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Comparative in vitro activity of minocycline and selected antibiotics against carbapenem-resistant Acinetobacter baumannii from Thailand
International Journal of Antimicrobial Agents 47 (2016) 101–106
Contents lists available at ScienceDirect
International Journal of Antimicrobial Agents journal homepage: http://www.elsevier.com/locate/ijantimicag
Letters to the Editor Comparative in vitro activity of minocycline and selected antibiotics against carbapenemresistant Acinetobacter baumannii from Thailand Sir, Infections due to carbapenem-resistant Acinetobacter baumannii are very prevalent in Asia [1]. Up to 90% of A. baumannii isolated from hospital-acquired infections at Siriraj Hospital in Bangkok, Thailand, are resistant to carbapenems. Polymyxins have been used for therapy of carbapenem-resistant A. baumannii infections at Siriraj Hospital over the past decade with a modest clinical response and frequent nephrotoxicity [2]. Minocycline is an antimicrobial agent that has drawn attention over the last few years as a possible therapeutic option against multidrug-resistant A. baumannii clinical isolates [3]. Minocycline has been shown to be an alternative antibiotic for therapy of infections due to A. baumannii in a small case series [3]. Minocycline is among a few agents available that have been approved by the US Food and Drug Administration (FDA) for the treatment of infections due to Acinetobacter spp. The objective of this study was to compare the in vitro activity of minocycline with tetracycline, tigecycline, meropenem, polymyxin B, sulbactam, sitafloxacin and levofloxacin against carbapenemresistant A. baumannii isolated from hospitalised patients in Thailand. In total, 215 strains of A. baumannii isolated from different hospitalised patients with pneumonia, bloodstream infections, urinary tract infections and skin and soft-tissue infections at Siriraj Hospital were used in this study. Only one isolate per infected patient episode was included. All isolates were resistant to amikacin, ceftazidime, meropenem and imipenem. Minimum inhibitory concentrations (MICs) were determined using the reference broth microdilution method as described by the Clinical and Laboratory Standards Institute (CLSI). The distributions of MIC values of all the tested antibiotics and the cumulative percent inhibited at each MIC are shown in Table 1.
The results of the present study showed that polymyxin B, tigecycline, sitafloxacin and minocycline were the most microbiologically potent agents against carbapenem-resistant A. baumannii isolates. In the case of polymyxins, which are used for the treatment of carbapenem-resistant A. baumannii infections with moderate effectiveness [4], the major concerns are their dosing regimens, the risk of nephrotoxicity and resistance development during the course of therapy. In the case of tigecycline, several observational studies revealed that it had lower microbiological eradication than colistin, that tigecycline-based therapy had higher mortality than colistin-based therapy, and that colistin/tigecycline combination had a trend of higher mortality than colistin/carbapenem combination [5]. With respect to sitafloxacin, if MIC cut-off values of 1 and 2 mg/L are considered susceptible, 94.0% and 97.7% of the carbapenem-resistant A. baumannii isolates will be considered susceptible. Sitafloxacin is an oral agent that has been available only in Japan and Thailand, and data on the efficacy and safety of sitafloxacin for therapy of infections due to carbapenem-resistant A. baumannii are not available. Based on the obtained results, MIC50 and MIC90 values for minocycline are 4 and 8 mg/L, respectively, and 81.4% of isolates will be susceptible at the breakpoint. This is in stark contrast to tetracycline with only 3.7% susceptible. The activity of minocycline against carbapenemresistant A. baumannii isolated from Thai patients is similar to previous observations from other countries [6]. Minocycline was found to be moderately effective for therapy of carbapenem-resistant A. baumannii infections [3]. Therefore, minocycline demonstrated good activity against carbapenemresistant A. baumannii isolated from Thai patients and it should be further investigated as a treatment option for patients with Acinetobacter infections when other treatment options may be limited. Funding: This study was supported by Health Systems Research and Development Project, Faculty of Medicine Siriraj Hospital, Health Systems Research Institute (Thailand) and Rempex Pharmaceuticals, Inc. (San Diego, CA). Competing interests: None declared. Ethical approval: Not required.
Table 1 Distributions of minimum inhibitory concentrations (MICs) of all the tested antibiotics and cumulative percent inhibited at each MIC. Antimicrobial agent
Minocycline Tetracycline Tigecycline Polymyxin B Sitafloxacin Levofloxacin Sulbactam Meropenem
Cumulative percent inhibited at an MIC (mg/L) of
MIC (mg/L)
<0.06
0.125
0.25
0.5
1
2
4
8
16
32
64
>64
MIC50
MIC90
0.9 0.0 1.9 0.0 0.0 0.0 0.0 0.0
2.8 0.0 4.2 0.0 1.4 0.0 0.0 0.0
9.3 0.0 17.7 8.8 8.8 0.0 0.0 0.0
14.4 0.0 71.6 81.4 55.8 0.0 0.0 0.0
25.6 0.0 94.9 97.7 94.0 0.5 0.5 0.0
29.3 0.0 99.1 99.5 97.7 9.3 0.5 0.0
81.4 3.7 100.0 100.0 98.1 70.2 1.9 0.0
94.0 15.3 100.0 100.0 99.1 95.8 7.9 0.0
100.0 15.8 100.0 100.0 99.5 97.7 20.5 0.9
100.0 15.8 100.0 100.0 100.0 98.6 87.4 22.3
100.0 15.8 100.0 100.0 100.0 99.5 98.6 68.8
100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
4 >64 0.5 0.5 0.5 4 32 64
8 >64 1 1 1 8 64 >64
MIC50/90 , concentration that inhibits 50% and 90% of the isolates, respectively. 0924-8579/© 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
102
Letters to the Editor / International Journal of Antimicrobial Agents 47 (2016) 101–106
References [1] Chung DR, Song JH, Kim SH, Thamlikitkul V, Huang SG, Wang H, et al. High prevalence of multidrug-resistant non-fermenters in hospitalacquired pneumonia in Asia. Am J Respir Crit Care Med 2011;184: 1409–17. [2] Koomanachai P, Tiengrim S, Kiratisin P, Thamlikitkul V. Efficacy and safety of colistin (colistimethate sodium) for therapy of infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii in Siriraj Hospital, Bangkok, Thailand. Int J Infect Dis 2007;11: 402–6. [3] Goff DA, Kaye KS. Minocycline: an old drug for a new bug: multidrug-resistant Acinetobacter baumannii. Clin Infect Dis 2014;59:S365–6. [4] Liu Q, Li W, Feng Y, Tao C. Efficacy and safety of polymyxins for the treatment of Acinetobacter baumannii infection: a systematic review and meta-analysis. PLOS ONE 2014;9:e98091. [5] Kwon SH, Ahn HL, Han OY, La HO. Efficacy and safety profile comparison of colistin and tigecycline on the extensively drug resistant Acinetobacter baumannii. Biol Pharm Bull 2014;37:340–6. [6] Castanheira M, Mendes RE, Jones RN. Update on Acinetobacter species: mechanisms of antimicrobial resistance and contemporary in vitro activity of minocycline and other treatment options. Clin Infect Dis 2014;59: S367–73.
Visanu Thamlikitkul ∗ Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand Surapee Tiengrim Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand Chrakrapong Seenama Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand ∗ Corresponding author. Present address: Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. Tel.: +66 82 412 5994; fax: +66 82 412 5994. E-mail address: [email protected] (V. Thamlikitkul)
3 November 2015 http://dx.doi.org/10.1016/j.ijantimicag.2015.11.006
Characterisation of OXA-244, a chromosomallyOXA-48-like -lactamase from encoded Escherichia coli Sir, During the last decade, the carbapenem-hydrolysing lactamase OXA-48 has rapidly and widely disseminated, now being the most commonly identified carbapenemase in most European and Mediterranean countries [1]. Since its discovery, ten variants of OXA-48 have been reported [1]. In most cases, blaOXA-48-like genes are plasmid-borne and have been identified associated with insertion sequences involved in their acquisition and expression [1,2]. Escherichia coli strain VAL was recovered from a urine sample of an 85-year-old patient with no history of travel abroad. The isolate was resistant to penicillins and penicillin/lactamase inhibitor combinations but remained susceptible to broad-spectrum cephalosporins, imipenem and meropenem, being of intermediate susceptibility to ertapenem. Multilocus sequence typing (MLST) showed that E. coli VAL belonged to sequence type ST38 [1], known to be a successful international clone [3]. Using PCR experiments followed by sequencing [2], E. coli VAL was found to harbour a blaOXA-48-like gene, termed blaOXA-244 (http://www.lahey.
org/studies/). Compared with OXA-48, OXA-244 exhibits a single Arg214Gln substitution. To compare the hydrolytic profile of OXA244 with that of OXA-48, the corresponding genes were cloned into the vector pCR-BluntII-TOPO as described previously [2] and were expressed in E. coli HB4, which lacks porins OmpF and OmpC. Expression of both carbapenemase genes conferred high-level resistance to imipenem, meropenem and ertapenem [minimum inhibitory concentrations (MICs) ≥ 32 mg/L]. Noteworthy, the MICs of imipenem and temocillin were lower for OXA-244 (32 mg/L and 96 mg/L, respectively) than those for OXA-48 (>32 mg/L and >1024 mg/L, respectively), suggesting a weaker activity towards these substrates for OXA-244. Similar results have been observed with OXA-232, differing from OXA-181 by a single amino acid substitution at position 214, which is located near the active site of the enzyme [2]. These two examples highlight the importance of the integrity of this residue at position 214 in the hydrolytic capacities of OXA-48-like -lactamases. Specific activities of OXA-244 for ertapenem and meropenem (2.2 and 4.3 mU/mg of protein, respectively) were close to those of OXA-48 (3.5 and 5.4 mU/mg of protein, respectively) [1]. However, the specific activity of OXA244 for imipenem (4.1 mU/mg of protein) was much lower than that determined for OXA-48 (111 mU/mg of protein), showing a weak hydrolysis of imipenem by OXA-244. Plasmid DNA analysis showed that E. coli VAL harboured three plasmids of 120, 80 and 10 kb (data not shown). Despite several attempts, no electrotransformant or transconjugant could be obtained, suggesting a chromosomal location of the blaOXA-244 gene. The genetic environment of the blaOXA-244 gene was determined by shotgun cloning performed as described previously [1]. Sequence analysis of the DNA fragment surrounding the blaOXA-244 gene revealed that it was part of a truncated Tn1999.2 transposon, made of two copies of insertion sequences IS1999 and a single IS1R element inserted into one of the IS1999 copies [4]. Compared with the structure identified in pOXA-48a, an inverted orientation of the truncated Tn1999.2 transposon was found in E. coli VAL (Fig. 1). Further analysis showed that the blaOXA-244 gene was bracketed by two IS1R copies forming an IS1R-made composite transposon. This 21 852-bp transposon was inserted into a gene encoding an intrinsic endonuclease from E. coli, further supporting a chromosomal integration of this IS1Rmade transposon. Identification of a 9-bp target site duplication (TGAATTGCT) at both extremities of the IS1R-made transposon was the signature of a transposition event. IS1R-made composite transposons harbouring the blaOXA-48 gene and integrated into the chromosome of E. coli isolates from Lebanon have been recently described [5]. This study characterised OXA-244 possessing a weaker ability to hydrolyse imipenem and temocillin compared with OXA-48. Identification of such a variant raises again the issue of the threshold to be chosen for classifying a -lactamase as a carbapenemase or not. Along with OXA-232, OXA-244 is another OXA-48 variant possessing a weaker ability to hydrolyse temocillin. Since this molecule has been integrated in screening culture media for detecting carbapenemase-producers, it might be interesting to evaluate the performances for detection of all those producers of OXA-48-like variants. ST38-type E. coli isolates harbouring a chromosomal blaOXA-48 gene have been recovered from Lebanon, Egypt, Turkey, Switzerland and France [3]. Dissemination of OXA48-like-producing E. coli isolates might therefore be linked to the dissemination of the ST38 clone at least in several countries [3,5]. Nevertheless, this diffusion has also been shown to be related to the mobility of blaOXA-48 -carrying IS1R-made composite transposons, inserted into different loci among various E. coli backgrounds [5]. The nucleotide sequence data reported in this work has been deposited in the GenBank nucleotide database under accession no. KR364794.
Contents lists available at ScienceDirect
International Journal of Antimicrobial Agents journal homepage: http://www.elsevier.com/locate/ijantimicag
Letters to the Editor Comparative in vitro activity of minocycline and selected antibiotics against carbapenemresistant Acinetobacter baumannii from Thailand Sir, Infections due to carbapenem-resistant Acinetobacter baumannii are very prevalent in Asia [1]. Up to 90% of A. baumannii isolated from hospital-acquired infections at Siriraj Hospital in Bangkok, Thailand, are resistant to carbapenems. Polymyxins have been used for therapy of carbapenem-resistant A. baumannii infections at Siriraj Hospital over the past decade with a modest clinical response and frequent nephrotoxicity [2]. Minocycline is an antimicrobial agent that has drawn attention over the last few years as a possible therapeutic option against multidrug-resistant A. baumannii clinical isolates [3]. Minocycline has been shown to be an alternative antibiotic for therapy of infections due to A. baumannii in a small case series [3]. Minocycline is among a few agents available that have been approved by the US Food and Drug Administration (FDA) for the treatment of infections due to Acinetobacter spp. The objective of this study was to compare the in vitro activity of minocycline with tetracycline, tigecycline, meropenem, polymyxin B, sulbactam, sitafloxacin and levofloxacin against carbapenemresistant A. baumannii isolated from hospitalised patients in Thailand. In total, 215 strains of A. baumannii isolated from different hospitalised patients with pneumonia, bloodstream infections, urinary tract infections and skin and soft-tissue infections at Siriraj Hospital were used in this study. Only one isolate per infected patient episode was included. All isolates were resistant to amikacin, ceftazidime, meropenem and imipenem. Minimum inhibitory concentrations (MICs) were determined using the reference broth microdilution method as described by the Clinical and Laboratory Standards Institute (CLSI). The distributions of MIC values of all the tested antibiotics and the cumulative percent inhibited at each MIC are shown in Table 1.
The results of the present study showed that polymyxin B, tigecycline, sitafloxacin and minocycline were the most microbiologically potent agents against carbapenem-resistant A. baumannii isolates. In the case of polymyxins, which are used for the treatment of carbapenem-resistant A. baumannii infections with moderate effectiveness [4], the major concerns are their dosing regimens, the risk of nephrotoxicity and resistance development during the course of therapy. In the case of tigecycline, several observational studies revealed that it had lower microbiological eradication than colistin, that tigecycline-based therapy had higher mortality than colistin-based therapy, and that colistin/tigecycline combination had a trend of higher mortality than colistin/carbapenem combination [5]. With respect to sitafloxacin, if MIC cut-off values of 1 and 2 mg/L are considered susceptible, 94.0% and 97.7% of the carbapenem-resistant A. baumannii isolates will be considered susceptible. Sitafloxacin is an oral agent that has been available only in Japan and Thailand, and data on the efficacy and safety of sitafloxacin for therapy of infections due to carbapenem-resistant A. baumannii are not available. Based on the obtained results, MIC50 and MIC90 values for minocycline are 4 and 8 mg/L, respectively, and 81.4% of isolates will be susceptible at the breakpoint. This is in stark contrast to tetracycline with only 3.7% susceptible. The activity of minocycline against carbapenemresistant A. baumannii isolated from Thai patients is similar to previous observations from other countries [6]. Minocycline was found to be moderately effective for therapy of carbapenem-resistant A. baumannii infections [3]. Therefore, minocycline demonstrated good activity against carbapenemresistant A. baumannii isolated from Thai patients and it should be further investigated as a treatment option for patients with Acinetobacter infections when other treatment options may be limited. Funding: This study was supported by Health Systems Research and Development Project, Faculty of Medicine Siriraj Hospital, Health Systems Research Institute (Thailand) and Rempex Pharmaceuticals, Inc. (San Diego, CA). Competing interests: None declared. Ethical approval: Not required.
Table 1 Distributions of minimum inhibitory concentrations (MICs) of all the tested antibiotics and cumulative percent inhibited at each MIC. Antimicrobial agent
Minocycline Tetracycline Tigecycline Polymyxin B Sitafloxacin Levofloxacin Sulbactam Meropenem
Cumulative percent inhibited at an MIC (mg/L) of
MIC (mg/L)
<0.06
0.125
0.25
0.5
1
2
4
8
16
32
64
>64
MIC50
MIC90
0.9 0.0 1.9 0.0 0.0 0.0 0.0 0.0
2.8 0.0 4.2 0.0 1.4 0.0 0.0 0.0
9.3 0.0 17.7 8.8 8.8 0.0 0.0 0.0
14.4 0.0 71.6 81.4 55.8 0.0 0.0 0.0
25.6 0.0 94.9 97.7 94.0 0.5 0.5 0.0
29.3 0.0 99.1 99.5 97.7 9.3 0.5 0.0
81.4 3.7 100.0 100.0 98.1 70.2 1.9 0.0
94.0 15.3 100.0 100.0 99.1 95.8 7.9 0.0
100.0 15.8 100.0 100.0 99.5 97.7 20.5 0.9
100.0 15.8 100.0 100.0 100.0 98.6 87.4 22.3
100.0 15.8 100.0 100.0 100.0 99.5 98.6 68.8
100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
4 >64 0.5 0.5 0.5 4 32 64
8 >64 1 1 1 8 64 >64
MIC50/90 , concentration that inhibits 50% and 90% of the isolates, respectively. 0924-8579/© 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
102
Letters to the Editor / International Journal of Antimicrobial Agents 47 (2016) 101–106
References [1] Chung DR, Song JH, Kim SH, Thamlikitkul V, Huang SG, Wang H, et al. High prevalence of multidrug-resistant non-fermenters in hospitalacquired pneumonia in Asia. Am J Respir Crit Care Med 2011;184: 1409–17. [2] Koomanachai P, Tiengrim S, Kiratisin P, Thamlikitkul V. Efficacy and safety of colistin (colistimethate sodium) for therapy of infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii in Siriraj Hospital, Bangkok, Thailand. Int J Infect Dis 2007;11: 402–6. [3] Goff DA, Kaye KS. Minocycline: an old drug for a new bug: multidrug-resistant Acinetobacter baumannii. Clin Infect Dis 2014;59:S365–6. [4] Liu Q, Li W, Feng Y, Tao C. Efficacy and safety of polymyxins for the treatment of Acinetobacter baumannii infection: a systematic review and meta-analysis. PLOS ONE 2014;9:e98091. [5] Kwon SH, Ahn HL, Han OY, La HO. Efficacy and safety profile comparison of colistin and tigecycline on the extensively drug resistant Acinetobacter baumannii. Biol Pharm Bull 2014;37:340–6. [6] Castanheira M, Mendes RE, Jones RN. Update on Acinetobacter species: mechanisms of antimicrobial resistance and contemporary in vitro activity of minocycline and other treatment options. Clin Infect Dis 2014;59: S367–73.
Visanu Thamlikitkul ∗ Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand Surapee Tiengrim Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand Chrakrapong Seenama Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand ∗ Corresponding author. Present address: Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. Tel.: +66 82 412 5994; fax: +66 82 412 5994. E-mail address: [email protected] (V. Thamlikitkul)
3 November 2015 http://dx.doi.org/10.1016/j.ijantimicag.2015.11.006
Characterisation of OXA-244, a chromosomallyOXA-48-like -lactamase from encoded Escherichia coli Sir, During the last decade, the carbapenem-hydrolysing lactamase OXA-48 has rapidly and widely disseminated, now being the most commonly identified carbapenemase in most European and Mediterranean countries [1]. Since its discovery, ten variants of OXA-48 have been reported [1]. In most cases, blaOXA-48-like genes are plasmid-borne and have been identified associated with insertion sequences involved in their acquisition and expression [1,2]. Escherichia coli strain VAL was recovered from a urine sample of an 85-year-old patient with no history of travel abroad. The isolate was resistant to penicillins and penicillin/lactamase inhibitor combinations but remained susceptible to broad-spectrum cephalosporins, imipenem and meropenem, being of intermediate susceptibility to ertapenem. Multilocus sequence typing (MLST) showed that E. coli VAL belonged to sequence type ST38 [1], known to be a successful international clone [3]. Using PCR experiments followed by sequencing [2], E. coli VAL was found to harbour a blaOXA-48-like gene, termed blaOXA-244 (http://www.lahey.
org/studies/). Compared with OXA-48, OXA-244 exhibits a single Arg214Gln substitution. To compare the hydrolytic profile of OXA244 with that of OXA-48, the corresponding genes were cloned into the vector pCR-BluntII-TOPO as described previously [2] and were expressed in E. coli HB4, which lacks porins OmpF and OmpC. Expression of both carbapenemase genes conferred high-level resistance to imipenem, meropenem and ertapenem [minimum inhibitory concentrations (MICs) ≥ 32 mg/L]. Noteworthy, the MICs of imipenem and temocillin were lower for OXA-244 (32 mg/L and 96 mg/L, respectively) than those for OXA-48 (>32 mg/L and >1024 mg/L, respectively), suggesting a weaker activity towards these substrates for OXA-244. Similar results have been observed with OXA-232, differing from OXA-181 by a single amino acid substitution at position 214, which is located near the active site of the enzyme [2]. These two examples highlight the importance of the integrity of this residue at position 214 in the hydrolytic capacities of OXA-48-like -lactamases. Specific activities of OXA-244 for ertapenem and meropenem (2.2 and 4.3 mU/mg of protein, respectively) were close to those of OXA-48 (3.5 and 5.4 mU/mg of protein, respectively) [1]. However, the specific activity of OXA244 for imipenem (4.1 mU/mg of protein) was much lower than that determined for OXA-48 (111 mU/mg of protein), showing a weak hydrolysis of imipenem by OXA-244. Plasmid DNA analysis showed that E. coli VAL harboured three plasmids of 120, 80 and 10 kb (data not shown). Despite several attempts, no electrotransformant or transconjugant could be obtained, suggesting a chromosomal location of the blaOXA-244 gene. The genetic environment of the blaOXA-244 gene was determined by shotgun cloning performed as described previously [1]. Sequence analysis of the DNA fragment surrounding the blaOXA-244 gene revealed that it was part of a truncated Tn1999.2 transposon, made of two copies of insertion sequences IS1999 and a single IS1R element inserted into one of the IS1999 copies [4]. Compared with the structure identified in pOXA-48a, an inverted orientation of the truncated Tn1999.2 transposon was found in E. coli VAL (Fig. 1). Further analysis showed that the blaOXA-244 gene was bracketed by two IS1R copies forming an IS1R-made composite transposon. This 21 852-bp transposon was inserted into a gene encoding an intrinsic endonuclease from E. coli, further supporting a chromosomal integration of this IS1Rmade transposon. Identification of a 9-bp target site duplication (TGAATTGCT) at both extremities of the IS1R-made transposon was the signature of a transposition event. IS1R-made composite transposons harbouring the blaOXA-48 gene and integrated into the chromosome of E. coli isolates from Lebanon have been recently described [5]. This study characterised OXA-244 possessing a weaker ability to hydrolyse imipenem and temocillin compared with OXA-48. Identification of such a variant raises again the issue of the threshold to be chosen for classifying a -lactamase as a carbapenemase or not. Along with OXA-232, OXA-244 is another OXA-48 variant possessing a weaker ability to hydrolyse temocillin. Since this molecule has been integrated in screening culture media for detecting carbapenemase-producers, it might be interesting to evaluate the performances for detection of all those producers of OXA-48-like variants. ST38-type E. coli isolates harbouring a chromosomal blaOXA-48 gene have been recovered from Lebanon, Egypt, Turkey, Switzerland and France [3]. Dissemination of OXA48-like-producing E. coli isolates might therefore be linked to the dissemination of the ST38 clone at least in several countries [3,5]. Nevertheless, this diffusion has also been shown to be related to the mobility of blaOXA-48 -carrying IS1R-made composite transposons, inserted into different loci among various E. coli backgrounds [5]. The nucleotide sequence data reported in this work has been deposited in the GenBank nucleotide database under accession no. KR364794.