LETTER
Acinetobacter baumannii causes life-threatening infections in critically ill patients, with subsequent treatments mostly based on carbapenems. Unfortunately, oxacillinases (OXAs) that hydrolyze carbapenems, especially OXA-23, have dramatically spread in humans and even started to be reported in animals (1–4). As OXA-producing isolates are still rare in nonhuman sources, a comprehensive picture of their occurrence in animals is lacking.
We analyzed 41 A. baumannii isolates from nonduplicate diseased animals from 2011 to 2015 in the framework of the French Surveillance Network for Antimicrobial Resistance in Animal Pathogens (RESAPATH; https://www.resapath.anses.fr/) for susceptibility to carbapenems, the presence of blaOXA genes, and clonal relatedness.
Identification was based on rpoB gene sequencing (5). According to the CA-SFM/EUCAST breakpoints (http://www.sfm-microbiologie.org/UserFiles/files/casfm/CASFM2016_V1_0_FEVRIER.pdf), seven isolates demonstrated high-level resistance to meropenem and imipenem (MICs of >32 µg/ml) and were also multidrug resistant (Table 1).
TABLE 1.
Origins and antimicrobial resistance profiles of ST25 OXA-23-producing A. baumannii isolates from companion animals in France
| Isolate | Host | Diseasea | Yr | Municipality | Inhibition zone diam, mm (category)b |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CTX | CTX + CLOc | CAZ | CAZ + CLO | FEP | FEP + CLO | TOB | GN | AK | NET | CIP | SXT | |||||
| 34972 | Cat | UTI | 2013 | 94110 | 14 (R) | 16 | 21 (S) | 24 | 8 (R) | 11 | 19 (S) | 6 (R) | 27 (S) | 14 (R) | 6 (R) | 6 (R) |
| 38208 | Cat | UTI | 2014 | 94000 | 15 (I) | 16 | 21 (S) | 24 | 10 (R) | 11 | 18 (S) | 6 (R) | 26 (S) | 11 (R) | 6 (R) | 6 (R) |
| 40104 | Cat | UTI | 2015 | 94140 | 11 (R) | 15 | 19 (S) | 23 | 12 (R) | 14 | 21 (S) | 6 (R) | 29 (S) | 13 (R) | 6 (R) | 6 (R) |
| 40293 | Dog | UTI | 2015 | 95600 | 12 (R) | 18 | 22 (S) | 24 | 9 (R) | 11 | 25 (S) | 23 (S) | 26 (S) | 21 (S) | 6 (R) | 6 (R) |
| 41133 | Cat | UTI | 2015 | 75020 | 14 (R) | 18 | 23 (S) | 25 | 9 (R) | 12 | 19 (S) | 6 (R) | 26 (S) | 9 (R) | 6 (R) | 6 (R) |
| 41134 | Dog | UTI | 2015 | 77230 | 15 (I) | 17 | 22 (S) | 23 | 8 (R) | 11 | 17 (S) | 6 (R) | 26 (S) | 10 (R) | 6 (R) | 6 (R) |
| 41833 | Cat | UTI | 2015 | 69240 | 16 (I) | 19 | 22 (S) | 28 | 11 (R) | 16 | 21 (S) | 9 (R) | 28 (S) | 14 (R) | 6 (R) | 6 (R) |
UTI, urinary tract infection.
Isolates were highly resistant to imipenem and meropenem (MICs of >32 μg/ml). Categorization was based on the breakpoints provided by CA-SFM/EUCAST for Acinetobacter spp. (www.sfm-microbiologie.org/UserFiles/files/casfm/CASFM2016_V1_0_FEVRIER.pdf). Abbreviations (breakpoints): CTX, cefotaxime (S, ≥23; R, <15); CAZ, ceftazidime (S, ≥18; R, <15); FEP, cefepime (S, ≥18; R, <15); TOB, tobramycin (S, ≥17; R, <17); GN, gentamicin (S, ≥17; R, <17); AK, amikacin (S, ≥18; R, <15); NET, netilmicin (S, ≥16; R, <16); CIP, ciprofloxacin (S, ≥21; R, <21); SXT, trimethoprim-sulfamethoxazole (S, ≥16; R, <13).
Cloxacillin (CLO) was added to the medium at a concentration of 250 μg/ml to unveil the hydrolytic mechanism responsible for β-lactam resistance.
PCR screening, performed as previously described (6), demonstrated the presence of blaOXA-23 in the seven isolates. ISAba1 was inserted 34 bases upstream from the starting codon of blaOXA-23. This organization, resembling that of transposons Tn2008B, Tn2006, and Tn2009, provided a −35 (TCGTTA) and −10 (TGACATTAT) extended promoter region for the overexpression of blaOXA-23 (7). Similarly to Tn2008B, no copy of ISAba1 was present downstream of blaOXA-23 in our isolates. According to DNA-DNA hybridization, blaOXA-23 was located on the bacterial chromosome and attempts of conjugation with Escherichia coli K-12 strain J53 (8) did not produce transconjugants on selective medium containing rifampin (250 μg/ml) and imipenem (2 μg/ml) or ticarcillin (8 μg/ml).
The seven isolates were clonally related (similarity, ≥98.8%) according to repetitive-sequence-based PCR performed with DiversiLab (bioMérieux, Marcy l'Etoile, France) (9). Multilocus sequence typing based on the Pasteur scheme (10) assigned the isolates to sequence type 25 (ST25). Remarkably, the isolates were found to be associated with urinary tract infections in pets originating in five departments in two regions (Ile de France and Rhône-Alpes) from 2013 to 2015, for the first time demonstrating the clonal dissemination of OXA-23-producing A. baumannii among companion animals. Three isolates (40293, 41133, and 41134) were recovered from pets attending the same clinic, outlining the occurrence of a small outbreak. The remaining isolates (38208, 40104, 34972, and 41833) originated from unrelated and distant animals, suggesting a nationwide spread of OXA-23-producing ST25 A. baumannii in pets. Our findings expand recent data on two isolates recovered from healthy dogs in the region of Nantes (11) and highlight an emerging and worrying epidemiological picture, with a possible endemicity of OXA-23-producing ST25 A. baumannii in pets in France.
So far, OXA-23-producing A. baumannii isolates from animals have belonged to ST2 (3, 4, 12), suggesting cross-transmission of such isolates from humans to animals (4). Looking at human clinics in France, OXA-23-producing ST2 A. baumannii is the predominant clone (2, 13). However, Jeannot et al. have also reported the occurrence of ST25 A. baumannii among human isolates, albeit mostly harboring OXA-58 (2). Our results suggest that the epidemiology of carbapenem-resistant A. baumannii in companion animals might be independent of that in humans. Nonetheless, incidental transmission of OXA-23-producing ST25 A. baumannii from humans to pets cannot be excluded, even though the process that might favor the persistence and circulation of this clone among different individuals remains to be elucidated. On the other hand, carbapenems do not belong to the therapeutic arsenal used in veterinary medicine but penicillins or penicillin–β-lactamase inhibitor combinations might select for OXA-23-producing A. baumannii. Moreover, many other veterinary antibiotics can coselect intrinsic resistances of A. baumannii and contribute to a further clonal spread. In light of the remarkable prevalence of ST25 A. baumannii associated with urinary tract infections in our study, a possible special tropism of such a clone as a uropathogen needs further evaluation. These findings make it urgent to investigate the processes favoring the emergence and spread of OXA-producing A. baumannii in veterinary settings.
ACKNOWLEDGMENTS
This work was supported by the French Agency for Food, Environmental and Occupational Health, and Safety (ANSES).
We are grateful to Veronique Métayer and Alison Manele for their technical support. We thank all of the laboratories participating in the RESAPATH network.
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