Panresistant extended-spectrum β-lactamase SHV-5-producing Acinetobacter baumannii from New York City

Sir, Over the last decade, nosocomial infections of Acinetobacter baumannii have been described with an increasing trend towards multidrug resistance, mostly in intensive care units. 1 The main mechanisms of resistance to extended-spectrum cephalosporins in A . baumannii are the overexpression of chromosome-encoded cephalosporinases and plasmid-encoded Ambler class A, B and D β-lactamases. 1A . baumannii producing extended-spectrum β-lactamases (ESBLs) have also been reported: PER-1 from Turkey, Korea, Russia, Romania, Belgium and France; VEB-1 from France and Belgium; TEM-116 and SHV-12 from China and the Netherlands; and CTX-M-2 from Korea. 2 , 3 However, ESBL-producing A . baumannii strains remain susceptible to carbapenems. 1 , 2 Recently, a carbapenem-resistant PER-1-producing strain from Russia has been described. 2 Here, we report the first ESBL-producing A . baumannii isolate from the USA being susceptible only to colistin and rifampicin. An 80-year-old man with a 5 year history of prostatic carcinoma and metastasis was admitted at the Cochin Hospital in Paris for acute urine retention in the right nephrostomy in February 2005. The bilateral nephrostomy was performed in December 2004 at a New York City hospital. Between his stay in New York and his emergency hospitalization in Paris, no hospitalization or antibiotic treatment is known. This patient also had urine and blood cultures with Klebsiella pneumoniae YC producing the plasmid-encoded class A carbapenemase KPC-2. 4 At the day of his admission, cultures from rectal swabs revealed a carbapenem-resistant A . baumannii strain YC. During the same period of time, no other A . baumannii isolate with a similar antibiotic resistance pattern was recovered from the Cochin Hospital. Disc diffusion susceptibility testing 2 revealed that A . baumannii strain YC was susceptible only to rifampicin and colistin. No synergy image could be observed between clavulanic acid and cefepime- or ceftazidime-containing discs. The use of cloxacillin-containing Mueller-Hinton plates (200 mg/L) allowed detection of a synergy image, the signature of the presence of an ESBL. A . baumannii YC was resistant to all the β-lactams tested (amoxicillin, ticarcillin, piperacillin, ceftazidime, aztreonam, cefepime and imipenem). The MIC of imipenem was >32 mg/L, and clavulanic acid addition (2 mg/L) decreased the ticarcillin MIC from >512 to 256 mg/L and the ceftazidime MIC from 512 to 128 mg/L, but did not affect the MIC values of imipenem. Furthermore, the MIC of tigecycline was 24 mg/L. PCR experiments with primers for the detection of most of the Ambler class A, class B and class D β-lactamase genes, 2 , 4 followed by sequencing, identified the blaSHV-5 gene. 5 A β-lactamase extract from A . baumannii YC culture subjected to analytical isoelectric focusing 2 identified two pI values (8.1 for SHV-5 and >8.5 for AmpC). A crude β-lactamase extract of that isolate had no significant imipenem hydrolysis activity, suggesting that the carbapenem resistance was not β-lactamase-mediated. 2 Using a series of successive PCR primers, the surrounding sequences of the blaSHV-5 gene were found to be identical to those surrounding the blaSHV-5 gene in Enterobacteriaceae (Figure 1 a). 5 Several conserved genes, such as repF and deoR that originated from the K . pneumoniae chromosome, were found along with IS 26 insertion elements, likely involved in the mobilization of the blaSHV-5 gene (Figure 1 b). Attempts to demonstrate plasmids or transfer genes encoding SHV-5, as previously described, into azide-resistant Escherichia coli J53 or to rifampicin-resistant A . baumannii CIP7010 failed (data not shown), suggesting that the gene was probably chromosomally encoded. 2 (a) Arrangement of gene contexts of chromosomal and mobile blaSHV alleles. Sizes of genes and intergenic regions are drawn to scale. The predicted transcriptional orientations of the different genes are represented with arrows. Gene names, derived from Ford and Avison 5 and Naas et al ., 8 are noted. The blaSHV gene is black, and the IS 26 elements (which include the transposase gene and the appropriate repeat sequences) are dark grey. The primers are indicated as small triangles. Sequences of primers used in this work are available as Supplementary data [see Table S1 at JAC Online ( http://jac.oxfordjournals.org/ )]. (b) Arrangement of gene contexts of chromosomal blaSHV gene from A . baumannii YC. (c) Schematic representation of IS Aba1 insertion in front of blaAMPC , blaOXA-113 and aac6′Ib genes. The nucleotide sequences reported in this paper have been assigned to the GenBank nucleotide database under the accession numbers EF653398–EF653401. The naturally occurring blaAMPC - and blaOXA-51 -like genes of A . baumannii YC were also amplified and sequenced. 1 The deduced amino acid sequences identified an AMPC β-lactamase that has two amino acid changes (T341A and V376A) when compared with AMPC characterized from China (unpublished GenBank AQB45322) and a novel variant of the naturally occurring oxacillinase, OXA-113, point mutant derivative of OXA-71 (L167V). IS Aba1 was inserted upstream of blaOXA-113 and blaAMPC genes, but also in front of the aminoglycoside resistance gene aac6′Ib (Figure 1 c). The emergence and spread of the ESBL-producing A . baumannii strains is worrisome, as it will enhance extensive use of carbapenems, thus increasing the risk of emergence of carbapenem-resistant isolates. A . baumannii YC is the second description of an ESBL-producing A . baumannii isolate being also resistant to carbapenems and the first description of an ESBL-producing A . baumannii isolate from the USA, a country where blaSHV-5 is the most prevalent ESBL gene in Enterobacteriaceae. 6 Multidrug-resistant A . baumannii has emerged as a serious nosocomial pathogen in the New York area. 7 A citywide surveillance revealed that approximately two of three isolates were resistant to carbapenem antibiotics. 7 The decreased production of outer membrane porins, together with an increased expression of a class C cephalosporinase, appeared to be important factors leading to carbapenem resistance. It would be interesting to test these strains for the presence of blaSHV-5 , especially as nothing could predict its presence on a routine antibiogram. These results highlight the importance of international patient transfer in the spread of antimicrobial resistance. Rapid identification of A . baumannii YC and increased awareness and implementation of strict barrier precautions prevented this strain from spreading to other patients. This work was funded by a grant from the Ministère de l'Education Nationale et de la Recherche (UPRES-EA3539), Université Paris Sud and by the European Community (6th PCRD, LSHM-CT-2005-018705). We are grateful to Gaelle Cuzon for technical assistance. None to declare.