CITATION: Urban C, Rahal JJ.1995. Acinetobacter baumannii: A newly emerging nosocomial pathogen. APUA Newsletter 13(2):1-3.


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Acinetobacter baumannii: A newly emerging nosocomial pathogen
Carl Urban and James J Rahal
Department of Medicine, The New York Hospital Medical Center of Queens, Queens, New York, USA and Cornell University Medical College, Ithaca, New York, USA


Certain strains of
Acinetobacter baumannii (formerly Acinetobacter calcoaceticus biotype anitratus) have acquired resistance to all commonly prescribed antibiotics. Only within the last three years did these strains become resistant to the beta-lactam of last resort, imipenem (7,8,10). Resistance to imipenem in Acinetobacter can be due to enzymes that inactivate the antibiotic (5), altered penicillin-binding proteins (PBPs)(2) or a combination of altered PBPs and reduced outer membrane permeability (3). Only polymyxin, and in some instances sulbactam, have demonstrated bactericidal activity against these multiresistant bacteria. This report reviews events leading to a nosocomial outbreak of Acinetobacter baumannii strains susceptible only to polymyxin and sulbactam in a 487 bed teaching hospital. It will present epidemiological characteristics of the outbreak and discuss activities of key personnel which led to eradication of this strain from the hospital environment.

During the mid to late 1980's, two populations of Acinetobacter baumannii with distinct antibiograms were observed in our institution. Multiresistant isolates were susceptible to ceftazidime, amikacin and imipenem while sensitive strains were also susceptible to tobramycin, trimethoprim/sulfamethoxazole, gentamicin and ticarcillin/clavulanate. Ceftazidime was selected as the major beta lactam agent of choice for treatment of patients infected with multiresistant A. baumannii isolates. The necessary use of ceftazidime from 1987 to 1989 led to an epidemic of ceftazidime-resistant Klebsiella pneumoniae. Detailed in vitro experiments showed that imipenem was the only beta-lactam agent consistently bactericidal for the organisms tested (4 ). In addition, the genes encoding ceftazidime resistance were located on plasmids which medicated resistance to many beta-lactam agents as well as other classes of antimicrobials. Thus, imipenem was chosen as the therapeutic agent for patients infected with ceftazidime resistant Klebsiella pneumoniae. As imipenem usage increased in 1990, our multiresistant Acinetobacter soon became resistant to imipenem.

In September of 1991 our first isolates of imipenem resistant Acinetobacter baumannii were identified in the clinical microbiology laboratory. These isolates were resistant to all antibiotics except polymyxin and the beta-lactamase inhibitor, sulbactam. When we first reported these multiresistant isolates in 1993, imipenem resistance was a rare finding in Acinetobacter (8). We also demonstrated that sulbactam, a beta-lactamase inhibitor was bactericidal in vitro and was effective therapeutically for patients infected with these Acinetobacter strains. A subsequent report on the mechanisms of action of sulbactam showed that it bound to penicillin-binding proteins (PBPs) 2 and 1 at clinically achievable levels in both imipenem-susceptible and resistant strains (9). While these experiments were being performed in the laboratory, investigations into the clinical and molecular epidemiology of Acinetobacter infections susceptible only to polymyxin B and sulbactam were initiated (1). Four major antibiograms were associated with isolates of A. baumannii (ACB). Imipenem resistant (IR-ACR) isolates were resistant by Kirby Bauer susceptibility testing to imipenem, amikacin, gentamicin, tobramycin, ceftazidime, trimethoprim/sulfamethoxazole, ciprofloxacin, tetracycline and ticarcillin/clavulanate. Imipenem-sensitive (IS-ACB) isolates were susceptible only to imipenem. Imipenem and amikacin sensitive (IAS-ACB) isolates were susceptible only to imipenem and amikacin. Very sensitive (VS-ACB) isolates were susceptible to imipenem, amikacin, gentamicin, tobramycin, ciprofloxacin, trimethoprim/sulfamethoxazole and ticarcillin/clavulanate. ACB isolates were monitored from the clinical microbiology laboratory and patient records were reviewed over a twelve month period. Patients infected as defined by the CDC with IR-ACB were also recorded. Isolation of IR-ACB from different sites in one patient was identified as one case and isolation of more than one ACB with identical susceptibility patterns from a single site was recorded as once per site. Environmental surveillance was conducted to determine inanimate and personnel reservoirs from December 1991 to January 1992 which corresponded to the peak of the outbreak. Sterile swabs from bed rails, counter tops, faucets, sinks, vents, monitor keyboards, door knobs, charts, laryngoscopes, blades and handles and intravenous drip supports were placed into 5 milliliters of sterile brain heat infusion broth. Hand cultures were randomly performed on hospital personnel. Individuals were instructed to wash their hands in 100 milliliters of trypticase soy broth in a large plastic bag. Media from environmental and hospital personnel cultures were incubated at 37°C for 24 hours and subcultured onto MacConkey agar.

Organisms that grew on the plates were identified using standard microbiological media and the Vitek System (Hazelwood, MO). Bacteria identified as ACB were subjected to Kirby-Bauer disk diffusion methods and resulting antibiograms were recorded. ACB strains isolated were categorized according to antibiogram, and representative strains were subjected to both Hind III and Xba restriction endonuclease digestion to determine specific genetic patterns. Results from these investigations revealed that 72 isolates of IR-ACB were obtained from 59 patients during an outbreak period from September 1991 to September 1992. Restriction patterns demonstrated that these isolates were derivatives of a single strain. Thirty-six patients were male and 23 female with ages ranging from 16-93. Thirty-nine or 54% of IR-ACB were isolated from the respiratory tract and another 12 (16.6%) isolated from skin or surgical wound infection. The remaining isolates were recovered from intra-operative biliary drainage, blood, peritoneal fluid, pleural fluid and urinary tract specimens. All patient had received prior intravenous antibiotics in the hospital and had been on mechanical ventilatory support. Eighteen of 59 patients were considered infected with IR-ACB. The majority of respiratory isolates were recovered from patients in the surgical intensive care unit (SICU). A multitude of inanimate objects including tables, beds, monitors, charts, ventilators and intravenous drip supports in the SICU, were positive for IR-ACB, IS-ACB or IAS-ACB. Hand cultures of personnel were positive in the SICU, while those of personnel in the medical intensive care unit (MICU) or surgical progressive care unit were negative. Laryngoscopes used in the SICU, and hands of respiratory therapists also yielded multiresistant Acinetobacter (IR-ACB, IS-ACB or IAS-ACB). Restriction endonucleases digestion of ACB suggested that isolates with these three antibiotic susceptibility patterns had the same genetic pattern, while VS-ACB showed a completely different genetic profile.

Increased selection pressure imposed by imipenem for the treatment of patients infected with ceftazidime-resistant Klebsiella pneumoniae resulted in evolution to imipenem resistance in a previously multiresistant bacterium. The identical digestion patterns of IS-ACB and IAS-ACB suggest that isolates with these two antibiotype patterns were derived from a single clone which evolved to the totally resistant IR-ACB, also possessing the same genetic pattern. It is likely that our restriction endonuclease digestion experiments were not sufficiently sensitive to detect mutation(s) leading to imipenem resistance. We also suspect that imipenem resistance occurred by a stepwise chromosomally mediated mechanism. The absence of any beta-lactamases which hydrolyze imipenem in our strains (K. Bush and P. Bradford, personal communication), and relatively low MIC of imipenem (16 uglm) in resistant isolates support this hypothesis.

The outbreak of IR-ACB probably originated in the SICU as demonstrated by the recovery of this strain from both personnel and environmental cultures. Contamination of mechanical ventilatory equipment was not implicated as an intermediate vector for spreading organisms in this investigation. However, laryngoscopes used only in the SICU were found to harbor resistant IR-ACB. Infection control efforts were principally directed towards the SICU including monitoring and enforcing handwashing techniques, glove changing and use of polymyxin B for wound irrigation. The SICU was also freshly painted and all inanimate objects within the unit were cleaned with a disinfectant solution. Since the nosocomial outbreak was recognized early in its development and concentrated in the SICU, the coordinated effects of the Infectious Disease Section, its Research Laboratory, Infection Control, and Pharmacy were able to eradicate the IR-ACB from the hospital. Although sensitive strains of Acinetobacter remain, IR-ACB has not been isolated from patients or from the hospital environment since October, 1992.
Following the description of our outbreak, two other reports of imipenem-resistant episodes have been reported (7,10). The first occurred in 1990 with five patients having imipenem and sulbactam resistant isolates identified (10). Three of these patients were considered colonized; and two were treated with colistimethate (polymyxin E). We were fortunate in that sulbactam still retained bactericidal activity against our isolates and was used therapeutically (ampicillin/sulbactam). We have subsequently identified sulbactam resistant Acinetobacter isolates that remain susceptible to other antibiotics. These possess a different restriction pattern from that of our previously described imipenem-resistant isolates (unpublished results). A more recent report describes an outbreak of imipenem resistant Acinetobacter which occurred in France from February 1991 to March 1992(7). The epidemiological characteristics were similar to ours since they demonstrated both environmental and hospital personnel as contributory factors in the dissemination of these organisms. The use of antibiotyping, biochemical biotyping and pulse-field gel electrophoresis resolved their imipenem resistant isolates into two genotypes (7).

An abstract presented at the 1994 IDSA meetings (Orlando, Fla.) has demonstrated the successful treatment of a patient with meningitis and ventriculitis with polymyxin B caused by an initially reported imipenem susceptible isolate of Acinetobacter that failed therapy (6).

In addition, we have had personal communications with two institutions in New York City which have experienced outbreaks of imipenem resistant Acinetobacter that were susceptible to polymyxin B and sulbactam. Acinetobacter is truly an emerging pathogen in our geographical area. Although these organisms remain susceptible to polymyxins, given time and selective pressure, resistance to polymyxins, a rare phenomenon, may yet occur. Cautious and selective use of late generation beta- lactam agents is critical to the prevention of multiresistance, and "total" resistance.

References

  1. Go ES, Urban C, Burns J, Kreiswirth B, Eisner W, Mariano N, Mosinka-Snipas K, and Rahal JJ (1994). Acinetobacter infections resistant to all antibiotics except polymyxin B and sulbactam: clinical and molecular epidemiology. Lancet, 344:132a-1332.
  2. Gehrlein M, Leying H, Cullmann W, Wendt S. and Opferkuch W. (1991) Imipenem resistance in Acinetobacter baumannii is due to altered penicillin-binding proteins. Chemotherapy 37, 405-412.
  3. Obara M, and Nakae T. (1991) Mechanisms of resistance to B-lactam antibiotics in Acinetobacter calcoaceticus. J Antimicrob Chemother, 28, 791-800.
  4. Meyer, KS, Urban, C, Eagon, JA, Berger, BA, and Rahal, JJ (1993) Nosocomial-outbreak of Klebsiella infection resistant to late generation cephalosporins. Ann.Intern, Med. 119:353-358.
  5. Paton R, Miles RS and Amyes SGB. (1993) ARI1:B-lactamase-mediated imipenem resistance in Acinetobacter baumannii. International. J. of Antimicrob. Agents. 2: 81-88.
  6. Simon B.C., Lang F., and Holzman R.S.(1994) Successful treatment of Acinetobacter calcoaceticus ventriculitis and development of subsequent chemical meningitis following intraventricular polymyxin B. abstract #207 In: Program and Abstracts of 32nd Infectious Disease Society of America, Orlando, Florida.
  7. Tankovic J, Legrand P, DeGatines G, Chemineau V, Brun-Buisson C. and Duval J. (1994) Characterization of a hospital outbreak of imipenem resistant Acinetobacter baumannii by phenotypic and genotypic typing methods. Antimicrob. Agents Chemother. 32:2677-2681.
  8. Urban C, Go E, Mariano N, Berger BJ, Avraham I, Rubin D and Rahal JJ. (1993). Effect of sulbactam on infections caused by imipenem-resistant Acinetobacter calcoaceticus biotype anitratus. J. Infect Dis. 167, 448-451.
  9. Urban C, Go E, Mariano N, and Rahal JJ. (1995). Interaction of sulbactam, clavulanic acid and tazobactam with penicillin binding proteins of imipenem-resistant and susceptible Acinetobacter baumannii. Fems. Microb. Letters. 125: 193-198.
  10. Wood CA, and Reboli (1993). Infections caused by imipenem-resistant Acinetobacter calcoaceticus biotype anitratus. J. Infect Dis.168:1602-1603.
 

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