ABSTRACT This study evaluated the in vitro activity of ceftolozane-tazobactam and comparator agents tested against Latin American isolates of Enterobacteriaceae and Pseudomonas aeruginosa from patients with health care-associated infections. Ceftolozane-tazobactam is an antipseudomonal cephalosporin combined with a well-established β-lactamase inhibitor.A total of 2415 Gram-negative organisms (537 P. aeruginosa and 1878 Enterobacteriaceae) were consecutively collected in 12 medical centers located in four Latin American countries. The organisms were tested for susceptibility by broth microdilution methods as described by the CLSI M07-A10 document and the results interpreted according to EUCAST and CLSI breakpoint criteria. Results: Ceftolozane-tazobactam (MIC50/90, 0.25/32 µg/mL; 84.2% susceptible) and meropenem (MIC50/90, ≤0.06/0.12 µg/mL; 92.6% susceptible) were the most active compounds tested against Enterobacteriaceae. Among the Enterobacteriaceae isolates tested, 6.6% were carbapenem-resistant Enterobacteriaceae and 26.4% exhibited an extended-spectrum β-lactamase non-carbapenem-resistant phenotype. Whereas ceftolozane-tazobactam showed good activity against extended-spectrum beta-lactamase, non-carbapenem-resistant phenotype strains of Enterobacteriaceae (MIC50/90, 0.5/>32 µg/mL), it lacked useful activity against strains with a (MIC50/90, >32/>32 µg/mL; 1.6% S) carbapenem-resistant phenotype. Ceftolozane-tazobactam was the most potent (MIC50//90, 0.5/16 µg/mL) β-lactam agent tested against P. aeruginosa isolates, inhibiting 86.8% at an MIC of ≤4 µg/mL. P. aeruginosa exhibited high rates of resistance to cefepime (16.0%), ceftazidime (23.6%), meropenem (28.3%), and piperacillin-tazobactam (16.4%). Conclusions: Ceftolozane-tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than available cephalosporins and piperacillin-tazobactam when tested against Enterobacteriaceae.

BACKGROUND: Pathogen frequency and resistance patterns may vary significantly from country to country and also in different hospitals within a country. Thus, regional surveillance programs are essential to guide empirical therapy and infection control measures. METHODS: Rank order of occurrence and antimicrobial susceptibility of pathogenic species causing bloodstream infections (BSI), lower respiratory tract infections (LRTI), wound or skin and soft tissue infections (WSSTI), and urinary tract infections (UTI) in hospitalized patients were determined by collecting consecutive isolates over a specified period of time, as part of the SENTRY Antimicrobial Resistance Surveillance Program (SENTRY). All isolates were tested by reference broth microdilution. RESULTS AND CONCLUSIONS: A total of 3,728 bacterial strains were obtained from January, 1997, to December, 1999, from 12 Brazilian hospitals located in 4 states. The largest number of isolates were obtained from patients with BSI (2,008), followed by LRTI (822 cases), UTI (468 cases), and WSSTI (430 cases). Staphylococcus aureus was the most frequently isolated pathogen in general (22.8% - 852 isolates), followed by E. coli (13.8% - 516 cases) and Pseudomonas aeruginosa (13.3% - 496 cases). Staphylococcus aureus was also the most common species isolated from BSI (23.6%) and WSSTI (45.8%), and P. aeruginosa was the most frequent species isolated from patients with LRTI (29.4%). The main bacterial resistance problems found in this study were: imipenem resistance among P. aeruginosa (69.8% susceptibility) and Acinetobacter spp. (88.1% susceptibility); ESBL production among K. pneumoniae (48.4%) and E. coli (8.9%); resistance to third generation cephalosporins among Enterobacter spp. (68.1% susceptible to ceftazidime) and oxacillin resistance among S. aureus (34.0%) and coagulase negative staphylococci (80.1%). Only the carbapenems (88.1% to 89.3% susceptibility) showed reasonable activity against the Acinetobacter spp. isolates evaluated.

Introdução: Pneumonia hospitalar é a mais fatal das infecções hospitalares, com taxas de mortalidade de 30 a 60%. Estima-se que 15% de todas as mortes associadas à hospitalização estejam diretamente relacionadas a pneumonias hospitalares. O SENTRY é um estudo de vigilância de resistência a antimicrobianos envolvendo centros médicos em todo o mundo. Objetivo: Avaliar a sensibilidade a antimicrobianos de bactérias isoladas no trato respiratório baixo de pacientes com pneumonia internados em hospitais brasileiros. Material e métodos: Foram avaliadas 525 amostras bacterianas de 11 hospitais brasileiros, como parte do programa SENTRY. Os isolados foram testados por microdiluição em caldo contra um grande número de antimicrobianos. Resultados: As cinco espécies mais freqüentes foram (n/%): Pseudomonas aeruginosa (158/30,1%), Staphylococcus aureus (103/19,6%), Acinetobacter spp. (68/13,0%), Klebsiella spp. (50/9,5%), e Enterobacter spp. (44/8,4%). Essas cinco espécies representam mais de 80% de toda a amostragem. A P. aeruginosa apresentou altas taxas de resistência à maioria dos antimicrobianos testados. As maiores taxas de sensibilidade foram apresentadas por piperacilina/tazobactam (71,5%) e meropenem (69,0%). Os compostos com maior atividade in vitro contra Acinetobacter spp. foram imipenem e meropenem (80,9% de sensibilidade) seguido pela tetraciclina (63,2%). A sensibilidade das amostras de Klebsiella spp. foi muito baixa. MICs > ou = 2mig/mL para ceftriaxona ou ceftazidima, indicando produção de ESBL, foram encontrados em 36,0% das amostras. Os antimicrobianos mais ativos contra Klebsiella spp. foram os carbapenens (100% de sensibilidade) e as quinolonas (92,0% de sensibilidade). Ceftriaxona foi ativa contra somente 56,8% das amostras de Enterobacter spp. (MIC50, 1mig/mL), enquanto a cefepima foi ativa contra 88,6% destes isolados (MIC50, <= 0,12mig/mL). A resistência à oxacilina foi detectada em 43,7% dos isolados de S. aureus. As drogas mais ativas contra essa espécie foram: vancomicina, teicoplanina, quinupristin-dalfopristin e linezolida. Conclusões: Os resultados do presente estudo mostraram alta prevalência de Acinetobacter spp. e altas taxas de resistência entre bacilos gram-negativos quando comparados com resultados de estudos norte-americanos e europeus.

Background: Nosocomial pneumonia is the most common fatal nosocomial infection with attributable mortality rates ranging from 30 to 60% and a rapid initiation of optimal antimicrobial therapy is important to obtain treatment success. SENTRY is a comprehensive antimicrobial surveillance study involving a great number of medical centers distributed worldwide. Objective: To evaluate the antimicrobial susceptibility of bacterial isolates collected from the lower respiratory tract of inpatients with pneumonia. Material & methods: The authors report the antimicrobial susceptibility of 525 isolates collected in 11 Brazilian hospitals, as part of the SENTRY program. The isolates were tested for susceptibility by broth micro-dilution against a large number of drugs. Results: The five most frequently isolated species were (n/%): Pseudomonas aeruginosa (158/30.1%), Staphylococcus aureus (103/19.6%), Acinetobacter spp. (68/13.0%), Klebsiella spp. (50/9.5%), and Enterobacter spp. (44/8.4%). These five species represented more than 80% of all isolates. P. aeruginosa demonstrated high rates of resistance to most antimicrobial agents tested. The highest susceptibility rates were shown by piperacillin/tazobactam (71.5%) and meropenem (69.0%). Acinetobacter spp. also showed very high rates of resistance. The most active compounds against this species were imipenem and meropenem (80.9% susceptibility) followed by tetracycline (63.2% susceptibility). Cephalosporin susceptibilities among Klebsiella spp were very low and 36.0% of isolates were considered ESBL producers based on increased MICs, > 2 mug/mL) to ceftriaxone or ceftazidime or aztreonam. Ceftriaxone was active against only 56.8% of Enterobacter spp. isolates (MIC50 1 mug/mL), while cefepime was active against 88.6% of these isolates (MIC, < 0.12 mg/mL). Oxacillin-resistance was detected in 43.7% of S. aureus isolates. The most active drugs against this species were vancomycin, teicoplanin, quinupristin/dalfopristin, and linezolid. Conclusion: The results of this study demonstrated a higher prevalence of Acinetobacter spp. and higher resistance rates among Gram-negative rods when compared with results from North American and European studies.