Yao Xue Xue Bao, 1997 May, 32(5), 352 - 6 {Structure determination of new antifungal antibiotics, polaramycins A and B}; Meng W et al.; Antifungal antibiotics, polaramycins A and B have been isolated from the culture of Streptomyces hygroscopicus LP-93 . Polaramycins A and B are 36-membered polyol macrolide antibiotics containing hemiacetal monoester of malonic acid and guanidyl groups . Based on spectral evidence including UV, IR, FABMS, 1HNMR, 13CNMR, DEPT, 1H-1H COSY, HETCOR, HMBC, the structure of polaramycins A and B have been assigned as shown in Fig 1 (A, R = H; B, R = CH3). Zhonghua Er Bi Yan Hou Ke Za Zhi, 1998 Apr, 33(2), 67 - 70 {Screening for the 1555G mutation in mitochondrial DNA in pedigrees with aminoglycoside antibiotic induced deafness}; Yuan H et al.; OBJECTIVE: To identify the relationship between the 1555G mutation in mitochondrial DNA and aminoglycoside antibiotic induced deafness and provide theoretical evidence for establishing diagnostic method . METHODS: Blood samples were obtained from three pedigrees with aminoglycoside antibiotic induced deafness . DNA was extracted from the isolated leukocytes . The mitochondrial DNA fragments were amplified by PCR, 1555G mutation was detected by Alw26 I restriction endonuclease digestion, allele-specific oligonucleotide hybridization and DNA sequencing . RESULTS: Seven individuals from pedigrees A and C carried homoplasmic 1555G mutation, six individuals from pedigree B did not have 1555G mutation . CONCLUSION: 1555G mutation is not the only pathologic mitochondrial DNA mutation associated with aminoglycoside antibiotic induced deafness . This is the first finding of aminoglycoside antibiotic induced deafness pedigree without 1555G mutation. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi, 2000 Sep, 14(3), 247 - 9 {Selective inhibition of HSV-1 DNA and protein synthesis by antiviral antibiotic 17997}; Chen E et al.; OBJECTIVE: To study the effects of 17997 on the HSV-1 DNA and protein synthesis . METHODS: DNA synthesis was determined by isopycnic separation of cellular and viral DNA in CsCl gradients centrifugation . Protein synthesis was determined by SDS-PAGE and Western blot . RESULTS: The inhibition rates of 0.5 micromol/L, 1.0 micromol/L, 2.0 micromol/L and 4.0 micromol/L of 17997 on HSV-1 DNA synthesis were 63.1%,74 . 1%, 93.9% and 100%, respectively . 4.0 micromol/L of 17997 did not inhibit VERO cell DNA synthesis . The above concentrations of 17997 did not show any inhibitory effects on cellular protein synthesis, but selectively inhibited on viral protein synthesis . CONCLUSIONS: 17997 selectively displayed inhibitive effects on HSV-1 DNA and protein synthesis. Drug Resist Updat, 2000 Oct, 3(5), 303 - 311 The impact of antibiotic use on resistance development and persistence; Barbosa TM et al.; The intense use and misuse of antibiotics are undoubtedly the major forces associated with the high numbers of resistant pathogenic and commensal bacteria worldwide . Both the volume and the way antibiotics are applied contributes to the selection of resistant strains . Still, other social, ecological and genetic factors affect a direct relationship between use and frequency of resistance . Resistant bacteria, following their emergence and evolution in the presence of antibiotics, appear to acquire a 'life of their own' . They proliferate and maintain the resistance traits even in the absence of antibiotics, thus jeopardizing the reversal of bacterial resistance by simple reduction in antibiotic use . Reversing resistance requires restoration of the former susceptible flora in people and in the environment . Australas J Dermatol, 2001 Aug, 42(3), 196 - 9 Drug-induced linear IgA bullous disease following antibiotics; Wiadrowski TP et al.; A 69-year-old woman presented with pneumonia and subacute bacterial endocarditis . Nine days after intravenous vancomycin and ciprofloxacin were commenced, the patient developed a bullous mucocutaneous eruption . Clinical presentation and histopathology were consistent with drug-induced linear IgA bullous disease (LABD) . The patient's lesions resolved with cessation of antibiotics . A review of the features of drug-induced LABD and the drugs that have been implicated are presented. Eur J Med Res, 2001 Jul 30, 6(7), 277 - 91 Antibiotic therapy in intra-abdominal infections--a review on randomised clinical trials; Holzheimer RG et al.; There have been 79 randomised antibiotic studies in intra-abdominal infections retrieved . The overall success rate of the studied antibiotics ranges from 70-100% . Unfortunately only about one fourth of the studies have used a disease severity classification, e.g., APACHE II score, despite clear recommendations by the Surgical Infections Society of North America . The mortality rate in the published antibiotic studies is still rather low (approximately 4%) and does not correspond to the average mortality in peritonitis (30-40%) . Failure analysis is not uniform and only performed in about 1/5 of retrieved studies . Failure analysis included data on diagnosis, type of operation, pathogen isolated at first operation, susceptibility and persistence of pathogen, re-operation or change of antibiotic regimen, and follow-up (ICU duration, death or survival, hospitalisation) . Only one study has performed an analysis of the adequacy of the surgical treatment (source control) . The clinical success rate of the antibiotics studied in a larger population is comparable for gentamicin + clindamycin (80%), tobramycin + clindamycin (83%), meropenem (89%), imipenem (85%), aztreonam + clindamycin (89%), cefoxitin (88%), cefotetan (92%), moxalactam (83%), cefotaxime + metronidazole (87%), ampicillin/sulbactam (87%) . Piperacillin/tazobactam has in most studies a success rate of approximately 90% . The aggregated data on adverse events and clinical failure rate do not show a major advantage for any of these antibiotics . It is striking that the adverse event rate reported for ticarcillin/clavulanic acid is low when compared to all other antibiotics, which is in contrast to severe adverse events reported for clavulanic acid . The data of quinolone studies in intra-abdominal infections do not yet allow a recommendation, even when it is acknowledged that two studies were performed with good results and a good study plan . In conclusion, the comparability of antibiotic studies in intra-abdominal infections is limited due to a lack of disease severity stratification and a relatively small study population for most antibiotics . The clinical success rate of the best-studied antibiotics is similar and the choice which antibiotic is used depends on the expected pathogens and the resistance rate in a clinical setting. Pancreas, 2001 Aug, 23(2), 204 - 11 Liver injury in acute pancreatitis and mitigation by continuous arterial infusion of an antibiotic via the superior mesenteric artery; Miyahara S et al.; Macrophage-derived inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha), have been shown to play a central role in aggravation of acute pancreatitis (AP), but little is known about their roles in liver injury . We investigated the pathogenesis of the liver injury in AP and assessed the efficacy of arterial infusion of an antibiotic via the superior mesenteric artery (SMA) . Infusion of saline (group A) or imipenem (group B) was started 6 hours after induction of AP in dogs by intraductal administration of autologous gallbladder bile . The survival rate in group B was significantly improved compared with group A . Serum alanine aminotransferase levels in peripheral blood and endotoxin levels in portal vein blood were both significantly higher at 18 hours in group A than in group B . When hepatocytes and Kupffer cells were isolated at 18 hours and cultured for 24 hours thereafter, there was significant exacerbation of the hepatocyte injury and significantly greater production of TNF-alpha in the coculture of hepatocytes and Kupffer cells in group A, indicating that the Kupffer cells had been activated . By contrast, both of these manifestations were significantly mitigated in group B . These findings suggest that TNF-alpha secreted by endotoxin-activated Kupffer cells contributes to liver injury in AP, and that SMA infusion of an antibiotic mitigates the liver injury by controlling endotoxin translocation. Arch Pediatr Adolesc Med, 2001 Jul, 155(7), 800 - 6 Parent expectations for antibiotics, physician-parent communication, and satisfaction; Mangione-Smith R et al.; OBJECTIVES: To explore how parents communicate their preferences for antibiotics to their child's physician and to examine whether physicians can communicate why antibiotics are not being prescribed in a way that maintains satisfaction with the visit . DESIGN: Previsit survey of parents, audiotaping of the study encounters, and a postvisit survey of parents and physicians . SETTING: Two private pediatric practices . PARTICIPANTS: Ten physicians (response rate = 77%) and a consecutive sample of 295 eligible parents (response rate = 86%) who attended acute care visits for their children between October 1996 and March 1997 . MAIN OUTCOME MEASURES: Physician-perceived pressure to prescribe antibiotics and parental visit-specific satisfaction . RESULTS: Fifty percent of parents expressed a previsit expectation for antibiotics . Among these parents, only 1% made a direct verbal request for them . Even when no direct requests for antibiotics were made, physicians still perceived an expectation for antibiotics 34% of the time . Among parents who did not receive expected antibiotics, those offered a contingency plan from the physician (i.e., the possibility of receiving antibiotics in the future if their child did not get better) had a higher mean satisfaction score than parents not receiving a contingency plan (76 vs . 58.9; P<.05) . CONCLUSION: Physicians should consider providing a contingency plan to parents who expect antibiotics for their children when there is no clinical indication . Further study is needed to determine how parents indirectly communicate their desire for antibiotics and what additional communication techniques physicians can use to resist the overprescribing of antibiotics. Proc Natl Acad Sci U S A, 2001 Aug 14, 98(17), 9814 - 8 Epub 2001 Jul 31. Spatial-temporal imaging of bacterial infection and antibiotic response in intact animals; Zhao M et al.; We describe imaging the luminance of green fluorescent protein (GFP)-expressing bacteria from outside intact infected animals . This simple, nonintrusive technique can show in great detail the spatial-temporal behavior of the infectious process . The bacteria, expressing the GFP, are sufficiently bright as to be clearly visible from outside the infected animal and recorded with simple equipment . Introduced bacteria were observed in several mouse organs including the peritoneal cavity, stomach, small intestine, and colon . Instantaneous real-time images of the infectious process were acquired by using a color charge-coupled device video camera by simply illuminating mice at 490 nm . Most techniques for imaging the interior of intact animals may require the administration of exogenous substrates, anesthesia, or contrasting substances and require very long data collection times . In contrast, the whole-body fluorescence imaging described here is fast and requires no extraneous agents . The progress of Escherichia coli-GFP through the mouse gastrointestinal tract after gavage was followed in real-time by whole-body imaging . Bacteria, seen first in the stomach, migrated into the small intestine and subsequently into the colon, an observation confirmed by intravital direct imaging . An i.p . infection was established by i.p . injection of E . coli-GFP . The development of infection over 6 h and its regression after kanamycin treatment were visualized by whole-body imaging . This imaging technology affords a powerful approach to visualizing the infection process, determining the tissue specificity of infection, and the spatial migration of the infectious agents. J Antibiot (Tokyo), 2001 May, 54(5), 434 - 40 Streptocidins A-D, novel cyclic decapeptide antibiotics produced by Streptomyces sp . Tü 6071 . II . Structure elucidation; Holtzel A et al.; The structures of the new antibiotics streptocidins A approximately D were elucidated as cyclic decapeptides cyclo{L-Val1-L-Orn2-L-Leu3-D-Phe4-L-Pro5-L-Leu6-X7-L-Asn8-L-Gln9-X10} with X7=D-Trp (A, B, C) or D-Phe (D) and X10=L-Tyr (A), L-Trp (B, D), or D-Trp (C) . The amino acid composition (including the configuration) of the substances was determined by chiral-phase GC-MS of the hydrolysates . The sequences were established by EDMAN degradation following linearisation of the cyclic peptides upon treatment with LiAlH4 . NMR spectroscopic studies of streptocidins C and D confirmed the proposed sequences and provided conformational data which indicate a molecular topology of streptocidins C and D similar to those of tyrocidine A and gramicidin S. Ceska Slov Farm, 2001 Jul, 50(4), 166 - 72 {Enantiomeric separation of drugs based on macrocyclic antibiotics}; Rojkovicova T et al.; The present review paper describes the properties of the macrocyclic antibiotics vancomycin, teikoplanin, and ristocetin A, which can be used as stationary phases for separation of the enantiomers of drugs containing a stereogenic centre . It analyzes the results obtained in the separation of amino acids, its derivatives, loxiglumide, clenbuterol, practolol, carnitine, levodopa, methyldopa, ceftazidine, alkoxyphenylcarbamic acid derivatives, dichloroprop, ketoprofen, warfarin, and ergot alkaloids by means of high-performance liquid chromatography (HPLC). Nat Struct Biol, 2001 Aug, 8(8), 684 - 9 Structure of beta-lactam synthetase reveals how to synthesize antibiotics instead of asparagine; Miller MT et al.; The enzyme beta-lactam synthetase (beta-LS) catalyzes the formation of the beta-lactam ring in clavulanic acid, a clinically important beta-lactamase inhibitor . Whereas the penicillin beta-lactam ring is generated by isopenicillin N synthase (IPNS) in the presence of ferrous ion and dioxygen, beta-LS uses ATP and Mg2+ as cofactors . According to sequence alignments, beta-LS is homologous to class B asparagine synthetases (AS-Bs), ATP/Mg2+-dependent enzymes that convert aspartic acid to asparagine . Here we report the first crystal structure of a beta-LS . The 1.95 A resolution structure of Streptomyces clavuligerus beta-LS provides a fully resolved view of the active site in which substrate, closely related ATP analog alpha,beta-methyleneadenosine 5'-triphosphate (AMP-CPP) and a single Mg2+ ion are present . A high degree of substrate preorganization is observed . Comparison to Escherichia coli AS-B reveals the evolutionary changes that have taken place in beta-LS that impede interdomain reaction, which is essential in AS-B, and that accommodate beta-lactam formation . The structural data provide the opportunity to alter the synthetic potential of beta-LS, perhaps leading to the creation of new beta-lactamase inhibitors and beta-lactam antibiotics. Spectrochim Acta A Mol Biomol Spectrosc, 2001 Jul, 57(8), 1643 - 8 Metal complexes of antibiotic drugs . Studies on dicluxacillin complexes of FeII, FeIII, CoII NiII and CuII; Mohamed GG; The synthesis and characterization of dicluxacillin (DC) complexes with di- and tri-valent metal ions are described . The nature of bonding of the chelated DC and its metal complexes structures have been elucidated on the basis of their spectroscopic (infrared, solid reflectance, magnetic spectra, mass and thermal analysis) properties . In all the complexes studied, the DC acts as a chelate monoanionic ligand with coordination involving the carboxylate O atom and the endocyclic N of the thiazole ring . The DC ligand forms mono-ligand complexes of the general formula {M(DC)(H2O)x(A)} . yH2O where DC is the uninegatively charged bidentate ligand and A = OAc in case of CuII and Cl in case of FeIII, FeII, CoII and NiII ions . IR, solid reflectance spectra and magnetic moment measurement are used to infer the structure and to illustrate the coordinating capacity of the ligand . From the thermal decomposition curves, the water molecules of crystallization are removed in a single stage while the decomposition of the ligand and coordinated water molecules occur in the second and subsequent stages . Different thermodynamic kinetic parameters namely activation energy (E*), enthalpy of activation (AH*), entropy of activation (AS*) and free energy change of activation (AG*) are calculated using Coats and Redfern equation. Therapie, 2001 Mar-Apr, 56(2), 139 - 42 {Impact of Opposable Medical References (RMO) prescription guidelines for antibiotic prescriptions in ambulatory medicine}; Choutet P; The French RMO (References Medicales Opposables) are prescription guidelines based on a critical assessment of antibiotic drug prescription . The RMO 2, which concerns the prescription of commonly used antibiotics for otorhinolaryngological/respiratory infections, provides an example of the advantages and drawbacks of such an approach . Its effect on prescription behaviour is probably significant . The economic impact in terms of health cost has remained within acceptable limits. Sheng Li Xue Bao, 2001 Apr, 53(2), 158 - 62 {Inhibitory effect of aminoglycoside antibiotics on rabbit carotid baroreceptor activity in vitro}; Liu DX et al.; The present study was to investigate the effects of aminoglycoside antibiotics, changes in extracellular Ca2+ concentration and antagonists of L-type Ca-channels on the activity of rabbit carotid sinus baroreceptors (CS-BRA) in isolated and superperfused carotid sinus-carotid sinus nerve (CS-CNS) preparations, using extracellular recording technique . The results are as follows . (1) Streptomycin (0.25-0.75 mmol/L) and gentamycin (0.43-1.29 mmol/L) inhibited CS-BRA in a dose-dependent manner, which recovered after the drugs were washed out . (2) Perfusion with high Ca2+ (3.3 mmol/L) solution inhibited CS-BRA, while perfusate with trace Ca2+ (in the order of 10(-5) mol/L) increased it . (3) Verapamil and diltiazem had no effect on CS-BRA at a concentration of 10(-7) mol/L, but inhibited it at higher concentrations (> 10(-6) mol/L) . These results suggest: (1) aminoglycoside antibiotics can inhibit CS-BRA specifically, thus providing a new tool for the study of baroreceptors; (2) calcium ions are not necessary for producing generator potentials of baroreceptors, and the L-type calcium channel does not seem to be involved in CS-BRA per se; and (3) the inhibitory effects of aminoglycoside antibiotics on CS-BRA may not be related to the blocking of L-type calcium channels. Ophthalmic Epidemiol, 2001 Sep, 8(4), 205 - 14 The SAFE strategy for trachoma control: planning a cost-effectiveness analysis of the antibiotic component and beyond; Frick KD et al.; AIM: A limited literature addresses the cost-effectiveness of the prevention and treatment of trachoma and its sequelae . The literature focuses on government costs . This paper motivates the inclusion of and details methods for measuring the costs for the target population . METHODS: Costs to the targeted population can be measured while studying efficacy or effectiveness . These costs can be added to the more frequently measured costs to the government to calculate costs for the entire society . This section indicates the types of costs to consider, refines the concept of costs, describes the necessary data, outlines how the methods of data collection fit with the methods that would be employed for a general effectiveness study, and describes the appropriate calculation of a cost-effectiveness ratio . RESULTS: The costs to the targeted population can be measured with few additional resources . Placing a value on villagers' time or translating clinical results into summary, preference-based health-related quality of life measures would increase the resources required more substantially . DISCUSSION: For theoretical and practical reasons, future cost-effectiveness analyses of the full SAFE strategy and the antibiotic component of the strategy should be done from a perspective that includes both the government and the targeted population . This can be useful in policy making and increase our understanding of reasons for less than universal participation. J Org Chem, 2001 Jul 27, 66(15), 5217 - 31 Total synthesis of rutamycin B, a macrolide antibiotic from Streptomyces aureofaciens; White JD et al.; Rutamycin B (2) was synthesized from three principal subunits, spiroketal 75, keto aldehyde 83, and aldehyde 108 . First, triol 62 was assembled by Julia coupling of sulfone 56 with aldehyde 58 followed by an acid-catalyzed spiroketalization . The three hydroxyl functions of 62 were successfully differentiated, leading to phosphonate 75 . The latter was condensed in a Wadsworth-Emmons reaction with 83, prepared in six steps from (R)-aldehyde 76, to give 92 . Coupling of the titanium enolate of 92 with 108 afforded Felkin product 109 with high stereoselectivity in a process that is critically dependent on the presence of the p-methoxybenzyl ether in the aldehyde . Transformation of 109 via aldehyde 116 to vinylboronate 122 was followed by macrocyclization under Suzuki conditions to yield 123 . Exhaustive desilylation of the latter yielded rutamycin B. Clin Infect Dis, 2001 Aug 15, 33(4), 436 - 44 Epub 2001 Jul 11. Antibiotic-resistant pneumococci carried by young children do not appear to disseminate to adult members of a closed community; Borer A et al.; Although antibiotic-resistant pneumococci have been frequently detected among day care center (DCC) attendees, the transmission of these organisms to other members of the community has not been adequately studied . Nasopharyngeal cultures were obtained from 152 children and 244 adult members of a closed community (a kibbutz) in Israel . Serotyping, antibiogram, and pulsed-field gel electrophoresis were performed to determine the relatedness of isolated pneumococci . Twenty (30%) of the 66 isolates from children showed decreased susceptibility to penicillin and 9 isolates (14%) were resistant to > or =3 drugs . Of the 16 isolates from adults, 5 (31%) were intermediately resistant to trimethoprim-sulfamethoxazole . Resistant strains carried by DCC attendees were not isolated either from their parents or from other adult members of the community . Despite the high degree of interpersonal contact occurring in a closed community, resistant pneumococcal strains carried by DCC attendees do not appear to be easily transmitted to the adult population, which suggests the existence of an immunological barrier. Int Immunopharmacol, 2001 Jul, 1(7), 1385 - 92 Suppression of co-stimulatory molecule expressions on splenic B lymphocytes by a macrolide antibiotic, roxithromycin in vitro; Asano K et al.; The influence of a macrolide antibiotic, roxithromycin (RXM), on co-stimulatory molecule expression was examined using in vitro cell culture technique . Spleen cells obtained from BALB/c mice 10 days after immunization with 8.0 micrograms of haemocyanin absorbed to 4.0 mg aluminum hydroxide were cultured in the presence of 100.0 micrograms/ml haemocyanin and various concentrations of RXM for 72 h . Low concentrations (1.0 and 2.5 micrograms/ml) of RXM did not influence cell activation induced by antigenic stimulation, whereas RXM showed a suppressive effect on blastic activity of the cells when the agent was added to the cultures at more than 5.0 micrograms/ml . RXM did not affect blastic activity of splenic T cells by anti-CD3 monoclonal antibody stimulation even when the cells were cultured in the presence of 10.0 micrograms/ml RXM . Addition of anti-CD80 and anti-CD86 monoclonal antibody to cell cultures caused significant suppression of cell activation by antigenic stimulation . We next examined the influence of RXM on co-stimulatory molecule expressions on splenic B cells in response to antigenic stimulation . Addition of RXM at a concentration of 5.0 micrograms/ml into cell cultures remarkably suppressed co-stimulatory molecule, CD40, CD80 and CD86, expressions, which enhanced by antigenic stimulation in vitro. J Am Chem Soc, 2001 Apr 11, 123(14), 3214 - 22 Enantioselective total synthesis of a potent antitumor antibiotic, fredericamycin A; Kita Y et al.; The asymmetric total synthesis of both enantiomers of the potent antitumor antibiotic fredericamycin A (1) is detailed based on the protocol for the construction of its peri-hydroxy polyaromatic skeleton bearing the chirality at the spiro carbon via a strong base-induced cycloaddition of suitably substituted homophthalic anhydrides (AB-ring unit) with an optically active CDEF-ring unit . Particular attention has been given to the novel synthesis of the optically active spiro carbon center by a stereospecific rearrangement of optically active benzofuzed-trans-epoxy acylates leading to spirocyclopentane-1,1'-indane systems . This method is quite useful for the construction of an optically active spiro compound and was applied to the synthesis of the optically pure CDEF-ring unit of 1 . Cycloaddition of the optically pure CDEF-ring unit to AB-ring units prepared via benzyne afforded two natural and unnatural-type hexacyclic compounds, which were converted to natural and unnatural enantiomers of synthetic 1, and the absolute configuration of natural 1 was determined as S. Yonsei Med J, 2001 Jun, 42(3), 291 - 8 Preparation of collagen modified hyaluronan microparticles as antibiotics carrier; Lee JE et al.; Hyaluronan (HA), a natural glycoaminoglycan featuring an extracellular matrix, has been suggested as an effective biocompatible material . In this study, the effectiveness of HA microparticles as a carrier system for antibiotics was evaluated, and their physicochemical characteristics were determined . Microparticles were fabricated by the gelation of sulfadiazine (SD) loaded HA solution with calcium chloride through either a granulation (GR-microparticles) or encapsulation (EN-microparticles) process, and atelocollagen was incorporated into the microparticles as an additive in order to improve their physical properties . The characteristics of the microparticles were examined by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and swelling test . In vitro release experiments were performed for 7 days and the released amount of SD was determined using high-performance liquid chromatography (HPLC) . Microscopic observations revealed that the collagen incorporated HA particles had a more compact surface than the HA particles . DSC analysis determined a loss of SD crystallinity in the particles . Calcium chloride retarded the swelling of particles, whereas the loaded drug contents did not affect this property . Both GR-and EN-microparticles sustained SD release with initial bursting effect . SD release from EN-microparticles was faster than from GR-microparticles . In addition, the release rate was dependent on the SD content in the microparticles . These results suggest that collagen modified HA microparticles have a potential as a release rate controlling material for crystalline drugs such as SD. J Microbiol Immunol Infect, 2001 Jun, 34(2), 97 - 102 The use of antibiotics critical to human medicine in food-producing animals in Taiwan; McDonald LC et al.; There are increasing public health concerns about antibiotics used in food-producing animals that may contribute to the development of resistance in human pathogens . Such resistance may be critical to human medicine when resistance develops to drugs that treat certain pathogens of which there is no good alternative therapy . We surveyed 10 farms, eight feed mills, and one animal drug distributor in Taiwan to determine the major antibiotics used in food-producing animals, and the extent of use of five drugs that may select for resistance to antibiotics that are critical for human medicine . The five animal drugs, and the resistance of human drug/class they may select for, included avoparcin (vancomycin/glycopeptides), avilomycin (ziracin/envirninomycins), enrofloxacin (ciprofloxacin/fluoroquinolones), virginiamycin (quinupristin and dalfopristin combination/streptogramins), and kanamycin (gentamicin/aminoglycosides) . Tetracyclines were the class of antibiotic that was most widely used in the greatest amounts . Over the past 12 months, the number of farms, chicken feed mills, and pig feed mills, that have respectively reported the use of avoparcin was 1 (10%), 5 (63%), 0; avilomycin 0, 0, 3 (50%); enrofloxacin 4 (40%), 1 (13%), 3 (50%); virginiamycin 2 (20%), 5 (63%), 0; and kanamycin 3 (30%), 1 (13%), 1 (17%) . We conclude that although the most commonly used antibiotics (ie tetracyclines) have little effect on human medicine, there is a widespread use of antibiotics that may select for critical forms of resistance in human pathogens in food-producing animals. Cutis, 2000 Oct, 66(4 Suppl), 7 - 13 Systemic therapy for rosacea: focus on oral antibiotic therapy and safety; Del Rosso JQ; Although potentially significant adverse reactions and drug interactions have been reported in association with erythromycin, oral tetracyclines, and trimethoprim-sulfamethoxazole, overall these agents are associated with excellent safety profiles, especially considering their widespread use over many years . It must be considered that when these antibiotics are used for the treatment of rosacea and also for acne vulgaris, their use is on a long-term basis rather than their typical short-course regimens for most infectious diseases . As a result, dermatologists prescribing these agents may feel assured that most patients will not encounter any significant problems, but they do need to be aware of potential adverse reactions to allow for early recognition and discontinuation of the offending drug when needed . Early recognition also allows for favorable management of adverse reactions . In addition, potentially significant drug interactions may be recognized by obtaining a thorough medical history and avoiding combinations of drugs that may interact unfavorably . Fortunately, there are several choices that allow us to individually select a treatment regimen that is optimal for the individual patient, allowing for effective control of rosacea. Mol Microbiol, 2001 Jul, 41(1), 167 - 78 Involvement of N-acetylmuramyl-L-alanine amidases in cell separation and antibiotic-induced autolysis of Escherichia coli; Heidrich C et al.; N-acetylmuramyl-L-alanine amidases are widely distributed among bacteria . However, in Escherichia coli, only one periplasmic amidase has been described until now, which is suggested to play a role in murein recycling . Here, we report that three amidases, named AmiA, B and C, exist in E . coli and that they are involved in splitting of the murein septum during cell division . Moreover, the amidases were shown to act as powerful autolytic enzymes in the presence of antibiotics . Deletion mutants in amiA, B and C were growing in long chains of unseparated cells and displayed a tolerant response to the normally lytic combination of aztreonam and bulgecin . Isolated murein sacculi of these chain-forming mutants showed rings of thickened murein at the site of blocked septation . In vitro, these murein ring structures were digested more slowly by muramidases than the surrounding murein . In contrast, when treated with the amidase AmiC or the endopeptidase MepA, the rings disappeared, and gaps developed at these sites in the murein sacculi . These results are taken as evidence that highly stressed murein cross-bridges are concentrated at the site of blocked cell division, which, when cleaved, result in cracking of the sacculus at this site . As amidase deletion mutants accumulate trimeric and tetrameric cross-links in their murein, it is suggested that these structures mark the division site before cleavage of the septum. J Agric Food Chem, 2001 Jul, 49(7), 3463 - 70 Solid-phase extraction followed by liquid chromatography-mass spectrometry for trace determination of beta-lactam antibiotics in bovine milk; Bruno F et al.; A confirmatory assay able to unambiguously identify and quantify 10 approved-for-use beta-lactam antibiotics in milk below stipulated U.S . and EU tolerance levels is presented . beta-Lactams are extracted from 10 mL of intact milk by a Carbograph 4 cartridge . After solvent removal, residue reconstitution, and filtration, a completely transparent and uncolored extract is injected into a liquid chromatography -mass spectrometry (LC-MS) instrument equipped with an electrospray (ES) ion source and a single quadrupole . During the chromatographic run, the ES/MS system is operated first in the positive-ion mode (PI) and then in the negative-ion (NI) mode . This is done to circumvent matrix interferences resulting in remarkable signal weakening of the last-eluted analytes, when detecting them as {M+H}+ adduct ions . MS data acquisition is performed by a time-scheduled three-ion selected ion monitoring program . At the 5 ng/mL level, recoveries of the beta-lactams are between 70 (nafcillin) and 108% (cephalin), with relative standard deviations ranging between 5 (oxacillin) and 11% (amoxicillin and ceftiofur) . The response of the ES/MS detector is linearly related to injected amounts up to 500 ng, irrespective of the chemical characteristics of the beta-lactams and the acquisition mode selected (PI or NI modes) . Limits of quantification, based on a minimal value of the signal-to-noise ratio of 10, were estimated to be within 0.4 (cephalin) and 3 ng/mL (dicloxacillin) . Analyses of milk samples taken after intramammary application of amoxicillin showed that 1.2 ng/mL of this penicillin was still present 6 days after treatment . At this concentration level, the identification power of the method is not weakened, as signals of the three product ions of amoxicillin are still well distinguishable from the background noise. Vopr Med Khim, 2001 Mar-Apr, 47(2), 256 - 62 {Effect of antibiotic therapy on embryotropic antibody level in women}; Morozov SG et al.; Embriotropic antibodies (e-Ab) serum contents were analysed in 29 serum samples obtained from women suffering with primary lues . Before treatment the content of e-Ab against MBP, S100, ACBP14/18, and MP65 were markedly elevated in 28 samples . Two injections of Retarpen (2.5 mln Units with one week interval) were enough for effective treatment of lues . At the same time treatment caused deep and reversible inhibition of e-Ab production . One or two months later the levels of e-Ab returned to normal values in 21% of women, in 52% patients the hypoproduction, and in 27% the hyperproduction of e-Ab were noted . Deviations of e-Ab production after effective retarpen treatment suggest the existence of additional reasons which may influence e-Ab production, and necessity of additional diagnostic and curative measures for such women during pregravidal period. Int J Technol Assess Health Care, 2001 Spring, 17(2), 171 - 80 A randomized trial to measure the optimal role of the pharmacist in promoting evidence-based antibiotic use in acute care hospitals; Dranitsaris G et al.; BACKGROUND: There is a considerable gap between randomized clinical trials and implementing the results into practice . This is particularly relevant in the use of broad-spectrum antibiotics in hospitals . Hospital pharmacists can be effective vehicles for bridging this gap and promoting evidence-based medicine . To determine the most effective way of using the pharmacist in this role, a prospective cefotaxime intervention study was conducted with randomization incorporated into the design as well as patient-related therapeutic outcomes . METHODS: A total of 323 patients who were prescribed cefotaxime were randomized into an intervention or nonintervention group where only the former was challenged by pharmacists for inappropriate cefotaxime usage relative to hospital guidelines . The primary outcome was the appropriateness of cefotaxime prescribing between groups . Logistic regression analysis was then used to identify factors that were associated with successful clinical response . RESULTS: Overall, 94% of orders in the intervention group met cefotaxime dosage criteria compared with 86% in the control group (p = .018) . However, there was no impact with respect to promoting cefotaxime use for an appropriate indication (81% vs . 80%; p = .67) . There was a trend for improved clinical outcomes in patients who received cefotaxime within hospital guidelines (OR = 1.73; p = .31) . CONCLUSIONS: The pharmacist as a vehicle for promoting the appropriate use of broad-spectrum antibiotics in the acute care hospital setting can improve the dosing of such agents . However, several barriers to optimizing the impact of the pharmacist were implied by the data . Removing these barriers could increase the pharmacists' utility as an agent for improved patient care. Prikl Biokhim Mikrobiol, 2001 May-Jun, 37(3), 309 - 16 {Biosynthes of polyketide antibiotics by various actinomycin producing Streptomyces species}; Alekhova TA et al.; A collection of actinomycin-producing Streptomyces strains, their variants with different levels of antibiotic biosynthesis, and recombinant strains were screened in order to select new strains that produce polyketide antibiotics . Screening with the use of the cloned act gene encoding a component of actinorhodin polyketide synthase (PKS) multienzyme complex from Streptomyces coelicolor revealed that many strains tested can synthesize polyketide antibiotics along with actinomycins . A relationship between biosynthetic pathways of actinomycins and polyketides is discussed. G Chir, 2001 May, 22(5), 181 - 4 {Antibiotic and immunostimulating prophylaxis in colorectal surgery}; Di Pietro N et al.; The Authors, after considering post-operatory sepsis as cause of failures and as an important economic damage, make among them a distinction according to the arising area and to the seriousness of their manifestations . They, later, describe corrective and prophylactic measures which in colo-rectal surgery ase campulsory assumptions for sepsis prevention . After relating their experience, Authors reaffirm short-term protocol validity and point out validity of alternation of large spectrum molecules in order to avoid possible arising of bacterial resistances. Clin Infect Dis, 2001 Aug 1, 33(3), 364 - 9 Epub 2001 Jul 05. Dissemination of antibiotic-resistant bacteria across geographic borders; Okeke IN et al.; The development of antibiotic-resistant (AR) bacteria in any country is of global importance . After their initial selection and local dissemination, AR bacteria can be transferred across international borders by human travelers, animal and insect vectors, agricultural products, and surface water . The sources and routes of importation of strains of AR bacteria are most often unknown or undetected, because many bacteria carrying resistance genes do not cause disease, and routine surveillance often does not detect them . Control of international dissemination of AR bacteria depends on methods to reduce selection pressure for the development of such bacteria and improved surveillance to detect their subsequent spread. Jpn J Thorac Cardiovasc Surg, 2001 May, 49(5), 279 - 81 Prevention of surgical site infection by antibiotic spraying in the operative field during cardiac surgery; Yoshii S et al.; OBJECTIVE: Despite the many procedures introduced to prevent surgical site infection during cardiothoracic surgery, serious infections still occur . We attempted to reduce surgical site infection by spraying antibiotic solution in the operative field--a procedure since introduced at 4 other Japanese institutions . METHODS: In the latter half of 1990, we began spraying an antibiotic solution of cefazolin (1g) and gentamicin (40 mg)/40 ml of saline placed in a 50 ml syringe and dispensed through an 18 G needle bent at 60 to 80 degrees to clean the wound during surgery . RESULT: No deep surgical site infections or deaths due to infection have occurred among the 502 patients undergoing cardiothoracic surgery under cardiopulmonary bypass at our hospital . This method was used in over 2,100 cases of similar procedures at 4 other institutions . There were 3 deaths due to severe surgical site infection (0.11%) . At one institution treating over 1,000 cases a year, the incidence of death due to surgical site infection decreased significantly after this method was introduced . CONCLUSION: These preliminary experiences show that spraying antibiotic solution in the operative field reduces the risk of surgical site infection in cardiothoracic surgery. J Pharm Pharmacol, 2001 Jun, 53(6), 823 - 9 Inhibition by carbapenem antibiotic imipenem of intestinal absorption of valproic acid in rats; Torii M et al.; The concomitant use of carbapenem antibiotics with valproic acid has been prohibited because panipenem induced a decrease in plasma concentration of valproic acid in epileptic patients during valproic acid therapy . To clarify the possible mechanism of the carbapenem-valproic acid interaction, we investigated the effect of imipenem on the pharmacokinetic behaviour of valproic acid in rats . Co-administration of imipenem (30 mg kg(-1), i.v.) induced a decrease in the peak plasma concentration of valproic acid after oral administration . However, the imipenem-induced decrease in plasma concentrations of valproic acid was not observed within 60 min after intravenous injection of valproic acid . By utilizing in-situ vascular and luminal perfused small intestine, it was confirmed that absorption of valproic acid from the luminal to the vascular perfusate was decreased in the presence of imipenem (0.5 mM) in the vascular perfusate . The everted gut sac method was used to determine the effect of imipenem on active transport of valproic acid . The accumulation of valproic acid on the serosal side of the intestinal sac against the concentration gradient was reduced by lactic acid that inhibits the carrier-mediated transport of valproic acid across the intestinal brush-border membrane . However, imipenem did not affect the active transport of valproic acid . Therefore, the inhibition by imipenem of valproic acid absorption may be caused by a mechanism different from that of lactic acid . In conclusion, imipenem inhibits the intestinal absorption of valproic acid, which contributes to the decrease in plasma concentration of valproic acid after oral administration. Science, 2001 Jun 22, 292(5525), 2326 - 9 A protein antibiotic in the phage Qbeta virion: diversity in lysis targets; Bernhardt TG et al.; A(2), a capsid protein of RNA phage Qbeta, is also responsible for host lysis . A(2) blocked synthesis of murein precursors in vivo by inhibiting MurA, the catalyst of the committed step of murein biosynthesis . An A(2)-resistance mutation mapped to an exposed surface near the substrate-binding cleft of MurA . Moreover, purified Qbeta virions inhibited wild-type MurA, but not the mutant MurA, in vitro . Thus, the two small phages characterized for their lysis strategy, Qbeta and the small DNA phage phiX174, effect host lysis by targeting different enzymes in the multistep, universally conserved pathway of cell wall biosynthesis. Res Microbiol, 2001 Apr-May, 152(3-4), 341 - 50 The role of ABC transporters in antibiotic-producing organisms: drug secretion and resistance mechanisms; Mendez C et al.; Knowledge about biosynthetic gene clusters from antibiotic-producing actinomycetes is continuously increasing and the presence of an ABC transporter system is a fairly general phenomenon in most of these clusters . These transporters are involved in the secretion of the antibiotic through the cell membrane and also contribute to self resistance to the produced antibiotic. Spectrochim Acta A Mol Biomol Spectrosc, 2001 May, 57(6), 1317 - 23 Fluorescence characteristic study of the ternary complex of fluoroquinolone antibiotics and cobalt (II) with ATP; Wu S et al.; The results from the measurement of the fluorescence spectra of fluoroquinolone antibiotics including ofloxacin (OF), norfloxacin (NOR) and ciprofloxacin (CIP) complexed with cobalt (II) and ATP give information concerning the antibiotics-nucleotide interactions . From the fluorescence spectral data, it appears that the fluoroquinolone antibiotic cannot directly complex with ATP but indirectly complex with cobalt (II), which is playing an intermediary role . The interaction of fluoroquinolone antibiotic with the nucleotide occurs mainly through the phosphate group . The conclusion offers a more complete mechanism, which is important for understanding the interaction of these drugs with DNA. Clin Infect Dis, 2001 Jul 15, 33(2), 203 - 9 Epub 2001 Jun 20. Patient selection criteria and management guidelines for outpatient parenteral antibiotic therapy for native valve infective endocarditis; Andrews MM et al.; Outpatient parenteral antibiotic therapy (OPAT) for infective endocarditis (IE) is being applied widely, despite the absence of controlled data that demonstrates that outcomes are equivalent to those with standard inpatient antibiotic therapy . We review existing OPAT guidelines, published data on the timing of complications from IE, and data on risk factors that can be used to predict complications . These data are used to propose more stringent criteria for patient selection and clinical management of OPAT for native valve IE . We recommend a conservative approach (inpatient or daily outpatient follow-up) during the critical phase (weeks 0-2 of treatment), when complications are most likely, and we recommend consideration of OPAT for the continuation phase (weeks 2-4 or 2-6 of treatment) when life-threatening complications are less likely. Dtsch Tierarztl Wochenschr, 2001 May, 108(5), 195 - 200 {The tissue distribution of antibiotics in the udder--comparison of the situation in vivo with the isolated perfused bovine udder.}; Ehinger AM et al.; Especially for animal protection reasons, tissue concentrations of intracisternally administered antibiotics in the mammary gland hardly can be determined in the live cow . Therefore, this paper assessed the use of the isolated perfused bovine udder to study the distribution of penicillins in glandular tissue . With this intention, the in vitro results acquired with this model were compared to tissue concentrations as well as absorption data from the few in vivo studies in the literature and differences were interpreted . This approach must consider inevitable deviations of experimental materials and methods . Furthermore, in vivo the udder is included in a closed circulatory system with other metabolism and excretion feasibilities than the isolated model . Moreover, the lower flow rate in the vessels in vitro has to be taken into account with respect to absorption capacities . Nevertheless, the tissue concentrations and the distribution equilibrium across the blood-udder-barrier in both experimental concepts corresponded with each other, if the deviating conditions are considered by calculating correction factors . Advantages and disadvantages of the isolated udder are discussed critically . In conclusion, this method is a useful completion of pharmacokinetic in vivo studies that are supposed to compare intracisternally administered formulations. Pediatr Pulmonol, 2001 Jul, 32(1), 38 - 43 Effect of intravenous antibiotics on exercise tolerance (3-min step test)) in cystic fibrosis; Pike SE et al.; Most children with cystic fibrosis (CF) feel better and display more energy after a course of intravenous antibiotics (IVABs), but this is not always reflected by a satisfactory improvement in lung function . We assessed the change in exercise tolerance after treatment with IVABs using the 3-min step test, and compared it with changes in spirometric lung function and arterial oxygen saturation (SaO(2)) . Thirty-six children (mean age, 13.8 years) were enrolled from two tertiary CF centers during an inpatient stay for IVABs . After 10-14 days of treatment, there was a significant improvement in median FEV(1) from 43% to 57% of predicted values (P < 0.0001), and median FVC from 66% to 73% of predicted values (P < 0.0001), while median SaO(2) significantly increased from 95% to 96.5% (P < 0.05) . This was accompanied by a reduction in resting heart rate (median 118 bpm to 109 bpm, P < 0.005) and subjective breathlessness at rest (median visual analogue score 2.2 to 0.8, P < 0.005) . All outcomes of exercise tolerance were improved after IVABs . There was a reduction in maximum heart rate (median 156 bpm to 150 bpm, P < 0.05) and an increase in minimum SaO(2) (median 93.5% to 94.5%, P = 0.08) measured during the step test . There was also a reduction in subjective breathlessness (median visual analogue score of 5.5 to 4.2, P < 0.005) and objective breathlessness (median 15-count score of 3 to 2, P < 0.0001) measured immediately after the step test . Exercise testing was a useful outcome measure for monitoring effectiveness of inpatient therapy, and complemented spirometry and SaO(2) monitoring . The simple ward-based 3-min step test was found to be a particularly suitable method for measuring changes in exercise tolerance in children with CF . Farmaco, 2001 Mar, 56(3), 211 - 8 Pyrocatechol violet in pharmaceutical analysis . Part I . A spectrophotometric method for the determination of some beta-lactam antibiotics in pure and in pharmaceutical dosage forms; Amin AS; A fairly sensitive, simple and rapid spectrophotometric method for the determination of some beta-lactam antibiotics, namely ampicillin (Amp), amoxycillin (Amox), 6-aminopenicillanic acid (6APA), cloxacillin (Clox), dicloxacillin (Diclox) and flucloxacillin sodium (Fluclox) in bulk samples and in pharmaceutical dosage forms is described . The proposed method involves the use of pyrocatechol violet as a chromogenic reagent . These drugs produce a reddish brown coloured ion pair with absorption maximum at 604, 641, 645, 604, 649 and 641 nm for Amp, Amox, 6APA, Clox, Diclox and Flucolx, respectively . The colours produced obey Beer's law and are suitable for the quantitative determination of the named compounds . The optimization of different experimental conditions is described . The molar ratio of the ion pairs was established and a proposal for the reaction pathway is given . The procedure described was applied successfully to determine the examined drugs in dosage forms and the results obtained were comparable to those obtained with the official methods. Aten Primaria, 2001 May 31, 27(9), 642 - 8 {Suitability of antibiotic prescription in primary care in the Basque Autonomous Community}; Rotaeche del Campo R et al.; OBJECTIVE: To study the variability and suitability of antibiotic prescription in primary care in the Basque Country . DESIGN: Prospective, descriptive study . SETTING: Basque Country health care centres both within and not in the reformed network . MEASUREMENTS AND MAIN RESULTS: 3182 infections from consultations for infectious disease were studied through sampling stratified by health area during February, March and April 1998 . The appropriateness of antibiotics (ATB) prescription was compared with some standards after an extensive bibliographic review . 68.6% of consultations were infections not needing ATB (infections of respiratory airways, acute bronchitis, flu and gastro-enteritis) . ATB were used in 28.5% of these cases (CI: 26.6-30.5), especially in acute bronchitis (90.7%) (CI: 87.3-93.4) . Unnecessary prescription supposes 39.7% of total antibiotic prescription (CI: 37.2-42.1%), which means unnecessary annual expenditure of 1155 million pesetas . In 31.4% of the infections that require ATB treatment, in 23.7% inappropriate treatment was chosen (CI: 21-26.7%) . Overall appropriateness of treatment was 72.2% (CI: 70.6-73.8) . Working in the reformed system was linked to better prescription in all cases . Paediatricians prescribed better in the case of infections not susceptible to ATB treatment . CONCLUSIONS: ATB prescription is not consistent with the available scientific evidence . Incorrect treatments occur especially in benign and self-limiting processes . A local policy of ATB use that includes multi-disciplinary collaboration and effective ongoing training is necessary. Am J Orthop, 2001 Jun, 30(6), 495 - 8 Madura foot: treatment of Nocardia nova infection with antibiotics alone; Miller SD; This case report documents the presentation of a 29-year-old woman with a deep Nocardia nova infection of the foot involving the bones . The patient responded well to prolonged antibiotic therapy, with essentially complete resolution of her symptoms . The results suggest that surgical intervention in these unusual cases may be unnecessary and that good clinical results can be obtained pharmacologically. J Vet Med Sci, 2001 May, 63(5), 553 - 6 Enzyme-linked immunosorbent assay for screening the plasma residues of tetracycline antibiotics in pigs; Lee HJ et al.; The recommended therapeutic doses of three kinds of tetracyclines, oxytetracycline (OTC, withdrawal period, 10 days), chlortetracycline (CTC, withdrawal period, 5 days) and tetracycline (TC, withdrawal period, 5 days), were each administered to a group of 15 pigs . Blood was sampled before drug administration and during the withdrawal period . The concentration of tetracyclines in plasma, determined by semi-quantitative ELISA, was compared with that of internal standard (10 ppb as oxytetracycline) . The absorbance ratio of internal standard to sample (B/Bs) was employed as an index to determine the tissue residues in pigs . All 45 plasma samples from nontreated pigs showed negative in the residue of any of three tetracycline antibiotics . OTC was detected in plasma of pigs treated until the 8th day, CTC until the 4th day, and TC was detected until the 3rd day of its withdrawal period . The present study showed that the semi-quantitative ELISA easily be adopted in predicting tissue residues for tetracycline antibiotics in live pigs. Int J Clin Pract, 2001 May, 55(4), 272 - 4 A study of the appropriateness of antibiotic use in the medical wards of a tertiary teaching hospital in Malaysia; Hooi PY et al.; A prospective study was conducted to determine the proportion of patients who received an antibiotic within 12 hours of admission to the medical wards . During the four-week study, 234 patients were admitted to medical wards from casualty; 68 patients (29%) received an antibiotic . The survey indicated that antibiotics were inappropriate in 22-65% of those treated . This study also shows that as many as 67% of patients who received intravenous antibiotics could have been equally well treated with oral preparations. J Biomater Sci Polym Ed, 2001, 12(2), 195 - 207 Biodegradable polyhydroxyalkanoate implants for osteomyelitis therapy: in vitro antibiotic release; Turesin F et al.; Various random copolyesters of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV) and 3-hydroxybutyrate and 4-hydroxybutyrate P(3HB-4HB) were used in the construction of biodegradable, implantable rods for the local delivery of antibiotics (Sulperazone and Duocid) in chronic osteomyelitis therapy . Drug loading, type of active agent, and additional coating of the implant surface all have significant contributions to the in vitro release profile . The rate and duration of Sulperazone release from P(3HB-4HB) rods were controlled by the polymer/drug ratio (drug loading) . The rate of drug dissolution was substantially higher than that of polymer degradation . Therefore, the release phenomenon was more dependent on drug dissolution rather than on polymer degradation or diffusion . Coating rods with the same type of polymer substantially reduced the initial burst effect observed with the uncoated rods, and significantly decreased the release rate so that the release kinetics became almost zero order . Antibiotic release from coated rods was sustained for over a period of 2 weeks at a constant rate, whereas uncoated rods released their contents in less than a week . Impregnation of Duocid into the hydrophobic polymer matrix yielded a rod with a smoother surface topography . The release from these rods was significantly higher than for rods loaded with Sulperazone and a zero order release could not be obtained with these samples. Intensive Care Med, 2001 Apr, 27(4), 640 - 7 Usefulness of a strategy based on bronchoscopy with direct examination of bronchoalveolar lavage fluid in the initial antibiotic therapy of suspected ventilator-associated pneumonia; Timsit JF et al.; OBJECTIVES: To evaluate (a) the routine accuracy of bronchoalveolar lavage by direct examination (BAL-D) in diagnosing ventilator-associated pneumonia (VAP), and (b) the impact of a diagnostic strategy including clinical judgment, bronchoscopy, and BAL-D on the initial diagnosis and appropriateness of treatment when VAP is suspected . DESIGN AND SETTING: Prospective cohort study in two academic ICUs in Paris, France . PATIENTS AND PARTICIPANTS: Mechanically ventilated patients with suspected VAP underwent bronchoscopy with BAL and protected specimen brush (PSB) . BAL-D results were available within 2 h, BAL on culture and PSB results after 24 h, and antibiotic susceptibility after 48 h . At each step in the strategy the senior and the resident in charge of the patient were asked their diagnosis and their therapeutic plan on the basis of presently available data . Definite diagnosis of suspected VAP was based on histology, appearance of cavitation, positive pleural fluid culture, results of PSB and BAL culture, and follow-up . MEASUREMENT AND RESULTS: A total of 110 episodes of suspected VAP were studied; 94 definite diagnoses were made (47 VAP, 47 no VAP) . Using a threshold 1% of infected cells, BAL-D discriminated well between patients with and those without VAP (sensitivity 93.6%, specificity 91.5%, area under the receiver-operating characteristic curve 0.953) . The senior clinical judgment was correct in 71% cases . It was correct in 78% and 94% of cases after airway visualization and BAL-D findings, respectively . After BAL-D the positive and negative predictive values in diagnosing VAP were 90% and 98%, respectively . However, the therapeutic plan was correct in only 65% using clinical judgment (15 untreated patients, 3 ineffective treatment, 15 useless treatment), 66% using airway visualization (14 untreated VAP, 4 ineffective treatment, 14 useless treatment), and 88% using BAL-D results (1 untreated patients, 6 ineffective, 4 useless), according to definite diagnosis and final antibiotic susceptibility testings . CONCLUSIONS: A strategy based on bronchoscopy and BAL-D generally leads to a rapid and appropriate treatment of nosocomial pneumonia in ventilated patients. J Chromatogr B Biomed Sci Appl, 2001 May 5, 755(1-2), 57 - 64 Study on the electrochemical detection of the macrolide antibiotics clarithromycin and roxithromycin in reversed-phase high-performance liquid chromatography; Pappa-Louisi A et al.; The optimal conditions of the amperometric detection of the macrolide antibiotics clarithromycin and roxithromycin were found by cyclic voltammetric studies and HPLC-electrochemical detection responses obtained in different temperatures (25.5-60 degrees C) and different but almost isoelutropic binary, ternary and quaternary mixtures of aqueous buffer (pH 7), methanol, acetonitrile and isopropanol . These conditions were also proved to be applicable for the quantitative detection of clarithromycin in human plasma using roxithromycin as an internal standard and vice versa . It was demonstrated that increased attention has to be paid to eluent composition and column temperature to ensure sensitive and reproducible electrochemical responses as well as regularly shaped peaks for both macrolides tested. Pharmacol Toxicol, 2001 May, 88(5), 277 - 81 Beta-lactam antibiotic-mediated changes in platelet reactivity and vascular endothelial functions; Togna GI et al.; To evaluate vascular and platelet compatibility of intravenous administration of beta-lactam antibiotics, we assessed the effects of therapeutic concentrations of ceftriaxone, aztreonam, and ceftazidime on platelet reactivity to different agonists (sodium arachidonate, collagen and adenosine diphosphate) and on selected vascular endothelial functions (adenosine diphosphatase activity, prostacyclin production and t-PA release) . Ceftriaxone and, to a lesser degree, aztreonam, enhanced platelet reactivity, evaluated as onset of platelet aggregating response, and increased thromboxane production to subthreshold concentrations of arachidonate . There was no modification in platelet reactivity after ceftazidime treatment . Ceftriaxone and ceftazidime, but not aztreonam, inhibited endothelial adenosine diphosphatase activity . Prostacyclin production and t-PA release were inhibited only by ceftriaxone at high concentrations . While it is difficult to establish which marker (platelet or endothelial functions) has more clinical reference in human vascular compatibility, it seems feasible to consider aztreonam the most compatible of the beta-lactams studied. J Formos Med Assoc, 2001 Mar, 100(3), 155 - 61 Antibiotic use in public hospitals in Taiwan after the implementation of National Health Insurance; Chang SC et al.; BACKGROUND AND PURPOSE: Only limited data is available on the patterns of antibiotic use in hospitals in Taiwan before and after the implementation of national health insurance . This study aimed to determine the patterns of use of antibiotics in public hospitals in Taiwan after the implementation of the National Health Insurance program and to compare these with patterns prior to the implementation . METHODS: Data on the annual use of all antibiotics in public hospitals in Taiwan during the period from fiscal year (FY) 1994-1995 to 1997-1998 were collected and analyzed . Hospitals included seven medical centers, 19 regional hospitals, 53 district hospitals, and eight specialty service hospitals . RESULTS: The annual cost of antibiotics made up 17.4% of the annual cost of all medication used in these hospitals in FY 1994-1995, and decreased year by year to 12.6% in FY 1997-1998 . During the study period, 57.4% of the total cost of antibiotics were incurred by medical centers, 24.6% by regional hospitals, 16.2% by district hospitals, and 1.8% by specialty service hospitals . The most commonly used class of antibiotic was cephalosporins, accounting for 48.0% to 54.3% of total antibiotic costs . The second most commonly used class of antibiotic was penicillins, accounting for 15.9% to 17.4% of total antibiotic costs . In FY 1994-1995, the next most commonly used classes of antibiotics were aminoglycosides, fluoroquinolones, and other beta-lactams, respectively, but by FY 1997-1998 these had changed to fluoroquinolones, glycopeptides, and aminoglycosides, respectively . Among the various cephalosporins used, first-generation cephalosporins accounted for 76.1% of all cephalosporins used in FY 1994-1995, which increased year by year to 84.0% in FY 1997-1998 . Second-generation cephalosporins accounted for 20.7% of all cephalosporins used in FY 1994-1995, decreasing to 13.2% in FY 1997-1998 . CONCLUSION: The introduction of the National Health Insurance program in Taiwan brought about a major change in antibiotic use patterns in public hospitals. Trends Microbiol, 2001 Jun, 9(6), 286 - 92 Antibiotic and insecticide resistance modeling--is it time to start talking? Peck SL. Mathematical models have played an important part in understanding both antibiotic and insecticide resistance . However, there has been little, if any, interdisciplinary work between these two areas of active research . One primary reason for this is that bacterial population genetics differ substantially from the population genetics of diploid organisms . This article examines these differences and their effect on resistance . It explores what efforts have gone into modeling resistance mathematically in both arenas, and offers suggestions on how the two groups could work together to gain a more comprehensive understanding of the resistance phenomenon Clin Infect Dis, 2001 Jul 1, 33(1), 76 - 82 Epub 2001 Jun 05. Pathways for inappropriate dispensing of antibiotics for rhinosinusitis: a randomized trial; Contopoulos-Ioannidis DG et al.; We evaluated the extent of and factors that determine the inappropriate use of antibiotics that are obtained without a physician's prescription . Ninety-eight Greek pharmacists were visited by actress-researchers who played clients requesting antibiotics without a physician's prescription . Pharmacists were randomly challenged in a scenario that involved simulated cases of acute uncomplicated rhinosinusitis with either low fever (38.5 degrees C) or high fever (40 degrees C) . Antibiotics were offered by 34 (69%) of 49 pharmacists who were presented with the high-fever scenario and by 42 (86%) of 49 pharmacists who were presented with the low-fever scenario (risk difference, 16.3%; P = .05) . Thirty-two (65%) and 35 (71%) pharmacists in the high- and low-fever study arms, respectively, agreed to sell the actress-researchers broad-spectrum antibiotics . Only 28 (57%) and 17 (35%) pharmacists, respectively, recommended that the patient visit a physician (P = .03) . Inappropriate recommendations regarding antibiotic use were very common in the studied setting . Antibiotics were more likely to be offered to persons who did not have a prescription when they were less likely to be clinically indicated. Ann Thorac Surg, 2001 May, 71(5 Suppl), S371 - 4 Repair of truncus arteriosus in early infancy with antibiotic sterilized aortic homografts; Alexiou C et al.; BACKGROUND: To evaluate the fate of the truncal valve, the antibiotic sterilized aortic homografts, and the survival after repair of truncus arteriosus in the first 6 months of life . METHODS: Between 1974 and 1994, 23 infants (mean age 1.7 months, range 5 days to 6 months) underwent primary repair of truncus arteriosus by one surgeon (J.L.M) . Sixteen were neonates (age range 5 to 30 days) . Continuity between the right ventricle and the pulmonary artery was established with an aortic antibiotic sterilized homograft (mean diameter 14.9 mm, range 11 to 17 mm) . Follow-up was 100% complete . RESULTS: Four neonates with severe truncal regurgitation died early (17.4%) . Fourteen patients underwent reoperations . Five had a truncal valve replacement (mean time 7 years, range 6 months to 17 years) . Ten-year freedom from truncal valve replacement was 78.2% . Eleven patients had homograft replacement (mean time 12.7 years, range 2 to 26.2 years) . Ten-year freedom from homograft replacement for any cause was 77.1% (for homograft-related problems it was 86.7%) . Seven patients retained the original homografts (mean time 14.3 years, range 6 to 18.7 years) . There was one late death . Overall 10-year survival was 79% and for the hospital survivors it was 95% . All survivors are in New York Heart Association functional class I . CONCLUSIONS: Abnormal truncal valves pose serious early and late problems but the patients with normal truncal valves do well and seem unlikely to need replacement of these valves . The durability of the antibiotic sterilized aortic homograft even in sizes less than 14 mm is remarkably good . Late survival is excellent. Recenti Prog Med, 2001 Apr, 92(4), 274 - 7 {Lyell syndrome and antibiotic therapy}; Grifoni S et al.; Lyell syndrome is an idiosyncratic reaction to drug treatment associated with high mortality due to difficulty in the diagnosis and lack of treatment with proven efficacy . We present the case of a patient treated with antibiotics who developed an exantema-like eruption, diagnosed as Lyell syndrome . The warning signs are represented by a diffuse exantema-like erythema generally associated with fever, large and soft bullae, resembling pemfigo, with subsequent transformation into diffuse erosions following detachment of the epidermis . Skin biopsy is decisive for a correct diagnosis . Negative direct and indirect immunostain, and negative Tzank cytodiagnostic test, associated with histologic findings consistent with "epidermic necrosis with diffuse vacuolar basal stratum degeneration", allow a rapid diagnosis of Lyell syndrome . In our patient, aggressive treatment did not obtain the positive results reported in the literature, possibly due to the advanced stage of the disease. Antonie Van Leeuwenhoek, 2000 Dec, 78(3-4), 269 - 76 Effects of increased and deregulated expression of cell division genes on the morphology and on antibiotic production of streptomycetes; van Wezel GP et al.; This paper describes the effects of increased expression of the cell division genes ftsZ, ftsQ, and ssgA on the development of both solid- and liquid-grown mycelium of Streptomyces coelicolor and Streptomyces lividans . Over-expression of ftsZ in S . coelicolor M145 inhibited aerial mycelium formation and blocked sporulation . Such deficient sporulation was also observed for the ftsZ mutant . Over-expression of ftsZ also inhibited morphological differentiation in S . lividans 1326, although aerial mycelium formation was less reduced . Furthermore, antibiotic production was increased in both strains, and in particular the otherwise dormant actinorhodin biosynthesis cluster of S . lividans was activated in liquid- and solid-grown cultures . No significant alterations were observed when the gene dosage of ftsQ was increased . Analysis by transmission electron microscopy of an S . coelicolor strain overexpressing ssgA showed that septum formation had strongly increased in comparison to wild-type S . coelicolor, showing that SsgA clearly influences Streptomyces cell division . The morphology of the hyphae was affected such that irregular septa were produced with a significantly wider diameter, thereby forming spore-like compartments . This suggests that ssgA can induce a process similar to submerged sporulation in Streptomyces strains that otherwise fail to do so . A working model is proposed for the regulation of septum formation and of submerged sporulation. Clin Excell Nurse Pract, 2001 May, 5(3), 159 - 67 Factors influencing the antibiotic-prescribing decisions of nurse practitioners; Wright SK et al.; Decision-making about treatment options is a complex process that is influenced by many variables . An instrument for studying this decision-making process and the factors influencing it was designed . A survey of the antibiotic-prescribing practices of nurse practitioners (NPs) was then conducted via mail and the World Wide Web . NPs who treat adult patients were presented with scenarios in which antibiotic prescription would be an appropriate choice . Participants were asked to evaluate the clinical scenarios and describe their decision-making about treatment and the rationale for treatment . Responses were analyzed to determine the factors that played a role in antibiotic decision-making and their relative importance in that process . The ranks of categories of factors by the respondents were similar across the 4 scenarios . Antibiotic-prescribing patterns and the rationale of the antibiotic-prescribing decision of the respondents for the presented scenarios are also described. Hepatogastroenterology, 2001 Mar-Apr, 48(38), 465 - 7 Efficacy and tolerability of antibiotics in patients undergoing H . pylori eradication; Danese S et al.; BACKGROUND/AIMS: Helicobacter pylori (H . pylori) infection is one of the most common gastrointestinal diseases . An increasing number of people undergo different treatment options . Unfortunately, H . pylori therapy may be troublesome for drug side effects and inefficacious for resistance to antibiotics . METHODOLOGY: One hundred and ninety-three (193) H . pylori-positive patients were randomly assigned to one of the following 7-day treatments: Group A (N = 64): amoxicillin, clarithromycin and rabeprazole; Group B (N = 64): tinidazole, clarithromycin and ranitidine bismuth citrate; Group C (N = 65): tinidazole, clarithromycin and rabeprazole Eradication was assessed by 13C-Urea Breath Test 6-8 weeks after the end of the therapy . Not-eradicated patients underwent a second cycle with tinidazole, tetracycline, bismuth and rabeprazole . All patients were asked to complete a validated questionnaire regarding presence and intensity of drug side effects . RESULTS: One hundred and eighty-eight out of the 193 H . pylori-positive patients (96%) completed therapy . No significant difference in eradication rates was observed among the three groups both in intention to treat analysis and in per protocol analysis . No significant difference in incidence of side effects occurred among groups after the first-line regimens: 48% in group A, 44% in group B and 46% in group C . Twenty-two out of the 193 enrolled subjects (11%) were not eradicated after the first-line therapy . Among them, 86% were successfully eradicated by the tinidazole, tetracycline, bismuth and rabeprazole therapy . Moreover, during quadruple therapy, a higher prevalence and intensity of side effects than in each one of the groups submitted to the first-line triple therapy was observed . CONCLUSIONS: This study shows that triple rabeprazole-based eradicating regimens are effective and safe . Incidence of side effects seems low and similar in different three-drug regimens used . Quadruple therapy, which appear highly efficacious as a second line therapy, is associated with a significantly higher incidence of side effects when compared to first-line treatment. Oral Oncol, 2001 Jul, 37(5), 471 - 5 Pulmonary infiltration with eosinophilia (PIE) syndrome induced by antibiotics, PIPC and TFLX during cancer treatment; Yamamoto T et al.; Drugs induce a variety of pulmonary diseases including pulmonary infiltration with eosinophilia (PIE) syndrome . We report a case of PIE syndrome which was observed after neck dissection . An 83-year-old male patient attended our clinic complaining of upper neck swelling and was diagnosed as advanced lymph node metastasis related to previously resected oral carcinoma and underwent neck dissection . Despite administration of antibiotics (piperacillin sodium, PIPC; and tosufloxacin tosilate, TFLX), fever and an elevation of the c-reactive protein (CRP) level with neutrophilia appeared, and an infiltration shadow was observed in the right lower pulmonary field . With the suspicion of pneumonia, the antibiotics were exchanged for panipenem/betamipron . However, the pulmonary infiltration spread widely, CRP increased to 12.9 mg/dl and severe eosinophilia (23%) was observed a few days after changing the antibiotics . PIE syndrome was suspected, and the patient underwent steroid mini-pulse therapy consisting of methylprednisolone sodium succinate (500 mg) and prednisolone (60 mg) . After steroid therapy, the pulmonary condition largely improved . However, about 2 weeks after the start of steroid administration, a fever and a further elevation of CRP were observed with an increase of beta-D-glucan in serum . Roentgenography revealed diffuse infiltration shadows throughout the lungs, and the patient died about 3 weeks after the onset from respiratory distress . In vitro, blastogenesis of patient's peripheral blood lymphocytes was strongly enhanced by PIPC and TFLX, and they generated a large amount of interleukin-5 in the presence of PIPC or TFLX . The clinical course and laboratory examination results revealed that PIE syndrome may have been induced by PIPC and TFLX and that PIE syndrome should be suspected in treatment of carcinomas when dyspnea and pulmonary infiltration are complicated with eosinophilia. J Antibiot (Tokyo), 2001 Mar, 54(3), 220 - 33 Cephaibols, new peptaibol antibiotics with anthelmintic properties from Acremonium tubakii DSM 12774; Schiell M et al.; Two groups of new peptaibol-type antibiotics termed cephaibols have been isolated from the fungus Acremonium tubakii, DSM 12774 . These 16- or 17-unit straight-chain peptides, whose structures were characterized by amino acid analyses, 2-D NMR experiments, and by mass spectrometric sequencing, have a high content of the unusual amino acids aminoisobutyric acid and isovaline . The principal constituent of the novel peptaibol mixture is cephaibol A, which is formed in abundance in cultures of the wild strain . The striking biological property of cephaibol A is its pronounced anthelmintic action and activity against ectoparasites. Protein Sci, 2001 Jun, 10(6), 1254 - 9 Interaction energies between beta-lactam antibiotics and E . coli penicillin-binding protein 5 by reversible thermal denaturation; Beadle BM et al.; Penicillin-binding proteins (PBPs) catalyze the final stages of bacterial cell wall biosynthesis . PBPs form stable covalent complexes with beta-lactam antibiotics, leading to PBP inactivation and ultimately cell death . To understand more clearly how PBPs recognize beta-lactam antibiotics, it is important to know their energies of interaction . Because beta-lactam antibiotics bind covalently to PBPs, these energies are difficult to measure through binding equilibria . However, the noncovalent interaction energies between beta-lactam antibiotics and a PBP can be determined through reversible denaturation of enzyme-antibiotic complexes . Escherichia coli PBP 5, a D-alanine carboxypeptidase, was reversibly denatured by temperature in an apparently two-state manner with a temperature of melting (T(m)) of 48.5 degrees C and a van't Hoff enthalpy of unfolding (H(VH)) of 193 kcal/mole . The binding of the beta-lactam antibiotics cefoxitin, cloxacillin, moxalactam, and imipenem all stabilized the enzyme significantly, with T(m) values as high as +4.6 degrees C (a noncovalent interaction energy of +2.7 kcal/mole) . Interestingly, the noncovalent interaction energies of these ligands did not correlate with their second-order acylation rate constants (k(2)/K') . These rate constants indicate the potency of a covalent inhibitor, but they appear to have little to do with interactions within covalent complexes, which is the state of the enzyme often used for structure-based inhibitor design. Pediatr Infect Dis J, 2001 May, 20(5), 541 - 3 Complications of outpatient parenteral antibiotic therapy in childhood; Gomez M et al.; Complications in children receiving outpatient parenteral antibiotic therapy were reviewed . Catheter-associated complications and/or adverse drug reactions occurred in 50% of courses . Most complications were minor, and almost all infections were successfully treated . Even with early discontinuation of parenteral antibiotics because of adverse drug reactions in 24% of the courses, the outcome was excellent. Pediatrics . 2001 May;107(5):E76. Influence of day care attendance on the use of systemic antibiotics in 0- to 2-year-old children; Thrane N et al.; OBJECTIVE: To examine the association between time spent in different public day care settings and prescription of systemic antibiotics . Design . Population-based cohort study of 5035 Danish children born in 1997 followed from birth to June 30, 1999 . METHODS: The study was performed by the linkage of records drawn from administrative registries . Exposure was the total time spent in a day care home or day care center . Outcome was the first prescription of a systemic antibiotic . Possible perinatal and sociodemographic confounding factors were considered by statistical analysis . RESULTS: During the first year of life, 39.8% of the girls and 51.1% of the boys received at least 1 antibiotic prescription drug . Enrollment in a day care setting doubled a child's risk of receiving a prescription drug (adjusted relative risk in day care home 1.9, 95% confidence interval: 1.7-2.0; adjusted relative risk in day care center 2.0, 95% confidence interval: 1.7-2.3) . Only age confounded the analyses . Age >1 year at the starting time in day care reduced the risk of receiving antibiotic prescriptions during the first 3 months after enrollment . CONCLUSIONS: Enrollment in public day care facilities raised the risk of receiving an antibiotic prescription drug to the same extent in day care homes as well as in day care centers, so we cannot recommend one facility over the other based on the present study . Children <1 year old at enrollment were most at risk, suggesting that extension of parental leave may reduce the use of antibiotics. Drug Chem Toxicol, 2001 May, 24(2), 191 - 200 Evaluation of UV-induced superoxide radical generation potential of some common antibiotics; Ray RS et al.; Photosensitization reaction of drugs leading to the formation of reactive oxygen species (ROS) cause tissue injury causing damage to various cellular macromolecules . The aim of this study was to determine the superoxide anion (O2-) generation potential of commonly used antibiotics so that due precaution could be exercised to minimize their photosensitizing action and oxidative stress potential . The selected antibiotics were examined for their ability to produce (O2-) under sunlight and artificial UVA (320-400 nm) and UVB (290-320 nm) . Lincomycin, cephalothin and erythromycin generated significant amount of O2- under various irradiation conditions . Superoxide dismutase (SOD), an enzymatic quencher of O2- inhibited O2- production in all drugs tested . The results suggest that due precaution are necessary to avoid ultraviolet radiation (UVR) after the intake of photoreactive drugs, especially in tropical and sub tropical countries. Clin Infect Dis, 2001 Jun 15, 32(12), 1685 - 90 Epub 2001 May 21. Introduction of a practice guideline for penicillin skin testing improves the appropriateness of antibiotic therapy; Forrest DM et al.; We hypothesized that the introduction of a practice guideline for penicillin skin testing would increase the appropriateness of skin testing and reduce antibiotic costs for patients with a history of penicillin allergy who have infections caused by penicillin-susceptible pathogens . We measured the appropriateness of skin testing and daily antibiotic costs before and after the introduction of a guideline for penicillin skin testing . For patients who had negative results of skin testing and were subsequently treated with a penicillin instead of an alternative antibiotic, we calculated the difference between the actual costs and the projected costs of continuing alternative antibiotics without skin testing . After the guideline was introduced, appropriateness of skin testing increased from 17% to 64%, but daily antibiotic costs did not change . For patients who had negative results of skin testing and who were subsequently treated with a penicillin, there was no difference between actual costs and the projected costs if they had not been skin tested . We conclude that introduction of a guideline for penicillin skin testing increases the percentage of eligible patients who have a skin test, and it does so without increasing costs. Aust Endod J, 2000 Apr, 26(1), 30 - 9 Selective and intelligent use of antibiotics in endodontics; Abbott PV; Antibiotics have been used extensively for the management of odontogenic infections since their discovery early this century . Although they have been invaluable in the management of acute and severe infections, many members of the dental and medical professions have unfortunately used these drugs inappropriately for the management of dental pain when "local" dental treatment would have sufficed . This, and the general over-use of antibiotics in other situations such as for growth enhancement in animals for human consumption, is leading to the widespread development of strains of bacteria that are resistant to antibiotics--hence, their effectiveness is being reduced at a rapid rate . The dental profession has a responsibility to patients and to the community as a whole to restrict the use of antibiotics to those situations that actually require them . This philosophy should also be extended to other professions who may be called upon to manage dental pain at times. Bull World Health Organ, 2001, 79(4), 313 - 20 Epub 2003 Jul 02. Improving antibiotic prescribing in Hai Phong Province, Viet Nam: the "antibiotic-dose" indicator; Chalker J; OBJECTIVE: To improve the use and dosage of antibiotics prescribed at Commune Health Stations in Viet Nam, and in so doing find out whether antibiotic dosage can be easily and reliably measured as a drug-use indicator . METHODS: All commune health workers from the 217 commune health stations in Hai Phong Province, Viet Nam, were enlisted over an 18-month study period during 1994-96 . The study design was a longitudinal time series, with each new district baseline acting as a rolling control . Each health station was monitored monthly by district supervisors . Two formal evaluations by doctors external to the study were compared with the supervisors' results . Basic medical equipment was provided three times over nine months, conditional on improvements in prescribing practices and adequate supervision of prescribing practices . FINDINGS: The supervisors' data showed that the percentage of encounters in which a patient was prescribed an antibiotic decreased from over 65% to around 45% . When antibiotics were given, the percentage of patients who received an adequate dose increased from under 30% to 98% . These changes were stable for 17 months after the intervention stopped . CONCLUSIONS: Such initiatives require the active collaboration of health personnel and civic leaders at every level . Conditional equipment donation was shown to be effective . A simple indicator measuring adequacy of antibiotic dose can be an effective tool to improve the use of antibiotics in a sustainable way. Fam Pract, 2001 Jun, 18(3), 246 - 8 Re-evaluation of a randomized controlled trial of antibiotics for minor respiratory illness in general practice; Fahey T et al.; BACKGROUND: A systematic review examining the efficacy of antibiotics in acute respiratory illness concluded that antibiotics are of little benefit . However, that review was based on analysis of only six randomized controlled trials, one of which was excluded because its analysis included patients with multiple episodes of illness; treatment group, either antibiotic or placebo, might have confounded the likelihood of suffering a subsequent episode of illness . METHODS: This previously excluded randomized controlled trial of 301 patients with symptoms of minor respiratory illness was re-analysed to examine the efficacy of antibiotic versus placebo in terms of resolution of symptoms, most particularly cough . RESULTS: Antibiotic had no impact on the resolution of symptoms of cough at 1 and 2 weeks, respectively; adjusted odds ratio 1.2 {95% confidence interval (CI) 0.7--2.1} and 0.8 (95% CI 0.4--1.6) . In those 220 (73%) individuals who suffered a cough, 48 (44%) and 19 (17%) of patients taking placebo were still coughing after 1 and 2 weeks, respectively . CONCLUSION: It appears that an antibiotic is likely to have, at best, a marginal impact on resolution of symptoms for most patients with minor respiratory illness in the community. Med J Aust, 2001 Apr 2, 174(7), 333 - 7 The efficacy of an antibiotic protocol for community-acquired pneumonia; Dobbin CJ et al.; OBJECTIVE: To assess the efficacy of an antibiotic protocol to avoid empirical use of third-generation cephalosporins in community-acquired pneumonia (CAP) . DESIGN AND SETTING: Retrospective case review of patients with CAP one year after implementing the protocol . Comparison was made with patients with CAP treated at a metropolitan tertiary referral hospital (where use of third-generation cephalosporins was common) . PARTICIPANTS: 86 patients (district hospital with an antibiotic protocol) and 72 patients (metropolitan tertiary referral hospital), January - June 1999 . Outcome measures: Rate of staff adherence to the protocol; patient characteristics associated with poor protocol adherence; demographic and prognostic features of both groups at presentation; duration of intravenous therapy, time to defervescence, length of stay; inpatient mortality rates; and drug cost savings per patient treated according to the protocol . RESULTS: Overall protocol adherence rate was 60% . Patients with penicillin allergy were significantly less likely to receive treatment according to the protocol (P<0.001) . At the district hospital, patients were generally older and taking more regular medications . Patients at each hospital had similar prognostic factors and demographic features at presentation . Inhospital mortality (P=0.92; 95% CI, -0.08 to 0.07), duration of fever (P=0.57) and length of stay (P=0.78) were not significantly different between patients treated empirically with penicillin and those treated empirically with third-generation cephalosporins . Treating a patient according to the protocol saved an average of $77.44 in drug costs . CONCLUSION: One year after implementation, our protocol for treating CAP is proving efficacious, although levels of adherence could improve. Ann Thorac Cardiovasc Surg, 2001 Feb, 7(1), 14 - 6 Prophylactic intracavitary (pneumonectomy space) antibiotic instillation: a comparative study; Miller JD et al.; BACKGROUND AND OBJECTIVES: Postpneumonectomy empyema is a dreaded complication of pneumonectomy . The effectiveness of prophylactic intracavitary antibiotic instillation is not known . We conducted a retrospective review to assess the effect of pneumonectomy space antibiotic instillation on septic complications (empyema and bronchial fistula) of pneumonectomy . METHODS: Ninety-three consecutive patients underwent pneumonectomy at our institution over a three-year period . Their charts were reviewed retrospectively and data was collected on age, gender, diagnosis, intravenous antibiotics, intracavitary (pneumonectomy space) antibiotics, empyemas, bronchial fistulas, length of hospital stay, and operative mortality . RESULTS: All 93 patients received 3 perioperative doses of prophylactic intravenous antibiotics . One group (n=47) of patients also received intraoperative intracavitary instillation of an antibiotic solution (penicillin G: 5 million units, bacitracin: 50,000 units, gentamicin: 60 mg, in 1 litre of saline) while the other group (n=46) did not . Age, gender, diagnosis, and length of stay were not significantly different in the two groups . There were no empyemas or bronchial fistulas in the intracavitary antibiotic group . Postpneumonectomy empyemas occurred in 6 (13%) patients (empyema with bronchial fistula: 5, empyema alone: 1) that had not received intracavitary antibiotics (p=0.012) . There were 4 deaths (9%) in each group (p=0.63) . CONCLUSIONS: Prophylactic intraoperative intracavitary antibiotic instillation may reduce the incidence of empyemas after pneumonectomy . However, a randomized trial would be needed to prove the effectiveness of this form of prophylactic antibiotic strategy. Biopolymers, 2001, 62(3), 131 - 40 Differential interactions of antitumor antibiotics chromomycin A(3) and mithramycin with d(TATGCATA)(2) in presence of Mg(2+); Chakrabarti S et al.; The antitumor antibiotics chromomycin A(3) (CHR) and mithramycin (MTR) are known to inhibit macromolecular biosynthesis by reversibly binding to double stranded DNA with a GC base specificity via the minor groove in the presence of a divalent cation such as Mg(2+) . Earlier reports from our laboratory showed that the antibiotics form two types of complexes with Mg(2+): complex I with 1:1 stoichiometry and complex II with 2:1 stoichiometry in terms of the antibiotic and Mg(2+) . The binding potential of an octanucleotide, d(TATGCATA)(2), which contains one potential site of association with the above complexes of the two antibiotics, was examined using spectroscopic techniques such as absorption, fluorescence, and circular dichroism . We also evaluated thermodynamic parameters for the interaction . In spite of the presence of two structural moieties of the antibiotic in complex II, a major characteristic feature was the association of a single ligand molecule per molecule of octameric duplex in all cases . This indicated that the modes of association for the two types of complexes with the oligomeric DNA were different . The association was dependent on the nature of the antibiotics . Spectroscopic characterization along with analysis of binding and thermodynamic parameters showed that differences in the mode of recognition by complexes I and II of the antibiotics with polymeric DNA existed at the oligomeric level . Analysis of the thermodynamic parameters led us to propose a partial accommodation of the ligand in the groove without the displacement of bound water molecules and supported earlier results on the DNA structural transition from B --> A type geometry as an obligatory requirement for the accommodation of the bulkier complex II of the two drugs . The role of the carbohydrate moieties of the antibiotics in the DNA recognition process was indicated when we compared the DNA binding properties with the same type of Mg(2+) complex for the two antibiotics . Biochim Biophys Acta, 2001 Feb 16, 1517(3), 410 - 5 Transcriptional analysis and regulation of the sigma-E gene of Streptomyces antibioticus; Bralley P et al.; We report here the mapping of the transcriptional start point and identification of the promoter for the sigE gene of Streptomyces antibioticus . Sequence analysis revealed a conserved genetic organization of five genes encompassing sigE in S . antibioticus and S . coelicolor . Upstream of sigE a number of direct repeats, while conserved in both species, are arranged differently . Gel shift analysis demonstrated binding of a component of both S . antibioticus and S . coelicolor crude protein extracts to a 30 bp sequence encompassing one repeat, the A-rich box . Deletion analysis in promoter probes showed that maximal activity of the S . antibioticus promoter depends upon the presence of the sequence surrounding the A-rich box, as well as the region further upstream carrying other direct repeats. Biochim Biophys Acta, 2001 Feb 9, 1510(1-2), 125 - 35 A photophysical study of the polyene antibiotic filipin . Self-aggregation and filipin--ergosterol interaction; Loura LM et al.; Filipin, a macrolide polyene antibiotic, is known to interact selectively with ergosterol, a constituent of fungi membranes . In this work, the fluorescence resonance energy transfer (FRET) between a fluorescent analog of ergosterol, dehydroergosterol (DHE), and filipin was measured in small unilamellar vesicles of dipalmitoylphosphatidylcholine at 25 degrees C . The time-resolved FRET results were rationalized in the framework of the mean concentration model, and were complemented with steady-state fluorescence intensity, anisotropy and absorption measurements . The results point to the formation of both DHE--filipin aggregates (evidence from static quenching of DHE fluorescence by filipin) and filipin--filipin aggregates (evidence from: (i) the FRET acceptor concentration distributions; (ii) spectral changes of filipin absorption in the vesicles, the excitonic interaction suggesting a stack arrangement; (iii) filipin fluorescence self-quenching), even in presence of DHE and low antibiotic mole fractions (<1 mol%) . These results point out that apparently contradictory biochemical models for the action of filipin (some based on the presence of sterols, others not) can be equally valid . Moreover, since results (ii) and (iii) are also observed when a sterol is present, both models of action can actually coexist in membranes with a low sterol content. Clin Infect Dis, 2001 Jun 1, 32(11), 1651 - 5 Epub 2001 Apr 30. Usefulness of blood culture for hospitalized patients who are receiving antibiotic therapy; Grace CJ et al.; We conducted a retrospective study to determine the yield of blood samples drawn for culture during the initial 72 h of antibiotic therapy given to 139 patients who were admitted to the hospital for community-acquired infections or fever . The yield of these blood cultures was predictable and rarely (in only 1 patient {0.72%}) isolated new pathogens. J Chromatogr B Biomed Sci Appl, 2001 Apr 5, 753(2), 189 - 202 Identification and quantification of five macrolide antibiotics in several tissues, eggs and milk by liquid chromatography-electrospray tandem mass spectrometry; Dubois M et al.; We present an electrospray high-performance liquid chromatographic tandem mass spectrometric (HPLC-MS-MS) method capable of determining in several tissues (muscle, kidney, liver), eggs and milk the following five macrolides: tylosin, tilmicosin, spiramycin, josamycin, erythromycin . Roxithromycin was used as an internal standard . The method uses extraction in a Tris buffer at pH 10.5, followed by protein precipitation with sodium tungstate and clean-up on an Oasis solid-phase extraction column . The HPLC separation was performed on a Purospher C18 column (125 x 3 mm I.D.) protected by a guard column, with a gradient of aqueous 0.1 M ammonium acetate-acetonitrile as the mobile phase at a flow-rate of 0.7 ml min(-1) . Protonated molecules served as precursor ions for electrospray ionisation in the positive ion mode and four product ions were chosen for each analyte for multiple reaction monitoring (MRM) . A validation study was conducted to confirm the five macrolides by MRM HPLC-MS-MS analysis of a negative control and fortified samples . All of the samples analysed were confirmed with four ions . The ion ratio reproducibility limit ranged from 2.4 to 15% . All compounds could be detected and quantified at half-maximum residue limits (MRLs) . The method is specific, quantitative and reproducible enough to conform to European Union recommendations within the concentration range 0.5 MRL-2 MRL (accuracy: 80 to 110%, relative standard deviation: 2 to 13%) . This whole method allows extraction and analysis of up to 50 samples per day. South Med J, 2001 Apr, 94(4), 365 - 9 Antibiotic prescribing practices in a teaching clinic: comparison of resident and staff physicians; Mincey BA et al.; BACKGROUND: The widespread and often inappropriate use of broad spectrum antibiotics in the outpatient setting is recognized as a significant contributing factor to the spread of bacterial resistance . We hypothesized that residents prescribe broader spectrum antibiotics more frequently than staff physicians and adopt more appropriate prescribing practices with increasing levels of training . METHODS: All patient visits for acute sinusitis in our teaching practice between July 1, 1995, and June 30, 1997, were reviewed . Comparisons of antibiotics prescribed were made between staff and residents at each level of training . RESULTS: First- and second-year residents were more likely to prescribe narrow spectrum antibiotics (56%) than third-year residents (35%) or staff (34%) . CONCLUSIONS: Junior residents in our program are more likely to prescribe narrow spectrum antibiotics for the treatment of acute sinusitis than are senior residents or staff . With advancement in level of training, prescribing practices of residents come to resemble those of their supervising staff physicians. J Gastrointest Surg, 2001 Mar-Apr, 5(2), 113 - 8; discussion 118-20 Early treatment with antibiotics reduces the need for surgery in acute necrotizing pancreatitis--a single-center randomized study; Nordback I et al.; Pancreatic infection is the main indication for surgery and the principal determinant of prognosis in acute necrotizing pancreatitis . Previous studies on the effects of antibiotics have not, however, uniformly demonstrated any reduction in the need for surgery or any decrease in mortality among these patients, although the incidence of pancreatic infections was significantly reduced . This single-center randomized study was designed to compare early vs . delayed imipenem treatment for acute necrotizing pancreatitis . Ninety patients with acute necrotizing pancreatitis (C-reactive protein > 150 mg/L, necrosis on CT) were randomized within 48 hours either to a group receiving imipenem (1.0 g plus cilastatin intravenously 3 times a day) or a control group . Not included were those who had been started on antibiotics at the referring clinic, those who were taken directly to the intensive care unit for multiorgan failure, and those who refused antibiotics or might have had adverse reactions . Thirty-two patients were excluded because they were over 70 years of age (not potentionally operable) or for any study violation . There were 25 patients in the imipenem group and 33 patients in the control group . The main end point was the indication for necrosectomy due to infection (i.e., after the initial increase and decrease, there was a second continuous increase in temperature, white blood cell count {> 30%} and C-reactive protein {> 30%}, with other infections ruled out, or bacteria were found on Gram stain of the pancreatic fine-needle aspirate) . In the control group, imipenem was started when the operative indication was fulfilled . Conservative treatment was continued for at least 5 days before necrosectomy . The study groups did not differ from each other with regard to sex distribution, patient age, etiology, C-reactive protein concentration, and extent of pancreatic necrosis on CT . Two (8%) of 25 patients in the imipenem group compared to 14 (42%) of 33 in the control group fulfilled the operative indications (P = 0.003) . Nine patients in the control group responded to delayed antibiotics but five had to undergo surgery . Of those receiving antibiotics, 2 (8%) of 25 in the early antibiotic (imipenem) group needed surgery compared to 5 (36%) of 14 in the delayed antibiotic (control) group (P = 0.04) . Two (8%) of 25 patients in the imipenem group and 5 (15%) of 13 patients in the control group died (P = NS {no significant difference}) . Seven (28%) of 25 in the imipenem group and 25 (76%) of 33 in the control group had major organ complications (P = 0.0003) . Based on the preceding criteria, early imipenem-cilastatin therapy appears to significantly reduce the need for surgery and the overall number of major organ complications in acute necrotizing pancreatitis, and reduces by half the mortality rate; this is not, however, statistically significant in a series of this size. J Chemother, 2001 Apr, 13(2), 107 - 11 Immunopharmacology of antibiotics: direct and indirect immunomodulation of defence mechanisms; Hamilton-Miller JM; Antibiotics can alter the host's reaction to an infection (itself an immunomodulating event) in various ways . Indirect actions involve killing of bacteria, changing the intestinal flora, intrinsic antigenicity and preventing bacteria making virulence factors . Direct actions are upon phagocytic function, chemotaxis and lymphocyte activities . Immunomodulation can be positive ("pro-host") or negative, and can be quantitated by means of the parameter "immune index" . Among the cephalosporins, cefodizime shows the greatest positive immunomodulating activity, due to the unique nature of the 3-sidechain . Cefotaxime has an immunodepressing effect in vitro . The oral cephalosporin cefaclor appears to have a beneficial effect on polymorph function . While immunomodulation by antibiotics may appear marked in in vitro and ex vivo experiments, and in animal models, this phenomenon does not appear to have decisive effects therapeutically. Cochrane Database Syst Rev . 2001;(1):CD002007. Single versus combination intravenous antibiotic therapy for people with cystic fibrosis; Elphick HE et al.; BACKGROUND: Choice of antibiotic, and the use of single or combined therapy are controversial areas in the treatment of respiratory infection in Cystic Fibrosis (CF) . Advantages of combination therapy include wider range of modes of action, possible synergy and reduction of resistant organisms; advantages of monotherapy include lower cost, ease of administration and reduction of drug related toxicity . Current evidence does not provide a clear answer and therefore the use of intravenous antibiotic therapy in CF requires further evaluation . OBJECTIVES: To assess the effectiveness of single compared to combination intravenous antibiotic therapy in the treatment of patients with CF . SEARCH STRATEGY: The Cochrane CF and Genetic Disorders Group Specialised Register of Controlled Trials and the abstract books of the three major CF conferences were searched to identify randomised controlled trials . The register was compiled by conducting detailed computer searches of Medline from 1966-present and Embase 1974-1995 . SELECTION CRITERIA: Randomised controlled trials comparing a single intravenous antibiotic with a combination of that antibiotic plus a second antibiotic in patients with CF . DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data . MAIN RESULTS: A total of nine studies including 386 patients compared a single agent to a combination of the same antibiotic and one other . There was a wide variation in the individual antibiotics used in each study . In total, the studies included eight comparisons of a beta-lactam antibiotic (penicillin-related or third generation cephalosporin) with a beta-lactam-aminoglycoside combination and three comparisons of an aminoglycoside with a beta-lactam-aminoglycoside combination . These two groups of studies were analysed as separate subgroups . There was considerable heterogeneity amongst these trials which led to difficulties in performing the review and interpreting the results . The meta-analysis did not demonstrate any significant differences between monotherapy and combination therapy, in terms of lung function, symptom scores and adverse effects . Single therapy was associated with an increase in the number of patients with resistant strains of Ps . aeruginosa at two to eight weeks follow-up . This is an important preliminary finding which needs further clarification with a good quality long-term study . These results should be interpreted with caution . All but two of the included trials were published between 1977 and 1988; these were single centre studies with flaws in the randomisation process and small sample size . Overall, the methodological quality was poor . REVIEWER'S CONCLUSIONS: The results of this systematic review of monotherapy versus combination therapy for pulmonary exacerbations in CF are inconclusive . The review raises important methodological issues . There is a need for a randomised controlled trial which needs to be well designed in terms of adequate randomisation allocation, blinding, power and long-term follow up . Results need to be standardised to a consistent method of reporting, in order to validate the pool