Effect of cationic micelles on the decomposition of alpha-aminophenyl cephalosporins

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of different media for the production of cephalosporins by Streptomyces clavuligerus ATCC 27064

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of the in vitro activity of cefepime compared to other broad-spectrum cephalosporins against clinical isolates from eighteen Brazilian hospitals by using the Etest

The in vitro activity of cefepime was compared to that of ceftazidime, ceftriaxone, and cefotaxime in a multicenter study involving 10 clinical microbiology laboratories and clinical isolates from 18 Brazilian hospitals from 7 cities (4 states). A total of 982 isolates consecutively collected between December 1995 and March 1996 were susceptibility tested by using Etest and following the NCCLS procedures for agar diffusion tests. The cefepime spectrum was broader than that of the other broad-spectrum cephalosporins against both Gram-negative rods and Gram-positive cocci. Cefepime tons particularly move active against Enterobacter sp. (MIC90, 2 mu g/ml), Serratia sp. (MIC90, 2 mu g/ml) and oxacillin-susceptible Staphylococcus aureus (MIC90, 3 mu g/ml). Against Pseudomonas aeruginosa, cefepime (MIC90 16 mu g/ml) was slightly more active than ceftazidime (MIC90 32 mu g/ml) and 8- to 16-fold more active than ceftriaxone or cefotaxime (MIC90 >256 mu g/ml). Our results show that nosocomial bacteria, especially Gram-negative rods, have a high rate of cephalosporin resistance in Brazil. However, part of these resistant bacteria remains susceptible to cefepime. The Etest was shown to be an excellent method for multicenter studies of the in vitro evaluation of new antimicrobial agents. (C) 1997 Elsevier B.V.

COMPARATIVE INVITRO ACTIVITY OF 3 CEPHALOSPORINS AGAINST STAPHYLOCOCCUS-AUREUS ISOLATED FROM BOVINE MASTITIS

This report compares the in vitro activity of three cephalosporins (cephalothin, cefoxitin and ceftriaxone) against 57 Staphylococcus aureus strains isolated from cows with clinical mastitis on the basis of the minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC). The majority of the S aureus strains showed resistance to cefoxitin and ceftriaxone and sensitivity to cephalothin. The highest MICs and MBCs were found for cefoxitin and ceftriaxone. Antimicrobial tolerance (MBC/MIC greater-than-or-equal-to 32:1) was observed in relation to cephalothin and ceftriaxone. The data suggest that these cephalosporins may not be effective for the treatment of staphylococcal bovine mastitis. The precise definition of their antimicrobial efficacies requires more detailed in vitro and in vivo studies.

Antimicrobial resistance of Salmonella serotypes isolated from slaughter-age pigs and environmental samples

The aim of this study was to determine the antimicrobial resistance patterns of Salmonella strains isolated from slaughter-age pigs and environmental samples collected at modern swine raising facilities in Brazil. Seventeen isolates of six serotypes of Salmonella enterica subsp. enterica were isolated out of 1,026 collected samples: Salmonella Typhimurium (1), Salmonella Agona (5), Salmonella Sandiego (5), Salmonella Rissen (1), Salmonella Senftenberg (4), and Salmonella Javiana (1). Resistance patterns were determined to extended-spectrum penicillin (ampicillin), broad-spectrum cephalosporins (cefotaxime and ceftriaxone), aminoglycosides (streptomycin, neomycin, gentamicin, amikacin, and tobramycin), narrow-spectrum quinolone (nalidixic acid), broad-spectrum quinolone (ciprofloxacin and norfloxacin), tetracycline, trimethoprim, and chloramphenicol. Antimicrobial resistance patterns varied among serotypes, but isolates from a single serotype consistently showed the same resistance profile. All isolates were resistant to tetracycline, streptomycin, and nalidixic acid. One isolate, Salmonella Rissen, was also resistant to cefotaxime and tobramycin. All serotypes were susceptible to ceftriaxone, norfloxacin, ciprofloxacin, ampicillin, gentamicin, and chloramphenicol. The high resistance to tetracycline and streptomycin may be linked to their common use as therapeutic drugs on the tested farms. No relation was seen between nalidixic acid and fluoroquinolone resistance.

Factors predictive of inappropriateness in requests for parenteral antimicrobials for therapeutic purposes: A study in a small teaching hospital in Brazil

Background: The identification of patterns of inappropriate antimicrobial prescriptions in hospitals contributes to the improvement of antimicrobial stewardship programs (ASP). Methods: We conducted a cross-sectional study to identify predictors of inappropriateness in requests for parenteral antimicrobials (RPAs) in a teaching hospital with 285 beds. We reviewed 25% of RPAs for therapeutic purposes from y 2005. Appropriateness was evaluated according to current guidelines for antimicrobial therapy. We assessed predictors of inappropriateness through univariate and multivariate models. RPAs classified as 'appropriate' or 'probably appropriate' were selected as controls. Case groups comprised inappropriate RPAs, either in general or for specific errors. Results: Nine hundred and sixty-three RPAs were evaluated, 34.6% of which were considered inappropriate. In the multivariate analysis, general predictors of inappropriateness were: prescription on week-ends/holidays (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.20-2.28, p = 0.002), patient in the intensive care unit (OR 1.57, 95% CI 1.11-2.23, p = 0.01), peritoneal infection (OR 2.15, 95% CI 1.27-3.65, p = 0.004), urinary tract infection (OR 1.89, 95% CI 1.25 -2.87, p = 0.01), combination therapy with 2 or more antimicrobials (OR 1.72, 95% CI 1.15-2.57, p = 0.008) and prescriptions including penicillins (OR 2.12, 95% CI 1.39-3.25, p = 0.001) or 1(st) generation cephalosporins (OR 1.74, 95% CI 1.01-3.00, p = 0.048). Previous consultation with an infectious diseases (ID) specialist had a protective effect against inappropriate prescription (OR 0.34, 95% CI 0.24-0.50, p < 0.001). Factors independently associated with specific prescription errors varied. However, consultation with an ID specialist was protective against both unnecessary antimicrobial use (OR 0.04, 95% CI 0.01-0.26, p = 0.001) and requests for agents with an insufficient antimicrobial spectrum (OR 0.14, 95% CI 0.03-0.30, p = 0.01). Conclusions: Our results demonstrate the importance of previous consultation with an ID specialist in assuring the quality of prescriptions. Also, they highlight prescription patterns that should be approached by ASP policies.

Effect of the addition of invert sugar on the production of cephalosporin C in a fed-batch bioreactor

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudo voltamétrico de redissolução catódica de cefaloglicina em meio aquoso sobre eletrodo de mercúrio

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Tris-EDTA no teste de sensibilidade antimicrobiana in vitro em amostras de Pseudomonas aeruginosa

In vitro antimicrobial susceptibility of strains of Pseudomonas aeruginosa by standard diffusion disk test and a modified method, by the addition Tris-EDTA, was evaluated. Increase in sensitivity of agent using modified method was observed mainly in aminoglycosides (amikacin, gentamicin, tobramycin), quinolones (ofloxacin and norfloxacin) and cephalosporins (cefoperazone and ceftazidime) groups. by standard diffusion disk test and a modified method, by the addition Tris-EDTA, was evaluated. Increase in sensitivity of agent using modified method was observed mainly in aminoglycosides (amikacin, gentamicin, tobramycin), quinolones (ofloxacin and norfloxacin) and cephalosporins (cefoperazone and ceftazidime) groups.

Dimetilsulfóxido - DMSO no teste de sensibilidade microbiana in vitro em cepas de Rhodococcus equi isoladas de afecções pulmonares em potros

Comparou-se a sensibilidade microbiana in vitro de isolados de Rhodococcus equi pelo teste padrão de difusão com discos, com o modificado, pela adição de 5% de dimetilsulfóxido-DMSO. Observou-se aumento da sensibilidade do R. equi no teste com DMSO, frente a aminoglicosídeos (canamicina, amicacina, estreptomicina) e ao cloranfenicol, enquanto para a eritromicina e derivados ß-lactâmicos (penicilina G, cefalosporinas, amoxicilina, oxacilina), constatou-se redução da sensibilidade do agente.

Atividade antimicrobiana in vitro da cefpiroma em comparação com outros beta-lactâmicos de amplo espectro contra 804 amostras clínicas de nove hospitais brasileiros

OBJETIVO: Avaliar a atividade in vitro da cefalosporina de quarta geração, cefpiroma em comparação com ceftazidima, ceftriaxona, cefotaxima e imipenem em um estudo multicêntrico envolvendo nove hospitais de seis cidades em quatro estados. MATERIAL E MÉTODOS: Foram estudadas 804 amostras clínicas isoladas em pacientes internados em unidades de terapia intensiva ou unidades de oncohematologia. As amostras foram coletadas no período de junho a novembro de 1995, isto é, antes da cefpiroma estar disponível comercialmente no Brasil, e testadas através do método de microdiluição em placas conforme descrito pelo National Committee for Clinical Laboratory Standards (NCCLS). Todas as amostras resistentes à cefpiroma foram retestadas utilizando-se o E-test. RESULTADOS: Contra as amostras de enterobactérias (n= 344), a cefpiroma apresentou atividade de 2 a 32 vezes superior àquela apresentada pelas cefalosporinas de terceira geração (CTGs) e semelhante àquela apresentada pelo imipenem. As porcentagens de enterobactérias sensíveis foram: 88% para a cefpiroma, 69% para as CTGs e 96% para o imipenem. O espectro de ação da cefpiroma foi maior ou igual ao do imipenem contra as espécies Citrobacter freundii, E. aerogenes, Morganella morganii e Serratia marcescens. Contra Acinetobacter sp. (n=77), a cefpiroma foi ligeiramente mais ativa que a ceftazidima, porém as porcentagens de resistência foram muito altas para esses compostos (84% e 88% respectivamente). As atividades da cefpiroma, ceftazidima e imipenem foram semelhantes contra Pseudomonas aeruginosa (n=128), com MIC50/porcentagem de sensibilidade de 8/59%, 8/62% e 4/62% respectivamente. Contra bactérias aeróbias gram-positivas, a cefpiroma foi de 4 a 16 vezes mais ativa que as CTGs. Contra S. epidermidis e outras espécies de estafilococos coagulase-negativos a cefpiroma foi ligeiramente superior ao imipenem, porém, contra as outras espécies de bactérias gram-positivas avaliadas, o imipenem apresentou atividade um pouco superior. CONCLUSÃO: Os resultados desse estudo sugerem que, no Brasil, a cefpiroma apresenta espectro de ação superior ao das CTGs contra bactérias gram-negativas (Enterobacteriaceae e não-fermentadares) e gram-positivas e semelhante ao do imipenem contra algumas espécies de enterobactérias e contra P. aeruginosa.

Cathodic stripping voltammetric determination of ceftazidime with reactive accumulation at a poly-L-lysine modified hanging mercury drop electrode

Ceftazidime is hydrolysed only slowly at pH 10 at room temperature. This is indicated by a small cathodic stripping voltammetric peak obtained at pH 10 at a hanging mercury drop electrode at about -0.6 V which corresponds to the reduction of the hydrolysis product. This peak is enhanced more than tenfold by the addition of poly-L-lysine (PLL) to the electrolyte solution. The optimum accumulation potential is between 0 and -0.1 V: the size of the peak decreases steadily, however, as the accumulation potential is moved to more negative potentials and is about one-sixth the size for accumulation at -0.4 V. Existing knowledge of the organic chemistry of cephalosporins indicates that the accumulation must involve an aminolysis reaction of the unprotonated PLL with the beta-lactam ring of the ceftazidime. The limit of detection (3 sigma) in standard solutions was calculated to be 1 x 10(-10) mol l(-1). The detection limit in buffer solution containing 1% of urine was calculated to be 5 x 10(-9) mol l(-1), i.e. 5 x 10(-6) mol l(-1) in the urine. (C) 1999 Elsevier B.V. B.V. AU rights reserved.

Predictors of incorrectness in antimicrobial prescription in the Bauru State Hospital (Bauru city, São Paulo State, Brazil)

The inappropriate use of antimicrobials in hospitals presents a negative impact on patient outcome and is associated with the emergence and spread of multidrug-resistant microorganisms. Antimicrobial stewardship programs (ASPs) have been instituted in order to improve the quality of prescriptions in hospitals. In this setting, the identification of patterns of inappropriate antimicrobial prescription is a valuable tool that allows ASPs to identify priorities for directing educative/restrictive policies. With this purpose, a study was conducted in the Bauru State Hospital, a teaching hospital with 285 beds affiliated to the Botucatu Medical School, São Paulo State University. The hospital maintains an active ASP since it was opened, in 2002. We selected 25% of the requests for parenteral antimicrobials (RPAs) from 2005 for analysis. Prescriptions for prophylactic purposes were excluded. All other RPAs were classified according to a modified Kunin and Jones categories. Univariate and multivariable analyses were performed to identify predictors of general inappropriateness and of specific prescription errors. Prescriptions classified as "appropriate'' or "probably appropriate" were selected as controls in all stages of the study. Among 963 RPAs included in our study, 34.6% were inappropriate. General predictors of inappropriateness were: prescription on weekends/holidays (OR = 1.67, 95% CI = 1.20-2.28, p = 0.002), patient from intensive care unit (OR = 1.57, 95% CI = 1.11-2.23, p = 0.01), peritoneal (OR = 2.15, 95% CI = 1.27-3.65, p = 0.004) or urinary tract infection (OR = 1.89, 95% CI = 1.25-2.87, p = 0.002), combined therapy with two or more antimicrobials (OR = 1.72, 95% CI = 1.15-2.57, p = 0.008) and prescriptions including penicillin (OR = 2.12, 95% CI = 1.39-3.25, p = 0.001) or first-generation cephalosporins (OR = 1.74, 95% CI = 1.01-3.00, p = 0.048). Previous consultation with an infectious diseases (ID) specialist had a protective effect against inappropriate prescription (OR = 0.34, 95% CI = 0.24-0.50, p < 0.001). Factors independently associated with specific prescription errors varied. However, consultation with an ID specialist was protective against both unnecessary antimicrobial use (OR = 0.04, 95% CI = 0.01-0.26, p = 0.001) and requests for agents with insufficient spectrum (OR = 0.14, 95% CI = 0.03-0.30, p = 0.01). In conclusion, the analysis of factors predictive of inappropriateness in antimicrobial prescription allowed us to identify issues requiring intervention. Also, it provided a positive feedback of the ASP efficacy, demonstrating the importance of previous consultation with an ID specialist to assure the quality of antimicrobial prescriptions.