a stepwise protocol that includes the use of IV antibiotics . SETTING: Academic tertiary care children's hospital . PATIENTS: Seventy patients, aged 10 months to 15 years, with the diagnosis of chronic sinusitis as defined by symptomatic disease for at least 12 weeks . All patients had persistent symptoms and radiographic evidence of sinus disease by computed tomographic scan after a minimum 3- to 4-week course of oral antibiotics . INTERVENTIONS: Patients were treated with maxillary sinus aspiration and irrigation with selective adenoidectomy, followed by a 1- to 4-week course of a culture-directed IV antibiotic . Most patients also underwent placement of a long-arm IV catheter . OUTCOME MEASURES: Medical charts were reviewed for clinical response to IV antibiotics, complications from IV antibiotic therapy, need for ESS, and recurrent episodes of sinusitis . RESULTS: Of the 70 patients studied, 62 (89%) had complete resolution of symptoms following IV therapy with selective adenoidectomy . Eight patients (11%) failed IV therapy and required ESS . Thirty-seven patients (53%) underwent concurrent adenoidectomy . Patients treated with concurrent adenoidectomy had equivocal response rates compared with patients treated with IV antibiotic therapy alone . Follow-up data were available for 52 patients (range, 6-62 months; mean, 25 months) . All recurrent episodes resolved with oral antibiotic therapy . Complications from IV therapy included superficial thrombophlebitis in 6 patients (9%) and dislodgement of a catheter guidewire during placement in 1 patient (1%), requiring venotomy . Antibiotic-related complications also occurred in 3 patients (4%) and included serum sickness, pseudomembranous colitis, and drug fevers . CONCLUSION: A stepwise protocol that includes IV antibiotic therapy is a safe and efficacious mode of therapy for the management of chronic sinusitis in children and adolescents and may be a reasonable alternative to pediatric ESS.

Otolaryngol Head Neck Surg, 2001 Sep, 125(3), 265 - 9
Treatment of chronic rhinosinusitis refractory to other treatments with topical antibiotic therapy delivered by means of a large-particle nebulizer: results of a controlled trial; Desrosiers MY et al.; OBJECTIVE: To study the efficacy of nebulized topical saline-tobramycin solution in patients with chronic rhinosinusitis refractory to medical and surgical therapy . STUDY DESIGN AND SETTING: Twenty patients in whom endoscopic sinus surgery failed to relieve symptoms entered a randomized, double-blind trial of tobramycin-saline solution or saline-only solution administered thrice daily to the nasal passages by means of a large-particle nebulizer apparatus for 4 weeks, followed by a 4-week observation period . Outcome measures of symptoms, quality of life, and endoscopic aspect of sinus mucosa were assessed . RESULTS: Both treatments were well tolerated and produced equivalent improvement in symptoms, quality of life, and mucosal aspect . Treatment with the tobramycin-saline solution gave more rapid improvement of pain, but led to the development of nasal congestion . CONCLUSION: Therapy with a 4-week course of large-particle nebulized aerosol therapy improves symptomatology and objective parameters of rhinosinusitis in patients refractory to surgical and medical therapies . Addition of tobramycin appears of minimal benefit . The mechanism of this effect is unexplained . SIGNIFICANCE: Large-particle nebulized aerosol therapy may offer a safe and effective management alternative for patients with refractory rhinosinusitis.

Mol Microbiol, 2001 Sep, 41(5), 1015 - 28
A complex role for the gamma-butyrolactone SCB1 in regulating antibiotic production in Streptomyces coelicolor A3(2); Takano E et al.; Many streptomycetes produce extracellular gamma-butyrolactones . In several cases, these have been shown to act as signals for the onset of antibiotic production . Synthesis of these molecules appears to require a member of the AfsA family of proteins (AfsA is required for A-factor synthesis of the gamma-butyrolactone A-factor and consequently for streptomycin production in Streptomyces griseus) . An afsA homologue, scbA, was identified in Streptomyces coelicolor A3(2) and was found to lie adjacent to a divergently transcribed gene, scbR, which encodes a gamma-butyrolactone binding protein . Gel retardation assays and DNase I footprinting studies revealed DNA binding sites for ScbR at - 4 to - 33 nt with respect to the scbA transcriptional start site, and at - 42 to - 68 nt with respect to the scbR transcriptional start site . Addition of the gamma-butyrolactone SCB1 of S . coelicolor resulted in loss of the DNA-binding ability of ScbR . A scbA mutant produced no gamma-butyrolactones, yet overproduced two antibiotics, actinorhodin (Act) and undecylprodigiosin (Red), whereas a deletion mutant of scbR also failed to make gamma-butyrolactones and showed delayed Red production . These phenotypes differ markedly from those expected by analogy with the S . griseus A-factor system . Furthermore, transcription of scbR increased, and that of scbA was abolished, in an scbR mutant, indicating that ScbR represses its own expression while activating that of scbA . In the scbA mutant, expression of both genes was greatly reduced . Addition of SCB1 to the scbA mutant induced transcription of scbR, but did not restore scbA expression, indicating that the deficiency in scbA transcription in the scbA mutant is not solely due to the inability to produce SCB1, and that ScbA is a positive autoregulator in addition to being required for gamma-butyrolactone production . Overall, these results indicate a complex mechanism for gamma-butyrolactone-mediated regulation of antibiotic biosynthesis in S . coelicolor.

J Am Geriatr Soc, 2001 Aug, 49(8), 1020 - 4
Antibiotic use, hospital admissions, and mortality before and after implementing guidelines for nursing home-acquired pneumonia; Naughton BJ et al.; OBJECTIVES: To compare two strategies for implementing guidelines for nursing home-acquired pneumonia (NHAP) and to measure outcomes associated with treatment in accordance with the guidelines . DESIGN: Randomized controlled trial . SETTING: Ten skilled nursing facilities (SNFs) from a single metropolitan area . PARTICIPANTS: Patients with an episode of pneumonia acquired more than 3 days after admission to SNF (N = 350): 226 preintervention episodes of pneumonia and 116 postintervention episodes . INTERVENTIONS: Multi-faceted education intervention including small-group consensus process limited to physicians and a similar intervention that included physicians and nurses within randomly selected SNFs . MEASUREMENTS: Antibiotic use at diagnosis compared with the guidelines, hospital admission, severity of pneumonia, and 30-day mortality . RESULTS: Data were complete for 344 episodes of NHAP . For the preintervention group (n = 226), 62.2% (79/127) of the episodes were treated with parenteral antibiotics (PA) when PA were recommended by the guidelines and 57.6% (57/99) of episodes were treated with oral antibiotics (OA) when OA were indicated by the guidelines . Postintervention, treatment with PA and OA according to the guidelines was not significantly different between the two groups of randomized SNFs . A multivariate analysis comparing PA use pre- and postintervention for all SNFs, adjusted for variation in the frequency and severity of pneumonia, found significantly more of the postintervention episodes were treated with PA in accordance with the guidelines (P < .02) . A preintervention significant difference in 30-day mortality observed between episodes with indications for PA (37.8% (48/127)) and episodes with indications for OA (6.1% (6/99)) (P < .001) was not present postintervention (11.5% (6/52); (23.8% (15/64); P = .06) . There was no significant difference in 30-day mortality preintervention and postintervention for episodes with guideline indications for OA (P = .35) or for PA (P = .05) (P = .16 for multivariate analysis) . The difference in PA use was not associated with significant differences in hospital admissions for episodes on NHAP . CONCLUSION: The increase in the use of PA provides evidence that care within SNFs can be significantly changed using standard quality improvement techniques . Use of the guidelines did not significantly affect mortality . The addition of a practical severity of NHAP model or a change in reimbursement structure may enhance the guidelines' impact on hospitalization for NHAP . The financial benefits available with use of the guidelines will be limited unless the guidelines contribute to a reduction in rates of hospitalization.

Aliment Pharmacol Ther, 2001 Sep, 15(9), 1493 - 7
Comparison of 1-week vs . 2- or 4-week therapy regimens with ranitidine bismuth citrate plus two antibiotics for Helicobacter pylori eradication; Kamberoglou D et al.; BACKGROUND: Helicobacter pylori eradication therapies based on ranitidine bismuth citrate have recently been introduced in clinical practice . AIM: To compare the efficacy of three regimens containing ranitidine bismuth citrate given for 1, 2 and 4 weeks, combined with two antibiotics for the first week, in the eradication of H . pylori . METHODS: Eighty-six consecutive patients (50 duodenal ulcer disease, 36 non-ulcer dyspepsia) with H . pylori infection were offered three eradication regimens: (a) 1-week group (n=28), ranitidine bismuth citrate 400 mg b.d . for 7 days; (b) 2-week group (n=29), ranitidine bismuth citrate 400 mg b.d . for 14 days; and (c) 4-week group (n=29), ranitidine bismuth citrate 400 mg b.d . for 28 days . In all patients, clarithromycin 500 mg b.d . and metronidazole 500 mg b.d . were given for the first week . Endoscopy was repeated 1 month after the end of treatment and eradication was considered to be successful if both rapid urease test and histology were negative . RESULTS: Overall, H . pylori was eradicated in 84% (72/86) patients on intention-to-treat analysis, whereas the per protocol cure rate was 89% (72/81) . Eradication rates were 23/27 (85%) (95% confidence interval (CI): 66-96%), 25/27 (92%) (95% CI: 76-99%) and 24/27 (89%) (95% CI: 71-98%) in the 1-, 2- and 4-week groups, respectively, on per protocol analysis, and 25/28 (82%) (95% CI: 63-94%), 25/29 (86%) (95% CI: 68-96%) and 24/29 (83%) (95% CI: 64-94%), respectively, on intention-to-treat analysis (P > 0.05, N.S.) . No significant differences were observed between groups concerning duodenal ulcer healing, resolution of symptoms and adverse effects . CONCLUSIONS: The 1-week regimen with ranitidine bismuth citrate, clarithromycin and metronidazole is effective in H . pylori eradication . Prolongation of treatment with ranitidine bismuth citrate for 2 or 4 weeks does not achieve a statistically significant more favourable outcome.

J Pept Sci, 2001 Aug, 7(8), 433 - 47
Sequences of polypeptide antibiotics stilboflavins, natural peptaibol libraries of the mold Stilbella flavipes; Jaworski A et al.; From the culture broths of the mold Stilbella flavipes CBS 146.81, a mixture of polypeptides could be isolated by adsorption on XAD polystyrene resin and purified by Sephadex LH-20 chromatography . Using preparative thin-layer chromatography (TLC) three groups of peptides, named stilboflavins (SF) A, B, and C could be separated . Each of the groups showed microheterogeneity when investigated by high-performance liquid chromatography (HPLC) . Employing on-line HPLC-electrospray ionization tandem mass spectrometry in the positive and negative ionization mode, together with gas chromatography-selected ion monitoring mass spectrometry, enantioselective GC and quantitative amino acid analysis, the sequences of stilboflavins A and B could be determined . Exchange of Glu in stilboflavins A peptides (acidic) against Gln in stilboflavins B peptides (neutral) is the rational for different polarity of the peptide groups and their separatability by TLC . Since SF A and B are bioactive N-acetylated 20-residue peptides with a high proportion of alpha-aminoisobutyric acid and C-terminal bonded amino alcohols (either leucinol, isoleucinol or valinol) the peptides belong to the group of peptaibol antibiotics.

Electrophoresis, 2001 Aug, 22(13), 2782 - 5
Determination of anthracycline antibiotics doxorubicin and daunorubicin by capillary electrophoresis with UV absorption detection; Gavenda A et al.; Sweeping preconcentration and electrokinetic injection was used for the capillary electrophoretic analysis of trace amounts of biologically active anthracyclines with UV absorption detection . Phosphate buffer (100 mM), pH 2.5, with addition of 40% v/v methanol was used as background electrolyte (BGE) . Sodium dodecyl sulfate (150 mM) was added to BGE in the inlet vial as the sweeping agent . The system enables effective separation of anthracyclines as well as cleanup from matrix impurities . Sweeping preconcentration of sample provides an excellent detection limit (1 x 10(-9) mol L(-1)) . The method was applied for the determination of therapeutic levels of doxorubicin in real plasma samples.

Biomaterials, 2001 Oct, 22(20), 2777 - 83
Study on gelatin-containing artificial skin IV: A comparative study on the effect of antibiotic and EGF on cell proliferation during epidermal healing; Hong SR et al.; Gelatin-hyaluronate sponge with and without antibiotic and epidermal growth factor (EGF) were prepared and compared . Four types of sponges were applied on the full-thickness dorsal skin defect of Wistar rat . The effects of antibiotic and EGF in gelatin-hyaluronate sponge on wound healing were investigated by light microscopy and image analyzer at postoperative days of 5, 12 and 21 . An immunohistochemical technique, employing PC10, a monoclonal antibody against proliferating cell nuclear antigen (PCNA) was applied to wounded tissue sections . The number of PC10-positive cells was very high for the sponge with EGF at postoperative day 5, then gradually decreased with time . Also we found that antibiotics restrained the cell proliferation during the migratory phase . The sponge with both antibiotic and EGF showed good wound healing performances on the whole for a healing period . The epithelium was regenerated fast with EGF-impregnated sponges at day 5, but each sample had nearly the same length of regenerated epithelium at day 12.

Antibiot Khimioter, 2001, 46(2), 10 - 6
{Alirinomycin C--a novel macrolide antibiotic from Streptomyces felleus VIZR 8}; Shenin IuD et al.; The culture of Streptomyces felleus VIZP 8 producing new macrolide antibiotic alirinomycin C was isolated in the screening of new insecticide substances . Antibiotic was related to the carbomycin-cirramycin group . Physico-chemical and biological properties investigation and identification were performed in comparison with other antibiotics of the same group, described in literature.

Microgravity Sci Technol, 1999, 12(1), 41 - 7
Long-term exposure to spaceflight conditions affects bacterial response to antibiotics; Juergensmeyer MA et al.; Bacteria exposed to the spaceflight environment have been shown to have an increased growth rate and an increased resistance to antibiotics . The mechanism of resistance has not yet been identified, as the resistance is quickly lost upon return to Earth . To more fully characterize the spaceflight-induced resistance to antibiotics, 4 species of bacteria were exposed to microgravity for 4 months on the Space Station MIR . Upon return to Earth, these cultures were challenged with a suite of 12 antibiotics of varying modes of action . In contrast to reports from short-term space flights, we find that long-term exposure to microgravity causes bacteria to become more susceptible to most, but not all, antibiotics . Each species responds differently to the suite of antibiotics, frequently becoming less resistant, but occasionally more resistant to the antibiotic . A pattern enabling prediction of response is not yet discernible . While contradicting the results from short-term pure culture research, this experiment confirms results from astronaut and cosmonaut skin flora samples.

J Am Coll Health, 2001 Jul, 50(1), 9 - 13
Antibiotic-seeking behavior in college students: what do they really expect?
Haltiwanger KA, Hayden GF, Weber T, Evans BA, Possner AB.
Injudicious use of antibiotics contributes to increased bacterial resistance, and patient expectations encourage physicians to overuse antibiotics . The authors evaluated the level of ill college students' antibiotic-seeking behavior to determine if receiving an antibiotic prescription influenced patients' satisfaction with visits to a clinician . Of 129 students with upper respiratory complaints presenting to a university health center, 55% expected an antibiotic prescription . Antibiotic expectation was significantly more likely among students who thought they had a bacterial versus a viral infection (90% vs 40%; p < .01) . A clear diagnosis, an explanation of the rationale for treatment, and an antibiotic prescription were significantly associated with patient satisfaction . Clinicians prescribed an antibiotic for 36% of the students; only 13% of these 46 had requested an antibiotic during the visit . At some previous time, one third of the students had taken an antibiotic prescribed for an earlier illness or for another person . Better patient education and improved clinician-patient communication can potentially help to reduce the injudicious use of antibiotics.

An Med Interna, 2001 Jul, 18(7), 361 - 3
{Comparative study of the eradication of Helicobacter pylori: ranitidine bismuth citrate versus omeprazole plus two antibiotics for seven days}; Bujanda L et al.; AIMS: To compare the efficacy of ranitidine bismuth citrate (RB) combined with two antibiotics during seven days in comparison with OCA-7 for treatment of Helicobacter pylori . METHODS: In a randomized clinical trial 200, consecutive patients infected by Helicobacter pylori were studied prospectively . One of two regimens was given for 7 days; OCA-7 (omeprazole 20 mg b.i.d., amoxycillin 1 gr b.i.d., clarithromycin 500 mg b.i.d.) or RBCA (RB 400 b.i.d., amoxicillin 1 gr b.i.d., clarithromycin 500 mg b.i.d.) . Eradication was defined as a negative breath test one month after therapy . RESULTS: 112 male and 88 female with a mean age of 48 years (range 18-82) . 100 patients were randomized to OCA-7 and 100 patients to RBCA-7 . Overall 186 patients completed the treatment . Intention to-treat eradication was in the group OCA-7 of 72% and 73% in group RBCA-7 . Per-protocol eradication was in the group OCA-7 of 78% and 77% in group RBCA-7 (p = 0.3) . Five patients in the group OCA-7 and nine in the group RBCA-7, had side effects, three of these patients did not complete therapy by diarrhea . CONCLUSIONS: RB with two antibiotics is as effective and safe as OCA-7 for the eradication of Helicobacter pylori.

J Antimicrob Chemother, 2001 Sep, 48(3), 435 - 40
Antibiotics and shared decision-making in primary care; Butler CC et al.; Antibiotics are often prescribed to patients with respiratory tract infections who are unlikely to benefit . Models of physician-patient interaction may help understanding of this problem and inform the design of communication skills interventions to enhance appropriate prescribing . The 'paternalistic model' of the consultation remains common in the setting of acute respiratory tract infections . However, the four assumptions that could support this model are not valid for most of these patients, because: best treatment is controversial; management is inconsistent; physicians are not in the best position to evaluate trade-offs between management options without understanding patients' perspectives; and many pressures (apart from patients' agendas) intrude into the consultation . One alternative is the 'informed model' of consulting, but this does not take society's interests into account . The 'shared decision-making model', however, provides a framework for addressing both clinicians' and patients' agendas, and could guide the development and evaluation of specific consultation strategies to promote more appropriate use of antibiotics in primary care.

Ann Fr Anesth Reanim, 2001 Aug, 20(7), 612 - 30
{Pulmonary diffusion of antibiotics . Critical analysis of the literature}; Boselli E et al.; OBJECTIVES: Collect exhaustive data from the literature concerning the diffusion of antibiotics into lung tissue and calculate their inhibitory quotient towards the germs most frequently encountered in pulmonary infections . DATA SOURCES: Review of the literature . Data collected from the Medline database with the key words: lung, diffusion, disposition, antibiotics . Inhibitory quotients calculated from these data . RESULTS: The results were relatively similar for the different types of samples, though some differences existed between the studies . These differences were caused in particular by methodological difficulties for the tissue dosage of antibiotics . CONCLUSION: Further standardized studies, measuring in particular the antibiotic concentration in the epithelial lining fluid and in the alveolar macrophages, are necessary to obtain more reliable results in terms of inhibitory quotients . Only clinical studies, perhaps with the help of these data, could establish the real efficiency of antibiotics in lung infections.

Org Lett, 2001 Sep 6, 3(18), 2927 - 30
A synthetic strategy for the cyclodepsipeptide core of the antitumor antibiotic verucopeptin; Hale KJ et al.; {reaction: see text} . An efficient {2 + 2 + 2}-fragment condensation strategy is described for obtaining the cyclodepsipeptide core of verucopeptin . The 19-membered macrocycle was established through a Carpino HATU mediated macrolactamization, which proceeded in good yield under high-dilution conditions.

Mol Biol (Mosk), 2001 Jul-Aug, 35(4), 597 - 609
{Ribosomal antibiotics}; Man'kin AS; In spite of decades of research, our understanding of the principles of antibiotic binding to the ribosome and the mechanisms of drug action remains only fragmentary . Recent progress in biochemical and genetic studies of some "old" and new antibiotics and the availability of high-resolution structures of the ribosome subunits allows mapping the antibiotic-binding sites at atomic resolution . In this review, interaction of three groups of antibiotics with the ribosome and the mechanisms of the drug action are discussed, considering the data used to map the binding sites of the new macrolide derivatives, ketolides, a novel clinically important antibiotic linezolid, and a still experimental drug evernimicin.

Clin Infect Dis, 2001 Sep 15, 33 Suppl 3, S170 - 3
Patients' interviews and misuse of antibiotics; Pechere JC; To better evaluate patient contribution in antibiotic use, we questioned 5379 subjects from 9 countries . Antibiotics are perceived as strong, efficient drugs, but they are believed to undermine immunity . Interviewees believe that most respiratory infections, except the common cold, require antibiotic therapy, and 11% of them had to exaggerate their symptoms to get an antibiotic prescription from their physician . About 1 patient in 4 saved part of the antibiotic course for future use . Sixty-nine percent of the patients claimed to have taken the course until the end (United Kingdom, 90%; Thailand, 53%), and 75% claimed that they actually took all the daily doses . In all countries, it was possible to get antibiotics from a pharmacist without a medical prescription . This study shows that patients exert pressure on their doctors to get antibiotics and should allow a design for precise educational action aimed at the public for better control of antibiotic use in the community.

Indian Pediatr, 2001 Aug, 38(8), 827 - 38
Improving antibiotic and bronchodilator prescription in children presenting with difficult breathing: experience from an urban hospital in India; Sachdev HP et al.; OBJECTIVE: To evaluate the relative frequency of other conditions that share a clinical overlap with pneumonia as defined by the WHO case management algorithm and to determine the possibility of refining the antibiotic and bronchodilator prescription on the basis of simple clinical features . DESIGN: Prospective observational . SETTING: Urban tertiary care center . METHODS: Two hundred children, between the ages of 6 months to 5 years, presenting with difficult breathing (as defined by WHO algorithm) were prospectively evaluated for the diagnosis and the need for bronchodilator and antibiotic therapy (clinician s diagnosis) . An additional independent blinded evaluation of the chest X-rays was done by a radiologist after the study (radiologist-aided diagnosis) . On the basis of reliable predictors (sensitivity > 70% and specificity > 70%) of antibiotic and bronchodilator prescription, irrespective of the exact diagnostic category, two viable modifications of WHO case management algorithm emerged, which were compared by paired proportion test . RESULTS: Acute asthma was the predominant condition (46% or 54%), pneumonia alone was rare (10%), co-existence of pneumonia with wheeze (bronchospasm) was more frequent (22% or 15%) and often diagnoses not related to the respiratory system were documented (18% or 17%) . All the subjects in whom a preceding history of cough was not elicited had non-respiratory illnesses . An audible wheeze was appreciated in only 44 of the 150 cases (29.3%) with an auscultable wheeze . The two alternatives represented a significant (p < 0.0001) improvement over the WHO algorithm preventing inappropriate usage of both antibiotics and bronchodilators, primarily by restricting over-prescription of the former (14% and 26.5% for proposed algorithms 1 and 2, respectively) and under-utilization of the latter (40%) . The performance of the alternative algorithms for the radiologist-aided diagnosis was marginally better for over-prescription of antibiotics (16.2% and 30.9% for proposed algorithms 1 and 2, respectively) . CONCLUSION: It is feasible to amalgamate simple clinical features (history of: (i) previous similar episode of cough and difficult breathing, and (ii) fever) in the WHO case management algorithm to significantly refine the antibiotic (95% CI range 7% to 33%) and bronchodilator (35%; 95% CI 27% to 43%) prescription.

J Nat Prod, 2001 Aug, 64(8), 1006 - 9
Dicerandrols, new antibiotic and cytotoxic dimers produced by the fungus Phomopsis longicolla isolated from an endangered mint; Wagenaar MM et al.; Bioassay-guided fractionation of the organic extract from a culture of Phomopsis longicolla, an endophytic fungus of the endangered mint Dicerandra frutescens, led to the isolation of dicerandrols A, B, and C . Extensive NMR and HRFABMS experiments were used to identify these new yellow antibiotic and cytotoxic compounds as 2,2'-dimeric tetrahydroxanthones.

Antonie Van Leeuwenhoek, 2001 Jun, 79(2), 127 - 33
Phylogeny of Streptomyces species and evidence for horizontal transfer of entire and partial antibiotic gene clusters; Egan S et al.; The phylogenetic relationships of a collection of streptomycete soil isolates and type strains were resolved by sequence analysis of trpB, a housekeeping gene involved in tryptophan biosynthesis . The analysis confirmed that two isolates were recipients in a gene transfer event, demonstrated by phylogenetic incongruency between trpB and strB1 trees . One strain had acquired the entire streptomycin biosynthetic cluster, whilst the other contained only strRAB1, the resistance gene and two flanking genes from the cluster . Sequence analysis of trpB, as part of a polyphasic approach, was a useful tool in determining intra-generic relationships within the genus Streptomyces.

J Chromatogr A, 2001 Aug 3, 925(1-2), 139 - 49
Application of coil centrifugal counter-current chromatography to the separation of macrolide antibiotic analogues III . Effects of flow-rate, mass load and rotation speed on the peak resolution; Wang-Fan W et al.; As the third part of our methodology studies on the application of centrifugal counter-current chromatography to the preparative separation of macrolide antibiotic analogues, we have investigated the effects of various parameters on the retention of stationary phase and peak resolution . Our results show that the retention percentage of the stationary phase has linear relationships with both flow-rate at 1 to 3 ml/min and rotation speed at 100 to 700 rpm, but their correlation coefficients are negative (-1.000) and positive (0.9821), respectively . The peak resolution (Rs) is inversely proportional to the flow-rate (Fr) and mass load (Ml), but directly proportional to the rotation speed (Rrev) . Their correlation coefficients in linear regression for the preparative separation in laboratory scale are -0.981 to -1.000 for Rs=a+bFr at flow-rates of 1 to 3 ml/min, -0.929 to -0.993 for Rs=a+bMl at mass loads of 12.5 to 100 mg, and 0.975 to 0.998 for Rs=a+bRrev at rotation speeds of 300 to 700 rpm, respectively . Preparative separation of six very closely related macrolide antibiotics, which belong to ascomycin and rapamycin analogues, has also been successfully achieved under optimized conditions.

Can Vet J, 2001 Aug, 42(8), 617 - 22
Comparison of 2 techniques for regional antibiotic delivery to the equine forelimb: intraosseous perfusion vs . intravenous perfusion; Butt TD et al.; The purpose of this study was to compare the synovial fluid concentrations and pharmacokinetics of amikacin in the equine limb distal to the carpus following intraosseous and intravenous regional perfusion . The front limbs of 6 horses were randomly assigned to either intraosseous or intravenous perfusion . A tourniquet was placed distal to each carpus and the limb perfused with 500 mg of amikacin . Systemic blood samples and synovial fluid samples were collected over 70 min from the distal interphalangeal (DIP) joint, metacarpophalangeal joint, and digital flexor sheath . The tourniquet was removed following the 30 min sample collection . The mean peak amikacin concentration for the DIP joint was significantly higher with intravenous perfusion . There were no significant differences in time to peak concentration or elimination half-life between methods at each synovial structure . Each technique produced mean peak concentrations ranging from 5 to 50 times that of recommended peak serum concentrations for therapeutic efficacy.

Int J Cancer, 2001 Sep, 93(6), 792 - 7
Induction of urokinase-type plasminogen activator by the anthracycline antibiotic in human RC-K8 lymphoma and H69 lung-carcinoma cells; Kiguchi T et al.; Current evidence has suggested the possible involvement of ROS as signaling messengers in IL-1beta- or LPS-induced gene expression . We previously reported that both IL-1beta and LPS induce uPA in RC-K8 human lymphoma cells . Here, we provide evidence that ROS-generating anthracycline antibiotics, including doxorubicin and aclarubicin, upregulate uPA expression in 2 human malignant cell lines, RC-K8 and H69 small-cell lung-carcinoma cells . Both doxorubicin and aclarubicin markedly increased uPA accumulation in RC-K8- and H69-conditioned medium in a dose-dependent manner . In each case, maximal induction was observed at a sublethal concentration, i.e., at a concentration where cell growth was slightly inhibited . Both doxorubicin and aclarubicin increased uPA mRNA levels, and induction in each case reached the maximal level 9 hr after stimulation . Doxorubicin barely changed the half-life of uPA mRNA and activated uPA gene transcription . Antioxidants such as NAC and PDTC inhibited doxorubicin-induced uPA mRNA accumulation . Microarray analysis, using Human Cancer CHIP version 2 (Takara Shuzo, Kyoto, Japan), in which 425 human cancer-related genes were spotted on glass plates, revealed that uPA is 1 of 3 genes that were clearly upregulated in H69 cells by doxorubicin stimulation . These findings suggest that the anthracycline induces uPA in human malignant cells by activating gene transcription in which ROS may be involved . Therefore, by upregulating uPA expression, the anthracycline may influence many biologic cell functions mediated by the uPA/plasmin system .

J Bacteriol, 2001 Sep, 183(18), 5358 - 63
Functional analysis of OleY L-oleandrosyl 3-O-methyltransferase of the oleandomycin biosynthetic pathway in Streptomyces antibioticus; Rodriguez L et al.; Oleandomycin, a macrolide antibiotic produced by Streptomyces antibioticus, contains two sugars attached to the aglycon: L-oleandrose and D-desosamine . oleY codes for a methyltransferase involved in the biosynthesis of L-oleandrose . This gene was overexpressed in Escherichia coli to form inclusion bodies and in Streptomyces lividans, producing a soluble protein . S . lividans overexpressing oleY was used as a biotransformation host, and it converted the precursor L-olivosyl-erythronolide B into its 3-O-methylated derivative, L-oleandrosyl-erythronolide B . Two other monoglycosylated derivatives were also substrates for the OleY methyltransferase: L-rhamnosyl- and L-mycarosyl-erythronolide B . OleY methyltransferase was purified yielding a 43-kDa single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis . The native enzyme showed a molecular mass of 87 kDa by gel filtration chromatography, indicating that the enzyme acts as a dimer . It showed a narrow pH range for optimal activity, and its activity was clearly stimulated by the presence of several divalent cations, being maximal with Co(2+) . The S . antibioticus OleG2 glycosyltransferase is proposed to transfer L-olivose to the oleandolide aglycon, which is then converted into L-oleandrose by the OleY methyltransferase . This represents an alternative route for L-oleandrose biosynthesis from that in the avermectin producer Streptomyces avermitilis, in which L-oleandrose is transferred to the aglycon by a glycosyltransferase.

J Chromatogr Sci, 2001 Aug, 39(8), 351 - 6
Multiresidue analysis of fluoroquinolone antibiotics in chicken tissue using automated microdialysis-liquid chromatography; Schneider MJ; An efficient procedure for the simultaneous extraction and analysis of six fluoroquinolone (FQ) antibiotics is developed using an automated microdialysis-liquid chromatographic (LC) system . In this method, samples extracted from chicken liver and muscle are further purified by microdialysis, separated on an LC column, and the FQs detected by their fluorescence . Recoveries from fortified chicken liver and muscle samples are at least 70% with limits of quantitation (microg/kg) for the FQs in liver (and muscle) as follows: 0.3 (0.4) for danofloxacin, 0.8 (0.2) for desethylene ciprofloxacin, 2 (1) for norfloxacin, 2 (0.8) for enrofloxacin, 3 (1) for ciprofloxacin, and 5 (2) for sarafloxacin . Enrofloxacin and ciprofloxacin are determined in enrofloxacin-incurred chicken liver and muscle samples using this method.

Arch Pharm (Weinheim), 2001 Jul, 334(7), 258 - 60
A comparative study of the enantiomeric resolution of several tetralone derivatives on macrocyclic antibiotic chiral stationary phases using HPLC under normal phase mode; Aboul-Enein HY et al.; The enantiomeric resolution of five substituted 2-(4-pyridylalkyl)-1-tetralone derivatives has been achieved on three macrocyclic glycopeptide antibiotic chiral stationary phases namely, Chirobiotic R, T, and V columns . The mobile phase used was hexane-ethanol-triethylamine (12:8:0.01, v/v/v) . The flow rates were 1 mL/min for Chirobiotic T and 2 mL/min for Chirobiotic R and V respectively . The UV detection was carried out at 254 nm . The values of alpha of the resolved enantiomers of the reported tetralone derivatives were in the range of 1.32 to 2.51 on Chirobiotic R, 2.02 to 2.88 on Chirobiotic T and 1.55 to 2.54 on Chirobiotic V respectively while the values of Rs were in the range of 1.00 to 2.50 on Chirobiotic R, 1.00 to 1.95 on Chirobiotic T and 1.00 to 1.60 on Chirobiotic V respectively . The best resolution was achieved on Chirobiotic R column.

Vestn Otorinolaringol, 2001, (3), 55 - 7
{Treatment policy in thrombophlebitis lesions of the sigmoid sinus and internal jugular vein during intensive use of antibiotics}; Gadzhimirzaev GA et al.; 152 patients were admitted to the ENT hospital with the diagnosis thrombophlebitis of the sygmoid sinus (62.1% of the total number of the admitted patients with otogenic intracranial complications) . The surgery was made early upon the admission . The authors advocate radical removal of the thrombus before, the start of hemorrhage from both sinus parts . In case of the absence of low hemorrhage the intervention on the internal jugular vein was decided on day 1-3 after the basic surgery depending on the clinical course . It is thought that in postoperative period antibiotic therapy should be supplemented with immune preparations made of donor blood, UV radiation of autoblood and hyperbaric oxygenation.

Biophys J, 2001 Sep, 81(3), 1547 - 54
Detergent-like action of the antibiotic peptide surfactin on lipid membranes; Heerklotz H et al.; Surfactin is a bacterial lipopeptide with powerful surfactant-like properties . High-sensitivity isothermal titration calorimetry was used to study the self association and membrane partitioning of surfactin . The critical micellar concentration (CMC), was 7.5 microM, the heat of micellization was endothermic with DeltaH(w-->m)(Su) = +4.0 kcal/mol, and the free energy of micellization DeltaG(O,w-->m)(Su) = -9.3 kcal/mol (25 degrees C; 100 mM NaCl; 10 mM TRIS, 1 mM EDTA; pH 8.5) . The specific heat capacity of micellization was deduced from temperature dependence of DeltaH(w-->m)(Su) as DeltaC(w-->m)(P) = -250 +/- 10 cal/(mol.K) . The data can be explained by combining the hydrophobicity of the fatty acyl chain with that of the hydrophobic amino acids . The membrane partition equilibrium was studied using small (30 nm) and large (100 nm) unilamellar POPC vesicles . At 25 degrees C, the partition coefficient, K, was (2.2 +/- 0.2) x 10(4) M(-1) for large vesicles leading to a free energy of DeltaG(O, w-->b)(Su) = -8.3 kcal/mol . The partition enthalpy was again endothermic, with DeltaH(w-->b)(Su) = 9 +/- 1 kcal/mol . The strong preference of surfactin for micelle formation over membrane insertion explains the high membrane-destabilizing activity of the peptide . For surfactin and a variety of non-ionic detergents, the surfactant-to-lipid ratio, inducing membrane solubilization, R(sat)(b), can be predicted by the simple relationship R(sat)(b) approximately K . CMC.

Life Sci, 2001 Jul 27, 69(10), 1115 - 21
Enhancement of endogenous corticosterone levels by a macrolide antibiotic, roxithromycin in mice; Yamamoto S et al.; The influence of roxithromycin (RXM), a macrolide antibiotic, on endogenous corticosterone (CS) levels was examined in BALB/c mice . Mice were sensitized intraperitoneally with two doses of Keyhole Limpet Hemocyanin at 1 week intervals . Mice were given orally 2.5 mg/kg RXM once a day for 14 days starting 7 days after the first sensitization . RXM administration caused markedly increase in endogenous plasma CS levels which was peaked at 60 min after the administration . However, josamycin did not influence on endogenous CS levels in plasma . Injection of dexamethasone inhibits the plasma CS hyperproduction induced by RXM treatment.

Bioelectrochemistry, 2001 Aug, 54(1), 11 - 5
Cation selective ion channels formed by macrodiolide antibiotic elaiophylin in lipid bilayer membranes; Grigoriev PA et al.; The macrodiolide antibiotic elaiophylin (1) forms stable, long-lasting cation selective ion channels in planar lipid bilayer membranes prepared from soybean phosphatidylcholine . Current of the single ion channel displayed two sublevels corresponding to the two substates of the channel conductance: a slow substate, with about 5 s of mean dwell time in the open state at 40% level of the total amplitude conductance, and a fast substate of higher conductance with dwell times in the open and closed state of about 0.1 s . Amplitude conductances of the single ion channels in 200 mM of LiCl, NaCl, KCl, RbCl and CsCl were 75, 140, 220, 240 and 226 pS, and the conductance was linear function of the electrolyte concentration . Ratios of cation to anion permeabilities of the channel for NaCl and KCl were 8+/-2 and >24, respectively . A molecular model of the channel structure is suggested.

Electrophoresis, 2001 Jul, 22(11), 2129 - 35
Chiral analysis of UV nonabsorbing compounds by capillary electrophoresis using macrocyclic antibiotics: 1 . Separation of aspartic and glutamic acid enantiomers; Bednar P et al.; Glycopeptide antibiotics, namely vancomycin or teicoplanin, were evaluated in capillary electrophoresis for the analysis of UV nonabsorbing compounds such as aspartic and glutamic acid enantiomers . Electrophoretic runs were performed in laboratory-made polyacrylamide-coated capillaries using the partial filling-counter current method in order to avoid the presence on the detector path of the absorbing chiral selector . The background electrolyte consisted of an aqueous or aqueous-organic buffer in the pH range of 4.5-6.5 of sorbic acid/histidine and the appropriate concentration of chiral selector . Several experimental parameters such as antibiotic concentration and type, buffer pH, organic modifier, type and concentration of absorbing co-ion (for the indirect UV detection) were studied in order to find the optimum conditions for the chiral resolution of the two underivatized amino acids in their enantiomers . Among the two investigated chiral selectors, vancomycin resulted to be the most useful chiral selector allowing relatively high chiral resolution of the studied compounds even at low concentration . The optimized method (10 mM sorbic acid/histidine, pH 5, and 10 mM of vancomycin) was used for the analysis of real samples such as teeth dentine and beer.

Pol Merkuriusz Lek, 2001 Jun, 10(60), 445 - 9
{Patient adherence in respiratory tract infections: ceftibuten versus other antibiotics (PARTICULAR study)}; Kardas P et al.; The study was conducted to evaluate patient compliance to antibiotic therapy in respiratory tract infections . The main aim of the study was to establish whether dosing frequency (1 vs 2 or 3 times daily) and other factors influence compliance . Patients aged 18 and over attending selected primary health facilities in Lodz region were enrolled . Patients were randomly assigned to receive ceftibuten, 400 mg once daily or other antibiotic on physician's choice with 2 or 3 times daily dosing . On the 5th day during the home visit the questionnaire study was performed and the compliance was measured by a pill count . Four hundred and six patients (205 in ceftibuten and 201 in other antibiotics group, respectively) were fully evaluable . Overall compliance was 76.6% with 97.6% for ceftibuten, 66.0% for antibiotics with b.i.d . dosing and 23.5% for antibiotics with t.i.d . dosing . Using a logistic regression analysis with a stepwise variable selection, dosing frequency was found to be a major variable associated with patient compliance (p = 0.00000, odds ratio 0.09, 95% confidence interval 0.057-0.165) . Non-compliance with antibiotics is a common phenomenon in respiratory tract infections therapy . Once-daily antibiotic dosing leads to the best possible compliance in such circumstances . Due to its once-daily dosing and rare side effects, ceftibuten ensures nearly perfect compliance in respiratory tract infections therapy.

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi, 2000 Jun, 14(2), 125 - 7
{The efficacy of antiviral antibiotic 17997 on treatment of HSV-1 infected guinea pig skin infection}; Tao P et al.; OBJECTIVE: To study the treatment efficacy of antiviral antibiotic 17997 against HSVl infected guinea pig skin infection . METHODS: Guinea pig skin was infected by HSV1 . 24hrs or 48hrs of post infection local treatment of 0.3% 17997 cream was started, tid for five days . In the mean time, acyclovir treatment, cream treatment and virus control were included . RESULTS: Local treatment of 0.3% 17997 cream showed therapeutic effects, it reduced the average scores of skin lesion, accelerated crusting-time and healing-time . CONCLUSIONS: 0.3% 17997 cream showed significant treatment efficacy when compared with cream and virus controls by reducing skin lesion scores and healing-time . The treatment efficacy of 3.0% acyclovir cream was a little bit better than 0.3% 17997 cream.

Antimicrob Agents Chemother, 2001 Sep, 45(9), 2414 - 9
Aminoglycoside resistance with homogeneous and heterogeneous populations of antibiotic-resistant ribosomes; Recht MI et al.; Aminoglycosides bind to rRNA in the small subunit of the bacterial ribosome . Mutations in the decoding region of 16S rRNA confer resistance to specific subsets of aminoglycoside antibiotics . The two major classes of 2-deoxystreptamine aminoglycosides are the 4,5- and the 4,6-disubstituted antibiotics . Antibiotics of the 4,5-disubstituted class include neomycin, paromomycin, and ribostamycin . Gentamicins and kanamycins belong to the 4,6-disubstituted class of aminoglycosides . Structural studies indicated the potential importance of position 1406 (Escherichia coli numbering) in the binding of ring III of the 4,6-disubstituted class of aminoglycosides to 16S rRNA . We have introduced a U1406-to-A mutation in a plasmid-encoded copy of E . coli 16S rRNA which has been expressed either in a mixture with wild-type ribosomes or in a strain in which all rRNA is transcribed from the plasmid-encoded rrn operon . High-level resistance to many of the 4,6-disubstituted aminoglycosides is observed only when all the rRNA contains the U1406-to-A mutation . In contrast to the partial dominance of resistance observed with other mutations in the decoding region, there is a dominance of sensitivity with the 1406A mutation . Chemical footprinting experiments indicate that resistance arises from a reduced affinity of the antibiotic for the rRNA target . These results demonstrate that although position 1406 is an important determinant in the binding and action of the 4,6-disubstituted aminoglycosides, other rRNA mutations that perturb the binding of ring I of both classes of 2-deoxystreptamine aminoglycosides confer higher levels of resistance as well as a partial dominance of resistance.

Eur J Cell Biol, 2001 Jul, 80(7), 466 - 78
Azithromycin, a lysosomotropic antibiotic, impairs fluid-phase pinocytosis in cultured fibroblasts; Tyteca D et al.; The dicationic macrolide antibiotic azithromycin inhibits the uptake of horseradish peroxidase (HRP) by fluid-phase pinocytosis in fibroblasts in a time- and concentration-dependent fashion without affecting its decay (regurgitation and/or degradation) . The azithromycin effect is additive to that of nocodazole, known to impair endocytic uptake and transport of solutes along the endocytic pathway . Cytochemistry (light and electron microscopy) shows a major reduction by azithromycin in the number of HRP-labeled endocytic vesicles at 5 min (endosomes) and 2 h (lysosomes) . Within 3 h of exposure, azithromycin also causes the appearance of large and light-lucentlelectron-lucent vacuoles, most of which can be labeled by lucifer yellow when this tracer is added to culture prior to azithromycin exposure . Three days of treatment with azithromycin result in the accumulation of very large vesicles filled with pleiomorphic content, consistent with phospholipidosis . These vesicles are accessible to fluorescein-labeled bovine serum albumin (FITC-BSA) and intensively stained with filipin, indicating a mixed storage with cholesterol . The impairment of HRP pinocytosis directly correlates with the amount of azithromycin accumulated by the cells, but not with the phospholipidosis induced by the drug . The proton ionophore monensin, which completely suppresses azithromycin accumulation, also prevents inhibition of HRP uptake . Erythromycylamine, another dicationic macrolide, also inhibits HRP pinocytosis in direct correlation with its cellular accumulation and is as potent as azithromycin at equimolar cellular concentrations . We suggest that dicationic macrolides inhibit fluid-phase pinocytosis by impairing the formation of pinocytic vacuoles and endosomes.

What Is Activated Sludge?, What Is Biofilter?, What Is Amino Acid?, What Is Bioreactor?, What Is MIC?, s, Bacteria, c, Microbe, r, Microbiology, o, Microorganisms, i, Bacteriology, n, Botulin, s, Bacillus, i, Escherichia coli, o, Bacteria, c, Staphylococcus, a, Acinetobacter, n, Staphylococcus aureus, e, Bactericidal, i, Bacteria, i, Culture medium, s, Serratia, s, Cell cultures, c, Staphylococcus aureus, i, Bactericidal, a, Corynebacter, r, Staphylococcus aureus, e, Bacillus, n, Fermentations, i, Candida albicans, e, Antibiotics, i, S. cerevisiae

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005