Abstract
The in vitro susceptibilities of 69 nosocomial Acinetobacter isolates were determined by the broth microdilution method. Fourteen (20%) isolates were resistant to at least two aminoglycosides and two extended-spectrum penicillins. Nine antimicrobial combinations were then tested for synergy against these 14 isolates by checkerboard titration: imipenem with ciprofloxacin, amikacin, and tobramycin and ampicillin-sulbactam, piperacillin-tazobactam, and ticarcillin-clavulanate with amikacin and tobramycin. Synergy was detected with one or more antimicrobial combinations against 9 of 14 (64%) isolates, partial synergy was detected with one or more combinations against all 14 isolates, and an additive effect alone was observed with two different combinations against two isolates. No antagonism was detected with any combination. Imipenem plus either amikacin or tobramycin resulted in a synergistic or partial synergistic response against all 14 isolates. Specific combinations showing synergy against A. baumannii isolates were imipenem with tobramycin (four isolates), imipenem with amikacin (three isolates), ampicillin-sulbactam with tobramycin (six isolates), ampicillin-sulbactam with amikacin (three isolates), and ticarcillin-clavulanate with tobramycin (one isolate). Genotyping by randomly amplified polymorphic DNA analysis showed that 9 of the 14 isolates were of one strain, 4 isolates were of a second strain, and the remaining isolate was of a different strain. Eight of 14 (57%) patients infected with resistant A. baumannii isolates died. Only 3 of 14 patients had received a therapeutic regimen which was tested for synergy. Clinical studies are needed to determine the significance of these findings.
Full Text
The Full Text of this article is available as a PDF (213.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anstey N. M. Use of cefotaxime for treatment of Acinetobacter infections. Clin Infect Dis. 1992 Aug;15(2):374–374. doi: 10.1093/clinids/15.2.374. [DOI] [PubMed] [Google Scholar]
- Bergogne-Bérézin E., Joly-Guillou M. L., Vieu J. F. Epidemiology of nosocomial infections due to Acinetobacter calcoaceticus. J Hosp Infect. 1987 Sep;10(2):105–113. doi: 10.1016/0195-6701(87)90135-6. [DOI] [PubMed] [Google Scholar]
- Bouvet P. J., Grimont P. A. Identification and biotyping of clinical isolates of Acinetobacter. Ann Inst Pasteur Microbiol. 1987 Sep-Oct;138(5):569–578. doi: 10.1016/0769-2609(87)90042-1. [DOI] [PubMed] [Google Scholar]
- Bouvet P. J., Jeanjean S., Vieu J. F., Dijkshoorn L. Species, biotype, and bacteriophage type determinations compared with cell envelope protein profiles for typing Acinetobacter strains. J Clin Microbiol. 1990 Feb;28(2):170–176. doi: 10.1128/jcm.28.2.170-176.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chang S. C., Chen Y. C., Luh K. T., Hsieh W. C. In vitro activities of antimicrobial agents, alone and in combination, against Acinetobacter baumannii isolated from blood. Diagn Microbiol Infect Dis. 1995 Nov;23(3):105–110. doi: 10.1016/0732-8893(95)00170-0. [DOI] [PubMed] [Google Scholar]
- Chopade B. A., Wise P. J., Towner K. J. Plasmid transfer and behaviour in Acinetobacter calcoaceticus EBF65/65. J Gen Microbiol. 1985 Oct;131(10):2805–2811. doi: 10.1099/00221287-131-10-2805. [DOI] [PubMed] [Google Scholar]
- Devaud M., Kayser F. H., Bächi B. Transposon-mediated multiple antibiotic resistance in Acinetobacter strains. Antimicrob Agents Chemother. 1982 Aug;22(2):323–329. doi: 10.1128/aac.22.2.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Douboyas J., Tzouvelekis L. S., Tsakris A. In-vitro activity of ampicillin/sulbactam against multiresistant Acinetobacter calcoaceticus var. anitratus clinical isolates. J Antimicrob Chemother. 1994 Aug;34(2):298–300. doi: 10.1093/jac/34.2.298. [DOI] [PubMed] [Google Scholar]
- Drusano G. L. Human pharmacodynamics of beta-lactams, aminoglycosides and their combination. Scand J Infect Dis Suppl. 1990;74:235–248. [PubMed] [Google Scholar]
- Eliopoulos G. M., Eliopoulos C. T. Antibiotic combinations: should they be tested? Clin Microbiol Rev. 1988 Apr;1(2):139–156. doi: 10.1128/cmr.1.2.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldstein F. W., Labigne-Roussel A., Gerbaud G., Carlier C., Collatz E., Courvalin P. Transferable plasmid-mediated antibiotic resistance in Acinetobacter. Plasmid. 1983 Sep;10(2):138–147. doi: 10.1016/0147-619x(83)90066-5. [DOI] [PubMed] [Google Scholar]
- Joly-Guillou M. L., Bergogne-Berezin E., Vieu J. F. A study of the relationships between antibiotic resistance phenotypes, phage-typing and biotyping of 117 clinical isolates of Acinetobacter spp. J Hosp Infect. 1990 Jul;16(1):49–58. doi: 10.1016/0195-6701(90)90048-s. [DOI] [PubMed] [Google Scholar]
- Joly-Guillou M. L., Bergogne-Bérézin E., Moreau N. Enzymatic resistance to beta-lactams and aminoglycosides in Acinetobacter calcoaceticus. J Antimicrob Chemother. 1987 Dec;20(6):773–776. doi: 10.1093/jac/20.6.773. [DOI] [PubMed] [Google Scholar]
- Klastersky J., Meunier-Carpentier F., Prevost J. M. Significance of antimicrobial synergism for the outcome of gram negative sepsis. Am J Med Sci. 1977 Mar-Apr;273(2):157–167. doi: 10.1097/00000441-197703000-00005. [DOI] [PubMed] [Google Scholar]
- Meyers B. R., Wilkinson P., Mendelson M. H., Walsh S., Bournazos C., Hirschman S. Z. Pharmacokinetics of ampicillin-sulbactam in healthy elderly and young volunteers. Antimicrob Agents Chemother. 1991 Oct;35(10):2098–2101. doi: 10.1128/aac.35.10.2098. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rogers J. D., Meisinger M. A., Ferber F., Calandra G. B., Demetriades J. L., Bland J. A. Pharmacokinetics of imipenem and cilastatin in volunteers. Rev Infect Dis. 1985 Jul-Aug;7 (Suppl 3):S435–S446. doi: 10.1093/clinids/7.supplement_3.s435. [DOI] [PubMed] [Google Scholar]
- Scully B. E., Chin N. X., Neu H. C. Pharmacology of ticarcillin combined with clavulanic acid in humans. Am J Med. 1985 Nov 29;79(5B):39–43. doi: 10.1016/0002-9343(85)90127-5. [DOI] [PubMed] [Google Scholar]
- Seifert H., Baginski R., Schulze A., Pulverer G. Antimicrobial susceptibility of Acinetobacter species. Antimicrob Agents Chemother. 1993 Apr;37(4):750–753. doi: 10.1128/aac.37.4.750. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sörgel F., Kinzig M. The chemistry, pharmacokinetics and tissue distribution of piperacillin/tazobactam. J Antimicrob Chemother. 1993 Jan;31 (Suppl A):39–60. doi: 10.1093/jac/31.suppl_a.39. [DOI] [PubMed] [Google Scholar]
- Tilley P. A., Roberts F. J. Bacteremia with Acinetobacter species: risk factors and prognosis in different clinical settings. Clin Infect Dis. 1994 Jun;18(6):896–900. doi: 10.1093/clinids/18.6.896. [DOI] [PubMed] [Google Scholar]
- Traub W. H., Spohr M. Antimicrobial drug susceptibility of clinical isolates of Acinetobacter species (A. baumannii, A. haemolyticus, genospecies 3, and genospecies 6). Antimicrob Agents Chemother. 1989 Sep;33(9):1617–1619. doi: 10.1128/aac.33.9.1617. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Urban C., Go E., Mariano N., Berger B. J., Avraham I., Rubin D., Rahal J. J. Effect of sulbactam on infections caused by imipenem-resistant Acinetobacter calcoaceticus biotype anitratus. J Infect Dis. 1993 Feb;167(2):448–451. doi: 10.1093/infdis/167.2.448. [DOI] [PubMed] [Google Scholar]
- Vila J., Almela M., Jimenez de Anta M. T. Laboratory investigation of hospital outbreak caused by two different multiresistant Acinetobacter calcoaceticus subsp. anitratus strains. J Clin Microbiol. 1989 May;27(5):1086–1089. doi: 10.1128/jcm.27.5.1086-1089.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vila J., Marcos A., Marco F., Abdalla S., Vergara Y., Reig R., Gomez-Lus R., Jimenez de Anta T. In vitro antimicrobial production of beta-lactamases, aminoglycoside-modifying enzymes, and chloramphenicol acetyltransferase by and susceptibility of clinical isolates of Acinetobacter baumannii. Antimicrob Agents Chemother. 1993 Jan;37(1):138–141. doi: 10.1128/aac.37.1.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang G., Whittam T. S., Berg C. M., Berg D. E. RAPD (arbitrary primer) PCR is more sensitive than multilocus enzyme electrophoresis for distinguishing related bacterial strains. Nucleic Acids Res. 1993 Dec 25;21(25):5930–5933. doi: 10.1093/nar/21.25.5930. [DOI] [PMC free article] [PubMed] [Google Scholar]