Emerg Infect DisEIDEmerging Infectious Diseases1080-60401080-6059Centers for Disease Control and Prevention19751609281595008-077210.3201/eid1508.080772Letters to the EditorExtreme Drug Resistance in Acinetobacter baumannii Infections in Intensive Care Units, South KoreaParkYoung Kyoung1PeckKyong Ran1CheongHae SukChungDoo-RyeonSongJae-HoonKoKwan SooSungkyunkwan 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)These authors contributed equally to this article.Address for correspondence: Kwan Soo Ko, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 300 Chunchun-dong, Jangan-gu, Suwon 440-746, South Korea; email: ksko@med.skku.ac.kr8200915813251327Keywords: Antimicrobial resistanceextremely drug resistantintensive care unitsAcinetobacter baumannii infectionsSouth Koreabacterialetter

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.

Clinical characteristics of 8 patients infected with extremely drug-resistant <italic>Acinetobacter baumannii</italic> isolates, South Korea*
Strain no.Patient age/sexUnderlying diseaseInfection†Days before isolation
Concurrent
bacteremia30-d outcomeInfection-related death
HospitalizedIn ICU
07AC–05260 y/FAcute myeloid leukemiaPneumonia158NoDiedYes
07AC–15979 y/MLymphomaPneumonia359NoDiedNo
07AC–19250 y/MStatus postliver transplantationPneumonia2562YesSurvivedNA
07AC–20455 y/FSteven-Johnson syndromePneumonia1313YesSurvivedNA
07AC–33616 mo/MMedulloblastomaPneumonia3213YesDiedYes
07AC–34717 mo/MHepatoblastomaPneumonia13528NoDiedYes
07AC–3291 mo/FEdward syndromeColonization‡3333NANANA
07AC–06356 y/MLung cancerColonization‡2621NANANA

*ICU, intensive care unit; NA, not applicable. All but 1 patient (with strain 07AC–192) had mechanical ventilators. Four patients (with strains 07AC–159, 07AC–192, 07AC–336, and 07AC–063) were immunocompromised hosts who had daily administration of corticosteroid (>20 mg/d of prednisolone or an equivalent drug) during >2 wk and treatment with chemotherapy for an underlying malignancy during 1 month before hospital admission.
†Infection is defined as invasion of the body tissues by microorganisms resulting in disease.
‡Colonization occurs when an agent’s presence in a host does not cause a specific immune response or infection.

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.

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://www.cdc.gov/EID/content/15/8/1325.htm

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).

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