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 microg/ml), azithromycin (4 microg/ml), netilmicin (1 microg/ml), rifampin (8 microg/ml), polymyxin (0.8 U/ml), meropenem (4 microg/ml), trovafloxacin (4 microg/ml), and sulbactam (8 microg/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.

FIG. 1

The activity of trovafloxacin against strain 12676 typifies all four strains. While a slight decrease in CFU per milliliter was noted after 8 h, the drug was essentially bacteriostatic after 24 to 48 h.

FIG. 2

The activity of doxycycline against strain 13801 typifies three of the strains. A slight decrease in CFU/milliliter was noted after 4 to 8 h, but regrowth started after 24 h, and the drug was essentially bacteriostatic. Strain 12770 was different in that doxycycline exerted a bactericidal effect after 24 h.

FIG. 3

Rifampin showed rapid bactericidal activity against two of the outbreak isolates: strains 13081 and 12770.

FIG. 4

Rifampin was bacteriostatic against the nonoutbreak strain 12676 and the outbreak strain 13009. The third outbreak strain was resistant to rifampin (MIC = 128 μg/ml).

FIG. 5

The activity of sulbactam against strain 12270 typifies its activity against all the strains. There was initial bactericidal activity after 4 to 24 h, with regrowth occurring at 48 h.

FIG. 6

Azithromycin was bactericidal against strain 13009 and the other outbreak strains after 8 to 24 h. Azithromycin was not as active against the nonoutbreak strain (MIC = 32 μg/ml) and was very slowly bactericidal after 48 h and 7 days.