JAC Advance Access originally published online on December 6, 2005
Journal of Antimicrobial Chemotherapy 2006 57(1):1-3; doi:10.1093/jac/dki425
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Leading article |
OXA ß-lactamases in Acinetobacter: the story so far
Molecular Chemotherapy, Centre for Infectious Diseases, University of Edinburgh, The Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK
* Corresponding author. Tel: +44-131-242-6652; Fax: +44-131-242-6611; E-mail: s.g.b.amyes{at}ed.ac.uk
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The emergence of carbapenem resistance in Acinetobacter baumannii has become a global concern since these ß-lactams are often the only effective treatment left against many multiresistant strains. A recent development has been the discovery of a novel group of narrow-spectrum OXA ß-lactamases in carbapenem-resistant strains, some of which have acquired the ability to hydrolyse the carbapenems. The first of these was found in a strain isolated in Edinburgh before imipenem was in use in the hospital. Whether these carbapenemases have been acquired or are part of the genetic make-up of this species has yet to be determined. More importantly, however, they represent an important stage in the evolution of antibiotic resistance in Acinetobacter. This paper discusses the emergence of these unusual enzymes over the past decade.
Keywords: Acinetobacter , OXA-type ß-lactamases , carbapenem resistance
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Antibiotic resistance in Gram-positive bacteria, notably methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, has been the focus of attention both in the clinical setting and the press, however, there has been a slow but steady emergence of resistant Gram-negative pathogens. One such organism, Acinetobacter, and in particular Acinetobacter baumannii, is recognized as playing a significant role in the colonization and infection of patients, especially those in intensive care units.1 A major problem facing clinicians is how to effectively treat infections caused by this organism. The carbapenems have been relied upon for treating infections caused by multidrug-resistant A. baumannii; however, resistance to this ß-lactam class is now a common occurrence, and pan-drug-resistant strains are beginning to emerge.2
The first reports of imipenem resistance in A. baumannii started to emerge over a decade ago.3,4 In 1993, the first of a novel group of narrow-spectrum OXA-type ß-lactamases was discovered in an imipenem-resistant A. baumannii strain from a patient in the Royal Infirmary of Edinburgh that was found to possess carbapenem-hydrolysing activity.5 The strain itself was isolated in 1985, before the use of imipenem in the hospital. Imipenem resistance was subsequently demonstrated to be transferable6 and sequence analysis of the gene discovered that it encoded an unusual OXA-type enzyme (designated OXA-23) of Ambler molecular class D.7 This raised concern at the time but appeared to be an isolated case. However, in 1997, another OXA ß-lactamase was found in an imipenem-resistant strain isolated in France.8 Although the encoding gene was never sequenced, the purified enzyme was shown to hydrolyse imipenem.
Three oxacillinases lacking carbapenemase properties were subsequently discovered. OXA-21 was found in an imipenem-susceptible A. baumannii strain in Spain but did not appear to be widely disseminated in Acinetobacter although the encoding gene was located on an integron.9 However, it was subsequently found in carbapenem-susceptible and -resistant Pseudomonas aeruginosa in France.10 The integron-borne enzyme OXA-37 was then discovered in a multidrug-resistant (but imipenem-susceptible) A. baumannii strain in Spain,11 which differed by one amino acid from the restricted-spectrum oxacillinase OXA-20, originally identified in P. aeruginosa.12 OXA-20 was subsequently found on class 1 integrons in multiresistant A. baumannii strains from France13 and Spain,14 and in an imipenem-resistant A. baumannii clone from Italy, although the observed carbapenem resistance was not attributed to the presence of this enzyme.15 There are some similarities in the integrons associated with these enzymes; however, it is uncertain which genus they have originated from.
The incidence of carbapenem-resistant strains and the OXA-type ß-lactamases associated with them has continued to increase (Figure 1). These strains have been associated with infection outbreaks and have contributed to patient mortality. Between the years 2000 and 2004, six novel OXA-type enzymes were characterized from carbapenem-resistant strains collected worldwide from 1995 onwards. OXA-24 was found in a highly carbapenem-resistant strain from Spain16 and represented a second subgroup of these enzymes since it shared <60% amino acid identity with OXA-23. A further three OXA-24-related ß-lactamases (OXA-25, OXA-26 and OXA-40) were subsequently identified in strains from Spain, Belgium and Portugal,17–19 and two OXA-23 variants, OXA-2717 and OXA-49 (AY288523 [GenBank] ), were found in resistant strains from Singapore and China, respectively.
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Within the last couple of years, OXA-23 has been found in Acinetobacter strains from Brazil,20 China (accession number AY554200 [GenBank] )21 and Singapore (accession number AY795964 [GenBank] ), and is now endemic in numerous hospitals in Southern England.22 It has also been found in related strains of Proteus mirabilis in France;23 however, its presence was insufficient to render them resistant to the carbapenems. Indeed, a common feature of these enzymes is their narrow-spectrum profiles and relative weak hydrolytic activity, compared with the metallo-carbapenemases, against the carbapenems, although the MIC values of the strains expressing them vary (typically from 16 to 256 mg/L),7,16–19 indicating the presence of additional resistance factors notably reduced permeability.24
More recently, a third subgroup of OXA ß-lactamases sharing <63% amino acid identity with subgroups 1 and 2 has been identified in A. baumannii. OXA-51 was characterized from two imipenem-resistant A. baumannii clones isolated in Argentina.25 A further seven enzymes were subsequently found in carbapenem-resistant strains collected worldwide, which share 98–99% identity with OXA-51,26 and at least another four derivatives have recently been identified (S. Brown and S. Amyes, unpublished results). A common feature of this subgroup is retention of the class D Y-G-N motif at positions 144–146 according to the numbering system of Couture et al.,27 in contrast to subgroups 1 and 2 OXA-type carbapenemases which possess a Phe-144.7,16–19 However, this Phe change is not thought to be associated with carbapenem-hydrolysing activity.19 An unrelated OXA ß-lactamase (OXA-58) has recently been found in unrelated carbapenem-resistant A. baumannii isolates in France.28,29 OXA-58 shares <50% amino acid identity to the other oxacillinases, and retains the Y-G-N motif. An OXA-58-like enzyme has also been found in strains from Argentina, Kuwait and Southern England.30
Unlike the majority of oxacillinases in other genera, none of the Acinetobacter OXA genes from carbapenem-resistant strains have been found on integrons. With the exception of the plasmid-encoded OXA-23 and OXA-58, the others have either been demonstrated or assumed to be chromosomally-mediated. At least four enzymes of subgroup 3 have been found in strains from more than one country, suggesting that dissemination between strains may have taken place.26 It also raises the question as to whether these enzymes always confer carbapenem insusceptibility. For instance, the subgroup 3 OXA-69 first reported by us in strains from Singapore and Turkey was associated with an intermediate resistance to carbapenems in the absence of other apparent resistance factors.26 A subsequent identification of a small number of A. baumannii strains harbouring this ß-lactamase was associated with carbapenem susceptibility despite the fact that the enzyme was shown to hydrolyse the carbapenems, albeit at a low level.31 This is further supported by recent findings which show that expression of these genes is not always closely related to carbapenem insusceptibility.32 It remains to be seen whether these genes are naturally occurring or have been acquired, although the known enzymes do not appear to be ubiquitous in this species (K. Towner, University Hospital, Nottingham, UK, personal communication).
What is certain is that carbapenem resistance in A. baumannii is becoming more prevalent, and resistant strains are now emerging in regions that have up to now managed to avoid the problem. In addition, strains are now emerging that harbour more than one OXA-encoding gene (S. Brown and S. Amyes, unpublished results). Further studies are needed to determine the exact roles that these enzymes play in the evolution of carbapenem resistance in this genus. Does Acinetobacter possess its own group of naturally-occurring oxacillinases, as has been found with other ‘environmental’ bacteria?33,34 Furthermore, will some become the progenitors of future derivatives that possess carbapenem-hydrolysing capabilities in response to prolonged antibiotic exposure, as seen with the extended-spectrum ß-lactamases and cephalosporin resistance in Enterobacteriaceae? The carbapenems are the drugs of choice for treating infections caused by ESBL-producing bacteria. An alternative therapeutic strategy for carbapenem-resistant A. baumannii is proving a bigger problem to solve and may only succeed if future research includes the development of inhibitors of class D carbapenemases.
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None to declare.
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1. Bergogne-Bérézin E, Towner KJ. Acinetobacter spp. as nosocomial pathogens: microbiological, clinical, and epidemiological features. Clin Microbiol Rev 1996; 9: 148–65.[Web of Science][Medline]
2. Hsueh PR, Teng LJ, Chen CY et al. Pandrug-resistant Acinetobacter baumannii causing nosocomial infections in a university hospital, Taiwan. Emerg Infect Dis 2002; 8: 827–32.[Web of Science][Medline]
3. Urban C, Go E, Mariano M et al. Effect of sulbactam on infections caused by imipenem-resistant Acinetobacter calcoaceticus biotype anitratus. J Infect Dis 1993; 167: 448–51.[Web of Science][Medline]
4. Go ES, Urban C, Burns J et al. Clinical and molecular epidemiology of Acinetobacter infections sensitive only to polymyxin B and sulbactam. Lancet 1994; 344: 1329–32.[CrossRef][Web of Science][Medline]
5. Paton R, Miles RS, Hood J et al. ARI-1: ß-lactamase-mediated imipenem resistance in Acinetobacter baumannii. Int J Antimicrob Agents 1993; 2: 81–8.
6.
Scaife W, Young HK, Paton RH et al. Transferable imipenem-resistance in Acinetobacter species from a clinical source. J Antimicrob Chemother 1995; 36: 585–7.
7.
Donald HM, Scaife W, Amyes SGB et al. Sequence analysis of ARI-1, a novel OXA ß-lactamase, responsible for imipenem resistance in Acinetobacter baumannii 6B92. Antimicrob Agents Chemother 2000; 44: 196–9.
8. Hornstein M, Sautjeau-Rostoker C, Péduzzi J et al. Oxacillin-hydrolyzing ß-lactamase involved in resistance to imipenem in Acinetobacter baumannii. FEMS Microbiol Lett 1997; 153: 333–9.[Web of Science][Medline]
9. Vila J, Navia M, Ruiz J et al. Cloning and nucleotide sequence analysis of a gene encoding an OXA-derived ß-lactamase in Acinetobacter baumannii. Antimicrob Agents Chemother 1997; 41: 2757–9.[Abstract]
10.
De Champs C, Poirel L, Bonnet R et al. Prospective study of ß-lactamases produced by ceftazidime-resistant Pseudomonas aeruginosa isolated in a French hospital in 2000. Antimicrob Agents Chemother 2002; 46: 3031–4.
11. Navia MM, Ruiz J, Vila J. Characterization of an integron carrying a new class D ß-lactamase (OXA-37) in Acinetobacter baumannii. Microb Drug Res 2002; 4: 261–5.
12.
Naas T, Sougakoff W, Casetta A et al. Molecular characterization of OXA-20, a novel class D ß-lactamase, and its integron from Pseudomonas aeruginosa. Antmicrob Agents Chemother 1998; 42: 2074–83.
13.
Ploy MC, Denis F, Courvalin P et al. Molecular characterization of integrons in Acinetobacter baumannii: description of a hybrid class 2 integron. Antimicrob Agents Chemother 2000; 44: 2684–8.
14.
Ribera A, Vila J, Fernández-Cuenca F et al. Type 1 integrons in epidemiologically unrelated Acinetobacter baumannii isolates collected at Spanish hospitals. Antimicrob Agents Chemother 2004; 48: 364–5.
15.
Zarilli R, Crispino M, Bagattini M et al. Molecular epidemiology of sequential outbreaks of Acinetobacter baumannii in an intensive care unit shows the emergence of carbapenem resistance. J Clin Microbiol 2004; 42: 946–53.
16.
Bou G, Oliver A, Martínez-Beltrán J. OXA-24, a novel class D ß-lactamase with carbapenemase activity in an Acinetobacter baumannii clinical strain. Antimicrob Agents Chemother 2000; 44: 1556–61.
17.
Afzal-Shah M, Woodford N, Livermore DM. Characterization of OXA-25, OXA-26, and OXA-27, molecular class D ß-lactamases associated with carbapenem resistance in clinical isolates of Acinetobacter baumannii. Antimicrob Agents Chemother 2001; 45: 583–8.
18.
Lopez-Otsoa F, Gallego L, Towner KJ et al. Endemic carbapenem resistance associated with OXA-40 carbapenemase among Acinetobacter baumannii isolates from a hospital in Northern Spain. J Clin Microbiol 2002; 40: 4741–3.
19.
Héritier C, Poirel L, Aubert D et al. Genetic and functional analysis of the chromosome-encoded carbapenem-hydrolyzing oxacillinase OXA-40 of Acinetobacter baumannii. Antimicrob Agents Chemother 2003; 47: 268–73.
20.
Dalla-Costa LM, Coelho JM, Souza HA et al. Outbreak of carbapenem-resistant Acinetobacter baumannii producing the OXA-23 enzyme in Curitiba, Brazil. J Clin Microbiol 2003; 41: 3403–6.
21.
Yu YS, Yang Q, Xu XW. Typing and characterization of carbapenem-resistant Acinetobacter calcoaceticus–baumannii complex in a Chinese hospital. J Med Microbiol 2004; 53: 653–6.
22. Coelho JM, Woodford N, Warner M et al. Spread of two OXA-23-producing Acinetobacter baumannii clones in England. In: Abstracts of the 6th International Symposium on the Biology of Acinetobacter, Dublin, Ireland, 2004. Abstract C3, p. 19.
23.
Bonnet R, Marchandin H, Chanal C et al. Chromosome-encoded class D ß-lactamase OXA-23 in Proteus mirabilis. Antimicrob Agents Chemother 2002; 46: 2004–6.
24.
Bou G, Cerveró G, Angeles Domínguez M et al. Characterization of a nosocomial outbreak caused by a multiresistant Acinetobacter baumannii strain with a carbapenem-hydrolyzing enzyme: high-level carbapenem resistance in A. baumannii is not due solely to the presence of ß-lactamases. J Clin Microbiol 2000; 38:3299–305.
25. Brown S, Young HK, Amyes SGB. Characterisation of OXA-51, a novel class D carbapenemase found in genetically unrelated clinical strains of Acinetobacter baumannii from Argentina. Clin Microbiol Infect 2005; 11: 11–5.
26. Brown S, Amyes SGB. The sequences of seven class D ß-lactamases isolated from carbapenem-resistant Acinetobacter baumannii from four continents. Clin Microbiol Infect 2005; 11: 326–9.[CrossRef][Web of Science][Medline]
27. Couture F, Lachapelle J, Levesque RC. Phylogeny of LCR-1 and OXA-5 with class A and class D ß-lactamases. Mol Microbiol 1992; 6: 1693–705.[Web of Science][Medline]
28.
Poirel L, Marqué S, Héritier C et al. OXA-58, a novel class D ß-lactamase involved in resistance to carbapenems in Acinetobacter baumannii. Antimicrob Agents Chemother 2005; 49: 202–8.
29.
Heritier C, Dubouix A, Poirel L et al. A nosocomial outbreak of Acinetobacter baumannii isolates expressing the carbapenem-hydrolysing oxacillinase OXA-58. J Antimicrob Chemother 2005; 55: 115–8.
30. Coelho J, Woodford N, Afzal-Shah M et al. Detection of novel OXA-58-like carbapenemase in Acinetobacter spp. from three continents. In: Abstracts of the 6th International Symposium on the Biology of Acinetobacter, Dublin, Ireland, 2004. Abstract pC7, p. 54.
31.
Héritier C, Poirel L, Fournier PE et al. Characterization of the naturally occurring oxacillinase of Acinetobacter baumannii. Antimicrob Agents Chemother 2005; 49: 4174–9.
32. Woodford N, Ellington MJ, Coelho JM et al. Multiplex PCR for genes encoding prevalent OXA carbapenemases in Acinetobacter spp. J Antimicrob Chemother 2005; 57: 152–3.
33.
Poirel L, Héritier C, Nordmann P. Chromosome-encoded Ambler class D ß-lactamase of Shewanella oneidensis as a progenitor of carbapenem-hydrolyzing oxacillinase. Antimicrob Agents Chemother 2004; 48: 348–51.
34.
Héritier C, Poirel L, Nordmann P. Genetic and biochemical characterization of a chromosome-encoded carbapenem-hydrolyzing Ambler class D ß-lactamase from Shewanella algae. Antimicrob Agents Chemother 2004; 48:1670–5.
35. Sanschagrin F, Couture F, Levesque RC. Primary structure of OXA-3 and phylogeny of oxacillin-hydrolyzing class D ß-lactamases. Antimicrob Agents Chemother 1995; 39: 887–93.[Abstract]
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