Antibiotics

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 pooling of results from multiple studies.

Am J Ther, 1999 Jul, 6(4), 217 - 22
Comparison of 7 versus 10 days of antibiotic therapy for hospitalized patients with uncomplicated community-acquired pneumonia: a prospective, randomized, double-blind study; Siegel RE et al.; The objective of this study was to compare the outcome of 7 versus 10 days of antibiotic therapy for inpatients with moderately severe community-acquired pneumonia (CAP) . A prospective, randomized, double-blind study with a follow-up period of 42 days was conducted . Fifty-two veterans were treated with 2 days of cefuroxime at 750 mg intravenously every 8 hours followed by group 1, 8 days oral therapy, and group 2, 5 days oral therapy followed by 3 days of placebo . Oral therapy consisted of cefuroxime axetil at 500 mg every 12 hours . No difference was seen in cure rates: 20 of 22 (90.9%) patients in group 1 and 21 of 24 (87.5%) patients in group 2 . There were no late recurrences . Potential US cost-savings is $27.2 million . Inpatients with moderately severe CAP can be treated with 2 days of intravenous antibiotics followed by 5 additional days of oral antibiotics . Longer treatment duration prolongs the cost of care, without increasing the cure rate or decreasing the pneumonia recurrence rate.

J Org Chem, 2001 May 4, 66(9), 3133 - 9
Enantioselective synthesis of the AB-ring system of the antitumor antibiotic tetrazomine; Wipf P et al.; The synthesis of the 1,2,3,4-tetrahydroisoquinoline moiety of tetrazomine was accomplished in 18 steps and in 3% overall yield from commercially available o-anisaldehyde . The reaction sequence utilizes a Sharpless asymmetric dihydroxylation to install the stereocenter and an intramolecular Friedel--Crafts hydroxyalkylation with an N-protected 2-oxo-acetamide to close the heterocyclic ring.

J Nat Prod, 2001 Apr, 64(4), 444 - 9
Cloning, sequencing, and heterologous expression of the elmGHIJ genes involved in the biosynthesis of the polyketide antibiotic elloramycin from Streptomyces olivaceus Tü2353; Rafanan ER Jr et al.; Elloramycin A (1) belongs to a small family of naphthacenequinones characterized by a unique highly hydroxylated cyclohexenone moiety . A cosmid clone 16F4, harboring genes for the production of 1 from Streptomyces olivaceus Tu2353, has been previously isolated . DNA sequence analysis of a 3.2-kb fragment from 16F4 revealed four open reading frames--the elmGHIJ genes . Heterologous expressions of the elmGHI genes in either Escherichia coli or Streptomyces lividans, followed by biochemical characterizations of the ElmGHI proteins, established ElmG as tetracenomycin B2 oxygenase, ElmH as tetracenomycin F1 monooxygenase, and ElmI as tetracenomycin F2 cyclase . These results provide direct biochemical evidence for the hypothesis that the biosynthesis of 1 in S . olivaceus parallels that of tetracenomycin C (2) in Streptomyces glaucescens and support the notion that the biosynthesis of the highly hydroxylated cyclohexenone moiety in other polyketides most likely follows the same paradigm as the tetracenomycin B2 or A2 oxygenase.

Cell Biochem Biophys, 2000, 33(3), 297 - 308
Aminoglycoside antibiotics bound to aminoglycoside-detoxifying enzymes and RNA adopt similar conformations; Cox JR et al.; Conformations of ribostamycin and isepamicin, aminoglycoside antibiotics, bound to an aminoglycoside antibiotic, 3'-phosphotransferase, were determined by transferred nuclear Overhauser effect spectroscopy and molecular modeling . Two major conformers of enzyme-bound ribostamycin, a neomycin-group aminoglyeoside were observed . The 3'- and 5"-OH groups (reactive hydroxyl groups) in the conformers are placed in approximate locations . One of the conformers is similar to the structure of paromomycin bound to a 27-nucleotide piece of ribosomal RNA that represents the A-site of the small ribosomal subunit, where rings A and C are in an orthogonal arrangement . Isepamicin, a kanamycin-group aminoglycoside antibiotic, also showed two major enzyme-bound conformations . Both conformations were similar to those observed for bound isepamicin in the active site of an aminoglycoside(6')-acetyl transferase-Ii . Conformations of other RNA-bound kanamycin-group aminoglycosides were also similar to the enzyme-bound conformations of isepamicin . These observations suggest that aminoglycosides may adopt similar conformations when bound to RNA and protein targets . This may have significant implications in the design of enzyme inhibitors and/or antibiotics.

J Ir Dent Assoc, 2000, 46(3), 92 - 4
Red man syndrome during administration of prophylactic antibiotic against infective endocarditis; Ngeow WC et al.; Red man syndrome (RMS) is the occurrence flushing, pruritus, chest pain, muscle spasm or hypotension during vancomycin infusion . It usually happens as a result of rapid infusion of the drug but may also occur after slow administration . The frequency and severity of this phenomenon diminish with repeated administration of vancomycin . A case is presented whereby RMS occurred while prophylactic antibiotic against infective endocarditis was administered.

FEBS Lett, 2001 Apr 20, 495(1-2), 52 - 5
Backbone dynamics of the channel-forming antibiotic zervamicin IIB studied by 15N NMR relaxation; Korzhnev DM et al.; The backbone dynamics of the channel-forming peptide antibiotic zervamicin IIB (Zrv-IIB) in methanol were studied by 15N nuclear magnetic resonance relaxation measurements at 11.7, 14.1 and 18.8 T magnetic fields . The anisotropic overall rotation of the peptide was characterized based on 15N relaxation data and by hydrodynamic calculations . 'Model-free' analysis of the relaxation data showed that the peptide is fairly rigid on a sub-nanosecond time-scale . The residues from the polar side of Zrv-IIB helix are involved in micro-millisecond time-scale conformational exchange . The conformational exchange observed might indicate intramolecular processes or specific intermolecular interactions of potential relevance to Zrv-IIB ion channel formation.

Pharmacol Toxicol, 2001 Apr, 88(4), 204 - 8
Short-term effects of four antibiotics on DNA synthesis in endothelial cells; Lanbeck P et al.; The irritating effect of parenterally administered antibiotics on vessels is a common clinical problem . In a previous study we found that solutions of three commonly used antibiotics, cefuroxime, erythromycin and dicloxacillin, exerted cytotoxic effects on endothelial cells after 24 hr exposure . In contrast benzylpenicillin did not have such effects . In the present study, endothelial cells of different origin were exposed to these four antibiotics at higher concentrations than in the previous investigation but only for 5, 30 and 60 min . Incorporation of 3H-thymidine in the cells as a measurement of DNA synthesis was used as cytotoxic assay . A concentration-dependent and time-related inhibition was found after exposure to erythromycin and dicloxacillin but not after exposure to cefuroxime and benzylpenicillin . The effects were similar on the three different cell types used in the experiments . This study demonstrates that the cytotoxic effects differ even after short-term exposure to the antibiotics . In contrast to the previous study, cefuroxime lacks cytotoxicity when endothelial cells are exposed for less than one hour . The short-term exposition model used in this study should be more predictive as it mimics in vivo conditions better.

Anal Chem, 2001 Apr 1, 73(7), 1614 - 21
Simultaneous determination of five beta-lactam antibiotics in bovine milk using liquid chromatography coupled with electrospray ionization tandem mass spectrometry; Riediker S et al.; A multiresidue method for the detection of five important beta-lactam antibiotics (amoxicillin, ampicillin, cloxacillin, oxacillin, penicillin G) in fresh milk is presented that allows quantitation of the analytes well below established legislative limits . The method avoids the use of acid during the extraction procedure and entails a cleanup step over a C18 cartridge . The analytes are separated and detected by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) using a stable isotope-labeled internal standard . Mass spectral acquisition is done in the positive ion mode by applying selected reaction monitoring of two or more fragmentation transitions per analyte to provide a high degree of sensitivity and specificity . The typical recoveries for all five beta-lactams in fresh milk ranged from 76 to 94% at a fortification level of 4 microg/kg . This study also addresses common problems encountered in the stability of penicillins during sample preparation as well as the employment of postcolumn infusion of a standard compound to verify potential matrix-induced signal suppression in ESI-MS.

Am J Gastroenterol, 2001 Apr, 96(4), 1251 - 5
Long-Term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function; Madrid AM et al.; OBJECTIVES: Altered small-bowel motility, lengthening of the orocecal transit time, and small-intestinal bacterial overgrowth have been described in patients with liver cirrhosis . These changes might be related to the progressive course and poor prognosis of the disease . We investigated the effect of a long-term treatment with cisapride and an antibiotic regimen on small-intestinal motor activity, orocecal transit time, bacterial overgrowth, and some parameters of liver function . METHODS: Thirty-four patients with liver cirrhosis of different etiology entered in the study . They were randomly allocated to receive cisapride (12), an alternating regimen of norfloxacin and neomycin (12), or placebo (10) during a period of 6 months . At entry and at 3 and 6 months, a stationary small-intestinal manometry was performed, and orocecal transit time and small-intestinal bacterial overgrowth were also investigated using the H2 breath test . Liver function was estimated with clinical and laboratory measurements (Child-Pugh score) . RESULTS: After 6 months, both cisapride and antibiotics significantly improved fasting cyclic activity, reduced the duration of orocecal transit time, and decreased small-intestinal bacterial overgrowth . Cisapride administration was followed also by an increase in the amplitude of contractions . No statistically significant variations in these parameters were observed with placebo . An improvement of liver function was observed at 3 and 6 months with both cisapride and antibiotics . CONCLUSIONS: Long-term treatment with cisapride or antibiotics reversed altered small-intestinal motility and bacterial overgrowth in patients with liver cirrhosis . These findings suggest a possible role for prokinetics and antibiotics as a modality of treatment in selected cases of decompensated cirrhosis.

J Public Health Med, 2001 Mar, 23(1), 69 - 73
Trends in antibiotic prescribing and associated indications in primary care from 1993 to 1997; Frischer M et al.; BACKGROUND: Recent concerns that evidence on the appropriate use of antibiotics is not having an impact on prescribing trends are based on UK prescribing data relating to 1980-1991 . The aim of this paper is to determine trends in antibiotic prescribing from 1993 to 1997 and link antibiotic prescriptions to diagnostic categories . METHODS: A retrospective analysis of antibiotic prescriptions linked to diagnostic codes was carried out using the West Midlands General Practice Research Database . RESULTS: The prescribing rate for antibiotics fell from 963 prescriptions/1,000 patients in 1993 to 807 prescriptions/1,000 patients in 1997 (p < 0.001) . The proportion of antibiotic prescribing for respiratory conditions fell from 65 per cent in 1993 to 59 per cent in 1997 (p < 0.001) . The main decreases in antibiotic prescribing are accounted for by non-specific lower respiratory tract infections (-22 prescriptions/1,000 patients), non-specific upper respiratory tract infections (-21/1,000 patients) and throat infections (-20/1,000 patients) . There was increased prescribing for non-respiratory miscellaneous conditions (+6 prescriptions/1,000 patients) . CONCLUSIONS: Overall antibiotic prescribing declined by 16 per cent between 1993 and 1997, primarily for respiratory conditions . These results of the current study are in marked contrast to an earlier review, which found an increase of 46 per cent between 1980 and 1991 in England . The level of antibiotic prescribing for conditions which may not be bacterial in origin is still high and there is scope for further reductions in antibiotic prescribing . This study highlights the need for regular epidemiological data to inform the debate on antibiotic prescribing.

EMBO Rep, 2001 Apr, 2(4), 318 - 23
Structural basis for selectivity and toxicity of ribosomal antibiotics; Bottger EC et al.; Ribosomal antibiotics must discriminate between bacterial and eukaryotic ribosomes to various extents . Despite major differences in bacterial and eukaryotic ribosome structure, a single nucleotide or amino acid determines the selectivity of drugs affecting protein synthesis . Analysis of resistance mutations in bacteria allows the prediction of whether cytoplasmic or mitochondrial ribosomes in eukaryotic cells will be sensitive to the drug . This has important implications for drug specificity and toxicity . Together with recent data on the structure of ribosomal subunits these data provide the basis for development of new ribosomal antibiotics by rationale drug design.

Nippon Rinsho, 2001 Apr, 59(4), 781 - 4
{Combination therapy of antibiotics and intravenous immunoglobulin}; Masaoka T; A large scale multicenter randomized controlled study was conducted to evaluate the efficacy of intravenous immunoglobulin in combination with IPM/CS and AMK in 504 evaluable patients who did not respond by 3 day therapy with beta-lactum and aminoglucoside . Immunoglobulin 5 g was administered 3 days to the patients allocated to immunoglobulin group . A completely automatic computer evaluation was performed according to the criteria determined by the committee . The response rate was 61.5% in immunoglobulin group and 47.3% in control group(p < 0.001) . Intravenous immunoglobulin is considered effective for severe infection when used as combination therapy with antibiotics.

Scand J Prim Health Care, 2001 Mar, 19(1), 58 - 63
Antibiotic prescription for acute sinusitis in otherwise healthy adults . Clinical cure in relation to costs; de Bock GH et al.; OBJECTIVE: To determine which treatment strategy offers the most cost-effective option in managing acute sinusitis . DESIGN: The modelling procedure included five clinical strategies, varying from "wait and see for a week", to "prescribing antibiotics selectively" to "prescribing antibiotics immediately" and to "performing further diagnostics" . SETTING: Outpatient clinics and primary health care . PATIENTS: Data were derived from clinical trials that included otherwise healthy patients with acute sinusitis . MAIN OUTCOME MEASURES: The marginal cost-effectiveness . RESULTS: By using the strategy "wait and see for a week", 91.5% of the patients, by "prescribing antibiotics selectively", 93.2%, of the patients, and by "prescribing antibiotics immediately", 94.5% of the patients were cured after a 1-week period . The costs for curing one additional patient were Dutch Florin (DFL) 516 when antibiotics were selectively prescribed, and DFL 882 when antibiotics were immediately prescribed . Further diagnostic procedures did not improve outcome in terms of marginal cost-effectiveness . CONCLUSIONS: In patients presenting with acute sinusitis, postponing antibiotics for 1 week is the most cost-effective strategy.

Antimicrob Agents Chemother, 2001 May, 45(5), 1565 - 7
Vancomycin and ceftazidime bioactivities persist for at least 2 weeks in the lumen in ports: simplifying treatment of port-associated bloodstream infections by using the antibiotic lock technique; Haimi-Cohen Y et al.; The residual antibiotic concentration of vancomycin (2 mg/ml)- or ceftazidime (2 mg/ml)-heparin solutions instilled in ports in pediatric hematology-oncology patients 1 to 34 days earlier was measured . Antibiotic concentrations of > or = 100 microg of either antibiotic per ml persisted for at least 21 days . For treatment of lumenal port infections, antibiotic-heparin dwell times of > or = 2 weeks may be appropriate.

J Appl Microbiol, 2001 Mar, 90(3), 301 - 8
Induction, growth and antibiotic production of Streptomyces viridifaciens L-form bacteria; Innes CM et al.; AIMS: To induce, cultivate and investigate the characteristics of L-form bacteria derived from the filamentous actinomycete Streptomyces viridifaciens . METHODS AND RESULTS: L-forms were induced in a liquid medium supplemented with lysozyme and penicillin . A stable culture which no longer required inducing agents but could still revert, was obtained by the twelfth subculture . The specific growth rate of stable L-forms was faster (0.751) than unstable L-forms (0.361) . After the exponential growth phase, the cell diameter continued to increase, as did the percentage of vacuoles . Morphologically, the L-forms appeared as spherical bodies with no signs of differentiation and were sensitive to osmotic stress, indicating removal of the cell wall . The L-forms produced secondary metabolites although much lower levels of antibiotic were assayed in the L-forms compared with the cell walled forms . CONCLUSION: Stable L-form bacteria were induced from S . viridifaciens and their growth characterized . The L-forms produced secondary metabolites . SIGNIFICANCE AND IMPACT OF THE STUDY: Stable Streptomyces L-forms were induced and have potential as biocontrol agents.

Microbiol Res, 2001 Mar, 155(4), 315 - 23
Production of an antifungal antibiotic by Streptomyces aburaviensis 1DA-28; Raytapadar S et al.; A broad-spectrum antifungal Streptomyces isolate, 1DA-28, from Indian soil has been characterized and identified as Streptomyces aburaviensis var . ablastmyceticus (MTCC 2469) . Nutritional and cultural conditions for the production of antibiotic by this organism under shake-flask conditions have been determined . Antibiotic production in synthetic medium reached the maximum on the 5th day of incubation at 30 degreesC . Glucose and starch were found to be the best carbon sources while NH4NO3 was preferred as nitrogen source . Optimum temperature and pH for antibiotic production were 32 degreesC and 7.4, respectively . Phosphate at a concentration sub-optimal for growth enhanced antibiotic production . Supplementation of medium with casein hydrolysate improved both growth and antibiotic titre but yeast extract exhibited marked inhibition.

Lancet, 2001 Mar 31, 357(9261), 989 - 94
Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial . ORACLE Collaborative Group; Kenyon SL et al.; BACKGROUND: Preterm birth after spontaneous preterm labour is associated with death, neonatal disease, and long-term disability . Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results . We did a randomised multicentre trial to resolve this issue . METHODS: 6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were randomly assigned 250 mg erythromycin (n=1611), 325 mg co-amoxiclav (250 mg amoxicillin and 125 mg clavulanic acid; n=1550), both (n=1565), or placebo (n=1569) four times daily for 10 days or until delivery, whichever occurred earlier . The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital . Analysis was by intention to treat . FINDINGS: None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo (erythromycin 90 {5.6%}, co-amoxiclav 76 {5.0%}, both antibiotics 91 {5.9%}, vs placebo 78 {5.0%}) . However, antibiotic prescription was associated with a lower occurrence of maternal infection . INTERPRETATION: This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection.

Lancet, 2001 Mar 31, 357(9261), 979 - 88
Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial . ORACLE Collaborative Group; Kenyon SL et al.; BACKGROUND: Preterm, prelabour rupture of the fetal membranes (pPROM) is the commonest antecedent of preterm birth, and can lead to death, neonatal disease, and long-term disability . Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate, but the results were inconclusive . We did a randomised multicentre trial to try to resolve this issue . METHODS: 4826 women with pPROM were randomly assigned 250 mg erythromycin (n=1197), 325 mg co-amoxiclav (250 mg amoxicillin plus 125 mg clavulanic acid; n=1212), both (n=1192), or placebo (n=1225) four times daily for 10 days or until delivery . The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital . Analysis was by intention to treat . FINDINGS: Two women were lost to follow-up, and there were 15 protocol violations . Among all 2415 infants born to women allocated erythromycin only or placebo, fewer had the primary composite outcome in the erythromycin group (151 of 1190 {12.7%} vs 186 of 1225 {15.2%}, p=0.08) than in the placebo group . Among the 2260 singletons in this comparison, significantly fewer had the composite primary outcome in the erythromycin group (125 of 1111 {11.2%} vs 166 of 1149 {14.4%}, p=0.02) . Co-amoxiclav only and co-amoxiclav plus erythromycin had no benefit over placebo with regard to this outcome in all infants or in singletons only . Use of erythromycin was also associated with prolongation of pregnancy, reductions in neonatal treatment with surfactant, decreases in oxygen dependence at 28 days of age and older, fewer major cerebral abnormalities on ultrasonography before discharge, and fewer positive blood cultures . Although co-amoxiclav only and co-amoxiclav plus erythromycin were associated with prolongation of pregnancy, they were also associated with a significantly higher rate of neonatal necrotising enterocolitis . INTERPRETATION: Erythromycin for women with pPROM is associated with a range of health benefits for the neonate, and thus a probable reduction in childhood disability . However, co-amoxiclav cannot be routinely recommended for pPROM because of its association with neonatal necrotising enterocolitis . A follow-up study of childhood development and disability after pPROM is planned.

Appl Environ Microbiol, 2001 Apr, 67(4), 1885 - 92
Novel approach for improving the productivity of antibiotic-producing strains by inducing combined resistant mutations; Hu H et al.; We developed a novel approach for improving the production of antibiotic from Streptomyces coelicolor A3(2) by inducing combined drug-resistant mutations . Mutants with enhanced (1.6- to 3-fold-higher) actinorhodin production were detected at a high frequency (5 to 10%) among isolates resistant to streptomycin (Str(r)), gentamicin (Gen(r)), or rifampin (Rif(r)), which developed spontaneously on agar plates which contained one of the three drugs . Construction of double mutants (str gen and str rif) by introducing gentamicin or rifampin resistance into an str mutant resulted in further increased (1.7- to 2.5-fold-higher) actinorhodin productivity . Likewise, triple mutants (str gen rif) thus constructed were found to have an even greater ability for producing the antibiotic, eventually generating a mutant able to produce 48 times more actinorhodin than the wild-type strain . Analysis of str mutants revealed that a point mutation occurred within the rpsL gene, which encodes the ribosomal protein S12 . rif mutants were found to have a point mutation in the rpoB gene, which encodes the beta-subunit of RNA polymerase . Mutation points in gen mutants still remain unknown . These single, double, and triple mutants displayed in hierarchical order a remarkable increase in the production of ActII-ORF4, a pathway-specific regulatory protein, as determined by Western blotting analysis . This reflects the same hierarchical order observed for the increase in actinorhodin production . The superior ability of the triple mutants was demonstrated by physiological analyses under various cultural conditions . We conclude that by inducing combined drug-resistant mutations we can continuously increase the production of antibiotic in a stepwise manner . This new breeding approach could be especially effective for initially improving the production of antibiotics from wild-type strains.

Int J Antimicrob Agents, 2001 Mar, 17(3), 225 - 8
Enhancement of antibiotic activity against poly-drug resistant Mycobacterium tuberculosis by phenothiazines; Viveiros M et al.; Phenothiazines have been shown to inhibit the in vitro growth of multi-drug resistant (resistant to rifampicin and isoniazid) Mycobacterium tuberculosis (MDRTB) . They have been considered as potential adjuvants to regimens employing four or more antibiotics for the management of freshly diagnosed infections of M . tuberculosis in patients from areas known to have a high prevalence of MDRTB . Chlorpromazine has been shown to enhance the activity of antibiotics (except ethambutol) to which M . tuberculosis is susceptible . This might result in a reduction in the dose of some or all of the antibiotics employed without sacrificing the integrity of treatment . Chlorpromazine, thioridazine and promethazine were shown to enhance the activity of rifampicin and streptomycin when used in combinations at concentrations that are minimally effective when employed separately against clinical strains of M . tuberculosis resistant to two or more antibiotics (poly-drug resistant MTB) . The phenothiazines had no effect on the activity of isoniazid against poly-drug resistant MTB.

Biotechnol Appl Biochem, 2001 Apr, 33(Pt 2), 65 - 9
Synthesis and analysis of ethylated tetracycline, an antibiotic derivative that inhibits the growth of tetracycline-resistant XL1-Blue bacteria; Bartzatt R et al.; Bacterial resistance to antibiotics is a significant problem in medical care facilities, causing increased fatalities due to infection . The present study demonstrates that antibiotic structures can be selectively altered in a manner that revives their ability to inhibit bacterial growth . The antibiotic tetracycline was ethylated at the position of the phenolic hydroxy group with the use of diazoethane, forming an ethyl ether functional group . This derivative was dissolved in Luria-Bertani (LB) agar medium, then placed in tissue culture for screening against a tetracycline-resistant bacterial strain . The growth of this bacterial strain, designated XL1-Blue, was inhibited by the ethylated form of tetracycline . The procedure for synthesizing ethylated tetracycline utilizes diazoethane and is presented with the molecular structures and IR spectra . The ethylated form of tetracycline was stable at -20 degrees C for many weeks, and was soluble in LB agar plate medium . Ethylated tetracycline induced growth inhibition of XL1-Blue bacteria within the first 24 h of incubation . The level of bacterial growth inhibition was greater than 30% . Calculation of the partition coefficient, log P, was accomplished and indicates that ethylated tetracycline has an increased lipophilic tendency relative to unmodified tetracycline, and therefore has greater solubility in lipid bilayers.

Bioorg Med Chem Lett, 2001 Mar 26, 11(6), 769 - 72
Design, synthesis, and intracellular localization of a fluorescently labeled DNA binding polyamide related to the antibiotic distamycin; Sharma SK et al.; The design and synthesis of the lipophilic (9) and fluorescent (10) conjugates of a structural analogue of distamycin and their in vitro cellular localization studies are reported . Confocal laser scanning microscopy (CLSM) indicates that 10 rapidly enters human ovarian adenocarcinoma (SKOV-3) cells with principal uptake in mitochondria and uniform cytoplasmic distribution.

Gastrointest Endosc, 2001 Apr, 53(4), 431 - 7
Effect of antibiotic-loaded hydrophilic stent in the prevention of bacterial adherence: a study of the charge, discharge, and recharge concept using ciprofloxacin; Leung JW et al.; BACKGROUND: Ciprofloxacin prophylaxis significantly prolonged stent patency in cats, but human studies produced conflicting results, possibly due to varying drug levels in bile . The uptake (charge) and release (discharge) of ciprofloxacin from a hydrophilic stent (HS) in an antibiotic solution and the effect of a ciprofloxacin-loaded stent (CHS) in inhibiting Escherichia coli adherence were tested . The adjuvant effect of ciprofloxacin perfusion (recharge) in the inhibition of E coli adherence was also tested . METHODS: Uptake: segments of HS were immersed in 5 mL of ciprofloxacin solutions for 24 hours . Ciprofloxacin remaining in solution was measured to determine the uptake by the HS . Release: CHS were placed in 5 mL water for 24 hours, and released ciprofloxacin was measured . CHS were placed on culture plates with E coli and incubated; diameters of inhibited zones were measured . CHS 0.5 cm in length were incubated in separate 5 mL E coli suspension (10(7) colony forming units {CFU}/mL) in 2% ox bile for 4 hours . E coli adhered on CHS were measured and compared with control HS . An E coli (10(6) CFU/mL) suspension was perfused through a modified Robbins device (MRD)-containing CHS . Stents were removed at regular intervals and processed to determine the adherence of E coli; non-loaded HS served as controls . The experiment was repeated by using CHS together with perfusion of ciprofloxacin solution (0.3 microg/mL) into the MRD for up to 7 days; normal saline solution was used as a control in a second MRD . Stents were removed daily to determine the adherence of E coli . RESULTS: Uptake and release of ciprofloxacin by HS and CHS, respectively, were related to concentration of ciprofloxacin . Between 50% to 90% of the drug was released in 24 hours . Zonal inhibition of E coli growth was proportional to the concentration of ciprofloxacin on the CHS . There was an initial 10-fold reduction in attached E coli on CHS compared with controls, but this effect diminished after 24 hours . With ciprofloxacin perfusion, there was a 100-fold reduction in adhered E coli on CHS, although there was no change in E coli concentration in bile . CONCLUSIONS: There was a free exchange (uptake and release) of ciprofloxacin along a concentration gradient between the antibiotic solution and HS . CHS reduced the number of adhered E coli, but the effect was short-lived . Perfusion of ciprofloxacin offers an adjuvant benefit by enhancing inhibition of E coli adherence on CHS.

J Pharm Biomed Anal, 2001 Feb, 24(4), 561 - 7
Spectrophotometric determination of ampicillin, dicluxacillin, flucloxacillin and amoxicillin antibiotic drugs: ion-pair formation with molybdenum and thiocyanate; Mohamed GG; A sensitive spectrophotometric method is developed for the determination of some antibiotic drugs such as ampicillin (amp), dicluxacillin (dicl), flucloxacillin (fluc) and amoxicillin (amox) . The method involves the formation of ion-pairs between these drugs under investigation and inorganic complex of Mo (V) thiocyanate followed by its extraction with methylene chloride . The optimum conditions for the ion-pairs formation are established . The method permits the determination of amp, dicl, fluc and amox over a concentration range of 1.5-77.5, 3-75, 1.5-79 and 7.5-75 microg ml(-1) respectively . The sensitivity (S) is found to be 0.017, 0.061, 0.014 and 0.073 microg cm(-2) for amp, dicl, fluc and amox, respectively . The method is simple, rapid, reproducible and accurate within +/- 1% . The method is applicable for the assay of the four drugs under investigation in different dosage forms and the results are in good agreement with those obtained by the official method.

J Antibiot (Tokyo), 2001 Jan, 54(1), 22 - 8
New cyclic depsipeptide antibiotics, clavariopsins A and B, produced by an aquatic hyphomycetes, Clavariopsis aquatica . 2 . Structure analysis; Suzuki Y et al.; The structures of new cyclic decadepsipeptides, clavariopsins A and B, were determined to be cyclo{-(R)-2-hydroxyisovaleryl-L-pipecoyl-L-MeVal-L-Val-L-MeAsp-L-MeIle-L-MeIle-Gly L-MeVal-L-Tyr(OMe)-} and cyclo{-(R)-2-hydroxyisovaleryl-L-pipecolyl-L-Val-L-Val-L-MeAsp-L-Melle-L-MeIle-Gly-L-MeVal-L-Tyr(OMe)-}, respectively, by spectroscopic analyses, especially using 2D NMR techniques . The absolute stereochemistry was elucidated by the advanced Marfey's method and chiral HPLC analysis.

Enzyme Microb Technol, 2001 Apr 5, 28(6), 510 - 514
Diffusion of (de)acylated antibiotic A40926 in alginate and carrageenan beads with or without cells and/or soybean meal; Jovetica S et al.; Effective diffusion coefficients (D(e)) of antibiotic A40926 and its deacylated derivative were determined in Ca-alginate (2% wt/wt) and kappa-carrageenan (2.6% wt/wt) gel beads with or without immobilized Actinoplanes teichomyceticus cells and/or soybean meal (SBM) . The method used was based on transient concentration changes in a well-stirred antibiotic solution in which gel beads, initially free of solute, were suspended . Unsteady-state diffusion in a sphere was applied and D(e) determined from the best fit of experimental data . A40926 showed markedly different diffusion characteristics than its deacylated derivative . Diffusivity of deacyl-A40926 in alginate or carrageenan gel beads was six to seven times that of A40926 . Large differences in partition coefficients (Kp) were also found . In case of beads without additions, A40926, in contrast to deacyl-A40926, strongly partitioned to the liquid phase . Introduction of SBM and/or mycelium in the gel beads decreased the effective diffusivity of deacyl-A40926, but increased its partitioning to the solid phase . Our findings indicate that a relatively moderate structural change of a lipoglycopeptide molecule could lead to a major change in its diffusion/partition characteristics.

Yakugaku Zasshi, 2001 Mar, 121(3), 193 - 213
{Genetic and biochemical studies on the regulatory mechanism of the self-resistance and biosynthesis of antibiotics}; Ogawara H; The following topics are described: 1 . chemistry of beta-lactamases; 2 . beta-lactamases from Streptomyces including distribution of beta-lactamases in actinobacteria, properties of beta-lactamases from Streptomyces, cloning and regulatory mechanism of expression of beta-lactamase genes from Streptomyces and evolution and classification of beta-lactamases in general; 3 . penicillin-binding proteins from Streptomyces including beta-lactam-producing- and non-producing strains and 4 . eukaryotic-type protein kinases from Streptomyces including cloning of the genes and evolution and classification of eukaryotic-type protein kinases in general.

Fam Pract, 2001 Apr, 18(2), 209 - 13
Antibiotic prescribing in acute infections of the nose or sinuses: a matter of personal habit?
De Sutter AI, De Meyere MJ, De Maeseneer JM, Peersman WP.
BACKGROUND: A proper understanding of how and why GPs prescribe antibiotics in general practice is essential for the design of strategies aimed at making prescribing more rational . OBJECTIVE: The intention of this study is to contribute to such understanding by investigating which elements are important in the GP's decision to prescribe antibiotics for patients with acute infectious complaints of the nose and/or sinuses . METHODS: During their training in general practice, students observed the following elements while attending encounters between their trainer-GP and patients with a runny nose, blocked nose or cough: patient characteristics, contact characteristics, signs and symptoms, diagnosis and prescriptions . Information on practice characteristics and characteristics of the trainer-GP were collected . Data were analysed using multiple logistic regression and multiple linear regression . RESULTS: A total of 722 cases were analysed with the following results: the best independent predictor of an antibiotic prescription is the individual antibiotic prescribing rate (IAPR), which expresses the personal habit of the GP in prescribing antibiotics {adjusted odds ratio (OR) 5.27, 95% confidence interval (CI) 3.22-8.62} . Others are the diagnostic labels "sinusitis" (adjusted OR 2.80, 95% CI 1.2-6.49) and "flu-like syndrome" (adjusted OR 0.08, 95% CI 0.01-0.45), and the sign "sinus tenderness" (adjusted OR 4.37, CI 2.15-8.89) . The antibiotic prescribing behaviour intensifies with an increasing tendency to prescribe medication in general (beta = 0.46, P: < 0.00) and with an increasing defensive attitude (beta = 0.22, P: < 0.05) . CONCLUSIONS: Whether or not a patient with an acute infection of the nose and/or sinuses will be handed an antibiotic prescription seems to depend more on the attending doctor's prescribing behaviour than on the clinical picture . Further qualitative research into attitudes which may be related to a high tendency to prescribe antibiotics consequently is of the utmost importance.

Inorg Chem, 2001 Mar 26, 40(7), 1654 - 62
Ion pairing between Cl- or ClO4- and alkali metal complexes of ionophore antibiotics in organic solvents: a multinuclear NMR and FT-IR study; Wittenkeller L et al.; The extent of ion pairing in chloride and perchlorate salts was studied by measurement of the Cl- and ClO4- resonances and the observation of the perchlorate stretching frequency by use of nuclear magnetic resonance (NMR) spectroscopy and Fourier transform infrared spectroscopy (FT-IR), respectively, for a variety of ionophores in various solutions and in large unilaminar vesicles (LUVs) . The NMR line widths of chloride and perchlorate were larger in solutions containing the neutral ionophores valinomycin (Val) and nonactin (Non) than in solutions containing the negatively charged ionophores nigericin (Nig), lasalocid (Las), and monensin (Mon) . The viscosity-corrected perchlorate NMR line widths in solutions containing Val and Las were significantly negatively correlated (r2 > or = 0.99) with the dielectric constant of the solvent . Solvents with low dielectric constants favored ion pair formation . From methanolic solutions containing the Li+, Na+, K+, and Cs+ salts of Cl- and ClO4-, it was determined that the cation with the highest selectivity for the ionophore affords the most ion pairing . A decrease in pH from 7 to 3 had no significant effect on the NMR line widths of chloride and perchlorate in methanolic solutions containing Val, whereas a similar decrease in pH in a methanolic solution containing Mon caused a 2-fold increase in the line widths . The FT-IR difference spectrum of KClO4 in a methanolic solution containing Val showed splitting at the perchlorate stretching frequency . No band splitting was observed in the FT-IR difference spectrum of KClO(4) in methanolic solutions containing Las . The efflux of 35Cl in LUVs containing the neutral ionophore Val followed first-order kinetics with an efflux constant of 1.70 x 10(-3) x min(-1), as determined by 35Cl NMR spectroscopy . The induction of increased membrane permeability in LUVs by the ionophore was determined to be negligible for Val and Nig by fluorescence spectroscopy.

J Chromatogr A, 2001 Mar 2, 910(2), 285 - 90
Determination of macrolide antibiotics by liquid chromatography; Leal C et al.; The liquid chromatographic separation of seven macrolides used in food producing animals in the European Union has been studied . Separation was performed by using an end-capped high-purity silica-based C18 column and mobile phases consisting of phosphate buffer (pH 2.5)-acetonitrile mixtures . The effect of pH and acetonitrile percentage on the separation was examined . Two UV-based detection systems, wavelength programming and diode array, were assayed . Detection limits were in the range 6-33 microg l(-1) for spiramycin, tilmicosin, tylosin, kitasamicin and josamicin and about 400 microg l(-1) for erythromycin and oleandomycin . The suitability of the method for multiresidue determination of the five macrolides is demonstrated by the analysis of spiked samples of chicken muscle.

Can J Microbiol, 2001 Feb, 47(2), 148 - 52
Antibiotic production, accumulation of intracellular carbon reserves, and sporulation in Micromonospora echinospora (ATCC 15837); Hoskisson PA et al.; The physiology of the actinomycete Micromonospora echinospora was examined during growth . Biphasic accumulation of glycogen occurred, initially during the early exponential growth phase, and again following the onset of sporulation at 120 h . Lipid levels increased during growth eventually representing 25% of the cell mass . A significant proportion of the lipid was found to be in the form of triacylglycerols, which were found to accumulate markedly during the sporulation phase . The disaccharide trehalose was also found to accumulate during growth with levels rising to 5% of the dry weight during the mycelial production phase, then remaining constant during sporulation . Antibiotic was produced transiently by the cultures over the period preceding sporulation.

J Am Acad Dermatol, 2001 Apr, 44(4), 652 - 5
Six cases of confluent and reticulated papillomatosis alleviated by various antibiotics; Jang HS et al.; Confluent and reticulated papillomatosis (CRP) is a relatively rare disorder manifested by persistent papules that are confluent in the center and reticulated at the periphery with a characteristic distribution . Recently, many cases of CRP treated with minocycline have been reported, and their effect seems to be derived from their antibiotic properties . We report 6 cases of CRP alleviated by various antibiotics . The patient described in case 1 is a 16-year-old girl whose disease was alleviated by oral minocycline, 100 mg daily for 8 weeks . Cases 2 and 3 describe an 18-year-old woman and a 17-year-old male adolescent whose disease was reduced by oral fusidic acid, 1000 mg daily for 4 weeks . Case 4 describes a 14-year-old girl who received oral clarithromycin, 500 mg daily for 5 weeks . Case 5 describes a 22-year-old woman whose disease was reduced by oral erythromycin, 1000 mg daily for 6 weeks . Case 5 reports a 24-year-old man who received oral azithromycin, 500 mg daily 3 times per week for 3 weeks . Complete clearing after treatment with antibiotics raises the possibility that CRP is triggered by a bacterial infection and that antibiotics are the treatment of choice for CRP.

Acta Radiol, 2001 Mar, 42(2), 161 - 5
Abscesses of the breast . US-guided serial percutaneous aspiration and local antibiotic therapy after unsuccessful systemic antibiotic therapy; Imperiale A et al.; PURPOSE: The usual therapeutic approach to acute breast abscesses (ABAs) not responsive to systemic antibiotics is surgical incision and drainage . Our purpose was to assess the efficacy of treating ABAs with serial US-guided percutaneous aspiration and local injection of antibiotics . MATERIAL AND METHODS: Twenty-six patients with 28 ABAs, in whom systemic antibiotic therapy had failed, underwent serial US-guided aspiration with local injection a of large-spectrum antibiotic . The treatment was repeated weekly until complete resolution was observed at clinical and US examination . The volume of the ABAs was calculated before each US-guided aspiration . Follow-up US examinations were performed at 1, 4, and 12 weeks after clinical and US resolution . A comparison betweeen costs of surgical and US-guided treatment of ABAs in our institution was done . RESULTS: In 27 ABAs the treatment was successful: a progressive volume reduction and a complete resolution at clinical and US examination was observed within 1 to 7 weeks . In 1 case only, with a large ABA markedly increased in volume at the second examination, surgical drainage was performed . CONCLUSION: US-guided aspiration with local antibiotic injection is a safe and effective approach to ABAs, cheaper than surgical drainage of these lesions.

Hawaii Med J, 2001 Feb, 60(2), 31 - 3
Out-patient parenteral antibiotic therapy (OPAT): clinical outcomes and adverse events; Berman SJ et al.; A chart review was conducted of patients in a program featuring self directed, home infusion of antibiotics for serious infections utilizing an out-patient medical office for teaching, mixing of drugs, and monitoring of patients . 302 courses of out-patient parenteral antibiotic therapy (OPAT) were administered to 221 patients . Therapy was successful in 94% of the episodes . Objective adverse events were noted in 25% of patients . To maximize the chance for a successful outcome, treatment plans should be individualized and structured to include systematic monitoring for adverse effects.

Ned Tijdschr Geneeskd, 2001 Feb 24, 145(8), 353 - 7
{Optimizing antibiotics policy in the Netherlands . VI . SWAB advice: no selective decontamination of intensive care patients on mechanical ventilation}; Bonten MJ et al.; The Working Party on Antibiotic Policy (Dutch acronym is SWAB) has issued a guideline in which the pro and cons of the routine use of selective decontamination (SD) in patients in intensive care (IC) on mechanical ventilation are compared in order to decide whether SD is indicated . The effectiveness of SD in IC patients was evaluated in 28 prospective, randomized studies . In most studies a significant reduction in the incidence of pneumonia was demonstrated . The incidence of pneumonia in the control groups varied from 5 to 85% . The reduction in the incidence of pneumonia seems to have no effect on duration of mechanical ventilation and IC unit stay or the use of antibiotics . No effect on IC mortality was demonstrated . However, only major reductions could have been demonstrated with the size of the studies carried out so far . A significant reduction of about 20% was suggested in two meta-analyses . The validity of these meta-analyses is questionable . Based on the data available, it is not possible to reach the conclusion that SD will be cost-effective . The size of the studies is too small and the study duration too short to prove that the use of SD, if applied on a large scale, might not eventually lead to development of resistance . Selection of micro-organisms that are already intrinsically resistant or had already acquired resistance to one of the agents used, has been demonstrated . In the absence of clearly demonstrated advantages (decrease in mortality, reduction in the use of antibiotics, cost-effectiveness), the routine use of SD in IC patients on mechanical ventilation is not recommended.

Med Sci Monit, 2001 Mar-Apr, 7(2), 289 - 92
Are antibiotics necessary in nonperforated appendicitis in children? A double blind randomized controlled trial; Gorecki WJ et al.; BACKGROUND: The use of antibiotics in uncomplicated appendicitis in children, remains the area of controversy . The aim of the study was to assess the necessity of antibiotic administration in nonperforated appendicitis in children . MATERIAL AND METHODS: The design of the study was a double blind randomized controlled trial, with a follow-up of 4 to 20 months . Setting: Surgical Department in a University Pediatric Hospital . Patients: One hundred and eighty seven out of 249 children subjected to emergency appendectomies met the inclusion criteria, with 35 eligible but not included in the study . The remaining 152 patients were randomized; 41 had complicated appendicitis, 3 other diagnosis, 108 were analyzed within 3 study groups: 1 (n = 31) no antibiotic, 2 (n = 41) one dose, 3 (n = 36) 5-day course . Open appendectomy was a surgical procedure and Ceftriaxone 1.0 g i.v . was administered . Investigated parameters were: body temperature, WBC, bowel sounds, wound healing, recovery and morbidity . RESULTS: Valid outcome data were available for 90 of 108 randomized patients . Protocols of 18 children due to fever > 39 degrees C, upper airway infection or allergy were disclosed . In the remaining 90 children, there were no differences in WBC and oral feeding between groups 1 (n = 24), 2 (n = 35) and 3 (n = 31) . Group 1 and 2 had a higher mean temperature on day 1 post-op, without any clinical significance . A higher mean temperature was noted on day 5 post-op in group 1, due to wound infection in one patient . There were no intraabdominal abscesses . The only other complications were 2 adhesion small bowel obstructions (in groups 1 and 2 each) . CONCLUSION: Routine use of antibiotics in nonperforated appendicitis in children is not necessary.

Br J Gen Pract, 2001 Mar, 51(464), 200 - 5
A randomised controlled trial of delayed antibiotic prescribing as a strategy for managing uncomplicated respiratory tract infection in primary care; Dowell J et al.; BACKGROUND: Despite evidence that uncomplicated lower respiratory tract infection (cough) does not respond appreciably to antibiotics and that bacterial resistance is increasing, general practitioners (GPs) still prescribe frequently . AIM: To assess delayed antibiotic prescribing as a strategy for reducing the unnecessary use of antibiotics for cough in primary care . DESIGN OF STUDY: Open randomised controlled trial of delayed versus immediate prescribing of antibiotics . SETTING: One hundred and ninety-one adult patients with uncomplicated cough in 22 Scottish practices who would have received antibiotics under the GP's usual practice were randomised to receive either an immediate prescription (92 patients) or a delayed prescription (99 patients) . METHOD: Delayed subjects were asked to wait a week before deciding whether to collect their prescription . Outcome measures included symptom duration, prescription uptake, patient satisfaction, patient enablement, and subsequent consultation rates . The 48 GPs who recruited patients were surveyed six months after the trial to see whether they used delayed prescribing as a part of their normal practice . RESULTS: Study and control groups were similar at baseline . Of the subjects in the delayed arm, 55% did not pick up their prescription . Although most patients were satisfied, more patients in the immediate arm were very satisfied with the treatment (P = 0.001) and the consultation (P = 0.03) . The patients in the immediate arm were also more enabled (3.3 versus 2.4; P = 0.04), although more of them intended to consult for similar complaints in the future (85% versus 69%, P = 0.02) . We were unable to detect any difference in actual consulting behaviour in the follow-up period (mean = 15 months {SD = 5 months}) . Subsequently, 68% of GPs used delayed prescribing at least monthly; all gave the prescription to the patient . CONCLUSION: Delayed prescribing is effective at reducing the use of antibiotics for self-limiting cough; however, patients are less satisfied and enabled as a result . Patients may be deterred from consulting rather than becoming enabled.

Tidsskr Nor Laegeforen, 2001 Feb 10, 121(4), 455 - 8
{Can use of antibiotics in acute bronchitis be reduced?}; Fagan MS; BACKGROUND: Acute bronchitis is one of the most common illnesses treated in the primary care setting . Most patients are treated with antibiotics, despite the fact that acute bronchitis is often a viral infection . There is little evidence that antibiotics are of any value in the treatment of this illness . Inappropriate use of antibiotics in the treatment of this and other infectious diseases contributes to the development of resistant bacteria . The purpose of this study was to reduce the prescribing of antibiotics for acute bronchitis in patients without underlying lung disease in the acute care clinic in Arendal, Norway . MATERIAL AND METHODS: The study had three phases, the first of which was a pilot study showing that 87% of patients with acute bronchitis received a prescription for antibiotics . The next phase was an educational intervention in which the physicians were informed of the inappropriately high prescribing rate, the lack of evidence that antibiotics are useful in the treatment of acute bronchitis, and the potential of C reactive protein (CRP) in the diagnose of this illness . The third phase of the study examined the treatment given to patients after the intervention . RESULTS: The antibiotic prescribing rate was reduced from 87% to 71% after the intervention . Doxycycline was prescribed most often, followed by penicillin and erythromycin . The use of CRP increased, and the rate of antibiotic prescriptions for patients with CRP < or = 20 was reduced after the intervention . There were fewer bronchitis diagnoses and more pneumonia diagnoses made after the intervention . INTERPRETATION: An educational intervention designed for prescribing doctors may reduce the use of antibiotics in the treatment of acute bronchitis.

Genetika, 2001 Feb, 37(2), 197 - 206
{Damaging effect of antibiotics on the structure of synaptonemal complexes of meiotic chromosome of mice}; Kolomiets OL et al.; The structure of synaptonemal complexes (SCs) of chromosomes of mouse primary spermatocytes were studied using electron microscopy on days 1, 10, and 36 after the completion of per os administration of drugs belonging to three groups of antibiotics: tetracyclins, macrolides, and fluoroquinolones . The antibiotics were administered to mice during ten days . At the substages of early and middle pachytene, heteromorphic SC bivalents and fragments of chromosome-core elements were detected in spermatocytes at all times studied after the administration of the antibiotics of three groups . As cells passed through the period from early to middle pachytene, the number of cells containing heteromorphic SC bivalents and the fragments of chromosome cores gradually decreased, which could be an indication of selection of cells with chromosomal aberrations . A high level of associations between the X chromosome and autosome bivalents (including heteromorphic ones) also favors this suggestion . A gradual decrease in the number of chromosomal aberrations was detected, as time elapsed from the completion of antibiotics administration . The study of sperm obtained from epididymises of males did not reveal significant differences in both morphology and motility of sperm between males of the control and experimental groups.

J Antimicrob Chemother, 1999 Feb, 43(2), 177 - 85
The suppository form of antibiotic administration: pharmacokinetics and clinical application; Bergogne-Berezin E et al.; The rectal route of antibiotic administration might be used effectively when other routes of administration are inadequate or unsuitable . With the use of various adjuvants, the rectal route can provide satisfactory pharmacokinetics and acceptable local tolerance . Experiments in animals have demonstrated the influence of the pharmaceutical formulation of suppositories on the rectal absorption and systemic distribution of beta-lactams and aminoglycosides . In healthy volunteers and in children under treatment, similar adjuvants--mainly glyceride mixtures or non-ionic surface agents--have increased the rectal absorption of aminopenicillins, cephalosporins and macrolides . Other antibiotics, including metronidazole and cotrimoxazole, have been investigated in respect of their potential rectal administration.

Biochim Biophys Acta, 2001 Mar 9, 1511(1), 90 - 8
Spectrophotometric analysis of organisation of dipalmitoylphosphatidylcholine bilayers containing the polyene antibiotic amphotericin B; Gagos M et al.; Amphotericin B (AmB) is a polyene antibiotic widely used in the treatment of deep-seated fungal infections . The mode of action of AmB is directly related to the effect of the drug on the lipid phase of biomembranes . In the present work the effect of AmB on the properties of lipid bilayers formed with dipalmitoylphosphatidylcholine (DPPC) and the effect of the lipid phase on the molecular organisation of AmB were studied with application of spectrophotometry in the UV-Vis region . The absorption spectra of AmB in lipid membranes display a complex structure with hypsochromically and bathochromically shifted bands indicative of formation of molecular aggregates of the drug . Formation of molecular aggregates was analysed at different concentrations of the drug in the lipid phase in the range 0.05--5 mol% and at different temperatures in the range 5--55 degrees C . The aggregation level of AmB in the ordered phase of DPPC displayed a minimum corresponding to a concentration of 1 mol% with respect to the lipid . An increase in the aggregation level was observed in the temperature region corresponding to the main phase transition . The structure of molecular aggregates of AmB is analysed on the basis of spectroscopic effects in terms of the exciton splitting model . Analysis of the position of the absorption maximum of AmB in the lipid phase of DPPC in terms of the theory of solvatochromc effects makes it possible to ascribe the refractive indices n=1.40 and n=1.49 to the hydrophobic core of the membrane in the L(alpha) and the P(beta)' phase respectively . Analysis of the aggregation of AmB in the lipid phase in relation to the physical state of the membrane reveals that the temperature range of the main phase transition of a lipid cluster in the immediate vicinity of AmB depends on its concentration . The termination of the phase transition temperature, as read from the AmB aggregation, varies between 42 degrees C at 1 mol% AmB in DPPC and 49 degrees C at 5 mol% AmB in DPPC . The exciton splitting theory applied to the analysis of the spectroscopic data makes it possible to calculate the diameter of the AmB pore as 2.8 A in the gel phase and 3.6 A in the fluid phase of the DPPC membrane, on the assumption that the pore is formed by nine AmB molecules.

J Hosp Infect, 2001 Mar, 47(3), 235 - 8
Could irrigation, debridement and antibiotic therapy cure an infection of a total hip arthroplasty?
Krasin E, Goldwirth M, Hemo Y, Gold A, Herling G, Otremski I.
Seven patients suffering from an acute (less than two weeks) infection of a total hip arthroplasty were treated by irrigation and debridement, with appropriate antibiotic therapy and retention of the prosthesis . They were followed for an average of 30 months . Infection did not recur in five (71%) patients, but the other two required further surgery . We conclude that a cure can be obtained by this method, although the results are inferior to re-implantation . A minimal procedure spares a patient the morbidity and cost of a more extensive operation . Higher success rates might have been achieved by selecting patients infected with organisms of low virulence, but there are insufficient data to predict whether this treatment would decrease the success of subsequent re-implantation .

Yao Xue Xue Bao, 1997, 32(1), 28 - 32
{A monoclonal antibody directed against an enediyne antitumor antibiotic and its preliminary application}; Zhou CS et al.; C1027, composed of an enediyne chromophore and an apoprotein of 110 amino acid residues, is a new highly potent macromolecular antitumor antibiotic . In order to prepare monoclonal antibodies (McAb) against C1027 by hybridoma technique, natural C1027 was inactivated by ultraviolet and coupled with human serum albumin, then immunized BALB/c mice . After cell fusion and screening by ELISA, a hybridoma secreting anti-C1027 McAb designated as F9 was obtained . McAb F9 specifically reacted with C1027 as determined by immunoblot assay . No obvious difference was observed between the reactivity of McAb F9 to natural C1027 and that of McAb F9 to ultraviolet inactivated C1027 . This result indicates that the ultraviolet-sensitive chromophore of C1027 may not participate in the epitope for McAb F9 . The isotype of F9 is IgG1 and its affinity constant was found to be (2.2 +/- 0.47) x 10(7) L.mol-1 according to Beatty's method . By clonogenic assay, McAb F9 neither affected the cytotoxicity of C1027 to KB cells nor blocked the activity of the chromophore . McAb F9 also specifically reacted with the recombinant truncated C1027 apoprotein in which 16 amino acid residues at the C terminus were deleted . This study suggests that F9 is a valuable McAb for the research of C1027 apoprotein engineering, C1027 related immunoconjugates and screening of new macromolecular antitumor substances with homology to the protein part of C1027.

Physiol Plant, 2001 Mar, 111(3), 269 - 272
Advances in the selection of transgenic plants using non-antibiotic marker genes; Joersbo M; Production of transgenic plants started more than a decade ago, but it is still a time-consuming operation . One of the critical points is the selection procedure used for the recovery of transgenic shoots after transformation . Moreover, as more transgenic traits are to be incorporated into crops that already have been transformed, it is clear that there is a need for new methods with higher efficiencies . In this article, recently developed selection systems are reviewed . They differ from conventional selection techniques as they are based on supplementing the transgenic cells with a metabolic advantage rather than killing the non-transgenic cells . In many cases, these new selection systems have been found to be superior to conventional methods.

Paediatr Perinat Epidemiol, 2001 Jan, 15(1), 61 - 7
A prospective study of antibiotic use and associated infections in young children; Bergus GR et al.; This study examines antibiotic usage and associated infections in infants and young children in Iowa . Longitudinal data were collected using a cohort recruited at birth from eight hospitals in eastern Iowa . Parents of recruited children were mailed questionnaires at 6 weeks, and 3, 6, 9, 12, 16, and 20 months of age . The cumulative incidence of antibiotic use and associated infections was determined using Kaplan-Meier survival analysis . There were data on 1,368 children . Antibiotic use was common in our cohort and increased with age . Beginning at age 3 months, approximately 50% of the cohort was exposed to an antibiotic during each reporting period . Otitis media was the most common indication and was responsible for 67.3% of antibiotic use . Children were most frequently treated with amoxicillin, followed by the cephalosporins and sulphonamides . By 12 and 20 months of age 79.0% and 92.5% of the children, respectively, had been treated with at least one course of antibiotics . Children received antibiotics for a median of 43 days by 20 months of age . Males were more likely to experience any antibiotic exposure than females (hazard ratio = 1.18) and showed a trend for more days of use (P = 0.052) . There was a small but significant variation in antibiotic usage in the different recruitment communities (P = 0.02).

J Chromatogr B Biomed Sci Appl, 2001 Feb 25, 751(2), 357 - 63
Rapid antibiotic drug monitoring: meropenem and ceftazidime determination in serum and bronchial secretions by high-performance liquid chromatography-integrated sample preparation; Ehrlich M et al.; A sensitive and rapid HPLC assay for the determination of the beta-lactam antibiotics ceftazidime and meropenem in serum and bronchial secretions is described . HPLC-integrated sample preparation allows direct injection of serum samples without any pretreatment . Sputum samples need only a simple homogenisation and volume measurement but no liquefying reagents are necessary . The inline extraction technique is realized by automatically switching from the extraction column to the analytical column . After the matrix passed the extraction column, the retained analyte is quantitatively transferred to the analytical column where separation by isocratic HPLC is performed . Ceftazidime and meropenem are detected according to their absorption maxima at 258 and 296 nm, respectively . The detection limit of both antibiotics is estimated to be better than 0.5 microg/ml in serum as well as in sputum samples . The described procedure allows determination of the antibiotics within 30-45 min, thereby facilitating drug monitoring in clinical routine.

J Chemother, 2001 Feb, 13(1), 3 - 8
Immunomodulation by macrolide antibiotics; Labro MT et al.; Macrolide antibiotics are strongly concentrated within host cells, a property that sustains their activity against intracellular pathogens and is likely responsible for the modulation of cell metabolism and function . There is extensive literature on the subject of macrolide-induced modulation of immune responses . Erythromycin A derivatives seem to display anti-inflammatory activity in vitro, in some animal models and in various clinical settings such as diffuse panbronchiolitis (DPB) . The underlying mechanisms are not yet fully understood: inflammatory cytokine and oxidant production by phagocytes is down-regulated by these drugs, but other possible targets include bacterial virulence factors, bronchial and epithelial cells, etc . Also, a link has been suggested between the macrolide transmembrane carrier system and the P-glycoprotein family, which comprises MDR (multiple drug resistance) and CFTR (cystic fibrosis transmembrane conductance regulator), which are respectively involved in the chemotherapeutic resistance of cancer cells and in the genesis of cystic fibrosis.

J Med Microbiol, 2001 Mar, 50(3), 243 - 8
The effect of human serum DNAases on the ability to detect antibiotic-killed Escherichia coli in blood by PCR; Heininger A et al.; PCR has proved superior to conventional blood culture for diagnosing bacteraemia in the presence of antibiotics . Nevertheless, even PCR might yield false-negative results if the template DNA were to be cleaved by serum DNAases after antibiotics had induced bacterial death . To evaluate the cleavage of bacterial template DNA by human serum DNAase I, serum samples inoculated with purified Escherichia coli DNA were incubated with increasing amounts of recombinant human DNAase (rhDNAase) and then examined by a PCR specific for E . coli . As a prerequisite of potential DNAase attack, the release of E . coli DNA after antibiotic-induced bacterial death was quantified by fluorescence microscopy and flow cytometry . Finally, the influence of rhDNAase on the PCR-based detection of antibiotic-killed E . coli in serum was assessed . The results indicated that purified E . coli DNA is remarkably stable in human serum; positive PCR results did not decrease significantly until the ratio of recombinant human DNAase I:E . coli rose to 106:1 . As only 14.8-28.4% of the total E . coli DNA was released after antibiotic killing, the PCR-based detection of E . coli fell by only 10% when cefotaxime-killed E . coli were incubated with rhDNAase . It was concluded that human serum DNAases and antibiotic killing do not compromise the reliability of PCR examinations for bacteraemia.

Bioorg Med Chem Lett, 2001 Feb 26, 11(4), 591 - 4
Aminoglycoside antibiotics, neamine and its derivatives as potent inhibitors for the RNA-protein interactions derived from HIV-1 activators; Hamasaki K et al.; Neamine derivatives which have an arginine (RN), a pyrene (PCN) and both pyrene and arginine (PRN) have been prepared and their binding toward the RNA fragments derived from HIV-1 activator region, TAR and RRE RNA were examined . Among them, PRN bound either TAR RNA or RRE RNA with equivalent binding affinities as Tat and Rev peptide, respectively.

J Cataract Refract Surg, 2001 Feb, 27(2), 198 - 200
Topical anesthesia for phacoemulsification and painless subconjunctival antibiotic injection; Kayarkar VV et al.; Endophthalmitis is a serious postoperative complication of phacoemulsification surgery . Administration of a subconjunctival antibiotic is a common method of prophylaxis in the United Kingdom and other countries . Injection of subconjunctival cefuroxime can be very painful, especially after phacoemulsification under topical anesthesia . Our experience is that this could be the only painful step in the entire operation . We evaluated a technique in which buffered lignocaine is injected into the subconjunctival space before the antibiotic injection . The technique was used in 46 eyes (46 patients) that had phacoemulsification under topical anesthesia . Eighty-seven percent of patients found the injection painless, 6.5% reported that the pain was very negligible, and 6.5% reported a moderate degree of pain.

J Bacteriol, 2001 Mar, 183(6), 2041 - 5
Programmed cell death in Escherichia coli: some antibiotics can trigger mazEF lethality; Sat B et al.; The discovery of toxin-antitoxin gene pairs (also called addiction modules) on extrachromosomal elements of Escherichia coli, and particularly the discovery of homologous modules on the bacterial chromosome, suggest that a potential for programmed cell death may be inherent in bacterial cultures . We have reported on the E . coli mazEF system, a regulatable addiction module located on the bacterial chromosome . MazF is a stable toxin and MazE is a labile antitoxin . Here we show that cell death mediated by the E . coli mazEF module can be triggered by several antibiotics (rifampicin, chloramphenicol, and spectinomycin) that are general inhibitors of transcription and/or translation . These antibiotics inhibit the continuous expression of the labile antitoxin MazE, and as a result, the stable toxin MazF causes cell death . Our results have implications for the possible mode(s) of action of this group of antibiotics.

Med Clin (Barc), 2001 Feb 3, 116(4), 133 - 5
{Phlebitis due to intravenous administration of macrolide antibiotics . A comparative study of erythromycin versus clarithromycin}; de Dios Garcia-Diaz J et al.; BACKGROUND: To know and to compare the incidence of phlebitis due to intravenous administration of macrolide antibiotics erythromycin and clarithromycin . PATIENTS AND METHOD: Non-randomized prospective study of consecutive patients who were diagnosed of community pneumonia and treated with intravenous macrolides (19 with erythromycin and 25 with clarithromycin) . RESULTS: The cumulative incidence of phlebitis in patients treated with erythromycin was 78.9% (incidence rate of 0.40 episodes/patient-day) and in those treated with clarithromycin 76% (incidence rate of 0.35 episodes/patient-day) . CONCLUSIONS: The risk of phlebitis is high and similar with intravenous administration of both macrolides.

Nippon Rinsho, 2001 Feb, 59(2), 308 - 13
{Selection of antibiotics and planning of eradication for H . pylori infection}; Murakami K et al.; There is general agreement that H . pylori should be eradicated in patients with peptic ulcers . But the optimal therapeutical regimen to be used still remains a matter for many investigations . An increase in the prevalence of antibiotic-resistant H . pylori strains has been reported recently . The recommended drugs for the eradication in Japan are clarithromycin (CAM) and amoxicillin (AMPC) because metronidazole (MNZ) is anti-parasites drug in Japan . A total of 392 H . pylori strains in the last twelve years were tested for sensitivity to CAM, MNZ, and AMPC . The Primary resistance of H . pylori to CAM, MNZ, and AMPC were found in 10.2%, 26.5%, and 0.3% strains, respectively . The resistant strains to CAM were gradually increasing in the last few years . The eradication therapies which do not increase antibiotics resistant strains after eradication failure were reported . The recommendation for eradication in patients with peptic ulcer disease includes those with bleeding ulcers . The pretreatment with proton pump inhibitors (PPI) does not influence the success of PPI-based triple therapy in eradicating H . pylori.

Perit Dial Int, 2000 Nov-Dec, 20(6), 694 - 8
Correlation of intraperitoneal antibiotic pharmacokinetics and peritoneal membrane transport characteristics; Elwell RJ et al.; OBJECTIVE: To identify correlations between the pharmacokinetic variables that describe drug disposition in peritoneal dialysis (PD) patients and the measures used to assess dialysis adequacy . DESIGN AND METHODS: This retrospective study re-evaluated data collected during previous pharmacokinetic studies for intraperitoneally administered cefazolin, ceftazidime, and gentamicin in continuous ambulatory peritoneal dialysis (CAPD) patients, and intravenous cefazolin and tobramycin in automated PD patients . Pharmacokinetic variables were compared to creatinine clearance (CCr), Kt/V, and peritoneal equilibration test data using the Pearson product correlation coefficient (r) . RESULTS: Prominent correlations were found between renal CCr and renal Kt/V, with renal clearances of CAPD cefazolin and ceftazidime, and automated PD tobramycin and cefazolin (r values ranged from 0.698 to 0.986; p < 0.05) . CONCLUSION: These findings support current peritonitis treatment recommendations that patients with residual renal function may require higher doses or more frequent drug administration.

J Chromatogr A, 2001 Jan 12, 906(1-2), 91 - 103
High-performance liquid chromatographic and capillary electrophoretic enantioseparation of plant growth regulators and related indole compounds using macrocyclic antibiotics as chiral selectors; Hui F et al.; Enantioseparation of plant growth regulators, such as 3-(3-indolyl)-butyric acid, abscisic acid and structurally related molecules including a variety of substituted tryptophan compounds, has been achieved by HPLC and/or CE . The covalently bonded macrocyclic antibiotics, teicoplanin, ristocetin A and vancomycin, were used as chiral stationary phases (CSPs) in HPLC . Most of the racemates were baseline resolved in the reversed-phase mode (EtOH-H2O) using the teicoplanin CSP . The chiral recognition mechanism is discussed in regard to the structure of the analytes . In CE, the three aforementioned macrocyclic antibiotics were used as chiral additives in a phosphate run buffer . The effect of pH and the concentration of the organic modifiers were considered . The results obtained by HPLC and CE were compared.

J Chromatogr A, 2001 Jan 12, 906(1-2), 73 - 89
Chiral separations using the macrocyclic antibiotics: a review; Ward TJ et al.; The macrocyclic antibiotics have recently gained popularity as chiral selectors in CE, HPLC and TLC . The macrocyclic antibiotics used for chiral separations include the ansamycins, the glycopeptides, and the polypeptide antibiotic thiostrepton . Although not strictly considered macrocyclic antibiotics, the aminoglycosides are antibiotics that have been used for chiral separations in CE . More chiral analytes have been resolved using the glycopeptides than with the other macrocyclic antibiotics combined . The glycopeptides vancomycin, ristocetin A and teicoplanin have been used extensively as chiral selectors in CE, with ristocetin A appearing to be the most useful chiral selector followed by vancomycin and teicoplanin, respectively . The macrocyclic antibiotics have also been used as chiral bonded phases in HPLC, and HPLC stationary phases based on vancomycin, ristocetin A and teicoplanin have been commercialized . Ristocetin A seems to be the most useful glycopeptide HPLC bonded phase, but its greater expense can be a drawback . The macrocyclic antibiotics have been used with micelles to improve efficiency, provide unique selectivity, and extend the range of separations to neutral solutes . Changing the macrocyclic antibiotic used in CE or HPLC can significantly alter the enantioselectivity of the separations . In fact, the glycopeptide antibiotics are complementary to one another, where if a partial enantioresolution is obtained with one glycopeptide, there is a high probability that a baseline or better separation can be obtained with another.

Indian J Exp Biol, 2000 Jul, 38(7), 727 - 9
Hypolipidemic, hypoprostatic and pharmacological activity of oxohexaene polyene antibiotic (HA-1-92); Naik SR et al.; HA-1-92, a new oxohexaene polyene macrolide showed significant hypolipidemic and hypoprostatic activity both in rat and rabbit models . HA-1-92 did not elicit significant effect on blood pressure or respiration in anaesthetized rat or on various isolated tissue preparation studies.

Antibiot Khimioter, 2000, 45(10), 5 - 9
{Biosynthesis of the non-polyene antibiotic imbricin in the medium containing the producer culture filtrate}; Topkova OV et al.; Imbricin (macrolide nonpolyen antibiotic) biosynthesis conditions was investigated in the medium containing culture filtrate of its producer--Streptomyces imbricatus . It was demonstrated that filtrate contains some regulator substance affecting the antibiotic biosynthesis and metabolism processes of actinomycetes S . imbricatus . Maximum of regulator accumulation coincides with maximum of antibiotic biosynthesis, and amount of synthesized imbricin is proportional to the amount of the culture filtrate added to the medium . When low active mutant of S . imbricatus was grown in the medium with added regulator its activity achieved the control level . It was shown that stimulating activity of the producer's culture filtrate is not connected with pH changes or with supplement with some additional nutritional substrates.

Jpn J Antibiot, 2000 Nov, 53(11), 631 - 6
{Evaluation of antibiotic preparations for children from a standpoint of water-solubilities}; Honda Y et al.; The evaluation of seven widely-used antibiotic preparations {five cephem antibiotics; cefaclor (CCL), cefpodoxime proxetil (CPDX-PR), cefdinir (CFDN), cefditoren pivoxil (CDTR-PI), cefcapene pivoxil (CFPN-PI), one macrolide; clarithromycin (CAM) and one penem; faropenem sodium (FRPM)} for children were performed from a standpoint of water-solubilities, both as a preparation and as a component drug . As the results, these preparations showed great differences in the water-solubilities when added 10 ml water to 0.5 g of each preparation . That is, their solubilities differed from about 40% (CFPN-PI) to 100% (FRPM) as a preparation, and from nearly 0% (CAM) to 100% (FRPM, CCL) as a component drug . Additionally, about a half of the insoluble residues were found to be the component drug, in the cases of three preparations (CPDX-PX, CFDN, CDTR-PI) which were solubilized at 80-90% . From these results, it was suggested that the marketed antibiotic preparations for children might be classified into three categories; i.e., {A} preparation for solution and suspension (FRPM, CCL), {B} preparation suitable to suspension (CPDX-PR, CFDN, CDTR-PI), and {C} fine granule preparation for children unsuitable to suspension (CFPN-PI, CAM) . Consequently, the names for dosage-forms of these preparations should be standardized.

Zh Mikrobiol Epidemiol Immunobiol, 2000 Nov-Dec, (6), 48 - 51
{Immunocorrective effect of proteolytic enzymes on antibody genesis in mice subjected to infectious burn trauma and treatment with antibiotics}; Khmelevskaia IG; As revealed in this study, massive burn trauma manifestly suppresses the genesis of antibodies to T-dependent antigen (sheep red blood cells) . The administration of ampicillin to the burned animals enhances immunosuppression, while gentamicin produces no essential impact on immune processes under these conditions . Proteolytic enzymes, terrilytin and terridecase, have corrective influence on disturbances in immune response in animals with burns . Enzyme in the immobilized form (terridecase) has a more pronounced immunotropic activity in this type of pathology.

J Dairy Sci, 2001 Jan, 84(1), 100 - 6
Effect of composition of colostrum and transition milk from Holstein heifers on specificity rates of antibiotic residue tests; Andrew SM; The objective of this study was to evaluate the effects of colostrum and transition milk composition on specificity rates of antibiotic residue screening tests . Milk from 25 primigravid Holstein heifers was collected from either first, second, or third milking (colostrum) and from either fifth, sixth, or seventh milking (transition milk) following parturition . Milk sampled was visibly normal and heifers were not treated with an antibiotic within 30 d before parturition . Quarter foremilk samples were collected aseptically and analyzed for mastitis pathogens . A sample from the total composite milk was analyzed for somatic cell counts (SCC), milk protein and fat, immunoglobulin concentrations and for antibiotics using four antibiotic residue screening tests . Mastitis pathogens were present in colostrum from 36% of heifers (n = 9) and from 16% of heifers (n = 4) in the subsequent transition milk . Mean SCC were 2,458,000 and 866,000 counts/ml and IgG1 concentrations were 22.7 and 3.07 mg/ml for colostrum and transition milk, respectively . Specificity rates of the screening tests ranged from 0.16 to 0.88 for colostrum and 0.60 to 1.0 for transition milk . Increased milk protein and IgG1 concentrations in milk were associated with an increase in the probability of a false positive outcome for the Charm Cowside (Charm Sciences, Inc., Malden, MA), CITE Snap (IDEXX Laboratories, Westbrook, ME), and Penzyme (Cultor Food Science, Milwaukee, WI) tests . Fat content of milk was positively related to an increase in false positive rates for the CITE Snap test . Milk should not be tested for antibiotic residues before the sixth milking after parturition to avoid high rates of false positive outcomes.

Afr J Med Med Sci, 1999 Sep-Dec, 28(3-4), 193 - 4
Intra-operative antibiotic bead maker--point of technique; Alonge TO et al.; Chronic osteomyelitis is a disease of soft tissue and bone and it is common in the developing countries . The management of this debilitating disease requires the delivery of the appropriate chemotherapeutic agent at the site of the infection after adequate debridement . The search for a suitable carrier for these chemotherapeutic agents is the advent of the 'septopal' or gentamycin-polymethylmethacrylate (gentamycin-PMMA) beads . Septopal beads are expensive and are not affordable by patients in the developing countries . Moreover, most of the micro-organisms (mixed flora) responsible for chronic osteomyelitis in our hospitals are sensitive to ceftriaxone and only in a few cases were gentamycin-sensitive micro-organisms isolated . Therefore, it was imperative that patient-specific and antibiotic-specific PMMA beads would be the way forward and this is the reasoning behind the production of the intra-operative antibiotic bead maker (IABM) and the point of technique is hereby presented.

Eur J Clin Microbiol Infect Dis, 2000 Dec, 19(12), 938 - 42
Mycobacterial growth indicator tube versus the proportion method on Löwenstein-Jensen medium for antibiotic susceptibility testing of Mycobacterium tuberculosis; Cambau E et al.; The Mycobacterial Growth Indicator Tube, a reliable system for detection of mycobacterial growth, was compared with the reference proportion method on Lowenstein-Jensen medium for antibiotic susceptibility testing of Mycobacterium tuberculosis . A total of 62 clinical strains and four reference strains of Mycobacterium tuberculosis were tested for susceptibility to streptomycin, isoniazid, rifampicin and ethambutol . Of these, 36 were susceptible to all four antibiotics and 30 were resistant to at least one of them . Tests were repeated in cases of discrepant results . When each drug/strain combination was considered separately, the overall agreement between the two methods was 96.5% (98.4% for streptomycin, 95.3% for isoniazid, 96.9% for rifampicin and 95.3% for ethambutol) with regard to the initial testing and 98.8% (100, 98.5, 98.5 and 98.4%, respectively) after repeated testing . When the results were considered strain by strain, the agreement was 86% after the initial testing and 95% after repeated testing . The results were obtained after a mean time of 9.5 days . These results suggest that the Mycobacterial Growth Indicator Tube is a reliable method for testing susceptibility of mycobacterial strains to first-line antituberculous drugs.

Scand J Infect Dis, 2000, 32(6), 685 - 8
Duration of postoperative antibiotic therapy following revision for infected knee and hip arthroplasties; Houshian S et al.; In the period from 1990 to 1998 28 patients (14 males and 14 females) were treated for infected hip (19 cases) and knee (9 cases) arthroplasties . The median age at index operation was 72 y (range 34-82 y) and at revision surgery 74 y (range 36-83 y) . The primary diagnosis was osteoarthritis (16 cases), rheumatoid arthritis (5 cases), failed femoral neck fracture (6 cases) and arthritis secondary to congenital hip dislocation (1 case) . Nine cases were infected early, i.e . within 3 months postoperatively, and 19 had late infections . The median interval from index operation to diagnosis of the infected arthroplasty was 18 months (range 1-156 months) . Postoperatively, all patients received antibiotics based on susceptibility studies of the causative organism according to culture specimens . The erythrocyte sedimentation rate and CRP level were controlled twice a week during hospitalization and antibiotics were continued until normalization of CRP . The indication for the shift from intravenous to oral antibiotics was a rapid fall in CRP . Antibiotic therapy was terminated when CRP was close to or below 10 mg/l and there was evidence of clinical recovery . Based on the screening of ESR and CRP in this study we believe that CRP is a valuable parameter in deciding when to stop antibiotic therapy . However, it is not clear whether a shorter treatment period is effective or not.

Laryngorhinootologie, 2000 Dec, 79(12), 758 - 61
{Local antibiotic administration decreases risk of inner ear damage in effodation}; Fischer M et al.; BACKGROUND: Mobilising the stapes via the removal of the tympanosclerotic plaques from the oval window niche (effodation) and stapedectomy or malleovestibulopexy are the different procedures generally available for the surgical therapy of stapes fixation due to tympanosclerosis . These techniques bear a significant risk of sensory hearing loss . Here we analyse our results using the mobilisation technique together with locally applied antibiotics . PATIENTS: Nineteen ears in seventeen patients with tympanosclerosis involving the stapes and its footplate which underwent stapes mobilisation between 1991 and 1999 have been investigated retrospectively . According to the literature this operation has a high risk of cochlear hearing loss . To reduce this risk, azlocillin was instilled locally during removal of tympanosclerotic plaques . RESULTS: Different operation techniques have been used: classic type III with placement of a cartilage disc on the head of the stapes (4), interposition of the incus (3), interposition of the head of malleus (1), interposition of a ceramic-PORP (6) and cartilage columella in cases of significant stapes footplate erosion (3) . In two operations the chain was intact and no reconstruction was necessary . Pure-tone-audiometry showed no significant decrease of bone-conduction thresholds . Preoperatively 4 (21.1%) ears had an average air-bone-gap < or = 30 dB, while postoperatively 15 (78.9%) ears had this level of hearing . CONCLUSIONS: Until the exact causes of the loss of hearing after mobilisation or stapedectomy in cases of tympanosclerosis are known, the local administration of antibiotics is certainly recommended, bearing in mind the initial hypothesis that infection may be jointly responsible for cochlear hearing loss on mobilisation or stapedectomy in cases of tympanosclerosis.

N Z Med J, 2000 Nov 24, 113(1122), 493 - 6
General practitioner management of upper respiratory tract infections: when are antibiotics prescribed?
Arroll B, Goodyear-Smith F.
AIM: To assess General Practice (GP) description and management of upper respiratory tract infections (URTI), including conditions under which they prescribe antibiotics . METHOD: A telephone survey of a randomised sample of Auckland GPs . RESULTS: There was a 61% response rate . 82 of the 100 GPs interviewed agreed that most patients presenting with URTI expected antibiotics . Persistent symptoms and indication of specific infection (tonsillitis, otitis media, sinusitis, pharyngitis, purulent sputum) were common reasons for prescribing . Patients travelling overseas, expecting or requesting antibiotics and prior use of over-the-counter (OTC) medications increased antibiotic prescribing-rates . Most GPs (95%) issued as-needed prescriptions on occasion; 13% did this often . Amoxicillin and amoxicillin/clavulanic acid were most commonly used . Despite wide-ranging antibiotic use for URTI (0 to 90%), only 6% of GPs felt they prescribed more antibiotics than others . CONCLUSIONS: The results suggest over-prescription is common-place, but use of as-needed prescriptions to reduce antibiotic use is encouraging . Exploration of patient expectations in the consultation may assist in decreasing prescribing rates.

J Fam Pract, 2001 Jan, 50(1), 32 - 7
Use and perceptions of antibiotics for upper respiratory infections among college students; Zoorob RJ et al.; BACKGROUND: Upper respiratory infections (URIs) are mainly viral in nature, rendering antibiotics ineffective . Little is known about what college students believe concerning the effectiveness of antibiotics as a treatment for URIs . METHODS: Students (n=425) on 3 college campuses were surveyed using a survey describing 3 variations in presentation of an uncomplicated URI . Participants were questioned about their likelihood of using a variety of treatments for the URI and about their likelihood of seeking a physician's care . RESULTS: The percentage of students endorsing antibiotic use differed significantly by symptom complex . Likelihood of seeking medical care also differed significantly across symptom groups, with greater endorsement in the discolored nasal discharge and low-grade fever scenarios . Stepwise multiple regression analysis revealed that belief in antibiotic effectiveness for cold symptoms decreased with tic and Therapeutic increasing years of higher education . Likelihood of antibiotic use across different scenarios increased with age . Likelihood of seeking care across different scenarios was related to type of health insurance and belief in antibiotic effectiveness . CONCLUSIONS: Undergraduate college students show poor recognition of typical presentations of the common cold and have misconceptions about effective treatment . Although increasing years of college correlated with decreasing belief in antibiotics' effectiveness for a cold, more health education at the college level is recommended.

Can J Ophthalmol, 2000 Dec, 35(7), 373 - 8
Effect of prophylactic antibiotics and incision type on the incidence of endophthalmitis after cataract surgery; Colleaux KM et al.; BACKGROUND: There is controversy as to the efficacy of various measures in the prophylaxis of endophthalmitis after cataract surgery . In addition, it has been suggested that clear-corneal incisions may convey an increased risk of postoperative infection . We performed a retrospective review to assess the effect of prophylactic antibiotics and incision type on the incidence of endophthalmitis after cataract surgery . METHODS: A retrospective chart review and surgeon survey were used to collect data for the 13,886 consecutive cataract operations performed between Sept . 1, 1994, and Jan . 31, 1998 by nine surgeons at a hospital-based surgical unit in Saskatoon . All cataract extractions were by phacoemulsification . All cases of endophthalmitis arising from the unit are managed at the hospital except in extenuating circumstances . We assessed the effect of preoperative administration of antibiotic drops, subconjunctival antibiotic injections at the conclusion of surgery and clear-corneal versus scleral tunnel incisions on the incidence of endophthalmitis by means of univariate and multivariate Poisson regression analysis . RESULTS: The incidence of postoperative endophthalmitis was significantly lower with subconjunctival antibiotic injections than without such injections (0.011% vs . 0.179%) (p = 0.009, odds ratio 16.23 {95% confidence interval 1.92 to 137.14}) . The difference in the incidence of endophthalmitis with preoperative use of antibiotic drops (0.066%) and with no antibiotic drops preoperatively (0.115%) was not significant . Similarly, the difference in the incidence of endophthalmitis with clear-corneal (0.129%) and scleral tunnel (0.050%) incisions was not significant . INTERPRETATION: Our results suggest that prophylactic subconjunctival antibiotic injections at the conclusion of cataract surgery decrease the incidence of postoperative endophthalmitis.

Clin Resour Manag, 2000 Oct, 1(10), 151 - 3, 145
Antibiotic-related ADEs plummet and pharmacy costs shrink with computer-aided decision support; Antibiotic usage for respiratory tract infections in an era of rising resistance and increased cost pressure; Pharmacoeconomic study models have a number of inherent problems that significantly limit their use within the medical community . They are frequently retrospective and thus have only limited relevance in a field in which resistance patterns are highly volatile . Moreover, the study models do little to consider the numerous economic perspectives involved, such as the patients themselves as well as society at large . Prescribing patterns profoundly affect overall healthcare costs . As much as $8.4 billion is spent on community-acquired pneumonia each year; 8% of that cost is for antibiotic therapies . Moreover, studies show that inappropriate prescribing for upper respiratory tract infections is the norm not the exception, with significant cost and health consequences . Also adding to costs is patient noncompliance, which could possibly be reduced with once-daily dosing regimens and widespread patient education about appropriate use of antibiotics.

Stomatologiia (Mosk), 2000, 79(6), 35 - 7
{Dynamics of immune status in patients with phlegmons of the maxillofacial area during endolymphatic antibiotic therapy}}; Tereshenko AE et al.; Studies of immunotropic effects of ampicillin, gentamicin sulfate, lincomycin, and rifampicin SV used in endolymphatic therapy of patients with maxillofacial phlegmons demonstrated a pronounced immunomodulating effect of rifampicin SV in polygluquine . The immunomodulating effect of lincomycin was lower, and that of ampicillin virtually null . Gentamicin sulfate suppressed some parameters of the immune status.

Med Sci Monit, 2000 Jan-Feb, 6(1), 168 - 70
New formula for calculating antibiotic critical concentration by the disk diffusion method; Bednar M; New formula was designed for calculation of the antibiotic critical concentration: Cc = (1/pi Bh)e-A/B where h is agar depth, B is the slope, A is the intercept . The formula is derived from the second Fick's law . Neither diffusion constant nor critical time data apply . Three or more disks containing varied concentrations of the same antibiotic are used . Regression analysis of square of zone of inhibition radii is performed and subsequently the critical concentration is computed.

J Pharmacol Exp Ther, 2001 Mar, 296(3), 806 - 10
Potassium current antagonist properties and proarrhythmic consequences of quinolone antibiotics; Anderson ME et al.; Quinolones are clinically important antibiotic drugs . One quinolone antibiotic, sparfloxacin (SPX), has been recently reported to increase the QT interval, and another quinolone, grepafloxacin (GRX), was withdrawn because it induced torsade de pointes (TdP), a polymorphic ventricular tachycardia (VT) linked to excessive QT interval prolongation . To determine whether SPX, GRX, and other recently developed quinolones, gatifloxacin (GAT) and moxifloxacin (MOX), have similar, potentially deleterious, properties we compared these agents in two ways . First, we measured their relative antagonist potency against the rapid component of the delayed rectifier K(+) current (I(Kr)), and second we determined the QT interval prolongation and inducibility of VT and TdP using a well established in vivo rabbit arrhythmia model . All of these agents are I(Kr) antagonists with the following IC(50) values (mean +/- S.E.) for I(Kr) block: SPX, 0.23 +/- 0.07 microM; MOX, 0.75 +/- 0.31 microM; GAT, 26.5 +/- 13.4 microM; and GRX, 27.2 +/- 11.6 microM . All agents also increased the maximum QT interval (mean +/- S.E.) from baseline (241 +/- 10 ms): SPX, 370 +/- 30 ms; MOX, 270 +/- 30 ms; GRX, 280 +/- 25 ms; and GAT, 255 +/- 23 ms . No agents caused TdP during a standard 30-min observation period, but SPX-treated animals developed nonsustained VT (three of six) and TdP (one of six) during an extended 60-min observation period . These findings show that I(Kr) block may be a common feature of many quinolone antibiotics, and that the proarrhythmic consequences vary according to I(Kr) antagonist potency, but are also influenced by additional, unidentified factors.

ALTEX, 1993, 10(2), 27 - 49
{Problems of the prophylactic use of antibiotics in cell culture}; Kuhlmann I I; The article describes the historical development of the prophylactic use of antibiotics in cell culture as well as the effect of antibiotics on cells, i.e . the beta-lactam antibiotic penicillin, the aminoglycosid antibiotics (streptomycin, neomycin, kanamycin, gentamycin) and the polyene macrolids (nystatin, amphotericin B, fungizone) . The way in which antibiotics influence the morphology of cells, their degeneration, their death and their functions is summarized . The DNA- as well as the protein-synthesis is affected . By this, multiple metabolic processes are interfered with or changed . This fact should be considered, when cell culture research is concerned . As antibiotics are used in multifold ways, the otherwise standardized conditions in cell culture are no longer comparable . The prophylactic use of antibiotics is rejected for scientific reasons.

Curr Infect Dis Rep, 2001 Feb, 3(1), 35 - 43
Use of Modeling Techniques to Aid in Antibiotic Selection; Firsov AA et al.; Over the past decade, the use of modeling techniques in the development of novel antibiotics has been primarily associated with in vitro dynamic models . These models allow comparisons among different antibiotics by simulating human pharmacokinetics . Although dynamic models have been used extensively, their full potential has not been achieved because of inadequate experimental design and/or suboptimal quantitation of bacterial killing/regrowth curves inherent in many studies . These issues are discussed in this review, which is based on recent pharmacodynamic findings with novel fluoroquinolones.

Acta Crystallogr C, 2001 Jan, 57(Pt 1), 95 - 6
Polyether antibiotic CP44,161; Allen P et al.; The crystal structure of antibiotic CP44,161, 6-(7-(2-ethyl-2-{5-(1-hydroxymethyl)-5-methyl-2,3,4,5-tetrahydro-2-furyl}-4,10,-12-trimethyl-1,6,8-trioxadispiro{4.1.5.3}pentadec-13-en-9-yl)-4-hydroxy-3,5-dimethyl-6-oxononyl)-2-hydroxy-3-methylbenzoic acid monohydrate, C43H66O10.H2O, has been determined by X-ray crystallography . The molecule adopts a cyclic conformation, with a centrally located water molecule contributing to the stability of the conformation through hydrogen-bonding interactions.

Biochem J, 2001 Feb 1, 353(Pt 3), 709 - 17
Cysteine residues in the D-galactose-H+ symport protein of Escherichia coli: effects of mutagenesis on transport, reaction with N-ethylmaleimide and antibiotic binding; McDonald TP et al.; The galactose-H(+) membrane-transport protein, GalP, of Escherichia coli is similar in substrate specificity and susceptibility to cytochalasin B and forskolin, to the human GLUT1 sugar-transport protein; furthermore, they are about 30% identical in amino acid sequence . Transport activities of both GalP and GLUT1 are inhibited by the thiol-group-specific reagent, N-ethylmaleimide . GalP contains only three cysteine residues at positions 19, 374 and 389, each of which we have mutated, singly and in combination, to serine . Each single change of Cys-->Ser has only a minor effect on transport activity, whereas alteration of all three simultaneously profoundly diminishes V(max) for transport . The high level of expression of the GalP protein facilitates measurements of the reactivity of each mutant with N-ethylmaleimide or eosin 5-maleimide, which conclusively demonstrate that Cys(374) is the site of covalent modification by the reagents . By comparing the reactivity of Cys(374) in right-side-out and inside-out vesicles it appears that Cys(374) is located on the cytoplasmic face of the GalP protein . Although impaired in transport activity, the 'Cys-free' mutant, with all three cysteine residues mutated into serine, binds cytochalasin B and forskolin with wild-type affinities . All these results are interpreted in terms of a 12-helix model of the folding of the protein, in which the relative orientations of helix 10, containing the reactive Cys(374) residue, and helix 11, containing the unreactive Cys(389) residue, can now be defined.

Mol Microbiol, 2001 Feb, 39(3), 553 - 66
Genetic and transcriptional analysis of absA, an antibiotic gene cluster-linked two-component system that regulates multiple antibiotics in Streptomyces coelicolor; Anderson TB et al.; In Streptomyces coelicolor, the AbsA1-AbsA2 two-component system regulates the expression of multiple antibiotic gene clusters . Here, we show that the response regulator encoded by the absA2 gene is a negative regulator of these antibiotic gene clusters . A genetic analysis shows that the phosphorylated form of the AbsA2 response regulator (phospho-AbsA2), generated by the cognate AbsA1 sensor histidine kinase, is required for normal growth phase regulation of antibiotic synthesis . In the absence of phospho-AbsA2, antibiotics are produced earlier and more abundantly . Overexpression of AbsA1 also deregulates antibiotic synthesis, apparently shifting the AbsA1 protein from a kinase-active to a phospho-AbsA2 phosphatase-active form . The absA1 and absA2 genes, which are adjacent, are located in one of the antibiotic gene clusters that they regulate, the cluster for the calcium-dependent antibiotic (CDA) . The absA genes themselves are growth phase regulated, with phospho-AbsA2 responsible for growth phase-related positive autoregulation . We discuss the possible role and mechanism of AbsA-mediated regulation of antibiotic synthesis in the S . coelicolor life cycle.

Eur J Pharmacol, 2001 Jan 26, 412(2), 121 - 6
Effects of antibiotics on the contractility and Ca2+ transients of rat cardiac myocytes; Belus A et al.; We have compared the effects of streptomycin sulphate, gentamicin sulphate and neomycin sulphate on cell shortening (our index of contractility) and intracellular Ca2+ ({Ca2+}(i)) transients of rat ventricular myocytes . All three agents abolished shortening and {Ca2+}(i), transients but streptomycin was significantly less potent than the other agents . The IC(50) of streptomycin was 0.37 mM for shortening and 0.78 mM for {Ca2+}(i), approximately an order of magnitude greater than equivalent values for gentamicin and neomycin . Gentamicin and streptomycin shortened the action potential duration of most cells but prolonged the action potential duration of others . We therefore conclude that multiple ionic mechanisms affecting action potential duration are modulated by these antibiotics . Our observations are consistent with the negative inotropic effect of antibiotics being caused by a decrease in Ca2+ influx causing a reduction in the {Ca2+}(i) transient.

J, Exp . Mar . Biol . Ecol. . 2001 Jan 31, 256(2), 241 - 251
Anoxic survival of Macoma balthica: the effect of antibiotics, molybdate and sulphide; de Zwaan A et al.; In anoxic semi-closed systems, the survival time of the clam Macoma balthica was compared to clams which were incubated in the presence of several antibiotics (chloramphenicol, 5-oxytetracycline hydrochloride, penicillin, streptomycin, a mix of penicillin and streptomycin and a mix of chloramphenicol, polymyxin, neomycin and penicillin), sulphide and chloramphenicol at pH 6.8 and 8.2 and molybdate (specific inhibitor of the process of sulphate reduction) . The aim was to detect maximum survival times of this clam and indications for the cause of mortality under the conditions tested . Median survival time (LT(50)) of the clam was 4.8 days (at 19 degrees C) in incubations without any addition . Added sulphide (200 microM) decreased survival time . At pH 8.2, LT(50) decreased by 20.8% and at pH 6.8 by 35.2% . However, added molybdate, which suppressed biotic sulphide formation, did not improve survival time (LT(50)=4.4 days) . Biotic sulphide probably did not speed up mortality rate, but indicated excessive growth of sulphate reducing bacteria once mortality started . The presence of different antibiotics increased significantly survival time (LT(50)) from 8.9 to 14.9 days . Qualitative estimations were made of the numbers of bacteria present in the systems . Compared to a seawater control, highest numbers were observed in the incubation of clams without additions and in the presence of molybdate . Nevertheless, due to the presence of molybdate, bacteria numbers were significantly lower . However, very low numbers of bacteria were observed in the incubations of clams in the presence of chloramphenicol . These data demonstrated that the presence and proliferation of bacteria was probably the cause of death of the clams.

Cell, 2000 Dec 22, 103(7), 1143 - 54
The structural basis for the action of the antibiotics tetracycline, pactamycin, and hygromycin B on the 30S ribosomal subunit; Brodersen DE et al.; We have used the recently determined atomic structure of the 30S ribosomal subunit to determine the structures of its complexes with the antibiotics tetracycline, pactamycin, and hygromycin B . The antibiotics bind to discrete sites on the 30S subunit in a manner consistent with much but not all biochemical data . For each of these antibiotics, interactions with the 30S subunit suggest a mechanism for its effects on ribosome function.

J Bacteriol, 2001 Mar, 183(5), 1755 - 64
Growth-phase-dependent expression of the cyclopeptide antibiotic microcin J25; Chiuchiolo MJ et al.; Microcin J25 is a 2,107-Da, plasmid-encoded, cyclopeptide antibiotic produced by Escherichia coli . We have isolated lacZ fusions to mcjA (encoding the 58-amino-acid microcin precursor) and mcjB and mcjC (which are required for microcin maturation), and the regulation of these fusions was used to identify factors that control the expression of these genes . The mcjA gene was found to be dramatically induced as cells entered the stationary phase . Expression of mcjA could be induced by resuspending uninduced exponential-phase cells in spent supernatant obtained from an early-stationary-phase culture . Induction of mcjA expression was not dependent on high cell density, pH changes, anaerobiosis, or the buildup of some inducer . A starvation for carbon and inorganic phosphate induced mcjA expression, while under nitrogen limitation there was no induction at all . These results taken together suggest that stationary-phase induction of mcjA is triggered by nutrient depletion . The mcjB and mcjC genes were also regulated by the growth phase of the culture, but in contrast to mcjA, they showed substantial expression already during exponential growth . Induction of the microcin genes was demonstrated to be independent of RpoS, the cyclic AMP-Crp complex, OmpR, and H-NS . Instead, we found that the growth-phase-dependent expression of mcjA, mcjB, and mcjC may be explained by the concerted action of the positively acting transition state regulators ppGpp, Lrp, and integration host factor . Measurements of microcin J25 production by strains defective in these global regulators showed a good correlation with the reduced expression of the fusions in such mutant backgrounds.

Pediatrics . 2001 Feb;107(2):E15.
A randomized controlled trial of point-of-care evidence to improve the antibiotic prescribing practices for otitis media in children; Christakis DA et al.; CONTEXT: Prescribing practices for otitis media are not consistent with current evidence-based recommendations . OBJECTIVE: To determine whether point-of-care evidence delivery regarding the use and duration of antibiotics for otitis media decreases the duration of therapy from 10 days and decreases the frequency of prescriptions written . DESIGN: Randomized, controlled trial . SETTING: Primary care pediatric clinic affiliated with university training program . Intervention . A point-of-care evidence-based message system presenting real time evidence to providers based on their prescribing practice for otitis media . MAIN OUTCOME MEASURES: Proportion of prescriptions for otitis media that were for <10 days and frequency with which antibiotics were prescribed . RESULTS: Intervention providers had a 34% greater reduction in the proportion of time they prescribed antibiotics for <10 days . Intervention providers were less likely to prescribe antibiotics than were control providers . CONCLUSIONS: A point-of-care information system integrated into outpatient pediatric care can significantly influence provider behavior for a common condition.

J Biol Chem, 2000 Apr 14, 275(15), 11010 - 6
Purification and structural determination of SCB1, a gamma-butyrolactone that elicits antibiotic production in Streptomyces coelicolor A3(2); Takano E et al.; Early stationary phase culture supernatants of Streptomyces coelicolor A3(2) contained at least four small diffusible signaling molecules that could elicit precocious antibiotic synthesis in the producing strain . The compounds were not detected in exponentially growing cultures . One of these compounds, SCB1, was purified to homogeneity and shown to be a gamma-butyrolactone of structure (2R, 3R,1'R)-2-(1'-hydroxy-6-methylheptyl)-3-hydroxymethylbutanolide . Bioassays of chemically synthesized SCB1, and of its purified stereoisomers, suggest that SCB1 acts in a highly specific manner to elicit the production of both actinorhodin and undecylprodigiosin, the two pigmented antibiotics made by S . coelicolor.

Presse Med, 2000 Dec 2, 29(37), 2033 - 5
{Resistance and new antibiotic strategies . Consequences of the use of antibiotics: how to preserve they efficacy}; Bergogne-Berezin E; FACTORS CONTRIBUTING TO RESISTANCE: Several factors contribute to the spread of resistance (international travel, grouping together severely ill patients, etc.) and others contribute to the emergence of resistance (e.g., catheters for S . epidermidis) . The effect of these different factors on the spread and expression of resistance cannot be predicted . How can antibiotic efficacy be preserved? Less overuse of antibiotics, for example for bronchial infections, would be helpful . Educational programs, for patients and physicians alike, is also a crucial point, although its impact has been somewhat disappointing . OTHER ATTITUDES COULD ALSO BE IMPLEMENTED: Use of the most powerful member of a given antibiotic family, overall restriction on antibiotic use, improved diagnostic and laboratory methods . All of these propositions must be examined in light of real experience.

J Hum Lact, 2000 Nov, 16(4), 351 - 8
Use of anti-infective agents during lactation: Part 1--Beta-lactam antibiotics, vancomycin, quinupristin-dalfopristin, and linezolid; Chin KG et al.; Because many antibiotics are excreted into the breast milk, it can be difficult for a practitioner to choose an antibiotic for a lactating patient that will have minimal risks to her nursing infant . This article is the first of a three-part series discussing the use of anti-infective agents during lactation . The authors review general information regarding use and common side effects of several classes of antibiotics . They also summarize information, including documented milk concentrations, milk-to-plasma ratios, and other pharmacokinetic properties, in a table that can help practitioners choose antibiotics that may be considered safe for the lactating mother.

J Chemother, 2000 Dec, 12(6), 471 - 4
National and local antibiotic policies in Central and Eastern Europe; Krcmery V et al.; To assess the antibiotic policies of Central European countries, we performed an overview of antibiotic stewardship, prescription habits and antibiotic prescription regulatory procedures . Since most Central European countries have had centralized health care and drug policies, the situation 10 years after decentralization is surprising . Only 3 of 10 Central European countries have some regulation of prescription of antibiotics, only 4 restrict some antibiotics, only 5 have hospital and only 3 national antibiotic policies . In all but 3 countries physicians can prescribe quinolones and/or 3rd generation oral cephalosporins as first-line antibiotics . Information on local and national antibiotic policies in Central and Eastern European countries is given including prescription guidelines for antibiotic use in community and hospital.

J Orthop Trauma, 2000 Nov, 14(8), 529 - 33
Prospective, randomized, double-blind study comparing single-agent antibiotic therapy, ciprofloxacin, to combination antibiotic therapy in open fracture wounds; Patzakis MJ et al.; OBJECTIVE: The purpose of this study was to compare the efficacy of a single agent, ciprofloxacin, with that of combination antibiotic therapy consisting of cefamandole and gentamicin in all types of open fracture wounds . STUDY DESIGN: A prospective double-blind randomized clinical trial . SETTING: A Level 1 trauma center . PATIENTS: One hundred ninety-five consecutive patients with 203 open fractures were enrolled over a twenty-month period . Twenty-nine fractures from low-velocity gunshot wounds were excluded, and three other patients were excluded because of protocol violations . Our final number of patients were 163, with 171 open fractures . MAIN OUTCOME MEASUREMENT: The infection rates for Type I and Type II open fractures for both antibiotic groups were calculated . The infection rate of Type III open fractures for both antibiotic groups was also calculated . Chi-square analysis with Yates correction was used to assess statistical significance of two treatment groups . RESULTS: The infection rate for Types I and II open fractures in the ciprofloxacin group was 5.8 percent and 6 percent for the cefamandole/gentamicin group (p = 1.000) . The infection rate for Type III open fractures for the ciprofloxacin group was 31 percent (8 of 26) versus 7.7 percent (2 of 26) for the cefamandole/gentamicin group (p = 0.079) . There were no statistically significant differences in infection rate between the group treated with ciprofloxacin and that treated with cefamandole/gentamicin for Types I and II open fracture wounds . However, there appeared to be a high failure rate for the ciprofloxacin Type III open fracture group, with patients being 5.33 times more likely to become infected than those in the combination therapy group . Although this difference was not statistically significant, possibly because of the small sample size, there was a definite trend toward statistical significance . CONCLUSION: Single-agent antibiotic therapy with ciprofloxacin is effective in treatment of Type I and Type II open fracture wounds . However, on the basis of our results, we cannot recommend ciprofloxacin alone for Type III wounds . Possibly one can use fluoroquinolones in combination therapy, specifically as an alternate to an aminoglycoside.

Ann Pharm Fr, 2000 Dec, 58(6 Suppl), 455 - 63
{Residues of antibiotics and protection of the health of consumers . Notions of maximal residues limit and withdrawal time}; Enriquez B; The notion of "maximal residue limit" (MRL) takes into account a combination of data of three different sources: toxicity studies in laboratory animals, tissular distribution of veterinary drugs in animal species producing food-stuffs and habits of consumption by human beings . The determination of MRL is intended to protect the consumer from any risk due to the possible presence of dangerous residues in food-stuffs such as meat, offal milk, . The present article intends to explain the notions of admissible daily intake, MRL and withdrawal time, and to show their consequences, taking into account their ever evolving political context.

Trop Anim Health Prod, 2000 Dec, 32(6), 361 - 74
The use of trypanocides and antibiotics by Maasai pastoralists; Roderick S et al.; Information was collected on the use of veterinary drugs by Maasai pastoralists in an area of Kenya where tsetse flies and trypanosomosis occur . Three herds of cattle were followed for between 4 and 5 years and records were kept of every veterinary drug treatment given by the livestock owners . Almost all treatments were either with the trypanocides homidium or diminazene, or with oxytetracycline by intramuscular injection . The rate of trypanocide use varied between 0.66 and 1.56 treatments per animal per year, while oxytetracycline use was between 0.20 and 1.00 treatments per animal per year . Farmers were injecting these drugs in the absence of veterinary supervision, obtaining their supplies mainly from local village shops or informal traders . Underdosing with trypanocides appeared to be uncommon and the indications were that farmers generally gave the drugs at dosage rates above the recommended standard dose . Accurate information on the dose rates of oxytetracycline could not be obtained, but it was noted that in most cases farmers gave a single injection rather than a course of treatment . In a proportion of cases, trypanocides and antibiotics were mixed together before injection . The farmers administered the drugs when disease was recognized and were rarely using trypanocides as prophylactics . Although necessity forces the livestock owners to obtain and use these drugs without veterinary supervision, there are concerns with regard to the possibility of drug misuse and the development of drug resistance.

Postepy Hig Med Dosw, 2000, 54(5), 571 - 83
{Search for new methods of administering aminoglycoside antibiotics to attenuate side effects}; Nowak P; In the review some concepts of molecular mechanisms of nephrotoxic and ototoxic action of aminoglycosides was presented . The way to changes of aminoglycoside administration frequency, and reduction of side-effects was discussed.

Exp Brain Res, 2000 Dec, 135(3), 417 - 22
Transient and controllable opening of the blood-brain barrier to cytostatic and antibiotic agents by alkylglycerols in rats; Erdlenbruch B et al.; The blood-brain barrier hinders progress in the chemotherapy of brain tumors due to insufficient penetration of anticancer drugs into the brain tissue . Short-chain alkylglycerols affect the physicochemical properties of biological membranes . The enhancement of the blood-brain barrier permeability by intra-arterial administration of alkylglycerols was investigated in tumor-free and C6 astroglioma bearing rats . The antineoplastic agents cisplatin and methotrexate and the antibiotics vancomycin and gentamicin were selectively injected into the right internal carotid artery in the absence and presence of various alkylmono-, alkyldi-, and alkyltriglycerols . In normal rats the intra-arterial administration of the drugs without alkylglycerols resulted in low drug concentrations in brain tissue . In the presence of alkylglycerols (0.01-0.3 M) a reversible (within minutes) and concentration-dependent enrichment of the coinjected agents was found, preferentially in the ipsilateral hemisphere . The extent of drug accumulation in the brain was modified by changes in the chemical structure of the alkylglycerols . The effect increased with the chain length of the alkyl group, decreased with the number of glycerols, and varied from 2- to more than 230-fold compared to controls . In rats with C6 tumors 1-O-pentylglycerol increased the delivery of methotrexate 18-fold in the tumor, 28-fold in the surrounding brain, 18-fold in the contralateral brain, and 19-fold in the cerebellum compared to controls with methotrexate in the absence of pentylglycerol . In conclusion, the intra-arterial administration of alkylglycerols represents a novel and well controllable method for enhanced drug delivery to the brain and to brain tumors.

Fam Pract, 2001 Feb, 18(1), 9 - 13
Is it possible to decrease antibiotic prescribing in primary care? An analysis of outcomes in the management of patients with sore throats; Cox CM et al.; OBJECTIVES: The aim of this study was to assess whether it was possible to change clinical practice through the introduction of an evidence-based protocol for the management of sore throats . The impact of the changed clinical practice on patients was also assessed . METHOD: An observational study was carried out comparing management of patients with sore throats in a semi-rural general practice (14 000 patients), before and after the introduction of an evidence-based protocol, using a multidisciplinary approach . All patients over the age of 2 years presenting with sore throats as their chief presenting complaint were included in the study which ran for two 6-month periods: February-July 1997 (n = 435) and February-July 1998 (n = 350) . Antibiotic prescribing rates, consultation and reconsultation rates, duration of sore throat, analgesia requirements and satisfaction were assessed . RESULTS: Antibiotic prescribing was significantly reduced in period 2 (56% compared with 19%) . Consultation rates decreased by 19% in period 2 . Median number of days to recovery of sore throats was the same in both groups . Reconsultation rates and dissatisfaction rates were the same in both groups . CONCLUSION: Using a multidisciplinary approach, it is possible to reduce antibiotic prescribing for sore throats significantly without adversely affecting outcome.

Pediatr Infect Dis J, 2000 Dec, 19(12), 1172 - 7
Frequency of penicillin-resistant pneumococci in children is correlated to community utilization of antibiotics; Melander E et al.; OBJECTIVE: To study the impact of the utilization of antibiotics in children at the population level on the frequency of penicillin-nonsusceptible pneumococci (PNSP) . DESIGN: Children ages 0 to 6 years with a nasopharyngeal culture of PNSP were registered on place of residency in the 20 municipalities of the former Malmohus County (since 1998 a part of Skane County) . Where possible the total number of nasopharyngeal cultures with growth of pneumococci was registered as well . All antibiotic prescriptions for 0- to 6-year-old children were analyzed in the 20 municipalities . MAIN OUTCOME MEASURES: Correlation between the utilization of antibiotics and the frequency of PNSP in children at the municipality level . RESULTS: The proportion of PNSP among all isolates of pneumococci from nasopharyngeal cultures varied between 0 and 49.5% . The antibiotic utilization in children varied among the 20 neighboring municipalities from 8.5 to 19.7 defined daily doses per 1000 children per day . The municipalities with high total utilization also had more frequent use of macrolides and broad spectrum antibiotics . The was a significant correlation between antibiotic use and the proportion of PNSP (correlation coefficient, 0.96; P = 0.002), and the correlation coefficients for trimethoprim-sulfamethoxazole, amoxicillins, macrolides and cephalosporins were significant at the 0.001 level . There was no significant correlation between the use of penicillin V and the frequency of PNSP . CONCLUSIONS . There was a significant correlation between the frequency of PNSP and the utilization of antibiotics in children at the population level.

Pol Merkuriusz Lek, 2000 Oct, 9(52), 713 - 5
{Ototoxic mechanism of aminoglycoside antibiotics--role of glutaminergic NMDA receptors}; Bienkowski P et al.; Recent studies have indicated that glutamatergic NMDA receptors in the cochlea may be involved in ototoxic effects of aminoglycosides in animal subjects . Aminoglycoside antibiotics enhance the function of NMDA receptors by interaction with a polyamine modulatory site . Accordingly, high doses of aminoglycosides may increase calcium entry through the NMDA receptor-associated channel and promote degeneration of hair cells and cochlear nerve fibers . In line with the above, a polyamine site antagonist, ifenprodil as well as a high-affinity channel blocker, dizocilpine (MK-801) attenuates ototoxic effects of aminoglycosides in rats . Notably, ifenprodil as well as low-affinity channel blockers (e.g . memantine and amantadine) may be safely used in humans . Taken together, the above findings seem to open new avenues of research on selective pharmacotherapy of aminoglycosides-induced ototoxicity in humans.

Ir Med J, 2000 Oct, 93(7), 211 - 2
Antibiotics for sore throat: impact of feedback to patients on the probability of bacterial infection; Macnamara J et al.; Antibiotics are overused in the management of sore throat . Using a scoring system with 108 attenders, we provided feedback on the likelihood of bacterial infection and measured the impact on initial patient expectation for antibiotic therapy . Patient attitudes and beliefs regarding antibiotics were also examined . Of sixty two patients whose score suggested viral infection, 18(29%) opted not to take an antibiotic prescription . The 42(67%) who still wanted an antibiotic, despite being told it was "unlikely or highly unlikely" to help, had a higher mean attendance rate for sore throat (1.63 v 0.83 (p = 0.14)) and other illness (6.53 v 4.22 (p = 0.22)), and a higher mean re-attendance rate following the study (1.68 v 0.50 (p = 0.025)) . Qualitative analysis suggests that this subgroup may believe in the analgesic properties of antibiotics.

Infect Control Hosp Epidemiol, 2000 Dec, 21(12), 796 - 9
Antibiotic-use screening evaluations (ABUSE) for physicians and patients: featuring prizes and penalties for physicians; Lettau LA; The excessive use of antibiotics in the United States has been well documented and is a result of the knowledge base and behaviors of not only prescribing physicians but also patients and caregivers . An antibiotic-use screening evaluation (ABUSE) was developed for each group to promote better awareness among all parties as to ways that they may be overusing antibiotics . The ABUSE questionnaires also serve as tools for confidential self-scoring evaluation of the extent of personal antibiotic misuse

Biochem Pharmacol, 2001 Jan 1, 61(1), 67 - 72
Does the antitumor cyclopropylpyrroloindole antibiotic CC-1065 cross-link DNA in tumor cells?
Skladanowski A, Koba M, Konopa J.
We have found that a cyclopropylpyrroloindole antibiotic, compound CC-1065 (benzo{1,2-b:4,3-b'}dipyrrole-3(2H)-carboxamide, 7-{{1, 6-dihydro-4-hydroxy-5-methoxy-7-{(4,5,8, 8a-tetrahydro-7-methyl-4-oxocyclopropan{c}pyrrolo{3, 2-e}indol-2(1H)-yl)carbonyl}benzo{1,2-b:4, 3-b'}dipyrrol-3(2H)-yl}-carbonyl}-1,6-dihydro-4-hydroxy-5-methoxy, (7bR,8aS)), forms interstrand DNA cross-links of an apparently covalent nature in HeLa S(3) cells . This compound induced interstrand cross-links at concentrations ranging from 0.1 to 1 nM/3 hr in whole cells, but these cross-links were absent or marginally low when the drug was added to cell lysates with inactivated cellular enzymes or isolated nuclei, which suggests that metabolic activation of the drug is a necessary step for DNA cross-linking to occur . In contrast, an analog of CC-1065, Bizelesin, which forms DNA-DNA cross-links by direct alkylation, induced interstrand DNA cross-links in both whole cells and in cell lysates . Interestingly, a demethoxy analog of CC-1065, Adozelesin, did not induce DNA cross-links under the same conditions . CC-1065 was found to be extremely potent in terms of concentrations required to cross-link DNA of tumor cells, and this may be related to its remarkable cytotoxic activity.

Int J Pediatr Otorhinolaryngol, 2000 Dec 22, 56(3), 175 - 84
The variability and appropriateness of the antibiotic prescription of acute otitis media in childhood . The Spanish Study Group for Antibiotic Treatments; Solis G et al.; OBJECTIVE: To know the variability of treatment of acute otitis media in Spain and the appropriateness of such with respect to consensus . MATERIAL AND METHODS: A descriptive, multicentre, prospective study was carried out in the services of 11 Spanish hospitals . Children diagnosed with acute otitis media and treated on 30 days selected randomly between January and June 1997 were included . An analysis of treatment variability was made . The results were compared with consensus conference of a panel of experts . RESULTS: Out of the 29436 emergencies studied on 30 days, 821 were diagnosed with acute otitis media . Fifteen point seven percent of the cases were already receiving antibiotics (22% amoxicillin clavulanate, 20% amoxicillin and 11% cefuroxime axetil) . For the treatment, at discharge, of the 93% an antibiotic was prescribed (amoxicillin clavulanate in 41%, amoxicillin in 15%, cefuroxime axetil in 11%, cefaclor 6% and azithromycin 5%) . Two point eight percent of the children were admitted . According to the guidelines of the panel of experts consulted, appropriateness was 61% for antibiotics of first choice, 12% for drugs of alternate use and 25% for inadequate treatment . The different hospitals presented significant variability in the type of antibiotic used and the appropriateness of such . CONCLUSIONS: Acute otitis media is treated with antibiotics in 93% of the cases diagnosed in Spanish hospitals . The most commonly used antibiotics are amoxicillin clavulanate and amoxicillin alone . The prescription and its appropriateness present significant variability in the different hospitals studied.

Biopolymers, 2001, 62(1), 9 - 14
NMR interaction studies of aromatic guanyl hydrazones with micelles: model for mechanism of action of cationic antibiotics; Borges MN et al.; Interaction studies using hydrogen NMR spin-lattice relaxation time measurements of a series of five antiparasitic guanyl hydrazones with SDS and cetyl trimethylammonium bromide micelles are used as a simple model for the interaction of these compounds with the cell membrane of Trypanosoma cruzi . The results show that the activity of the compounds is related to their capacity to selectively interact with anionic micelles, which reinforces the hypothesis that the mechanism of action of these compounds is related to their selective interaction with the negatively charged parasite membrane.

Proc Natl Acad Sci U S A, 2001 Jan 2, 98(1), 87 - 92
Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin; Furumai R et al.; Trichostatin A (TSA) and trapoxin (TPX) are potent inhibitors of histone deacetylases (HDACs) . TSA is proposed to block the catalytic reaction by chelating a zinc ion in the active-site pocket through its hydroxamic acid group . On the other hand, the epoxyketone is suggested to be the functional group of TPX capable of alkylating the enzyme . We synthesized a novel TPX analogue containing a hydroxamic acid instead of the epoxyketone . The hybrid compound cyclic hydroxamic acid-containing peptide (CHAP) 1 inhibited HDAC1 at low nanomolar concentrations . The HDAC1 inhibition by CHAP1 was reversible as it was by TSA, in contrast to the irreversible inhibition by TPX . CHAP with an aliphatic chain length of five, which corresponded to that of acetylated lysine, was stronger than those with other lengths . These results suggest that TPX is a substrate mimic and that the replacement of the epoxyketone with the hydroxamic acid converted TPX to an inhibitor chelating the zinc like TSA . Interestingly, HDAC6, but not HDAC1 or HDAC4, was resistant to TPX and CHAP1, whereas TSA inhibited these HDACs to a similar extent . HDAC6 inhibition by TPX at a high concentration was reversible, probably because HDAC6 is not alkylated by TPX . We further synthesized the counterparts of all known naturally occurring cyclic tetrapeptides containing the epoxyketone . HDAC1 was highly sensitive to all these CHAPs much more than HDAC6, indicating that the structure of the cyclic tetrapeptide framework affects the target enzyme specificity . These results suggest that CHAP is a unique lead to develop isoform-specific HDAC inhibitors.

J Antibiot (Tokyo), 2000 Oct, 53(10), 1168 - 74
Double stage activity in aminoglycoside antibiotics; Hotta K et al.; Fourteen different aminoglycoside antibiotics (AGs) were challenged with aminoglycoside acetyltransferases (AACs) of actinomycete origin in order to examine their 'double stage activity' that is arbitrarily defined as antibiotic activity retainable after enzymatic modification . In kanamycin (KM)-group AGs tested {KM, dibekacin (DKB), amikacin and arbekacin (ABK)}, ABK retained activity after acetylations by AAC(3), AAC(2') and AAC(6') . DKB also retained a weak activity after acetylation by AAC(2') . In gentamicin (GM)-group AGs tested {GM, micronomicin, sisomicin (SISO), netilmicin (NTL) and isepamicin}, GM, SISO and NTL retained activites after acetylation by AAC(2') . In neomycin (NM)-group AGs tested {ribostamycin, NM, paromomycin}, NM retained activity after acetylation by AAC(6') and AAC(2') . None of astromicin (ASTM)-group AGs tested (ASTM and istamycin B) retained activity after acetylation by AAC(2') and AAC(6') . The activities of acetylated ABK derivatives by AAC(3) and AAC(2') were distinctively high, compared to the others . Streptomyces lividans TK21 containing the cloned aac genes were markedly sensitive to AGs that retained activities after acetylation, indicating the substantial effect of 'double stage activity'.

J Antibiot (Tokyo), 2000 Oct, 53(10), 1102 - 7
Tubelactomicin A, a novel 16-membered lactone antibiotic, from Nocardia sp . II . Structure elucidation; Igarashi M et al.; A novel 16-membered lactone antibiotic named tubelactomicin A was isolated from the culture broth of Nocaradia sp . MK703-102F1 . The structure of tubelactomicin A was assigned by spectroscopic analysis and the absolute configuration was determined by X-ray crystallographic analysis.

J Antibiot (Tokyo), 2000 Oct, 53(10), 1096 - 101
Tubelactomicin A, a novel 16-membered lactone antibiotic, from Nocardia sp . I . Taxonomy, production, isolation and biological properties; Igarashi M et al.; A novel 16-membered lactone antibiotic named tubelactomicin A was isolated from the culture broth of an actinomycete strain . The producing organism, designated MK703-102F1, was identified as a member of Nocardia . Tubelactomicin A was isolated from the culture broth by Diaion HP20 absorption, ethyl acetate extraction, silica gel and Sephadex LH-20 column chromatographies and centrifugal liquid-liquid partition chromatography (CPC) . Tubelactomicin A showed strong activity against acid-fast bacteria including the drug-resistant strains.

J Dairy Sci, 2000 Dec, 83(12), 2992 - 7
Effect of fat and protein content of milk from individual cows on the specificity rates of antibiotic residue screening tests; Andrew SM; The effect of high concentrations of milk protein and milk fat on the specificity rates of several antibiotic residue screening tests was evaluated in this study . Milk was sampled from 60 Jersey and 30 Holstein cows at one milking and analyzed for beta-lactam residues using four antibiotic residue screening tests . Cows selected were not treated with an antibiotic for at least 30 d prior to sample collection, and milk was visibly normal . Before milk collection, quarter foremilk was aseptically sampled for mastitis pathogen analysis . Milk subsamples were analyzed for fat and protein contents, and somatic cell counts (SCC) . Ten Jersey and four Holstein cows were infected with one or more mastitis pathogens . Concentrations of milk fat (4.78 vs . 3.39%) and protein (3.81 vs . 3.00%) were greater for Jersey cows compared with Holstein cows . Milk SCC averaged 148,000/ml and did not differ by breed . The specificity rates were greater than 0.9 for three of the four screening tests . Across breeds, there was an increased probability of a false-positive outcome for the Penzyme test (Coulter Food Science, Milwaukee, WI)), with increased milk protein content and decreased SCC . Increased milk fat content was associated with an increased probability of false-positive outcomes for the CITE Snap test (IDEXX Laboratories, Inc., Westbrook, ME) . High concentrations of milk protein and milk fat can adversely affect antibiotic residue test performance, but the degree of the effect is dependent upon the analytical method of the screening test.

J Dairy Sci, 2000 Dec, 83(12), 2805 - 9
The relationship between antibiotic residue violations and somatic cell counts in Wisconsin dairy herds; Ruegg PL et al.; The objective of this retrospective observational study was to characterize somatic cell counts (SCC) on Wisconsin dairy farms and to determine the relationship between SCC and the risk of antibiotic residue violation . Monthly official state regulatory data were used when both the bulk tank SCC value and antibiotic test results were available for the same date . Data were collected from Wisconsin dairy farms from January 1995 through November 1998 and consisted of results of tests performed on 805,772 grade A and 176,763 grade B milk samples . Herd-year SCC averages were used to classify herds (< or =250,000; 251,000 to 400,000, 401,000 to 550,000, 551,000 to 700,000, >700,000), and the relative risk of antibiotic residue by SCC class was determined . Arithmetic mean SCC values were 334,634 and 480,029 for grade A and grade B milk, respectively . SCC values were significantly higher for samples with positive antibiotic residue tests for grade A milk during all 4 yr tested . The SCC values were significantly higher for samples with positive antibiotic residue tests for grade B milk for 3 of 4 yr . The rate of antibiotic residue violation per 1000 herd-years increased with SCC class for both grade A and grade B milk . The relative risks of antibiotic residue violation by SCC class were 1.0, 1.43, 2.38, 2.78, and 7.10 for grade A milk and 1.0, 1.11, 2.67, 4.33, and 5.43 for grade B milk . Programs to reduce the level of subclinical mastitis on dairy farms may have an additional benefit of reducing the risk of antibiotic residue violations.

J Pediatr Hematol Oncol, 2000 Nov-Dec, 22(6), 533 - 8
Two cases of autoimmune neutropenia possibly induced by beta-lactam antibiotics in infants; Taniuchi S et al.; This report describes two infants who had neutropenia develop after treatment with beta-lactam antibiotics . The first patient, a 9-month-old girl, was administered flomoxef (FMOX); the second patient, a 14-month-old boy, was administered cefotiam (CTM) . Both infants were found to have neutropenia 4 to 5 days after they were placed on respective antibiotics, and neutropenia had persisted despite antibiotics withdrawal for 1 to 3 months . Drug-induced lymphocyte stimulation test (DLST), granulocyte-bound antibodies, serum granulocyte antibodies, and immunoblotting analysis indicated that beta-lactam antibiotics possibly triggered production of granulocyte autoantibody with resultant autoimmune neutropenia.

Br J Gen Pract, 2000 Oct, 50(459), 817 - 20
How effective are treatments other than antibiotics for acute sore throat?
Thomas M, Del Mar C, Glasziou P.
To estimate the benefits of treatments other than antibiotics for acute sore throat, and the differences between non-antibiotic interventions and controls in patient-perceived pain of sore throat, a systematic review of controlled trials in Medline and the Cochrane Library was carried out . Sixty-six randomised controlled trials (with or without additional antibiotics) were identified and 17 met the selection criteria . Twenty-two non-antibiotic managements for sore throat were compared . Their efficacy relative to placebo ranged from no effect to 93% . Some non-antibiotic treatments may be more effective than antibiotics; however, publication bias may have exaggerated the benefits . These treatments should be investigated further with respect to efficacy, safety, and side-effects as potential firstline management options for acute sore throat.

Pol Merkuriusz Lek, 2000 Sep, 9(51), 623 - 6
{Adverse effects of interactions of antibiotics with other drugs}; Zebrowska-Lupina I et al.; Many drugs used in combination with antibiotics may show different interactions of clinical significance (for instance: an increase of toxicity of the drugs used) . It is important especially among patients treated concurrently with antibiotics and other drugs in high doses for a long time . The most significant clinically are pharmacokinetic interactions of antibiotics that are inhibitors of microsomal enzymes (makrolide or quinolones antibiotics, metronidazole or imidazole antifungal agents) . Clinical caution is indicated when these antibiotics are combined with drugs that have a narrow therapeutic index such as warfarin, theophylline, phenytoin or digitalis glicosides . Moreover toxic reactions may be observed among patients receiving simultaneously antibiotics and the agents blocking neuromuscular transmission, oral hypoglycaemics, loop diuretics or digoxin . Some antibiotics (rifampicin, ampicillin, tetracyclines, griseofulvin) may decrease the efficacy of hormonal oral contraceptives.

Chemistry, 2000 Nov 3, 6(21), 3897 - 905
Total synthesis of the antitumor antibiotic (+/-)-fredericamycin A by a linear approach; Kita Y et al.; A linear approach to the total synthesis of racemic fredericamycin A (1) through the oxidative intramolecular {4 + 2} cycloaddition of a (phenylthio)acetylene-cobalt complex is described, which is applicable for the asymmetric total synthesis of naturally occuring 1 . The highlight of this work is the aromatic Pummerer-type reaction with 1-ethoxyvinyl chloroacetate, which effects the introduction of the oxygen functional group to the internal B-ring of the highly functionalized, congested polyaromatic ABC-ring moiety.

Carbohydr Res, 2000 Dec 1, 329(4), 861 - 72
A short and efficient transformation of rhamnose into activated daunosamine, acosamine, ristosamine and epi-daunosamine derivatives, and synthesis of an anthracycline antibiotic acosaminyl-epsilon-iso-rhodomycinone; Renneberg B et al.; 3-Amino-2,3,6-trideoxyhexopyranoses are essential constituents of most anthracycline antitumour antibiotics . For an investigation of structure-activity relationships, the four diastereomeric amino sugars daunosamine, acosamine, ristosamine, and epi-daunosamine were synthesised in short and efficient routes starting from commercially available rhamnose . Several glycosyl donors were provided and their use was exemplified in the synthesis of acosaminyl-epsilon-isorhodomycinone.

Curr Atheroscler Rep, 2000 Jul, 2(4), 336 - 41
Antibiotic therapy for treatment of Chlamydia to prevent coronary heart disease events; Muhlestein JB; Evidence is mounting that infectious agents might be involved in atherosclerosis . Therefore, antibiotic therapy might be helpful in its prevention . Early pilot therapeutic trials have targeted Chlamydia pneumoniae because it has the most evidence associating it with atherosclerosis . Small, randomized pilot trials that test the effect of macrolide therapy on future clinical events in patients with coronary artery disease have already shown promising but mixed results . Large clinical trials are presently underway that should provide more definitive information regarding the use of antibiotics in coronary artery disease . Until the results of these studies are available, it is not recommended that antibiotic therapy be routinely utilized for the treatment or prevention of complications of atherosclerosis.

Can Respir J, 2000 Nov-Dec, 7(6), 466 - 71
Outpatient antibiotic therapy and short term mortality in elderly patients with chronic obstructive pulmonary disease; Sin DD et al.; OBJECTIVE: To determine the association between outpatient use of oral antibiotics and 30-day all-cause mortality following hospitalization in a group of elderly chronic obstructive pulmonary disease (COPD) patients . DESIGN: A population-based retrospective cohort study . SETTING: Ontario, Canada . POPULATION STUDIED: All 26,301 patients, 65 years of age or older, who were hospitalized for COPD between 1992 and 1996 in Ontario . METHODS: All elderly patients admitted at least once with a most responsible diagnosis of COPD using the Canadian Institute for Health Information database were identified . They were then linked to the Ontario Drug Benefit database to determine the use of antibiotics within 30 days of the index hospitalization and to the Ontario registered persons database to determine the 30-day mortality following their index hospitalization . RESULTS: Outpatient use of antibiotics within 30 days before the index hospitalization was associated with a significant reduction in the 30-day mortality following hospitalization (odds ratio {OR} 0.83, 95% CI 0.75 to 0.92) . Use of macrolides had the lowest relative odds for mortality (OR 0.58, 95% CI 0.47 to 0.73), while use of fluoroquinolones had the highest relative odds (OR 0.98, 95% CI 0.84 to 1.15) . CONCLUSIONS: Use of antibiotics before hospitalization was associated with a significant reduction in the risk of short term mortality among a group of elderly COPD patients who eventually required hospitalization for their disease . These findings support the early use of antibiotics in COPD patients who experience an acute exacerbation.

Antimicrob Agents Chemother, 2001 Jan, 45(1), 145 - 9
Antimalarial activities of peptide antibiotics isolated from fungi; Nagaraj G et al.; Malaria caused by Plasmodium falciparum is a major public health problem in the developing countries of the world . Clinical treatment of malaria has become complicated due to the occurrence of infections caused by drug resistant parasites . Secondary metabolites from fungi are an attractive source of chemotherapeutic agents . This work reports the isolation and in vitro antiplasmodial activities of peptide antibiotics of fungal origin . The three peptide antibiotics used in this study were efrapeptins, zervamicins, and antiamoebin . The high-performance liquid chromatography-purified peptides were characterized by nuclear magnetic resonance and mass spectral analysis . All three fungal peptides kill P . falciparum in culture with 50% inhibitory concentrations in the micromolar range . A possible mode of action of these peptide antibiotics on P . falciparum is presented.

Int J Antimicrob Agents, 2000 Dec, 16(4), 507 - 9
Strategies to treat patients with antibiotic resistant Helicobacter pylori; Megraud F; Increased resistance to clarithomycin and metronidazole, the two main antibiotics used to treat Helicobacter pylori infection, has led to a search for alternatives to the proton pump inhibitor based triple therapies commonly used . The main rescuse therapy is a bismuth-based quadruple therapy . However, triple therapies with tetracycline and metronidazole or amoxicillin and metronidazole can be considered in the case of clarithomycin resistance . They can also be used in the case of metronidazole resistance by increasing the dose and duration of metronidazole . The only therapy without clarithomycin and metronidazole includes rifabutin and amoxicillin . Dual therapies with amoxicillin and a proton pump inhibitor at high dose can also be used.

J Am Board Fam Pract, 2000 Nov-Dec, 13(6), 398 - 402
Why are antibiotics prescribed for patients with acute bronchitis? A postintervention analysis; Hueston WJ et al.; BACKGROUND: Despite the findings in controlled trials that antibiotics provide limited benefit in the treatment of acute bronchitis, physicians frequently prescribe antibiotics for acute bronchitis . The aim of this study was to determine whether certain patient or provider characteristics could predict antibiotic use for acute bronchitis in a system where antibiotic use had already been substantially reduced through quality-improvement efforts . METHODS: A retrospective chart review was performed in an academic family medicine training center that had previously instituted a quality-improvement project to reduce antibiotic prescribing for acute bronchitis . Patients who had acute bronchitis diagnosed during an 18-month period and who had no other secondary diagnosis for respiratory distress or a condition that would justify antibiotics were selected from a computerized-record database and included in the study (n = 135) . Charts were reviewed to document patient symptoms, physical findings, provider and patient characteristics, and treatment . RESULTS: Thirty-five (26%) patients received antibiotics for their acute bronchitis . Adults were more likely to receive antibiotics than children (34% vs 3%, P < .001) . Analysis of 20 different symptoms and physical findings showed that symptoms and signs were poor predictors of antibiotic use . Likewise, no significant differences were found based on prescribing habits of individual providers or provider level of training . CONCLUSION: In a setting where antibiotic use for acute bronchitis had been decreased through an ongoing quality-improvement effort, it did not appear that providers selectively used antibiotics for patients with certain symptoms or signs . Other factors, such as nonclinical cues, might drive antibiotic prescribing even after clinical variation is suppressed.

J Orthop Res, 2000 Sep, 18(5), 721 - 7
Inhibitory effects of the quinolone antibiotics trovafloxacin, ciprofloxacin, and levofloxacin on osteoblastic cells in vitro; Holtom PD et al.; We studied the inhibitory effects of the fluoroquinolones levofloxacin, ciprofloxacin, and trovafloxacin on growth and extracellular matrix mineralization in MC3T3-E1 osteoblast-like cell cultures . Levofloxacin had the least inhibitory effect on cell growth, with a 50% inhibitory concentration of approximately 80 microg/ml at 48 and 72 hours . Ciprofloxacin had an intermediate degree of inhibition, with a 50% inhibitory concentration of 40 microg/ml at 48 and 72 hours . Trovafloxacin exerted a profound inhibitory effect on cell growth, with a 50% inhibitory concentration of 0.5 microg/ml, lower than clinically achievable serum levels . The decreased cell counts with up to 2.5 microg/ml of trovafloxacin and with up to 40 microg/ml of ciprofloxacin were not associated with decreased rates of 5-bromo-2'-deoxyuridine incorporation per cell . Alatrovafloxacin, the L-alanyl-l-alanine prodrug of trovafloxacin, exerted effects on proliferation and 5-bromo-2'-deoxyuridine incorporation similar to those of the parent compound . The quinolones evaluated also inhibited extracellular matrix mineralization by MC3T3-E1 cells . Treatment of confluent cultures with trovafloxacin, ciprofloxacin, or levofloxacin resulted in strong inhibition of calcium deposition, as determined on day 14 by alizarin red staining and biochemical analysis . The effect was apparent with 2.5-5 microg/ml of each of the three antibiotics tested and progressively increased to more than a 90% decline in the calcium/protein ratio with 20-40 microg/ml antibiotic concentration . Further in vivo studies are advocated to evaluate the relevance of the in vitro cytotoxicity reported here to bone healing in orthopaedic patients.

J Mass Spectrom, 2000 Nov, 35(11), 1252 - 8
High-resolution LC/MS for analysis of minor components in complex mixtures: negative ion ESI for identification of impurities and degradation products of a novel oligosaccharide antibiotic; Shipkova PA et al.; High-resolution mass spectrometry has been routinely used for structural confirmation and identification; however, it has mostly been applied to relatively pure samples . Exact mass measurement of minor components such as impurities, degradation products or metabolites in complex mixtures has been difficult without prior separation and isolation . Here we report the utilization of on-line liquid chromatography in combination with high-resolution mass spectrometry for the identification of impurities and base degradation products of Sch 27899, a member of the everninomicin class of antibiotics . Nine Sch 27899-related impurities and degradation products were detected by negative ion electrospray ionization using a magnetic sector mass spectrometer . Exact mass measurements were obtained at a resolution of 5000 using polyethylene glycol (PEG) sulfates as internal standards . Corresponding elemental compositions were determined within a 2 ppm error tolerance and structures were proposed for all components .

Biochemistry (Mosc), 2000 Nov, 65(11), 1299 - 304
Cytotoxic activity, accumulation, and intracellular distribution of anthracycline antibiotics and their conjugates with the epidermal growth factor in sensitive and resistant MCF-7 cells; Lutsenko SV et al.; Cytotoxic activities, accumulation levels and dynamics, and intracellular distribution of the anthracycline antibiotics doxorubicin (DR) and carminomycin (CM) in the free forms or within conjugates with the epidermal growth factor (EGF) were for the first time compared in human breast carcinoma cell lines MCF-7Wt and MCF-7AdrR . The cytotoxic activities of DR and CM conjugates with EGF were higher than the cytotoxic activities of the free antibiotics in both cell lines . The accumulation levels of the free anthracyclines in both cell lines were lower than those of the conjugates and significantly depended on the cell sensitivities to the antibiotics . On receptor-mediated endocytosis of the anthracycline-EGF conjugates, the accumulation levels did not significantly depend on the cell sensitivities to the antibiotics . Both DR and CM, either free or conjugated with EGF, were mainly accumulated in nuclei . The free drugs were accumulated more rapidly, and the accumulation rates of both free and EGF-conjugated CM were higher than those of DR preparations . The intracellular distribution of the free antibiotics significantly depended on the cell sensitivities to the anthracyclines, whereas the cell sensitivities had no effect on the distribution of the conjugates between the nucleus and cytoplasm . The rate of intracellular degradation of DR and CM delivered to target cells within conjugates with EGF was twice lower than that of the free antibiotics . The difference in the accumulation levels and dynamics and in the intracellular distribution of the free and conjugated DR and CM is likely to underlie the higher cytotoxic activities of the anthracycline conjugates with EGF compared to the free drugs.

Clin Infect Dis, 2001 Jan, 32(1), 36 - 43 Epub 2000 Dec 08.
Oral cefixime is similar to continued intravenous antibiotics in the empirical treatment of febrile neutropenic children with cancer; Shenep JL et al.; Empiric oral antibiotic therapy for febrile neutropenic cancer patients has been suggested as a means to decrease hospitalization, but the safety of this approach has not been adequately studied in children . We compared continued iv antibiotic therapy with switching treatment to orally administered cefixime in a group of selected febrile neutropenic children for whom blood cultures were sterile after 48 h of incubation . Two hundred episodes of febrile neutropenia were studied (156 patients), and 100 episodes were randomized to receive each treatment . Failure to respond to therapy was defined by documented or suspected bacterial infection, recurrent fever, or discontinuation of assigned therapy for any reason before neutropenia resolved . Rates of treatment failure were similar in the oral cefixime group (28%) and in the iv antibiotic group (27%; P=1.0) . Results support the safety of oral cefixime therapy for low-risk febrile neutropenic children, a therapeutic approach that would facilitate earlier outpatient management and decrease the costs of treatment.

Vet Rec, 2000 Oct 28, 147(18), 503 - 6
Use of an antibiotic footbath in the treatment of bovine digital dermatitis; Laven RA et al.; One hundred and eleven dairy cows with digital dermatitis, on six commercial farms, were used to test the efficacy of a footbath containing erythromycin for treating the condition . Four days after 55 of the cows had walked through the footbath after two successive milkings their lesions were significantly less active and painful than those of the 56 untreated cows . These 56 cows were then treated in the same way and both groups were re-examined seven days later . There were no significant differences between the clinical signs observed in the two groups, and the benefits of the treatment had persisted for the 11 days of the trial.

Int Microbiol, 1998 Dec, 1(4), 301 - 6
The evolution of function: a new method to assess the phylogenetic value of ribosomal sensitivity to antibiotics; Briones C et al.; Thirty-five archaeal, bacterial and eukaryotic translational systems have been proved against forty different protein synthesis inhibitors with diverse domain and functional specificities . The inhibition curves generated in every ribosome-antibiotic combination had previously shown interesting similarities among organisms belonging to the same phylogenetic group . This opened the possibility of using such functional information for developing evolutionary studies . A new mathematical method based on the main data components analysis has been developed to extract most of the information contained in the inhibition curves . The phenograms obtained closely resemble those generated by the small ribosomal subunit rRNA sequence comparison and such functional clustering is also congruent when a particular subset of organisms and/or antibiotics is used . These results prove the phylogenetic value of our functional analysis and suggest that the ribosome represents an interesting intersection between genotypic and phenotypic (functional) information stored in organisms.

J Antimicrob Chemother, 2000 Dec, 46(6), 1033 - 5
An analysis of antibiotic prescriptions from general dental practitioners in England; Palmer NO et al.; The aim of this study was to determine the antibiotics prescribed by general dental practitioners (GDPs) . Adult antibiotic prescriptions issued by GDPs from 10 Health Authorities (HAs) in England were analysed . The type of antibiotic prescribed, dose, frequency and duration were investigated . Most of the 17007 prescriptions were for generic antibiotics; nine different antibiotics were prescribed . Many practitioners prescribed antibiotics inappropriately with inconsistent frequency and dose, and for prolonged periods.

Braz J Infect Dis, 1998 Jun, 2(3), 109 - 117
Antibiotic Selection in the Treatment of Febrile Neutropenia: Current Approach and New Directions; Stefani SD et al.; The combination of neutropenia and fever, with or without documented infection is a common complication in cancer patients receiving chemotherapy . The prompt institution of empirical broad-spectrum antibiotic therapy for febrile neutropenic patients has been shown to reduce the rate of early death and morbidity in cancer populations undergoing chemotherapy . Three different regimens for consideration as initial empiric therapy are presented . Alternatives such as outpatient regimens to low risk patients and monotherapy are discussed . If confirmed prospectively, the results presented here may enable clinicians to identify low risk groups and treat neutropenia and fever with good results and better economic and psychological cost.

Biotechnol Prog, 2000 Nov-Dec, 16(6), 1098 - 105
Critical evaluation of models developed for monitoring an industrial submerged bioprocess for antibiotic production using near-infrared spectroscopy; Vaidyanathan S et al.; Near-infrared spectroscopy (NIRS) is known to have potential for cost-effective monitoring of bioprocesses . Although this has been demonstrated in many instances and several models have been reported, information regarding the complexity of models required and their utility over extended periods of time is lacking . In the present study, the complexity of the models required for the NIRS prediction of substrate (oil) and product (tylosin) concentration in an industrial bioprocess that employs a physicochemically heterogeneous medium for antibiotic production was assessed . Measurements made by both the diffuse reflectance and transmittance modes were investigated . SEP values for the prediction of the analytes averaged 5% or less, for the successful models, when evaluated using an external validation set, 2 years after the initial model development exercise . Diffuse reflectance measurements showed poorer results, compared to transmittance measurements, especially for monitoring tylosin . In general, this investigation provides evidence to support the fact that models built for the prediction of analytes in a commercial bioprocess that employs a physicochemically complex production medium can be robust in performance over an extended period of time and that simple models based on fewer terms or latent variables can perform well, even in the context of matrices that are relatively complex . It also indicates that sample presentation is likely to be a critical factor in the successful application of NIRS in bioprocess monitoring, which merits further detailed investigation.

Nucleosides Nucleotides Nucleic Acids, 2000 Aug, 19(8), 1337 - 53
DNA recognition by quinoline antibiotics: use of base-modified DNA molecules to investigate determinants of sequence-specific binding of luzopeptin; Bailly C et al.; The luzopeptin antibiotics contain a cyclic decadepsipeptide to which are attached two quinoline chromophores that bisintercalate into DNA . Although they bind DNA less tightly than the structurally related quinoxaline antibiotics echinomycin and triostin A, the molecular basis of their interaction remains unclear . We have used the PCR in conjunction with novel nucleotides to create specifically modified DNA for footprinting experiments . In order to study the influence that removal, addition or relocation of the guanine 2-amino group, which normally identifies G.C base pairs from the minor groove, has on the interaction of luzopeptin antibiotics with DNA . The presence of a purine 2-amino group is not strictly required for binding of luzopeptin to DNA, but the exact location of this group can alter the position of preferred drug binding sites . It is, however, not the sole determinant of nucleotide sequence recognition in luzopeptin-DNA interaction . Nor can the selectivity of luzopeptin be attributed to the quinoline chromophores, suggesting that an analogue mode of DNA recognition may be operative . This is in contrast to the digital readout that seems to predominate with the quinoxaline antibiotics.

Chemotherapy, 2001, 47 Suppl 1, 33 - 40
Treatment of lower respiratory tract infections in Italy: the role of outpatient parenteral antibiotic therapy; Esposito S; The use of outpatient parenteral antibiotic therapy (OPAT) has enjoyed substantial success in Italy, where patients generally believe that treatment at home is better than in the hospital . Intramuscular administration, which is commonplace in Italy, facilitates OPAT, requiring minimal training and circumventing intravenous access problems . The Italian OPAT model is a general practice-based model, but a team approach is used in the presence of severe disease, such as HIV . Seven centers in Italy are participating in the International OPAT Outcomes Registry, and have enrolled about 200 patients over 8 months . Eighty patients (40%) were treated for lower respiratory tract infections (60 pneumonia, 20 bronchitis) . Most pneumonia patients had concomitant disease, including chronic heart disease, HIV and cancer . The most frequently used therapy was ceftriaxone, which permits once-daily convenience due to its prolonged half-life . Antibiotics were administered intramuscularly in more than 50% of cases . Clinical outcome was excellent, and patient and physician satisfaction was high.

Chemotherapy, 2001, 47 Suppl 1, 17 - 23
The management of skin and soft tissue infections: outpatient parenteral antibiotic therapy in the United Kingdom; Nathwani D; In a study in Scotland, skin and soft tissue infections (SSTIs) accounted for 10% of hospitalizations, with mean stays of approximately 5 days, and were the second most common reason for hospital-based intravenous antibiotic therapy lasting more than 48 h . A total of 125 patients with SSTIs were recently treated using an outpatient parenteral antibiotic therapy (OPAT) service . The patients received intravenous antibiotic therapy for a mean duration of 5.32 days . The two primary agents administered were once-daily ceftriaxone and teicoplanin . Of the 125 patients, 123 (98.4%) were cured or improved; 2 worsened and required surgery . Patient satisfaction was very high . OPAT saved the inpatient facility 665 bed days . Economic benefits were realized despite use of more expensive agents . Data indicate that if the hospital stay of patients with SSTIs were reduced by only 1 day, savings would amount to pound(1/2)-1 million per year . OPAT is a feasible alternative to inpatient management of SSTIs and may safely, effectively and cost-effectively reduce the number of hospital days for these infections.

Drug Metab Dispos, 2000 Dec, 28(12), 1484 - 6
Panipenum, a carbapenem antibiotic, increases the level of hepatic UDP-glucuronic acid in rats; Yamamura N et al.; To investigate the mechanism for the enhanced glucuronidation of valproic acid (VPA) by panipenem (PAPM), a carbapenem antibiotic, in rat liver, we carried out studies to investigate whether PAPM increases the activity of UDP-glucuronosyltransferase or the level of hepatic UDP-glucuronic acid (UDPGA) in rats . PAPM had no effect on the UDP-glucuronosyltransferase activity toward VPA both in vivo and in vitro . On the other hand, in vivo treatment with PAPM significantly increased the hepatic UDPGA level by about 1.7-fold (control: 434.5 +/- 65.5 nmol/g of liver; PAPM-treated: 755.2 +/- 92.3 nmol/g of liver) . The in vitro formation of VPA glucuronide increased proportionally as a function of the UDPGA concentration up to 0.8 mM . Therefore, the increase in the level of hepatic UDPGA by PAPM is likely to be one of the causal factors for enhancing VPA glucuronidation in vivo.

Drug Metab Dispos, 2000 Dec, 28(12), 1391 - 3
Effects of macrolide antibiotics on CYP3A expression in human and rat hepatocytes: interspecies differences in response to troleandomycin; Ledirac N et al.; The effects of various macrolide antibiotics {triacetyloleandomycin (TAO), clarithromycin, azithromycin, roxithromycin, erythromycin base} and the new ketolide HMR3004 on CYP3A expression were evaluated in human and rat hepatocytes . Cells were treated for 3 days with nontoxic concentrations of the drugs, and CYP3A induction was assessed through midazolam hydroxylase activity and Western and Northern blot analyses . In rat hepatocytes, no induction of CYP3A1 expression was observed following exposure to macrolides, even to erythromycin base and TAO (well known in vivo CYP3A1 inducers), whereas dexamethasone and phenobarbital were confirmed to induce this enzyme . In contrast, treatment of fresh and thawed human hepatocytes with TAO, produced an increase of midazolam hydroxylation (4-fold over control) . This result was in agreement with the high amount of CYP3A4 protein and mRNA revealed by Western and Northern blot analyses . Other tested macrolides had no induction effect on CYP3A expression . These results confirmed the interspecies variability of CYP3A regulation in hepatocytes and raised the question of its mechanism of induction by macrolides in human liver.

Mol Biol Rep, 2000 Jun, 27(2), 107 - 11
Effect of peptidyltransferase inhibitors on ribonuclease P activity from Dictyostelium discoideum . Effect of antibiotics on RNase P; Stathopoulos C et al.; The effect of several peptidyltransferase inhibitors on ribonuclease P activity from Dictyostelium discoideum was investigated . Among the inhibitors tested puromycin, amicetin and blasticidin S revealed a dose-dependent inhibition of tRNA maturation . Blasticidin S and amicetin do not compete with puromycin for the same site on the enzyme, suggesting the existence of distinct antibiotic binding sites on D . discoideum RNase P . Inhibition experiments further indicate that binding sites for blasticidin S and amicetin overlap.

Poult Sci, 2000 Nov, 79(11), 1524 - 30
The effect of in ovo or day-of-hatch subcutaneous antibiotic administration on competitive exclusion culture (PREEMPT) establishment in neonatal chickens; McReynolds JL et al.; The effect of in ovo or day-of-hatch subcutaneous antibiotic administration on the detection of antibiotic residues in yolk sac or blood serum samples and the potential for observed residues to interfere with competitive exclusion (CE) culture establishment was compared in three experiments . The in ovo or subcutaneous administration of gentamicin sulfate or ceftiofur sodium was associated with detectable levels of antibiotic residues in yolk sac or blood serum samples in Experiment 1 . Further, the ability to detect antibiotic residues in day-of-hatch chicks was associated with reduced levels of CE culture establishment when cecal propionate level, an indicator of PREEMPT establishment, was determined following PREEMPT application by oral gavage on the day of hatch in Experiments 1 and 2 . Restricting chicks from feed, as opposed to providing access ad libitum to a starter ration, for 6 h immediately following administration of PREEMPT improved (P < 0.05) CE culture establishment in Experiment 2 in nonantibiotic injected control chicks, but did not affect (P > 0.05) experimental groups receiving either gentamicin sulfate or ceftiofur sodium by either in ovo or subcutaneous routes . The in ovo administration of 0.1 or 0.2 mg ceftiofur sodium to individual embryos on Day 18 of embryogenesis in Experiment 3 was associated with marked depressions (P < 0.05) in cecal propionate levels compared with uninjected control chicks . When feed was restricted and the time of PREEMPT administration was delayed for 48 or 72 h posthatch, mean cecal propionate levels in in ovo ceftiofur sodium-injected chicks were not significantly different (P > 0.05) from controls, indicating a time- and feed restriction-associated effect on improving CE culture establishment.

Int J Antimicrob Agents, 2000 Nov, 16(3), 291 - 4
The role of the hospital pharmacist in cost control and antibiotic policy; Milkovich G; The pharmacist provides a vital role in the management of antibiotic policy . Consumers and payers demand quality care at a significantly reduced price . It is imperative that health care adapt to the times . Physicians must be involved in all phases of programmes that are viewed as cost saving . These programmes should integrate and document both clinical and financial aspects of care.

Int J Antimicrob Agents, 2000 Nov, 16(3), 263 - 72
New antibiotics for community-acquired lower respiratory tract infections: improved activity at a cost?
Ball P.
Opinions are changing as to the continued validity of traditional beta-lactam and macrolide therapy of community acquired LRTI, partly because of resistance and partly because of early evidence that suggests that some new agents may be more effective . Guidelines are altering to reflect this view, although there is conflicting evidence on their effects on outcome . Fluoroquinolones are becoming accepted in the treatment of community acquired pneumonia and are established choices for acute exacerbations of chronic bronchitis . The 8-methoxy fluoroquinolones, moxifloxacin and gatifloxacin, have excellent anti-pneumococcal activity and may become drugs of choice for penicillin/macrolide resistant infections . They appear free of the serious idiosyncratic reaction profiles, possibly related to the immunologically reactive 1-difluorophenyl substituent, which characterised the recently withdrawn temafloxacin, trovafloxacin and tosufloxacin . All quinolones so far tested appear to prolong the QTc interval, but only sparfloxacin and grepafloxacin caused clinical effects . Nevertheless, caution is required until this effect is fully investigated.

J Mol Biol, 2000 Dec 1, 304(3), 471 - 81
Inhibition of the ribosomal peptidyl transferase reaction by the mycarose moiety of the antibiotics carbomycin, spiramycin and tylosin; Poulsen SM et al.; Many antibiotics, including the macrolides, inhibit protein synthesis by binding to ribosomes . Only some of the macrolides affect the peptidyl transferase reaction . The 16-member ring macrolide antibiotics carbomycin, spiramycin, and tylosin inhibit peptidyl transferase . All these have a disaccharide at position 5 in the lactone ring with a mycarose moiety . We have investigated the functional role of this mycarose moiety . The 14-member ring macrolide erythromycin and the 16-member ring macrolides desmycosin and chalcomycin do not inhibit the peptidyl transferase reaction . These drugs have a monosaccharide at position 5 in the lactone ring . The presence of mycarose was correlated with inhibition of peptidyl transferase, footprints on 23 S rRNA and whether the macrolide can compete with binding of hygromycin A to the ribosome . The binding sites of the macrolides to Escherichia coli ribosomes were investigated by chemical probing of domains II and V of 23 S rRNA . The common binding site is around position A2058, while effects on U2506 depend on the presence of the mycarose sugar . Also, protection at position A752 indicates that a mycinose moiety at position 14 in 16-member ring macrolides interact with hairpin 35 in domain II . Competitive footprinting of ribosomal binding of hygromycin A and macrolides showed that tylosin and spiramycin reduce the hygromycin A protections of nucleotides in 23 S rRNA and that carbomycin abolishes its binding . In contrast, the macrolides that do not inhibit the peptidyl transferase reaction bind to the ribosomes concurrently with hygromycin A . Data are presented to argue that a disaccharide at position 5 in the lactone ring of macrolides is essential for inhibition of peptide bond formation and that the mycarose moiety is placed near the conserved U2506 in the central loop region of domain V 23 S rRNA .

J Biomol Struct Dyn, 2000 Oct, 18(2), 209 - 18
Role of Mg2+ in the interaction of anticancer antibiotic, chromomycin A3 with DNA: does neutral antibiotic bind DNA in absence of the metal ion?
Chakrabarti S, Aich P, Sarker D, Bhattacharyya D, Dasgupta D.
Antitumor antibiotic, Chromomycin A3 (CHR), inhibits DNA replication and transcription via reversible interaction with double stranded DNA with GC-base specificity . The interaction, at and above physiological pH, requires the presence of bivalent metal ions, such as Mg2+ . Anionic antibiotic does not bind DNA in the absence of Mg2+ . In this paper we have examined the structural potential of neutral CHR at pH 5.2 to bind DNA in the absence of Mg2+ . We have demonstrated the ability of the neutral antibiotic to bind DNA by means of different spectroscopic techniques and evaluated the necessary thermodynamic parameters for elucidation of the molecular basis of recognition . The results are compared with the scenario when Mg2+ is present in the system, because the ultimate aim of these studies is to elucidate the role of Mg2+ in CHR-DNA recognition . Neutral CHR binds to Mg2+ with lesser affinity than its anionic form . Spectroscopic features of the drug and its Mg2+ complex indicate self association of the antibiotic in the absence and presence of Mg2+ . GC-base specificity of the drug and its Mg2+ complex are retained at pH 5.2, though the modes of recognition of DNA by the two ligands are different . Minor groove width of DNA plays a role in the accommodation of the ligand(s) during the GC base specific recognition while positive charge of Mg2+ in CHR:Mg2+ complex further facilitates the association . Relatively lower affinity of the neutral drug and its Mg2+ complex for DNA can be ascribed to the self association of these ligands in the absence of DNA.

Int J Pharm, 2000 Nov 19, 209(1-2), 15 - 26
Validation and in vitro characterization of antibiotic-loaded bone cement release; Frutos Cabanillas P et al.; Antibiotic-loaded polymeric bone cement is used in orthopedic surgery to deliver local high concentrations of antibiotics to the tissues . The precise mechanism by which antibiotic is released from the polymeric matrix is still not very well known . This research was conducted to investigate the in vitro drug release behavior of antibiotic from acrylic bone cement . A spectrophotometric method for the quantitative analysis of gentamicin sulfate using o-phtaldialdehyde as a derivatizing reagent was thoroughly validated, in order to assure a minimum quality level of the measures . The method proved to be quick, reliable, less expensive than methods such as polarization fluorescence immunoassay and others, and therefore more convenient for the routine analysis of the numerous samples generated during in vitro liberation assays . The release of gentamicin from commercial CMW1 acrylic bone cement samples was investigated following proposed in vitro release experiments.

Antimicrob Agents Chemother, 2000 Dec, 44(12), 3473 - 5
Short-term exposure to membrane-active antibiotics inhibits Cryptosporidium parvum infection in cell culture; Giacometti A et al.; A cell culture system and double fluorogenic staining were used to study the susceptibility of Cryptosporidium parvum to membrane-active antibiotics . Buforin II and magainin II exerted a cytotoxic effect on sporozoites but did not consistently affect oocyst viability . Lasalocid and nigericin demonstrated less activity against sporozoites but reduced the infectivity of oocysts.

Acta Paediatr, 2000 Oct, 89(10), 1250 - 6
Socio-economic differences in daycare arrangements and use of medical care and antibiotics in Swedish preschool children; Hjern A et al.; In this study we describe socio-economic patterns of daycare enrolment, medical care and antibiotics in children, 0-5 y, whose parents participated in the Swedish Survey of Living Conditions 1996-97 . Children in families with low socio-economic status and unemployed parents were less often enrolled in out-of-home care . Multivariate analyses (adjusted for various sociodemographic indicators, type of daycare and chronic morbidity) demonstrated that children 1-5 y in families with low social status (low parental education and/or low SES) were less likely to have paid a visit to a physician because of an acute infection during the previous 3 mo {odds ratio (OR) 0.6 (0.4-0.8)} or to have consumed antibiotics during the previous 12 mo {OR 0.8 (0.6-1.0)} compared to children with a higher social status . Children in out-of-home care more often had paid a visit to a physician because of an acute infection during the previous 3 mo {OR 1.5 (1.2-1.9)} and more often had consumed antibiotics during the previous 12 mo {OR 1.7 (1.3-2.1)} than children in home care . The effect of out-of-home care on use of medical care and antibiotics decreased with increasing age of the child, and deviated from the null hypothesis in children 1-3 y only . CONCLUSION: Preschool children in families with a low social status consume less medical care and are less likely to attend out-of-home care compared to children with a higher social status in Swedish society . This inequity needs to be addressed in social and health policy.

J Dent, 2000 Nov, 28(8), 539 - 48
Endodontics in the adult patient: the role of antibiotics; Longman LP et al.; OBJECTIVES: The aim of this study was to review the published work on the indications and efficacy for antibiotics in endodontic therapy . DATA SOURCES: Published works in the medical and dental literature . STUDY SELECTION: Evaluation of published clinical trials in endodontic and other pertinent literature . CONCLUSIONS: Antibiotics are not routinely indicated in the practice of endodontics . Therapeutic antibiotics may be required as an adjunct to operative treatment when there is pyrexia and/or gross local swelling; they are only rarely indicated in the absence of operative intervention . Prophylactic antibiotics may be required for certain patients who are susceptible to serious infective sequaelae.

J Org Chem, 2000 Nov 3, 65(22), 7541 - 53
Regiocontrolled synthesis of the antitumor antibiotic AT2433-A1; Chisholm JD et al.; The indolo{2,3-a}carbazole glycosides are potent antitumor antibiotics currently undergoing clinical trials for the treatment of numerous types of cancer . AT2433-A1 is the most complex member of this family of compounds possessing a unique disaccharide with a sensitive aminodeoxysugar and an unsymmetric aglycon . The synthesis of this natural product requires a method for glycosylation that sets the stereochemistry of the anomeric center and the regiochemistry of the aglycon . These goals were accomplished by carrying out the Mannich cyclization of a bis-3, 4-(3-indolyl)succinimide to give a key class of indoline intermediates that could be glycosylated stereoselectively with complex carbohydrates without hydroxyl protection or activation . The regiochemistry of the Mannich cyclization was precisely controlled by choosing between kinetic or thermodynamic conditions . This strategy culminated in the first synthesis of the antitumor antibiotic AT2433-A1.

Org Lett, 2000 Nov 16, 2(23), 3743 - 6
Rapid, high-yield, solid-phase synthesis of the antitumor antibiotic sansalvamide A using a side-chain-tethered phenylalanine building block; Lee Y et al.; A 10-step solid-phase synthesis of the cytotoxic depsipeptide sansalvamide A (1) has been accomplished in an overall yield of 67% with >95% purity employing polymer-bound phenylalanine building block 2 . Both the N- and C-termini of 2 are extended followed by on-resin head-to-tail macrocyclization of the linear peptide in a high yield . This should be a general stategy for the synthesis of diverse libraries of cyclic peptides and depsipeptides that contain exclusively phenylalanine and other hydrophobic side chains.

Int J Clin Pharmacol Ther, 2000 Oct, 38(10), 492 - 9
Comparison of two antibiotic regimens in the treatment of perforated appendicitis in pediatric patients; Rodriguez JC et al.; BACKGROUND AND PURPOSE: An increased incidence of post-surgical infectious complications in children admitted with a diagnosis of perforated appendicitis led to development of a disease-specific antibiogram and modification of our post-operative antibiotic regimen . METHODS: A historical control group comprised of 32 pediatric patients receiving ampicillin, gentamicin, and clindamycin (group AGC) was compared to a cohort of 32 children receiving ticarcillin/clavulanate plus gentamicin (group TG) . The surgical procedure, peri-operative management, and inclusion, exclusion and discharge criteria were the same for each group . Outcome measures including length of stay, time to defervesce, incidence of infectious complications, and clinical failures to the antibiotic regimen were compared . RESULTS: The groups were similar with respect to gender, age, weight, surgical time, pre-operative leukocytes, and number of intra-operative bacterial isolates cultured per patient . Length of stay was 10.1 days in group TG and 12.5 days for group AGC (p = 0.0197) . The number of clinical failures was reduced from 9 (28.1%) to 2 (6.3%) in group TG (p = 0.02) . The time to defervesce was decreased by 1.4 days, and the number of infectious complications was reduced to 2.5-fold in group TG patients . CONCLUSIONS: Ticarcillin/clavulanate plus gentamicin was clinically more effective than ampicillin, gentamicin, and clindamycin combination therapy in the management of perforated appendicitis in our pediatric population.

Parasitology, 2000 Oct, 121 ( Pt 4), 359 - 65
In vitro activity of the polyether ionophorous antibiotic monensin against the cyst form of Toxoplasma gondii; Couzinet S et al.; Toxoplasma gondii . The experiments were conducted in vitro using 2 methods; cysts produced either in mice or in cell culture were exposed to monensin in vitro, and the infectivity of the parasites was then assessed in vivo or in vitro . The data obtained from these 2 systems of evaluation showed that monensin inhibits the infectivity and the viability of the bradyzoites . Its activity was time and concentration dependent . The first effects were observed at very low drug concentrations (i.e . 0.0001 microg/ml) . Immunofluorescence and electron microscopy analysis showed significant cytological alterations of the monensin-treated bradyzoites: they were swollen, had a large number of vacuoles in their cytoplasm and were found lysed at higher concentrations in ionophore.

Clin Exp Allergy, 2000 Nov, 30(11), 1547 - 53
Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease?
Droste JH, Wieringa MH, Weyler JJ, Nelen VJ, Vermeire PA, Van Bever HP.
BACKGROUND: One of the mechanisms evoked to explain the increasing prevalences of asthma and allergy, in particular among children, is the 'Western lifestyle' or 'hygiene' hypothesis . As early childhood infections are assumed to hold a protective effect on the development of asthma and allergies, the use of antibiotics at that sensitive age may lead to an increased risk of asthma and allergy . OBJECTIVE: The aim of this study is to investigate the association between the use of antibiotics in the first year of life and the subsequent development of asthma and allergic disorders . METHODS: In a population-based sample of 7-and-8-year-old children questionnaire and skin prick test data were collected from 1206 and 675 subjects, respectively . Prevalence rates of asthma, allergic disorders and skin test positivity were compared between children with and without early life use of antibiotics, taking into account other possible risk factors including early respiratory infections . The effect of genetic predisposition was investigated by stratified analyses of children with and without parental hay fever . RESULTS: The use of antibiotics during the first year of life was significantly associated with asthma (OR = 1.7, 95% CI 1.0-3.1), hay fever (OR = 2.3, 95% CI 1.3-3.8) and eczema (OR = 1.3, 95% CI 1.0-1.8) . No significant relationship was found with skin test positivity (OR = 1.1, 95% CI 0.7-1.7) . After stratification for the presence of parental hay fever, children without parental hay fever did not show any significant associations between antibiotics use and asthma or allergy, whereas in children with parental hay fever the use of antibiotics was significantly related with asthma (OR = 2.3, 95% CI 1.1-5.1), hay fever (OR = 2.8, 95% CI 1.5-5.1) and eczema (OR = 1.6, 95% CI 1.0-2.6), and of borderline statistical significance with skin test positivity (OR = 1.6, 95% CI 0.9-3.0) . CONCLUSION: Early childhood use of antibiotics is associated with an increased risk of developing asthma and allergic disorders in children who are predisposed to atopic immune responses . These findings support recent immunological understanding of the maturation of the immune system.

Clin Orthop, 2000 Nov, (380), 250 - 9
Biodegradable alginate antibiotic beads; Ueng SW et al.; The authors investigated the poly-L-lysine-coated alginate beads as an antibiotic delivery system for the treatment of various surgical infections . The sodium alginate was mixed with vancomycin, coated with poly-L-lysine, and lyophilized to form five types of the biodegradable antibiotic beads . Type I, 2.5% alginate, nonpoly-L-lysine coated and nonlyophilized; Type II, 2.5% alginate, poly-L-lysine coated but nonlyophilized; Type III, 2.5% alginate, poly-L-lysine coated and lyophilized; Type IV, 5% alginate, poly-L-lysine coated and lyophilized; and Type V, 7.5% alginate, poly-L-lysine coated and lyophilized . Cytotoxicity of the alginate beads to fibroblasts and HeLa cells was evaluated by the MTT {3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide} colorimetric assay . A study of in vitro elution of vancomycin of the alginate antibiotic beads was performed . The results suggested that the alginate antibiotic beads present no obvious toxic risk to their use as a drug delivery system . The concentration of vancomycin in these five types of beads was well above the breakpoint sensitivity concentration (the antibiotic concentration at the transition point between bacterial killing and resistance to the antibiotic) for 9,11,12, 14, and 17 days respectively . The release was most marked during the first 3 days . The duration of antibiotic release was prolonged by using techniques of poly-L-lysine coating, lyophilization, and by increasing the content of alginate . This study offers a biodegradable delivery system of antibiotics to treat various surgical infections.

J Med Chem, 2000 Nov 2, 43(22), 4328 - 31
Hydrolytic stability versus ring size in lactams: implications for the development of lactam antibiotics and other serine protease inhibitors; Imming P et al.; beta-Lactam antibiotics act by acylating a serine hydroxyl group in the catalytic center of bacterial proteases . This requires, among other things, suitable reactivity of the lactam moiety . To evaluate the possible suitability of other lactam systems, kinetic studies were performed using the model reaction of lactams with hydroxide . Following the pace of the reaction by NMR, we found gamma-butyrolactam to be hydrolyzed considerably slower than beta-propiolactam . Surprisingly, delta-valerolactam and beta-propiolactam had the same reactivity . beta-Lactam antibiotics were more reactive than both by approximately a factor of 10(3) . Medium-sized lactams were least susceptible to hydrolysis . The study highlights the as yet overlooked six-membered lactam ring as a promising vantage point for the development of new classes of antiinfectives and other serine protease inhibitors.

Neurosurgery, 2000 Nov, 47(5), 1124 - 7; discussion 1127-9
The efficacy and cost of prophylactic and perioprocedural antibiotics in patients with external ventricular drains; Alleyne CH Jr et al.; OBJECTIVE: Prophylactic antibiotics are routinely administered to patients with external ventricular drains (EVDs); however, no conclusive evidence supports this practice . This study compared the efficacy and cost of prophylactic and periprocedural antibiotics in patients with EVDs . METHODS: We reviewed the charts of 308 patients who had an EVD in place for 3 or more days between January 1996 and June 1997 . Patients with EVDs placed for shunt infections or meningitis were excluded . A standard protocol was used to insert and monitor EVDs . Catheters were left in place as long as clinically indicated and changed only if they malfunctioned . Cerebrospinal fluid cultures were obtained twice weekly . Prophylactic antibiotics were used at the discretion of the attending neurosurgeon . Patients were divided into two groups: Group A comprised 209 patients who received prophylactic antibiotics for the duration of the EVD (intravenously administered cefuroxime, 1.5 g every 8 h); Group B comprised 99 patients who received only periprocedural antibiotics (intravenously administered cefuroxime, 1.5 g every 8 h, three or less doses) . RESULTS: Although there were significantly more males in Group A than in Group B, the two groups were otherwise well matched, with no significant differences in age, indications, or duration of EVD placement . The overall rate of ventriculitis was 3.9% . The infection rates for Group A (3.8%) and Group B (4.0%) were almost identical . CONCLUSION: Prophylactic antibiotics did not significantly reduce the rate of ventriculitis in patients with EVDs, and they may select for resistant organisms . Discontinuing the use of prophylactic antibiotics for EVDs at the authors' institution would save approximately $80,000 per year in direct drug costs.

Aust Dent J, 2000 Sep, 45(3), 179 - 86; quiz 214
Antibiotic prescribing practices by South Australian general dental practitioners; Jaunay T et al.; The prescribing habits of a randomly selected approximately 10 per cent sample of South Australian general dental practitioners were obtained by postal questionnaire . Sixty-eight (61 per cent) usable replies were received and analysed . Generally, there was an appropriate level of knowledge of antibiotic prescription . However, there was a tendency toward over-prescription and a demonstrated lack of knowledge of the incidence of adverse reactions, development of multiresistant strains and prophylaxis against bacterial endocarditis . All of these areas are real challenges to the profession, whether in an overall global community health sense or in a highly individualized clinical or medico-legal sense . These issues are discussed and the profession is urged to reconsider and re-educate itself on these challenges.

Bioorg Med Chem Lett, 2000 Oct 16, 10(20), 2311 - 3
Synthesis of pyrrolo{2,1-c{1,4}benzodiazepines via reductive cyclization of omega-azido carbonyl compounds by TMSI: an efficient preparation of antibiotic DC-81 and its dimers; Kamal A et al.; Azido carbonyl compounds on reaction with trimethylsilyl iodide (in situ prepared from TMSCl/NaI) led to the formation of diazepine imines in good yields under mild conditions . This methodology has been applied to the parent unsubstituted pyrrolobenzodiazepine, the natural product DC-81 and its dimers.

J Clin Oncol, 2000 Nov 1, 18(21), 3699 - 706
Time to clinical response: an outcome of antibiotic therapy of febrile neutropenia with implications for quality and cost of care; Elting LS et al.; PURPOSE: To determine whether antibiotic regimens with similar rates of response differ significantly in the speed of response and to estimate the impact of this difference on the cost of febrile neutropenia . METHODS: The time point of clinical response was defined by comparing the sensitivity, specificity, and predictive values of alternative objective and subjective definitions . Data from 488 episodes of febrile neutropenia, treated with either of two commonly used antibiotics (coded A or B) during six clinical trials, were pooled to compare the median time to clinical response, days of antibiotic therapy and hospitalization, and estimated costs . RESULTS: Response rates were similar; however, the median time to clinical response was significantly shorter with A-based regimens (5 days) compared with B-based regimens (7 days; P =.003) . After 72 hours of therapy, 33% of patients who received A but only 18% of those who received B had responded (P =.01) . These differences resulted in fewer days of antibiotic therapy and hospitalization with A-based regimens (7 and 9 days) compared with B-based regimens (9 and 12 days, respectively; P <.04) and in significantly lower estimated median costs ($8,491 v $11,133 per episode; P =.03) . Early discharge at the time of clinical response should reduce the median cost from $10,752 to $8,162 (P <.001) . CONCLUSION: Despite virtually identical rates of response, time to clinical response and estimated cost of care varied significantly among regimens . An early discharge strategy based on our definition of the time point of clinical response may further reduce the cost of treating non-low-risk patients with febrile neutropenia.

J Fam Pract, 2000 Oct, 49(10), 907 - 13
Back-up antibiotic prescriptions for common respiratory symptoms . Patient satisfaction and fill rates; Couchman GR et al.; BACKGROUND: In recent years much has been written about the overuse of antibiotics, especially for common respiratory illnesses . One approach to this issue is the use of a back-up prescription, only to be filled if a patient's condition deteriorates or fails to improve . The purpose of our study was to determine patient satisfaction, prescription fill rates, and correlates of these outcomes among patients receiving back-up antibiotic prescriptions . METHODS: In our observational study we obtained survey data from 28 physicians and 2 physician extenders in 3 family practice clinics and their patients presenting with complaints of common respiratory symptoms . We computed patient satisfaction and fill rates of back-up antibiotic prescriptions . Agreement between the perceived need of patients for antibiotics before the office visit and the subjective rating of their physicians of the clinical necessity to prescribe antibiotics for these patients was assessed using the kappa statistic . Finally, we determined correlates of satisfaction and the rate of filling back-up prescriptions . RESULTS: Of the 947 patients enrolled in the study, 46.6% received no antibiotic prescriptions, 30.2% received back-up antibiotic prescriptions, and 23.2% were given immediate-fill prescriptions for an antibiotic . Patients' self-reported satisfaction and fill rates for back-up antibiotic prescriptions were 96.1% and 50.2%, respectively . CONCLUSIONS: Our findings indicate that patients were very satisfied with a back-up antibiotic prescription . The fact that half of the patients chose not to fill these prescriptions suggests a potential health care cost savings.

Am J Physiol Heart Circ Physiol, 2000 Nov, 279(5), H2424 - 30
Bicarbonate exacerbates oxidative injury induced by antitumor antibiotic doxorubicin in cardiomyocytes; Konorev EA et al.; Doxorubicin, a broad-spectrum antitumor antibiotic, causes dose-dependent cardiomyopathy and heart failure . Although the exact molecular mechanisms of cardiotoxicity are not well established, oxidative mechanisms involving doxorubicin-induced superoxide anion production have been proposed . In this study, we show that bicarbonate, a physiologically relevant tissue component, greatly amplified doxorubicin-induced cardiomyocyte injury . Bicarbonate also enhanced inactivation of aconitase, a crucial tricarboxylic acid cycle enzyme, in cardiomyocytes exposed to doxorubicin . The cell-permeable superoxide dismutase mimetic, Mn(III)tetrakis (4-benzoic acid) porphyrin, reversed doxorubicin-induced cardiomyocyte injury . Bicarbonate enhanced the inactivation of purified mitochondrial aconitase in the xanthine/xanthine oxidase system, generating superoxide . The results suggest that bicarbonate amplifies the prooxidant effect of superoxide . Bicarbonate also caused an increased loading of cardiomyocytes with doxorubicin . We conclude that the bicarbonate-mediated increase in doxorubicin toxicity is due to increased intracellular loading of doxorubicin in cardiomyocytes and subsequent exacerbation of superoxide-mediated cardiomyocyte injury.

Berl Munch Tierarztl Wochenschr, 2000 Sep, 113(9), 344 - 7
{Determination of breakpoints for veterinary medically relevant antibiotics for resistance assessment of veterinary pathogens}; Bottner A et al.; This article describes the meaning of the term clinical breakpoint . This is followed by a discussion of the parameters that need to be considered when setting valid breakpoints for active substances in veterinary medicine; in doing so we closely follow equivalent regulations and guidelines on the establishment of breakpoints in human medicine . Along with pharmacokinetic data and the results of clinical efficacy tests, susceptibility data of relevant organisms play a key role in the establishment of breakpoints . Published breakpoints are currently only available for a few modern drugs in veterinary medicine.

Prikl Biokhim Mikrobiol, 2000 Sep-Oct, 36(5), 564 - 8
{An antibiotic complex produced by Streptomyces werraensis 1365T strain}; Rusanova EP et al.; An antibiotic complex comprising four components (A, B, C, and X) was extracted from a native solution and mycelium of Streptomyces werraensis 1365T . The components were purified by column and thin-layer (TLC) chromatographic procedures to study their physicochemical and biological properties . The results were used to identify the substances isolated . The preliminary data allowed us to identify the components X, A, and B as the previously described compounds undecylprodigiosin, anisomycin, and copiamycin, respectively, whereas component C is a natural compound, which probably has never been described.

Pancreas, 2000 Oct, 21(3), 279 - 89
Therapeutic efficacy of continuous arterial infusion of an antibiotic and a protease inhibitor via the superior mesenteric artery for acute pancreatitis in an animal model; Takagi K et al.; The major cause of death in acute pancreatitis is severe infection owing to bacterial translocation . As a new strategy, we investigated the effects of continuous intra-arterial infusion of an antibiotic (imipenem) or protease inhibitor (nafamostat mesylate) via the superior mesenteric artery (SMA) on bacterial translocation in acute pancreatitis . Infusion of saline (group I), nafamostat mesylate (group II), or imipenem (group III) was started 6 hours after inducing acute pancreatitis in dogs by infusing autologous gallbladder bile into the main pancreatic duct . The survival rate in group III was significantly improved compared to group I(100 vs . 30% at 24 hours), and bacterial infection of the peritoneal fluid, mesenteric lymph nodes, and pancreas was completely prevented in group III . Intestinal damage assessed by light and scanning electron microscopy and by biochemical parameters (mucosal protein content and myeloperoxidase activity) was also significantly mitigated in group III, which showed milder pancreatic necrosis as well . There was little beneficial effect in preventing bacterial translocation in group II, although the survival rate at 24 hours (70%) was improved . Continuous arterial infusion of an antibiotic via the SMA is effective in mitigating intestinal mucosal damage and preventing bacterial translocation in acute pancreatitis, thereby improving survival.

J Pediatr Hematol Oncol, 2000 Sep-Oct, 22(5), 405 - 11
Randomized placebo-controlled trial of oral antibiotics in pediatric oncology patients at low-risk with fever and neutropenia; Klaassen RJ et al.; PURPOSE: Fever combined with neutropenia in pediatric oncology patients has traditionally been managed in the hospital with broad-spectrum intravenous antibiotics until there is documented neutrophil recovery . Recent evidence has suggested that patients at "low-risk" can be discharged from the hospital before neutrophil recovery . Whether oral antibiotics are required at the time of discharge is not known . PATIENTS AND METHODS: Using a randomized, double-blind, placebo-controlled study design, 73 patients at low-risk with episodes of fever and neutropenia were discharged home while still neutropenic: 37 administered with oral cloxacillin and cefixime and 36 administered with corresponding placebos . Low-risk criteria included: afebrile for more than 24 hours, negative blood culture results at 48 hours, absence of clinical sepsis, cancer in bone marrow remission, and absence of comorbid conditions . RESULTS: Five patients (14%; 95% confidence interval {CI}; 2%-25%) in the antibiotic arm and two patients (6%; 95% CI; 0%-13%) in the placebo arm were readmitted to the hospital with recurrent fever while still neutropenic (P = 0.43) . One patient randomized to the placebo arm had a positive blood culture result on readmission, which responded to appropriate intravenous antibiotics . All of the readmissions were uneventful and there were no fatalities . The average cost per episode of fever and neutropenia was $1,821 Canadian dollars with only minimal incremental cost to the antibiotic arm . CONCLUSION: This study supports the discontinuation of antibiotics in pediatric oncology patients at low-risk who still have neutropenia at the time of discharge from the hospital.

Antimicrob Agents Chemother, 2000 Nov, 44(11), 3186 - 8
In vitro susceptibilities of Capnocytophaga isolates to beta-lactam antibiotics and beta-lactamase inhibitors; Jolivet-Gougeon A et al.; The susceptibilities of 43 pharyngeal isolates of Capnocytophaga to beta-lactam antibiotics, alone or in combination with beta-lactamase inhibitors, were tested by an agar dilution method . The 34 beta-lactamase-positive strains were highly resistant to beta-lactams, but the intrinsic activities of clavulanate, tazobactam, and sulbactam against Capnocytophaga, even beta-lactamase producers, indicates that these beta-lactamase inhibitors could be used for empirical treatment of neutropenic patients with oral sources of infection.

Proc Natl Acad Sci U S A, 2000 Oct 24, 97(22), 11942 - 7
Deoxysugars in glycopeptide antibiotics: enzymatic synthesis of TDP-L-epivancosamine in chloroeremomycin biosynthesis; Chen H et al.; The 2,3,6-trideoxysugar l-epivancosamine is the terminal sugar added to the aglycone scaffold in chloroeremomycin, a member of the vancomycin family of glycopeptide antibiotics . Five proteins from the chloroeremomycin biosynthetic cluster, ORF14 and ORF23 to ORF26, have been expressed heterologously in Escherichia coli and purified to near homogeneity, and each has been characterized for an enzymatic activity . These five enzymes reconstitute the complete biosynthesis of TDP-l-epivancosamine from TDP-4-keto-6-deoxy-d-glucose . This process involves C-2 deoxygenation, C-3 amination and methylation, C-5 epimerization, and C-4 ketoreduction . Intermediates and the final product of this pathway have been identified by mass spectrometry and NMR . The pathway established here represents the complete in vitro reconstitution of an unusual sugar for an important class of antibiotics and sets the groundwork for future combinatorial biosynthesis for new bioactive compounds.

Cochrane Database Syst Rev . 2000;(4):CD001305.
Antibiotics for preventing leptospirosis; Guidugli F et al.; BACKGROUND: Leptospirosis is an infectious disease transmitted by animals . Death occurs in about five per cent of the patients . In clinical practice, doxycycline is widely used for prevention . OBJECTIVES: To evaluate the effectiveness and safety of any antibiotic regimen versus placebo or other antibiotic regimens in the prophylaxis of leptospirosis . SEARCH STRATEGY: The sources used were: EMBASE, LILACS, MEDLINE, SCISEARCH, The Cochrane Controlled Trials Register, The Cochrane Hepato-Biliary Group Controlled Trials Register, bibliographies of published papers, and personal communication with authors . There were no language or date restrictions in any of the searches . SELECTION CRITERIA: STUDIES: All randomised clinical trials in which antibiotics were used as prophylactic regimen for leptospirosis . PARTICIPANTS: People potentially exposed to leptospirosis, such as people in endemic areas during the rainy season, health professionals and other professionals with high risk of infection . INTERVENTION: Any antibiotic regimen compared with a control group (placebo or another antibiotic regimen) . OUTCOMES: Infection (primary outcome) and adverse events (secondary outcome) . DATA COLLECTION AND ANALYSIS: Data were independently extracted and methodological quality of each trial was assessed by two reviewers as well as cross-checked . Details of the randomisation (generation and concealment), blinding, and the number of patients lost to follow-up were recorded . The results of each trial were summarised on an intention-to-treat basis in 2 x 2 tables for each outcome . MAIN RESULTS: Two trials comparing doxycycline with placebo met the inclusion criteria . We did not find trials comparing doxycycline versus other antibiotics, or other antibiotics versus placebo . One of the trials had excellent methodological quality . In the other trial, the allocation concealment process, generation of allocation sequence, and blinding methods were not described . Of the 1022 participants enrolled, 509 were treated with doxycycline and 513 with placebo . Of these, 940 participants were soldiers included in one trial . The patients assigned to the antibiotics group compared with the ones assigned to the placebo group showed: Symptomatic, verified leptospirosis: 0.6% (3/509) versus 4.9% (25/ 513); risk difference (random effects model) -4.1%, 95% confidence interval -5.9% to -2.3% . Number needed-to-treat 24 (95% confidence interval 17 to 43) . Adverse effects: 3% (13/469 participants) versus 0.2% (1/471 participants); random effects model 2.6%, 95% confidence interval 1.0% to 4.1% . Number needed-to-harm 39 (95% confidence interval 25 to 100) . REVIEWER'S CONCLUSIONS: Prophylaxis of leptospirosis may be achieved by administrating doxycycline to soldiers training in endemic areas with a high risk of exposure to leptospirosis . Whether these findings apply to other scenarios or not remains to be proven.

Int J Biol Macromol, 2000 Oct 10, 28(1), 75 - 9
The effects of daunomycin antibiotic on histone H(1): thermal denaturation and fluorescence spectroscopy studies; Zargar SJ et al.; Using thermal denaturation and fluorescence spectroscopy, we have investigated the interaction of antitumor antibiotic, daunomycin, with calf thymus histone H(1) under several ionic strengths . The results show that daunomycin binds to histone H(1) and increases its melting temperature . Increasing ionic strength elevates this effect . Fluorescence emission data show that the interaction of daunomycin with histone H(1) decreases the emission intensity at 325 nm and induces hyperchromicity in the emission spectrum of the drug . The results suggest that histone H(1) can be considered as a new target for drug action at the chromatin level.

Arch Fam Med, 2000 Sep-Oct, 9(9), 933 - 5
Improving quality or shifting diagnoses? What happens when antibiotic prescribing is reduced for acute bronchitis?
Hueston WJ, Slott K.
BACKGROUND: A quality improvement project in an academic practice demonstrated a reduction in antibiotic prescribing for acute bronchitis . However, it was unclear whether this represented a reduction in antibiotic use or whether physicians assigned new diagnoses to the same patients to avoid scrutiny and continue to use antibiotic therapy . OBJECTIVE: To examine whether a substantial amount of diagnostic shifting occurred while antibiotic prescribing for acute bronchitis decreased during a 14-month period (from January 1, 1996, to February 28, 1997) . METHODS: All patient diagnoses of acute bronchitis, acute sinusitis, upper respiratory tract infection, and pneumonia were determined for the 14 months of the acute bronchitis intervention . The relative distribution of patients among these 4 diagnostic categories was compared to determine if the percentage of patients with acute bronchitis decreased while those with acute sinusitis and pneumonia increased during the acute bronchitis intervention . RESULTS: The percentage of patients with the diagnosis of acute bronchitis remained unchanged during the 14-month period while antibiotic use for this condition decreased from 66% of cases to less than 21% of cases . Instead of the patients being assigned a different diagnosis such as acute sinusitis so that antibiotic prescribing would not be scrutinized, as we hypothesized, the relative number of diagnoses for acute sinusitis compared with acute bronchitis actually declined during the 14 months . No change was noted in the relative frequency of acute bronchitis cases compared with pneumonia cases . CONCLUSION: During a 14-month period when an intervention was successful at reducing antibiotic use for acute bronchitis, there was no evidence that physicians shifted patients from the diagnosis of acute bronchitis to other diagnoses.

Arch Fam Med, 2000 Sep-Oct, 9(9), 930 - 2
Are antibiotics necessary in the treatment of locally infected ingrown toenails?
Reyzelman AM, Trombello KA, Vayser DJ, Armstrong DG, Harkless LB.
CONTEXT: A wide variety of generalists and specialists treat locally infected ingrown toenails, with perhaps the most common treatment regimen including resection of the nail border coupled with oral antibiotics . OBJECTIVE: To determine whether oral antibiotic therapy is beneficial as an adjunct to the phenol chemical matrixectomy in the treatment of infected ingrown toenails . DESIGN: We prospectively enrolled healthy patients with infected ingrown toenails . Each patient was randomly assigned to 1 of 3 groups that received either 1 week of antibiotics and a chemical matrixectomy simultaneously (group 1), antibiotics for 1 week and then a matrixectomy (group 2), or a matrixectomy alone (group 3) . SETTING: Institutional ambulatory outpatient clinic . PATIENTS: Fifty-four healthy patients with infected ingrown toenails were studied . Patients with immunocompromised states, peripheral vascular disease, or cellulitis proximal to the hallux interphalangeal joint were excluded . Groups were age matched for comparison . RESULTS: Mean healing times for groups 1, 2, and 3 were 1.9, 2.3, and 2.0 weeks, respectively . Subjects receiving antibiotics and a simultaneous chemical matrixectomy (group 1) healed significantly sooner than those receiving a 1-week course of antibiotics followed by a matrixectomy (group 2) . There was not a significant difference in healing time between those that received a chemical matrixectomy alone (group 3) and those that received a matrixectomy coupled with a course of oral antibiotics (group 1) . CONCLUSION: The use of oral antibiotics as an adjunctive therapy in treating ingrown toenails does not play a role in decreasing the healing time or postprocedure morbidity.

J Org Chem, 2000 Oct 20, 65(21), 7187 - 94
Annulation strategies for benzo{b}fluorene synthesis: efficient routes to the kinafluorenone and WS-5995 antibiotics; Qabaja G et al.; Intramolecular palladium-mediated arylation approaches to benzo{b}fluorenes have been investigated . The methodology has been applied in a short synthesis of tri-O-methylkinafluorenone, providing an effective alternative to Friedel-Crafts-based approaches . During the course of this work, an acid-promoted quinolactonization of naphthoquinones was also developed, providing direct access to either ortho or para isomers as desired . Application of this methodology in syntheses of the antibiotics WS-5995A, WS-5995C, and functional analogues was demonstrated, and antitumoral activity of this class was determined.

Org Lett, 2000 Oct 19, 2(21), 3397 - 9
Solid-phase synthesis of bleomycin group antibiotics . Elaboration of deglycobleomycin A(5); Leitheiser CJ et al.; The solid-phase syntheses of two deglycobleomycin A(5) analogues were achieved using a commercially available polystyrene resin containing triphenylmethyl-linked spermidine . The final products were deblocked and released from the resin, analyzed, and purified by C(18) reversed phase HPLC and characterized by high-field (1)H NMR spectroscopy and mass spectrometry . The purified products relaxed supercoiled plasmid DNA in a concentration-dependent fashion and to the same extent as authentic material derived from natural BLM A(5).

Bioorg Med Chem, 2000 Sep, 8(9), 2347 - 54
Syntheses and biological evaluation of new glyco-modified angucyclin-antibiotics; Kirschning A et al.; The synthesis of novel aquayamycin-derived angucycline antibiotics 13a-d has been achieved . Glycosylation of aquayamycin (6) using 2-selenoglycosyl acetate 7 as glycosyl donor proceeded in excellent yield but attempts to reductively remove the selenyl group led to rearrangement or further aromatization of the aglycon . As a consequence of these results, it became possible to prepare urdamycinone B (10) starting from aquayamycin (6) . In addition, silyl protected D-olivals 12a,b were attached to the C-glycoside domain of aquayamycin (6) under protic conditions . As expected, the hydroxy and phenol groups of the benz{a}anthracene framework of 6 did not react under the glycosylation conditions employed . Stepwise removal of the silyl protecting group starting with tetrabutyl ammonium fluoride followed by use of the HF/pyridine complex suppressed a possible rearrangement of the aglycon and successfully terminated the sequence . The new angucycline-antibiotics 13a and 13b are some of the most potent xanthine oxidase inhibitors known and show cytotoxic activity with ED50-values in the range of 12.6-2.9x 10(-6) M.

Neurol India, 2000 Sep, 48(3), 272 - 5
Brainstem abscess complicating tetralogy of Fallot successfully treated with antibiotics alone; Pandian JD et al.; Medically treated brainstem abscess in a 11 year old boy with tetralogy of Fallot is reported . There was a complete resolution of the lesion without any neurologic sequelae during parenteral antibiotic therapy with crystalline penicillin, chloramphenicol and metronidazole . The pathogenesis and management of cardiogenic brain abscesses in general and brainstem abscess in particular has been reviewed.

Br Dent J, 2000 Jun 24, 188(12), 674 - 6
Antibiotic prescribing by general dental practitioners in the Greater Glasgow Health Board, Scotland; Roy KM et al.; OBJECTIVE: To investigate antibiotic prescribing patterns by general dental practitioners (GDPs) in the Greater Glasgow Health Board Area, Scotland . STUDY DESIGN: A 10% sample of prescriptions were selected at random from 35,545 prescriptions written by GDPs over a 6-month period . MAIN OUTCOME MEASURES: Absolute and relative frequencies were used to describe the different classes of antibiotics used and the variations in prescribing practice . RESULTS: GDPs prescribed a wide range of antibiotics . Seventeen different antibiotics were prescribed with amoxycillin, metronidazole and penicillin V accounting for almost 90% of the prescriptions . In general the antibiotics were prescribed at the British National Formulary (BNF) recommended doses . There were, however, wide variations in the frequencies and durations of the prescriptions for all antibiotics . CONCLUSIONS: The present study provides evidence of sub-optimal prescribing of antibiotics by dentists in Scotland, with considerable variation from the recommended frequencies and doses.

Fam Pract, 2000 Oct, 17(5), 386 - 8
Predictors of an antibiotic prescription by GPs for respiratory tract infections: a pilot; Murray S et al.; BACKGROUND: Antibiotics are over-prescribed for respiratory tract infections in Australia . OBJECTIVES: The aim of this study was to describe the clinical predictors of GPs' prescribing of antibiotics . METHODS: We used Clinical Judgment Analysis to study the responses of GPs to hypothetical paper-based vignettes of a 20-year-old with a respiratory tract infection . The nature of four symptoms and signs (colour of nasal mucous discharge; soreness of the throat; presence of fever; and whether any cough was productive of sputum) was varied and their effect on prescribing measured using logistic regression . RESULTS: Twenty GPs participated . The nature of each symptom and sign significantly predicted prescribing of an antibiotic . Cough productive of yellow sputum; presence of sore throat; fever; and coloured nasal mucus increased the probability of an antibiotic being prescribed . CONCLUSIONS: GPs are influenced by clinical signs and symptoms to use antibiotics for respiratory infections for which there is poor evidence of efficacy from the literature.

Fam Pract, 2000 Oct, 17(5), 380 - 5
Antibiotics for coughing in general practice: a qualitative decision analysis; Coenen S et al.; BACKGROUND: In family practice, medical decisions are prompted most often by complaints about coughing . There is no single yardstick for the differential diagnosis of respiratory tract infections (RTIs) . In 80% of cases, the excessive use of antibiotics in the treatment of RTIs is caused by the prescription behaviour of GPs . OBJECTIVE: Our aim was to explicate GPs' diagnostic (and therapeutic) decisions regarding adult patients who consult them with complaints about coughing, and to investigate what determines decision making . METHODS: Exploratory, descriptive focus groups were held with GPs . Hypotheses were generated on the basis of 'qualitative content analysis' . Results . Twenty-four GPs participated in four semi-structured group discussions . In order to differentiate RTIs from other possible diagnoses, less likely diagnoses were not ruled out explicitly . In the case of suspected RTI, there was a low degree of certainty in the differentiation between RTIs (e.g . between bronchitis and pneumonia) . Clinical signs and symptoms, which determine the probability of disease, often left GPs with reasonable diagnostic doubt . In the end, the decision whether or not to prescribe antibiotics was taken . GPs' prescription behaviour was also determined by doctor- and patient-related factors (e.g . having missed pneumonia once, patient expectations) . The 'chagrin factor' explains why these factors lead to a shift in the action threshold, in favour of antibiotics . CONCLUSION: This inductive research method enabled the generation of meaningful hypotheses regarding the complex decision processes pursued by GPs . The authors are developing an educational intervention that builds on these findings, focusing on the prescribing decision.

Br J Pharmacol, 2000 Oct, 131(3), 399 - 404
Cefaclor, a cephalosporin antibiotic, delays gastric emptying rate by a CCK-A receptor-mediated mechanism in the rat; Bozkurt A et al.; Studies in vitro suggest that cephalosporin antibiotics release the gut hormone cholecystokinin . Cholecystokinin is known to inhibit gastric emptying . Here we examine the effects of cefaclor on gastric emptying and intestinal motility . Male Sprague-Dawley rats were fitted with gastric cannulas . Following a 3-week recovery, the rate of gastric emptying of saline, peptone (4.5%) or cefaclor was determined after instillation into the gastric cannula, while intestinal transit was measured by using the propagation of arabic gum + charcoal mixture given intraduodenally . Gastric emptying of saline was significantly delayed by the addition of cefaclor (3, 10, 30 or 100 mM) . The CCK-A antagonist SR-27897B (1 mg kg(-1), i.p.) reversed the delay induced by 10 mM cefaclor, whereas the CCK-B antagonist CI-988 (1 mg kg(-1), i.p.) had no significant effect . In capsaicin-treated rats, 10 mM cefaclor emptied more rapidly than in vehicle-treated animals . Thirty-minute intestinal transit was increased at 30 and 100 mM of cefaclor, while the gastric acid secretion following cefaclor instillation was no different than the group which received saline . The cephalosporin antibiotic cefaclor appears to be a potent stimulant of CCK release from gut endocrine cells, resembling the effects of peptone . Cefaclor delays gastric emptying via capsaicin-sensitive afferent pathways, which involve CCK-A receptor interaction.

Nature, 2000 Sep 21, 407(6802), 340 - 8
Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics; Carter AP et al.; The 30S ribosomal subunit has two primary functions in protein synthesis . It discriminates against aminoacyl transfer RNAs that do not match the codon of messenger RNA, thereby ensuring accuracy in translation of the genetic message in a process called decoding . Also, it works with the 50S subunit to move the tRNAs and associated mRNA by precisely one codon, in a process called translocation . Here we describe the functional implications of the high-resolution 30S crystal structure presented in the accompanying paper, and infer details of the interactions between the 30S subunit and its tRNA and mRNA ligands . We also describe the crystal structure of the 30S subunit complexed with the antibiotics paromomycin, streptomycin and spectinomycin, which interfere with decoding and translocation . This work reveals the structural basis for the action of these antibiotics, and leads to a model for the role of the universally conserved 16S RNA residues A1492 and A1493 in the decoding process.

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