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Extensively drug-resistant Acinetobacter baumannii.

To the Editor: In the 1990s, patients infected with vancomycin-resistant Enterococcus faecium were successfully treated with new antimicrobial drugs. However, it is unlikely that new antimicrobial drugs will be available in the near future to treat patients infected with gram-negative pathogens such as Acinetobacter baumannii (1). No new antimicrobial drugs active against this organism are currently in clinical trials (www.clinicaltrials.gov). We report a patient infected with A. baumannii that lacked susceptibility to all commercially available antimicrobial drugs.

The patient, a 55-year-old woman, had a prolonged stay in an intensive care unit at the University of Pittsburgh Medical Center (Pittsburgh, PA, USA) after undergoing lung transplantation. In the tenth postoperative week, ventilator-associated pneumonia developed, which was caused by A. baumanni that lacked susceptibility to all antimicrobial drugs tested except colistin (MIC 0.5 [micro]g/mL). Therapy with colistin and tigecycline was begun. Colistin was administered intravenously and by inhalation. Although the pneumonia showed radiographic response to the antimicrobial drug therapy, A. baumannii continued to be isolated from respiratory secretions on numerous occasions. Despite another course of therapy with colistin and cefepime, the patient never recovered from respiratory failure. She eventually died of sepsis caused by vancomycin-resistant E. faecium. An A. baumannii isolate obtained just before she died lacked susceptibility to all commercially available antimicrobial drugs (Table).

Multidrug-resistant A. baumannii has emerged as a substantial problem worldwide (2). Such strains are typically resistant to all [beta]-lactams and fluoroquinolones and require salvage therapy with colistin, amikacin, or tigecycline. Unfortunately, notably high-level resistance to colistin and amikacin was found in the isolate we have described (Table). Tigecycline, a newly available glycylcycline antimicrobial drug, showed intermediate susceptibility. No randomized trials have been performed to specifically evaluate combination antimicrobial drug therapy for treatment of infection with A. baumannii.

Considerable media attention has been paid to extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (3). Infections with XDR strains are extremely difficult to treat and pose considerable infection control issues. We recently proposed that gram-negative bacilli lacking susceptibility to all commercially available antimicrobial drugs also be referred to as XDR because no therapeutic options are available (4).

Numerous outbreaks of A. baumannii infection have been reported worldwide (5). Unfortunately, multidrug-resistant A. baumannii strains have become endemic in some institutions. Experimental and clinical isolates lacking susceptibility to colistin, often considered the drug of last resort, are increasingly being reported (6-8). Therefore, we alert healthcare workers to the need for stringent care in adhering to infection control precautions when caring for patients infected with XDR A. baumannii. Use of contact isolation precautions, enhanced environmental cleaning, removal of sources of infection from the hospital environment, and prudent use of antimicrobial drugs can contribute to control of such outbreaks (5). Fortunately, no spread of the XDR strain affecting this patient occurred. A crisis is looming should XDR A. baumannii become established pathogens in hospitals.

Y.D. was supported by National Institutes of Health (NIH) training grant T32AI007333, and D.L.P. was supported in part by NIH research grant R01AI070896.

References

(1.) Talbot GH, Bradley J, Edwards JE Jr, Gilbert D, Scheld M, Bartlett JG. Bad bugs need drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin Infect Dis. 2006;42:657-68. DOI: 10.1086/499819

(2.) Perez F, Hujer AM, Hujer KM, Decker BK, Rather PN, Bonomo RA. Global challenge of multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2007;51:3471-84. DOI: 10.1128/ AAC.01464-06

(3.) Maartens G, Wilkinson RJ. Tuberculosis. Lancet. 2007;370:2030-43. DOI: 10.1016/ S0140-6736(07)61262-8

(4.) Paterson DL, Doi Y. A step closer to extreme drug resistance (XDR) in gram-negative bacilli. Clin Infect Dis. 2007;45:1179-81. DOI: 10.1086/522287

(5.) Fournier PE, Richet H. The epidemiology and control of Acinetobacter baumannii in health care facilities. Clin Infect Dis. 2006;42:692-9. DOI: 10.1086/500202

(6.) David MD, Gill MJ. Potential for underdosing and emergence of resistance in Acinetobacter baumannii during treatment with colistin. J Antimicrob Chemother. 2008;61:962-4. DOI: 10.1093/jac/dkn009

(7.) Ko KS, Suh JY, Kwon KT, Jung SI, Park KH, Kang CI, et al. High rates of resistance to colistin and polymyxin B in subgroups of Acinetobacter baumannii isolates from Korea. J Antimicrob Chemother. 2007;60:1163-7. DOI: 10.1093/jac/dkm305

(8.) Tan CH, Li J, Nation RL. Activity of colistin against heteroresistant Acinetobacter baumannii and emergence of resistance in an in vitro pharmacokinetic/pharmacodynamic model. Antimicrob Agents Chemother. 2007;51:3413-5. DOI: 10.1128/AAC.01571-06

DOI: 10.3201/eid1506.081006

Yohei Doi, Shahid Husain, Brian A. Potoski, Kenneth R. McCurry, and David L. Paterson

Address for correspondence: Yohei Doi, University of Pittsburgh Medical Center, S829 Scaife Hall, 3550 Terrace St, Pittsburgh, PA 15261, USA; email: yod4@pitt.edu

Author affiliations: University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA (Y. Doi, B.A. Potoski, D.L. Paterson); University of Toronto, Toronto, Ontario, Canada (S. Husain); Toronto General Hospital, Toronto (S. Husain); Cleveland Clinic, Cleveland, Ohio, USA (K.R. McCurry); University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia (D.L. Paterson); and Royal Brisbane and Women's Hospital, Brisbane (D.L. Paterson)
Table. MICs and antimicrobial drug susceptibility for an
extensively drug-resistant strain of Acinetobacter baumannii *

Drugs MIC, g/mL Interpretation

Carbapanems
Imipenem >32 Resistant
Meropenem >32 Resistant

Penicillins
 Ampicillin/sulbactam 32 Resistant
 Piperacillin/tazobactam >256 Resistant

Cephalosporins
 Ceftazidime 48 Resistant
 Cefepime 16 Intermediate

Aminoglycosides
 Gentamicin >256 Resistant
 Tobramycin >256 Resistant
 Amikacin >256 Resistant

Others
 Ciprofloxacin >32 Resistant
 Tigecycline 2 Intermediate
 Colistin >1,024 Resistant

* Susceptibility testing was performed by using the Etest (AB
Biodisk, Solna, Sweden), except for colistin, for which the standard
agar dilution method was used. Interpretation was according to
breakpoints provided by the Clinical and Laboratory Standards
Institute (CLSI; Wayne, PA, USA). No tigecycline breakpoints for
Acinetobacter spp. are provided by the CLSI, the European
Committee on Antimicrobial Susceptibility Testing (Basel,
Switzerland), or the US Food and Drug Administration (Silver Spring,
MD, USA). Breakpoints of the British Society for Antimicrobial
Chemotherapy (Birmingham, UK) are indicated for tigecycline.
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Article Details
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Title Annotation:LETTERS
Author:Doi, Yohei; Husain, Shahid; Potoski, Brian A.; McCurry, Kenneth R.; Paterson, David L.
Publication:Emerging Infectious Diseases
Article Type:Report
Geographic Code:1USA
Date:Jun 1, 2009
Words:1012
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