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Volume 15, Number 8—August 2009

Letter

Extreme Drug Resistance in Acinetobacter baumannii Infections in Intensive Care Units, South Korea

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To the Editor: Acinetobacter spp. have emerged as a cause of nosocomial infections, especially in intensive care units (ICUs). In South Korea, Acinetobacter spp. was ranked as the third most frequently found pathogen in ICUs (1). With the emergence of multidrug-resistant (MDR) or pandrug-resistant (PDR) isolates, few drugs are now available to treat MDR or PDR Acinetobacter infections; polymyxins are the only therapeutic option in many cases (2). Current polymyxin resistance rates among Acinetobacter isolates are low worldwide (3). We report the emergence of extreme drug resistance (XDR) in A. baumannii isolates from patients in ICUs of Samsung Medical Center in Seoul, South Korea. These isolates were resistant to all tested antimicrobial drugs, including polymyxin B and colistin, to which PDR isolates are normally susceptible.

Sixty-three nonduplicate Acinetobacter spp. isolates were collected from the ICUs from April through November 2007. Species identification was performed based on partial RNA polymerase β-subunit gene sequences, amplified rDNA restriction analysis, and the gyrase B gene–based multiplex PCR method (3). Forty-four isolates were identified as A. baumannii: 9 as genomic species 3, six as genomic species 13TU, 2 as A. baumannii-like species, and 1 each as A. junnii and genomic species 10.

In vitro susceptibility testing was performed and interpreted by using the broth microdilution method according to the Clinical and Laboratory Standards Institute guidelines (4). Colistin and polymyxin B resistances were defined as MIC >4 mg/L (4). MDR was defined as characterized by resistance to >3 classes of antimicrobial drugs, and PDR was defined as characterized by resistance to all antimicrobial drugs, regardless of colistin and polymyxin B susceptibility. XDR was defined as resistance to all antimicrobial drugs. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed for all PDR isolates according to previously described methods (5,6). Genes encoding oxacillinases, such as those classified as OXA-23-like, OXA-24/40-like, OXA-51-like, and OXA-58-like, were detected as previously described (7). PCR and sequence analyses were performed to detect and characterize the other antimicrobial resistance genes, according to methods reported (8).

Of 63 Acinetobacter isolates, 31.7% and 34.9% were resistant to imipenem and meropenem, respectively. Of the 63 isolates, 27.0% and 30.2% were resistant to polymyxin B and colistin, respectively. For the other antimicrobial drugs, Acinetobacter spp. isolates showed antimicrobial resistance rates >50%. Nineteen isolates (30.2%), all belonging to A. baumannii, were PDR. Most of these PDR isolates (16/19, 84.2%) were collected from endotracheal aspirate, and others were from peritoneal fluid and sputum. When characterized by PFGE and MLST, all PDR isolates belonged to a single clone, ST22, and all contained the blaOXA-23 and blaOXA-66 genes. ISAba1 was detected upstream of blaOXA-23 and blaOXA-66 in all PDR isolates. In addition, most PDR isolates contained blaTEM-116, blaPER-1, and blaADC-29 genes. TEM-116 is a point mutant derivative of TEM-1, Val84→Ile. All β-lactamase genes were located on a plasmid. Also, ISAba1 was located at the upstream of all the blaADC, which was shown by PCR. However, none of the isolates had blaCTX-M, blaVEB, blaIMP, blaVIM, or blaGIM.

Of the PDR isolates, 8 were resistant even to colistin and polymyxin B. These 8 isolates also showed resistance to tigecycline (MICs 4 mg/L). Thus, they were resistant to all antimicrobial drugs tested in this study and were considered to have XDR. The underlying diseases of the patients whose isolates were examined varied (Table). Although 2 isolates with XDR were colonizers, 6 caused infections. All but 1 patient was treated with mechanical ventilation before isolation of the pathogen. Number of hospital days before isolation of A. baumannii was 13–256 days, and the number of ICU days before isolation was 2–38 days. Four patients were immunocompromised, and 3 had bacteremia. Among the patients with infections characterized by XDR, the overall 30-day mortality rate was 66.7%, and the infection-related 30-day mortality rate was 50.0%. All 8 isolates with XDR showed common characteristics: ST22 containing OXA-23, OXA-66, TEM-116, PER-1, and ADC-29.

We report the emergence of XDR in PDR A. baumannii isolates in South Korea. Characteristics of PDR A. baumannii isolates suggest that they spread from a single clone. A single A. baumannii strain with XDR might evolve from the prevailing PDR A. baumannii and could disseminate in the ICU, probably after contamination of the hospital environment and by nosocomial transmission. In South Korea, a high resistance rate to imipenem and meropenem in Acinetobacter spp. isolates may lead to extensive use of polymyxins (3). Thus, we can hypothesize that the most prevalent carbapenem-resistant, or MDR A. baumannii clone, became PDR and then evolved into clones with XDR by acquisition of polymyxin resistance caused by antimicrobial pressure. Our investigation showed a simultaneous emergence of resistance to all antimicrobial agents available, including colistin, polymyxin B, and tigecycline. XDR poses serious problems in the treatment of patients with A. baumannii infections, especially given the slow development of new antimicrobial agents.

Young Kyoung Park1, Kyong Ran Peck1, Hae Suk Cheong, Doo-Ryeon Chung, Jae-Hoon Song, and Kwan Soo KoComments to Author 
Author affiliations: Sungkyunkwan University School of Medicine, Suwon, South Korea (Y.K. Park, K.R. Peck, H.S. Cheong, D.-R. Chung, J.-H. Song, K.S. Ko); Asian-Pacific Research Foundation for Infectious Diseases, Seoul, South Korea (J.-H. Song, K.S. Ko); 1These authors contributed equally to this article.

Acknowledgments

We thank Ji Young Choi for technical assistance.

This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health, Welfare, and Family Affairs, Republic of Korea (A080330).

References

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  2. Li J, Nation RL, Turnidge JD, Milne RW, Coulthard K, Rayner CR, Colistin: the re-emerging antibiotic for multidrug-resistant gram-negative bacterial infections. Lancet Infect Dis. 2006;6:589601. DOIPubMed
  3. Ko KS, Suh JY, Kwon KT, Jung SI, Park KH, Kang CI, High rates of resistance to colistin and polymyxin B in subgroups of Acinetobacter baumannii isolates from Korea. J Antimicrob Chemother. 2007;60:11637. DOIPubMed
  4. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; 16th informational supplement. Document M100-S18. Wayne (PA): The Insitute; 2008.
  5. Bartual SG, Seifert H, Hippler C, Luzon MAD, Wisplinghoff H, Rodriguez-Valera F. Development of a multilocus sequence typing scheme for characterization of clinical isolates of Acinetobacter baumannii. J Clin Microbiol. 2005;43:438290. DOIPubMed
  6. Seifert H, Dolzani L, Bressan R, van der Reijden T, van Strijen B, Stefanik D, Standardization and interlaboratory reproducibility assessment of pulsed-field gel electrophoresis-generated fingerprints of Acinetobacter baumannii. J Clin Microbiol. 2005;43:432835. DOIPubMed
  7. Lee JH, Choi CH, Kang HY, Lee JY, Kim J, Lee YC, Differences in phenotypic and genotypic traits against antimicrobial agents between Acinetobacter baumannii and Acinetobacter genomic species 13TU. J Antimicrob Chemother. 2007;59:6339. DOIPubMed
  8. Hujer KM, Hujer AM, Hulten EA, Bajaksouzian S, Adams JM, Donskey CJ, Analysis of antibiotic resistance genes in multidrug-resistant Acinetobacter sp. isolates from military and civilian patients treated at the Walter Reed Army Medical Center. Antimicrob Agents Chemother. 2006;50:411423. DOIPubMed

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Suggested citation for this article: Park YK, Peck KR, Cheong HS, Chung D-R, Song J-H, Ko KS. Extreme drug resistance in Acinetobacter baumannii infections in intensive care units, South Korea [letter]. Emerg Infect Dis [serial on the Internet]. 2009 Aug [date cited]. Available from http://wwwnc.cdc.gov/eid/article/15/8/08-0772

DOI: 10.3201/eid1508.080772

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Table of Contents – Volume 15, Number 8—August 2009

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Kwan Soo Ko, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 300 Chunchun-dong, Jangan-gu, Suwon 440-746, South Korea;

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