Ceftolozane-tazobactam activity against drug-resistant Enterobacteriaceae and Pseudomonas aeruginosa causing healthcare-associated infections in Latin America: report from an antimicrobial surveillance program (2013-2015)

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.

Patogen frequency and resistance patterns in brazilian hospitals: summary of results from three years of the sentry antimicrobial surveillance program

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 occurence and antimicrobial susceptibility to patogenic 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 conclusiones: 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 patogen in general (22.8 percent-852 isolates), followed by E. coli (13.8 percent - 516 cases) and pseudomonas aeruginosa (13.3 percent - 496 cases). Staphylococcus aureus was also the most common species isolated from BSI (23.6 percent) and WSSTI (45.8 percent), and P.aeruginosa was the most frequent species isolated from patients with LRTI (29.4 percent). The main bacterial resistance problems found in this study were: imipenem resistance among P.aeruginosa (69.8 percent susceptibility) and Acinetobacter spp. (88.1 percent susceptibility): ESBL production among K. pneumoniae (48.4 percent) and E. coli (8.9 percent); resistance to third generation cephalosporin among Enterobacter spp. (68.1 percent susceptible to ceftazidime) and oxacillin resistance among S. aureus (34.0 percent) and coagulase negative staphylococci (80.1 percent). Only the carbapenems (88.1 percent to 89.3 percent susceptibility) showed reasonable activity against the Acinetobacter spp. isolates evaluated.

Prevalence of antimicrobial resistance among respiratory tract isolates in Latin America: results from SENTRY antimicrobial surveillance program (1997-98)

One thousand seventy-three bacterial isolates were collected from patients with community acquired respiratory tract infections (CARTI) in 11 Latin American centers (7 countries) during 1997 and 1998. They were tested against numerous antimicrobial agents by the reference broth microdilution method as part of the ongoing multinational SENTRY Antimicrobial Surveillance Program. Among Streptococcus pneumonia (553 isolates), approximately 61 por cento were susceptible to penicillin. There was a great variation of the penicillin susceptibility rates among participating countries. The highest susceptibility rates were found in Argentina (76.7 porcento) and Brazil (71.9 por cento), while the lowest rate of penicillin susceptibility was detected in Mexico (33.3 por cento). High level resistance to penicillin and resistance to cefotaxime were observed in nearly 10 por cento of the isolates. The newer quinolones, levofloxacin (MIC 2 mg/mL) and gatifloxacin (MIC 0.5 mg/mL), were active against 100 por cento of the isolates tested. Among the other non-B-lactam drugs tested, the rank order of susceptibility against the pneumococci was: chloramphenicol (93.9 por cento) > clindamycin (93.2 por cento)> azithromycin (89.1 por cento) > clarithromycin (88.7 porcento) > tetracycline (78.5 por cento) > trimethoprim/sulfamethoxazole (55.7 por cento). The percentage of Haemophilus influenzae (361 isolates) isolates resistant to amoxicillin was 12.7 por cento (B-lactamase positive). Among Moraxella catarrhalis (159 isolates) isolates, only 8.2 por cento were susceptible. Clavulanic acid restored the activity of amoxicillin against both species. Trimethoprim/sulfamethoxazole was active against only 59.5 por cento of H. influenzae, while susceptibility to this compound among M. catarrhalis was 96.1 porcento. All other compounds tested were active against > 95 por cento of H. influenzae and M. catarrhalis isolates. These species were susceptible to levofloxacin (MIC90 (less or equal) 0.5 µg/mL for both) and gatifloxacin (MIC90 (less or equal) 0.03 µg/mL for both) with very low MICs. Our results indicate that penicillin resistance rates are particularly high among pneumococci in some countries. The never fluoroquinolones show and excellent potency and spectrum against pathogens causing community acquired respiratory infections in Latin America.

Antifungal susceptibility testing: Progress and future developments

The establishment of a standardized broth reference method for antifungal susceptibility testing of yeastshas opened the door to a number of interesting and useful developments. The adaptation of the reference macrodilution method to a microdilution method has significantly increased the clinical utility of antifungal susceptibility testing, and both methods are now included in the NCCLS document M27-A. The publication of quality control limits for five antifungal agents, coupled with the estabilisment of interpretive MIC breakpoints for three agents, provides useful parameters to survey clinical isolates of Candida and other yeast species. Adaptations of the M27 microdilution method for testing molds has also proved feasible. These developments have made it possible for a number of recent studies designed to expand the capabilities of laboratories to perform antifungal susceptibility testing and to enhance our understanging of trends in antifungal susceptibility. The availability of reference methods also provides a useful touchstone for the development of commercial products that promise to be more user friendly and to further improve test standartization. Products in varying stages of development include two colorimetric microdilution methods (Sensititre and KPI) and the Etest stable gradient MIC method. Preliminary data indicate that these methods are viable alternatives to the reference method for testing of yeasts. Furthermore, Etest may also prove useful for testing molds. Future expectations for antifungal susceptibility testing includes improved ability to detect amphotericin B resistence, development of an NCCLS document for susceptibility testing of molds, and application of these methods for testing dematophytes. Incorporation of antifungal susceptibility testing methods into the clinical trials of new antifungal agents will facilitate the establishment of clinical correlates and further enhance the clinical utility of antifungal susceptibility testing.

El programa de vigilancia antimicrobiana SENTRY en Colombia: hallazgos iniciales en tres hospitales de Medellín / The Sentry antimicrobial surveillance program in Colombia First findings in tree hospitals in Medellín

El programa SENTRY es una red de laboratorios alrededor del mundo, que vigila la prevalencia de patrones de sensibilidad / resistencia antimicrobiana en bacterias causantes de infecciones hospitalarias y de la comunidad. Este reporte resume los datos reunidos en 1997 por un laboratorio de referencia en Medellín. Los aislamientos (uno por paciente) fueron de bacteremias, neumonía, heridas de piel y tejidos blandos e infecciones urinarias. La identificación y pruebas de sensibilidad se realizarón en el laboratorio local y se confirmaron por el laboratorio coordinador en la Universidad de Iowa. Las pruebas de sensibilidad en este laboratorio se realizaron a cefalosporinas, betalactámicos, macrólidos, fluoroquinolonas, aminoglucósidos etc., utilizando microdilución en caldo. Fueron recolectados 212 aislamientos, los más frecuentes fueron: Escherichia coli (25.0 por ciento), responsible de la mayoría de las bacteremias, infecciones del tracto respiratorio inferior y tracto urinario; y Staphylococcus aureus (14.2 por ciento) obtenido de la mayoría de las infecciones de piel y tejidos blandos. La sensibilidad en bacilos gram negativos fue en su orden: imipenem (99.1 por ciento) > cefepime (92.5 por ciento) > amikacina (89.6 por ciento) > ciprofloxacina = ceftazidima = gatifloxacina = levofloxacina (88.7 por ciento) > gentamicina = trovafloxacina (87.7 por ciento) > aztreonam (85.8 por ciento) > ceftriaxona (80.2 por ciento) > piperacilina / tazobactam (77.4 por ciento) > tobramicina (76.4 por ciento) > cefuroxima (56.6 por ciento) > cefazolina (45.3 por ciento). Se encontraron aislamientos de klebsiella spp y E coli productores de betalactamasas de espectro extendido (BLEE) y una frecuenciaq alta de resistencia a fluoroquinolonas. 16.7 por ciento de Sa Aureus de resistente a oxacilina. Un aislamiento de enterococo tuvo sensibilidad intermedia a vancomicina. Estos datos pueden servir de referencia para futuros estudios y permitir la vigilancia de las tendencias de resistencia en Colombia en comparación con otros países de America Latina y el mundo

Bacterial pathogens isolated from patients with bloodstream infections in Latin America, 1997: Frequency of occurrence and antimicrobial susceptibility patterns from the SENTRY antimicrobial surveillance program

We report the antimicrobial susceptibility of 736 organisms isolated from bloodstream infections in 10 Latin American medical centers during the first six months of 1997. The data presented here is from the SENTRY Antimicrobial Surveillance Program, a comprehensive surveillance study involving 72 medical centers worldwide. The isolates were tested for in vitro susceptibility to 35 antimicrobial agents by the broth microdilution method. The five most frequently isolated species were(n/percent): Staphylococcus aureus (165/22.4 percent), Escherichia coli (118/16.0 percent), coagulase-negative staphylococci (CoNS - 115/15.6 percent), Pseudomonas aeruginosa (51/6.9 percent), Klebsiella ssp. (46/6.3 percent). Susceptibility to oxacillin was 70.9 percent for S.aureus and only 33.9 percent for CoNS. Vancomycin was active against all of staphylococci, while teicoplanin was active against 99.4 percent of S.aureus and only 90.4 percent of CoNS. The new fluoroquinolones sparfloxacin, gatifloxacin, and trovafloxacin, and the streptogramin, quinupristin/dalfopristin, were very active against these species. Only one vancomycin-resistant enterococcus was detected; however, high-level aminoglycoside resistance rates were common (66.7 percent). E.coli and Klebsiella spp. showed low susceptibilities for cefotaxime (90.7 percent and 41.3 percent) and for cefoxitin (85.6 percent and 78.3 percent respectively), indicating a high frequency of isolates that produce ESBL and/or stably derepressed ampC enzymes. These strains, phenotypically consistent with extended-spectrum ß-lactamase (ESBL) production, were typed using ribotyping and pulsed-field gel electrophoresis. The most active compounds (MIC90 in µg/mL/ percent susceptibility) against P. aeruginosa were meropenem (2/94.1 percent), followed by amikacin (>32/86.3 percent), and piperacillin alone or with tazobactam (128/84.3 percent). Ceftazidime and cefepime showed similar activity (70.6 percent susceptibility) and levofloxacin was the most active fluoroquinolone (MIC50 menor do que 0.5; 76.5 percent susceptibility) against this gram-negative species. These results show the unique pattern of bloodstream isolates for Latin America and they demonstrate the present utility of several classes of compounds against emerging antimicrobial-resistant species in this region.