In Vitro Activities of Nontraditional Antimicrobials against Multiresistant Acinetobacter baumannii Strains Isolated in an Intensive Care Unit Outbreak

Abstract

Fifteen multiresistant Acinetobacter baumannii isolates from patients in intensive care units and 14 nonoutbreak strains were tested to determine in vitro activities of nontraditional antimicrobials, including cefepime, meropenem, netilmicin, azithromycin, doxycycline, rifampin, sulbactam, and trovafloxacin. The latter five drugs were further tested against four of the strains for bactericidal or bacteriostatic activity by performing kill-curve studies at 0.5, 1, 2, and 4 times their MICs. In addition, novel combinations of drugs with sulbactam were examined for synergistic interactions by using a checkerboard configuration. MICs at which 90% of the isolates tested were inhibited for antimicrobials showing activity against the multiresistant A. baumannii strains were as follows (in parentheses): doxycycline (1 g/ml), azithromycin (4 g/ml), netilmicin (1 g/ml), rifampin (8 g/ml), polymyxin (0.8 U/ml), meropenem (4 g/ml), trovafloxacin (4 g/ml), and sulbactam (8 g/ml). In the kill-curve studies, azithromycin and rifampin were rapidly bactericidal while sulbactam was more slowly bactericidal. Trovafloxacin and doxycycline were bacteriostatic. None of the antimicrobials tested were bactericidal against all strains tested. The synergy studies demonstrated that the combinations of sulbactam with azithromycin, rifampin, doxycycline, or trovafloxacin were generally additive or indifferent.Acinetobacter baumannii is an aerobic, gram-negative, oxidase-negative, nonfermenting bacterium that has become an increasingly frequent cause of nosocomial infections, particularly in intensive care units (3,4,8,11). It has a propensity to develop antibiotic resistance extremely rapidly (2). Successive surveys have shown increasing resistance in clinical isolates, and high proportions of strains have become resistant to older, commonly used antibiotics (6, 10, 15). Only newer antibiotics, such as broad-spectrum cephalosporins, imipenem, tobramycin, amikacin, and fluoroquinolones, remain useful. The recent development of more universally resistant strains of A. baumannii has made the search for effective therapies more important and urgent (9, 13, 14; M. Wolff, M. L. Joly-Gillou, R. Farionotti, and C. Carbon, Abstr. 37th Intersci. Conf. Antimicrob. Agents Chemother., abstr. B-8, 1997).From 1996 through 1997, an outbreak of resistant A. baumannii infections involving 96 patients occurred in the intensive care units (ICUs) of Los Angeles County-University of Southern California (LAC-USC) Medical Center. The hospital clinical laboratory did routine susceptibility testing and reported that the isolates were resistant to imipenem, ceftazidime, cefotaxime, gentamicin, tobramycin, piperacillin-tazobactam, ticarcillin-clavulanate, ciprofloxacin, ofloxacin, and trimethoprim-sulfamethoxazole. The strains were moderately susceptible to ampicillin-sulbactam. Some strains were resistant to amikacin, and others were not. There was variability in susceptibility to amikacin among the strains, even among the same-patient strains, when testing was done ...

Reliability of the E-Test Method for Detection of Colistin Resistance in Clinical Isolates of Acinetobacter baumannii

“…The in vitro (1,4) and in vivo activities of colistin (polymyxin E) suggested that it would be an effective antimicrobial agent against A. baumannii (6,9,11,12,18). However, some polymyxin-resistant strains have been reported (15,16).…”

Clinicomicrobiological Study of Infections Caused by Acinetobacter Species

“…is the second most common non-fermenting bacteria isolated from clinical specimen especially in hospital settings [8]. The recent years have seen the emergence of this pathogen in ICUs [7].…”

Antibióticos intratecales en pacientes adultos

“…En adultos sin meninges inflamadas, la concentraciones máximas de meropenem en el LCR han sido menores (~0,6 µg/mL); sin embargo, las concentraciones obtenidas en el LCR con altas dosis de meropenem (con o sin meninges inflamadas), permiten asegurar la inhibición de las enterobacterias que se manifiestan susceptibles en el antibiograma para este compuesto 10,13 . No obstante, estas concentraciones pueden ser marginales o claramente insuficientes para superar las CIM 90 de meropenem contra P. aeruginosa (CIM 90 ~ 3 µg/mL) o A. baumannii (4 a 6,4 µg/mL), también involucrados como posibles agentes de ventriculitis 10,14,15 . Meropenem ha sido utilizado exitosamente en pacientes con ventriculitis por P. aeruginosa 16 , pero con selección de cepas resistentes in vivo en el manejo de pacientes con ventriculitis por A. baumannii 17 .…”

“…Los valores de CIM 90 de sulbactam sobre esta especie se aproximan a 8 µg/mL, sin presentar este compuesto una actividad sinérgica con ampicilina, aunque ha sido utilizado exitosamente en infecciones no severas por este agente 27 . El efecto bactericida de sulbactam sobre A. baumannii es transitorio y resulta ser más pronunciado con concentraciones superiores a la CIM (4 x CIM), las que son difíciles de obtener en el LCR 15 ; ello podría explicar resultados parciales obtenidos en el manejo de infecciones del SNC por esta especie 25 . Las fluoroquinolonas tienen una buena penetración al LCR y no requieren dosis intratecales complementarias.…”