- Email: [email protected]
Comparative in vitro activity of ertapenem against extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolated in Spain
International Journal of Antimicrobial Agents 28 (2006) 457–459
Short communication
Comparative in vitro activity of ertapenem against extended-spectrum -lactamase-producing Escherichia coli and Klebsiella pneumoniae isolated in Spain Jos´e R. Hern´andez ∗ , Carmen Velasco, Luisa Romero, ´ Lu´ıs Mart´ınez-Mart´ınez 1 , Alvaro Pascual Department of Microbiology, Faculty of Medicine, University of Seville, Av. S´anchez Pizju´an s/n, 41009 Seville, Spain Received 13 January 2006; accepted 4 July 2006
Abstract The in vitro activity of ertapenem was tested against extended-spectrum -lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolated in Spain. Ertapenem activity was similar to that of imipenem and meropenem and better than that of the other antimicrobials tested. No differences in activity were observed regarding the origin of the isolates or type of ESBL produced. © 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. Keywords: Ertapenem; ESBL; Escherichia coli; Klebsiella pneumoniae
1. Introduction
2. Material and methods
Ertapenem is a new carbapenem active against most Grampositive and Gram-negative aerobic and anaerobic microorganisms commonly recovered from non-hospitalised patients [1]. This once-daily parenteral -lactam agent was licensed in November 2001 in the USA for the treatment of complicated intra-abdominal infections, community-acquired pneumonia, acute pelvic infections, complicated urinary tract infections and complicated skin and soft tissue infections [2]. Licensure in Europe followed in April 2002 for the treatment of complicated intra-abdominal infections, communityacquired pneumonia and acute pelvic infections caused by susceptible strains of certain designated organisms. With the exception of metallo--lactamases and a few other carbapenemases, ertapenem is highly resistant to -lactamases, including extended-spectrum -lactamases (ESBLs).
Strains analysed in this work came from two Spanish studies of ESBL-producing Enterobacteriaceae: the first was undertaken in 2000 and included 40 hospitals representing 14 of the 17 regions in Spain [3]; the second was carried out at University Hospital Virgen Macarena (HUVM) in Seville with strains recovered between 1995 and 2001 [4]. Antimicrobial susceptibility and detection of ESBL production were carried out by broth microdilution according to the Clinical and Laboratory Standards Institute (CLSI; formerly the National Committee for Clinical Laboratory Standards) guidelines [5]. The clonal relationship of isolates was determined by repetitive extragenic palindromic polymerase chain reaction (REP-PCR) [6]. ESBLs were characterised by isoelectric focusing, by PCR with specific primers for the TEM, SHV and CTX-M groups, and by direct sequencing of ESBLencoding genes [7].
∗
Corresponding author. Tel.: +34 954 552 862; fax: +34 954 377 413. E-mail address: [email protected] (J.R. Hern´andez). 1 Present address: Department of Microbiology, University Hospital Marqu´es de Valdecilla, Av. de Valdecilla, 39008 Santander, Spain.
3. Results Here we evaluated the activity of ertapenem against 289 Escherichia coli and 174 Klebsiella pneumoniae isolates
0924-8579/$ – see front matter © 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. doi:10.1016/j.ijantimicag.2006.08.014
458
J.R. Hern´andez et al. / International Journal of Antimicrobial Agents 28 (2006) 457–459
Table 1 Minimum inhibitory concentration (MIC) distributions of carbapenems for extended-spectrum -lactamase-producing Escherichia coli and Klebsiella pneumoniae Microorganism (no. of isolates)/antimicrobial
MIC range (g/mL) ≤0.03
E. coli (289) Ertapenem Imipenem Meropenem
206 68 260
K. pneumoniae (174) Ertapenem Imipenem Meropenem
86 12 125
0.06
MIC50
MIC90
0.125
0.25
0.5
1
2
4
39 52 9
28 114 16
8 40 1
4 10 2
2 5
1
1
≤0.03 0.125 ≤0.03
0.125 0.25 ≤0.03
40 34 38
18 72 10
21 47 1
8 8
1
≤0.03 0.125 ≤0.03
0.25 0.25 0.06
1
1
MIC50 and MIC90 , MIC for 50% and 90% of the organisms, respectively.
producing known ESBLs. The ertapenem minimum inhibitory concentration for 90% of the organisms (MIC90 ) for E. coli isolates was 0.125 g/mL (Table 1); no resistant isolate was found. The ertapenem MIC for one E. coli isolate (HUVM190) was 4 g/mL and, according to CLSI breakpoints, should be included in the intermediate category [5]. In another E. coli isolate (HUVM194), the ertapenem MIC was 2 g/mL but remained in the susceptible range. Taking into account European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, both strains should be considered resistant (http://www.eucast.org/). Both isolates were clonally related to a group of isolates from HUVM, all of them expressing SHV-12. Imipenem and meropenem MICs were, respectively, 0.06 g/mL and ≤0.03 g/mL for HUVM190 and 0.25 g/mL and 0.06 g/mL for HUVM194. For the remainder of the isolates within this clone (n = 7), ertapenem MICs were <0.5 g/mL. The ertapenem MIC90 for K. pneumoniae isolates was 0.25 g/mL. The ertapenem MIC for one K. pneumoniae isolate (HUVM138) was 4 g/mL; imipenem and meropenem MICs were 0.25 g/mL and 0.06 g/mL, respectively. This isolate also expressed SHV-12. When the activities of the carbapenems were compared, it was observed that for E. coli the MIC50 of imipenem was at least four-fold higher than those of meropenem and ertapenem, and the MIC90 of meropenem was at least eight-fold and four-fold lower than that of imipenem and ertapenem, respectively. The MIC50 values for the three carbapenems for K. pneumoniae were exactly the same as for E. coli, but the MIC90 of meropenem was four-fold lower than those of imipenem and ertapenem. Antimicrobial susceptibility data for the carbapenems and other agents for the isolates included in the two studies were analysed for E. coli and K. pneumoniae strains. Compared with carbapenems, for which there was no resistant isolate, different levels of susceptibility were found among the remaining antimicrobial agents tested, including susceptibilities of 29% and 66% for ciprofloxacin, 35% and 58% for co-trimoxazole, 92% and 93% for amikacin, 64% and 52% for gentamicin and 56% and 37% for tobramycin for E. coli and K. pneumoniae isolates, respectively.
Ertapenem activity was also analysed separately for E. coli and K. pneumoniae isolated from patients in the community or in hospital. An isolate was considered as recovered from the community when the patient was not admitted to hospital or was in the first 48 h after admission and did not have an admission within the previous month [7]. Isolates with an ertapenem MIC > 0.5 g/mL were found only in hospitalised patients, although they included only 1 of 174 K. pneumoniae isolates and 4 of 289 E. coli isolates. This may reflect the higher selective pressure in some hospitals. Excluding these five isolates, there was no difference in ertapenem activity between community- and hospital-acquired E. coli and K. pneumoniae isolates. In the multicentre study, different REP-PCR patterns were obtained in 137 of the 170 E. coli and 26 of the 70 K. pneumoniae. The most frequently produced ESBLs were CTX-M-9, CTX-M-14 and SHV-12 [8]. In the HUVM study, different REP-PCR patterns were obtained for 84 of 119 E. coli and 5 of 104 K. pneumoniae. CTX-M-14 and SHV-12 were the most frequently expressed ESBLs [4]. The activity of ertapenem against organisms producing different ESBLs was also evaluated. For this approach, only those ESBLs present in at least 10 isolates were considered. Twenty-five E. coli isolates expressing CTX-M-9, 35 E. coli isolates expressing CTX-M-14, 14 K. pneumoniae isolates producing TEM-4 and 49 isolates (38 E. coli and 11 K. pneumoniae) expressing SHV-12 were selected. Fifty percent of selected isolates were inhibited by an ertapenem concentration of ≤0.03 g/mL and 0.06 g/mL for E. coli and K. pneumoniae, respectively. The ertapenem MIC90 was 0.125 g/mL for selected isolates with sequenced ESBL genes, with the exception of SHV-12-producing E. coli isolates, which had an MIC90 of 0.06 g/mL.
4. Discussion Isolation of ESBL-producing Enterobacteriaceae is increasing in Spain. A high proportion of ESBL-producing E. coli has been isolated from non-hospitalised patients in this country [3,4,6–8]. Bou et al. reported that only 7 of 30
J.R. Hern´andez et al. / International Journal of Antimicrobial Agents 28 (2006) 457–459
patients harbouring strains with ESBL ever had previous contact with the hospital environment before the clinical isolation of E. coli [6]. Our group has recently reported an ESBLproducing E. coli prevalence in Spain of 0.5%, and 51% of these were recovered from non-hospitalised patients [3]. Rodr´ıguez-Ba˜no et al. found that 39.5% of ESBL-producing E. coli isolated during a 1.5-year period was recovered from outpatients [7]. This situation is also described in other countries such as Canada, where Pitout et al. reported that 71% of patients included in their study had community-onset infections [9]. It is common for the plasmid encoding ESBL also to contain genes conferring resistance to several classes of antimicrobial agents, most frequently aminoglycosides and co-trimoxazole. On the other hand, concurrent quinolone resistance, particularly in K. pneumoniae, may be related not only to target mutations in DNA gyrase or topoisomerase IV but also to porin loss, the presence of active efflux pumps or target protection [3,10,11]. Bearing these circumstances in mind, very few therapeutic options remain for the management of infections caused by ESBL-producing microorganisms. In such cases, carbapenems are the only therapeutic option owing to the presence of resistance to the remaining antimicrobial classes. In fact, in the vast majority of published studies on ESBL-producing enterobacteria, carbapenems were the most active antimicrobial agents in vitro. However, Jacoby et al. reported an ertapenem MIC of 16 g/mL in one K. pneumoniae isolate producing SHV-2 and deficient in OmpK35 and OmpK36 [12], and Mart´ınez-Mart´ınez et al. demonstrated that porin loss in K. pneumoniae strains producing SHV-2 increased imipenem and meropenem MICs [13]. Among carbapenems, imipenem and meropenem should be restricted to the treatment of severe nosocomial infections, particularly those caused by multiresistant non-fermentative Gram-negative rods such as Pseudomonas aeruginosa and Acinetobacter baumannii. Ertapenem, with low activity against these bacteria, could potentially be used for the treatment of multiresistant ESBL-producing E. coli and K. pneumoniae infections. Ertapenem, a recently introduced single daily dose carbapenem, maintains its activity against most aerobic and anaerobic bacteria, excluding non-fermenters. Taking into account the good stability of carbapenems in the presence of ESBLs, the emerging production of these enzymes from enterobacteria recovered from non-hospitalised patients and the indications for ertapenem in complicated infections in the community, ertapenem may be a very good therapeutic option for the treatment of complicated infections caused by ESBL-producing E. coli and K. pneumoniae isolated in the community in Spain.
459
Acknowledgments The authors thank the Grupo Espa˜nol de Infecci´on Hospitalaria (GEIH) for kindly providing some of the strains used in this study. The study was developed under the auspices of the Red Espa˜nola de Investigaci´on en Patolog´ıa Infecciosa (REIPI) of the Ministerio de Sanidad in Spain (C03-014). The study was partially supported by a grant from Merck Sharp and Dohme.
References [1] Shah PM, Isaacs RD. Ertapenem, the first of a new group of carbapenems. J Antimicrob Chemother 2003;52:538–42. [2] Livermore DM, Sefton AM, Scott GM. Properties and potential of ertapenem. J Antimicrob Chemother 2003;52:331–44. [3] Hern´andez JR, Pascual A, Cant´on R, Mart´ınez-Mart´ınez L. Extendedspectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Spanish hospitals (GEIH-BLEE Project 2002). Enferm Infecc Microbiol Clin 2003;21:77–82 [in Spanish]. [4] Romero L, L´opez L, Rodr´ıguez-Ba˜no J, Hern´andez JR, Mart´ınezMart´ınez L, Pascual A. Long-term study of the frequency of Escherichia coli and Klebsiella pneumoniae isolates producing extended-spectrum beta-lactamases. Clin Microbiol Infect 2005;11:625–31. [5] National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 6th ed. Wayne, PA: NCCLS; 2003. [6] Bou G, Cartelle M, Tom´as M, et al. Identification and broad dissemination of the CTX-M-14 beta-lactamase in different Escherichia coli strains in the northwest area of Spain. J Clin Microbiol 2002;40:4030–6. [7] Rodr´ıguez-Ba˜no J, Navarro MD, Romero L, et al. Epidemiology and clinical features of infections caused by extended-spectrum betalactamase-producing Escherichia coli in nonhospitalized patients. J Clin Microbiol 2004;42:1089–94. [8] Hern´andez JR, Cant´on R, Mart´ınez-Mart´ınez L, Coque TM. Pascual A; Spanish Group for Nosocomial Infections (GEIH). Escherichia coli and Klebsiella pneumoniae producing extended-spectrum lactamases in Spain: a nationwide study. Antimicrob Agents Chemother 2005;49:2122–5. [9] Pitout JD, Hanson ND, Church DL, Laupland KB. Populationbased laboratory surveillance for Escherichia coli-producing extendedspectrum beta-lactamases: importance of community isolates with blaCTX-M genes. Clin Infect Dis 2004;38:1736–41. [10] Paterson DL, Mulazimoglu L, Casellas JM, et al. Epidemiology of ciprofloxacin resistance and its relationship to extended-spectrum betalactamase production in Klebsiella pneumoniae isolates causing bacteremia. Clin Infect Dis 2000;30:473–8. [11] Rodr´ıguez-Mart´ınez JM. Mechanisms of plasmid-mediated resistance to quinolones. Enferm Infecc Microbiol Clin 2005;23:25–31 [in Spanish]. [12] Jacoby GA, Mills DM, Chow N. Role of beta-lactamases and porins in resistance to ertapenem and other beta-lactams in Klebsiella pneumoniae. Antimicrob Agents Chemother 2004;48:3203–6. [13] Mart´ınez-Mart´ınez L, Pascual A, Hern´andez-Alles S, et al. Roles of beta-lactamases and porins in activities of carbapenems and cephalosporins against Klebsiella pneumoniae. Antimicrob Agents Chemother 1999;43:1669–73.
Short communication
Comparative in vitro activity of ertapenem against extended-spectrum -lactamase-producing Escherichia coli and Klebsiella pneumoniae isolated in Spain Jos´e R. Hern´andez ∗ , Carmen Velasco, Luisa Romero, ´ Lu´ıs Mart´ınez-Mart´ınez 1 , Alvaro Pascual Department of Microbiology, Faculty of Medicine, University of Seville, Av. S´anchez Pizju´an s/n, 41009 Seville, Spain Received 13 January 2006; accepted 4 July 2006
Abstract The in vitro activity of ertapenem was tested against extended-spectrum -lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolated in Spain. Ertapenem activity was similar to that of imipenem and meropenem and better than that of the other antimicrobials tested. No differences in activity were observed regarding the origin of the isolates or type of ESBL produced. © 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. Keywords: Ertapenem; ESBL; Escherichia coli; Klebsiella pneumoniae
1. Introduction
2. Material and methods
Ertapenem is a new carbapenem active against most Grampositive and Gram-negative aerobic and anaerobic microorganisms commonly recovered from non-hospitalised patients [1]. This once-daily parenteral -lactam agent was licensed in November 2001 in the USA for the treatment of complicated intra-abdominal infections, community-acquired pneumonia, acute pelvic infections, complicated urinary tract infections and complicated skin and soft tissue infections [2]. Licensure in Europe followed in April 2002 for the treatment of complicated intra-abdominal infections, communityacquired pneumonia and acute pelvic infections caused by susceptible strains of certain designated organisms. With the exception of metallo--lactamases and a few other carbapenemases, ertapenem is highly resistant to -lactamases, including extended-spectrum -lactamases (ESBLs).
Strains analysed in this work came from two Spanish studies of ESBL-producing Enterobacteriaceae: the first was undertaken in 2000 and included 40 hospitals representing 14 of the 17 regions in Spain [3]; the second was carried out at University Hospital Virgen Macarena (HUVM) in Seville with strains recovered between 1995 and 2001 [4]. Antimicrobial susceptibility and detection of ESBL production were carried out by broth microdilution according to the Clinical and Laboratory Standards Institute (CLSI; formerly the National Committee for Clinical Laboratory Standards) guidelines [5]. The clonal relationship of isolates was determined by repetitive extragenic palindromic polymerase chain reaction (REP-PCR) [6]. ESBLs were characterised by isoelectric focusing, by PCR with specific primers for the TEM, SHV and CTX-M groups, and by direct sequencing of ESBLencoding genes [7].
∗
Corresponding author. Tel.: +34 954 552 862; fax: +34 954 377 413. E-mail address: [email protected] (J.R. Hern´andez). 1 Present address: Department of Microbiology, University Hospital Marqu´es de Valdecilla, Av. de Valdecilla, 39008 Santander, Spain.
3. Results Here we evaluated the activity of ertapenem against 289 Escherichia coli and 174 Klebsiella pneumoniae isolates
0924-8579/$ – see front matter © 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. doi:10.1016/j.ijantimicag.2006.08.014
458
J.R. Hern´andez et al. / International Journal of Antimicrobial Agents 28 (2006) 457–459
Table 1 Minimum inhibitory concentration (MIC) distributions of carbapenems for extended-spectrum -lactamase-producing Escherichia coli and Klebsiella pneumoniae Microorganism (no. of isolates)/antimicrobial
MIC range (g/mL) ≤0.03
E. coli (289) Ertapenem Imipenem Meropenem
206 68 260
K. pneumoniae (174) Ertapenem Imipenem Meropenem
86 12 125
0.06
MIC50
MIC90
0.125
0.25
0.5
1
2
4
39 52 9
28 114 16
8 40 1
4 10 2
2 5
1
1
≤0.03 0.125 ≤0.03
0.125 0.25 ≤0.03
40 34 38
18 72 10
21 47 1
8 8
1
≤0.03 0.125 ≤0.03
0.25 0.25 0.06
1
1
MIC50 and MIC90 , MIC for 50% and 90% of the organisms, respectively.
producing known ESBLs. The ertapenem minimum inhibitory concentration for 90% of the organisms (MIC90 ) for E. coli isolates was 0.125 g/mL (Table 1); no resistant isolate was found. The ertapenem MIC for one E. coli isolate (HUVM190) was 4 g/mL and, according to CLSI breakpoints, should be included in the intermediate category [5]. In another E. coli isolate (HUVM194), the ertapenem MIC was 2 g/mL but remained in the susceptible range. Taking into account European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, both strains should be considered resistant (http://www.eucast.org/). Both isolates were clonally related to a group of isolates from HUVM, all of them expressing SHV-12. Imipenem and meropenem MICs were, respectively, 0.06 g/mL and ≤0.03 g/mL for HUVM190 and 0.25 g/mL and 0.06 g/mL for HUVM194. For the remainder of the isolates within this clone (n = 7), ertapenem MICs were <0.5 g/mL. The ertapenem MIC90 for K. pneumoniae isolates was 0.25 g/mL. The ertapenem MIC for one K. pneumoniae isolate (HUVM138) was 4 g/mL; imipenem and meropenem MICs were 0.25 g/mL and 0.06 g/mL, respectively. This isolate also expressed SHV-12. When the activities of the carbapenems were compared, it was observed that for E. coli the MIC50 of imipenem was at least four-fold higher than those of meropenem and ertapenem, and the MIC90 of meropenem was at least eight-fold and four-fold lower than that of imipenem and ertapenem, respectively. The MIC50 values for the three carbapenems for K. pneumoniae were exactly the same as for E. coli, but the MIC90 of meropenem was four-fold lower than those of imipenem and ertapenem. Antimicrobial susceptibility data for the carbapenems and other agents for the isolates included in the two studies were analysed for E. coli and K. pneumoniae strains. Compared with carbapenems, for which there was no resistant isolate, different levels of susceptibility were found among the remaining antimicrobial agents tested, including susceptibilities of 29% and 66% for ciprofloxacin, 35% and 58% for co-trimoxazole, 92% and 93% for amikacin, 64% and 52% for gentamicin and 56% and 37% for tobramycin for E. coli and K. pneumoniae isolates, respectively.
Ertapenem activity was also analysed separately for E. coli and K. pneumoniae isolated from patients in the community or in hospital. An isolate was considered as recovered from the community when the patient was not admitted to hospital or was in the first 48 h after admission and did not have an admission within the previous month [7]. Isolates with an ertapenem MIC > 0.5 g/mL were found only in hospitalised patients, although they included only 1 of 174 K. pneumoniae isolates and 4 of 289 E. coli isolates. This may reflect the higher selective pressure in some hospitals. Excluding these five isolates, there was no difference in ertapenem activity between community- and hospital-acquired E. coli and K. pneumoniae isolates. In the multicentre study, different REP-PCR patterns were obtained in 137 of the 170 E. coli and 26 of the 70 K. pneumoniae. The most frequently produced ESBLs were CTX-M-9, CTX-M-14 and SHV-12 [8]. In the HUVM study, different REP-PCR patterns were obtained for 84 of 119 E. coli and 5 of 104 K. pneumoniae. CTX-M-14 and SHV-12 were the most frequently expressed ESBLs [4]. The activity of ertapenem against organisms producing different ESBLs was also evaluated. For this approach, only those ESBLs present in at least 10 isolates were considered. Twenty-five E. coli isolates expressing CTX-M-9, 35 E. coli isolates expressing CTX-M-14, 14 K. pneumoniae isolates producing TEM-4 and 49 isolates (38 E. coli and 11 K. pneumoniae) expressing SHV-12 were selected. Fifty percent of selected isolates were inhibited by an ertapenem concentration of ≤0.03 g/mL and 0.06 g/mL for E. coli and K. pneumoniae, respectively. The ertapenem MIC90 was 0.125 g/mL for selected isolates with sequenced ESBL genes, with the exception of SHV-12-producing E. coli isolates, which had an MIC90 of 0.06 g/mL.
4. Discussion Isolation of ESBL-producing Enterobacteriaceae is increasing in Spain. A high proportion of ESBL-producing E. coli has been isolated from non-hospitalised patients in this country [3,4,6–8]. Bou et al. reported that only 7 of 30
J.R. Hern´andez et al. / International Journal of Antimicrobial Agents 28 (2006) 457–459
patients harbouring strains with ESBL ever had previous contact with the hospital environment before the clinical isolation of E. coli [6]. Our group has recently reported an ESBLproducing E. coli prevalence in Spain of 0.5%, and 51% of these were recovered from non-hospitalised patients [3]. Rodr´ıguez-Ba˜no et al. found that 39.5% of ESBL-producing E. coli isolated during a 1.5-year period was recovered from outpatients [7]. This situation is also described in other countries such as Canada, where Pitout et al. reported that 71% of patients included in their study had community-onset infections [9]. It is common for the plasmid encoding ESBL also to contain genes conferring resistance to several classes of antimicrobial agents, most frequently aminoglycosides and co-trimoxazole. On the other hand, concurrent quinolone resistance, particularly in K. pneumoniae, may be related not only to target mutations in DNA gyrase or topoisomerase IV but also to porin loss, the presence of active efflux pumps or target protection [3,10,11]. Bearing these circumstances in mind, very few therapeutic options remain for the management of infections caused by ESBL-producing microorganisms. In such cases, carbapenems are the only therapeutic option owing to the presence of resistance to the remaining antimicrobial classes. In fact, in the vast majority of published studies on ESBL-producing enterobacteria, carbapenems were the most active antimicrobial agents in vitro. However, Jacoby et al. reported an ertapenem MIC of 16 g/mL in one K. pneumoniae isolate producing SHV-2 and deficient in OmpK35 and OmpK36 [12], and Mart´ınez-Mart´ınez et al. demonstrated that porin loss in K. pneumoniae strains producing SHV-2 increased imipenem and meropenem MICs [13]. Among carbapenems, imipenem and meropenem should be restricted to the treatment of severe nosocomial infections, particularly those caused by multiresistant non-fermentative Gram-negative rods such as Pseudomonas aeruginosa and Acinetobacter baumannii. Ertapenem, with low activity against these bacteria, could potentially be used for the treatment of multiresistant ESBL-producing E. coli and K. pneumoniae infections. Ertapenem, a recently introduced single daily dose carbapenem, maintains its activity against most aerobic and anaerobic bacteria, excluding non-fermenters. Taking into account the good stability of carbapenems in the presence of ESBLs, the emerging production of these enzymes from enterobacteria recovered from non-hospitalised patients and the indications for ertapenem in complicated infections in the community, ertapenem may be a very good therapeutic option for the treatment of complicated infections caused by ESBL-producing E. coli and K. pneumoniae isolated in the community in Spain.
459
Acknowledgments The authors thank the Grupo Espa˜nol de Infecci´on Hospitalaria (GEIH) for kindly providing some of the strains used in this study. The study was developed under the auspices of the Red Espa˜nola de Investigaci´on en Patolog´ıa Infecciosa (REIPI) of the Ministerio de Sanidad in Spain (C03-014). The study was partially supported by a grant from Merck Sharp and Dohme.
References [1] Shah PM, Isaacs RD. Ertapenem, the first of a new group of carbapenems. J Antimicrob Chemother 2003;52:538–42. [2] Livermore DM, Sefton AM, Scott GM. Properties and potential of ertapenem. J Antimicrob Chemother 2003;52:331–44. [3] Hern´andez JR, Pascual A, Cant´on R, Mart´ınez-Mart´ınez L. Extendedspectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Spanish hospitals (GEIH-BLEE Project 2002). Enferm Infecc Microbiol Clin 2003;21:77–82 [in Spanish]. [4] Romero L, L´opez L, Rodr´ıguez-Ba˜no J, Hern´andez JR, Mart´ınezMart´ınez L, Pascual A. Long-term study of the frequency of Escherichia coli and Klebsiella pneumoniae isolates producing extended-spectrum beta-lactamases. Clin Microbiol Infect 2005;11:625–31. [5] National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 6th ed. Wayne, PA: NCCLS; 2003. [6] Bou G, Cartelle M, Tom´as M, et al. Identification and broad dissemination of the CTX-M-14 beta-lactamase in different Escherichia coli strains in the northwest area of Spain. J Clin Microbiol 2002;40:4030–6. [7] Rodr´ıguez-Ba˜no J, Navarro MD, Romero L, et al. Epidemiology and clinical features of infections caused by extended-spectrum betalactamase-producing Escherichia coli in nonhospitalized patients. J Clin Microbiol 2004;42:1089–94. [8] Hern´andez JR, Cant´on R, Mart´ınez-Mart´ınez L, Coque TM. Pascual A; Spanish Group for Nosocomial Infections (GEIH). Escherichia coli and Klebsiella pneumoniae producing extended-spectrum lactamases in Spain: a nationwide study. Antimicrob Agents Chemother 2005;49:2122–5. [9] Pitout JD, Hanson ND, Church DL, Laupland KB. Populationbased laboratory surveillance for Escherichia coli-producing extendedspectrum beta-lactamases: importance of community isolates with blaCTX-M genes. Clin Infect Dis 2004;38:1736–41. [10] Paterson DL, Mulazimoglu L, Casellas JM, et al. Epidemiology of ciprofloxacin resistance and its relationship to extended-spectrum betalactamase production in Klebsiella pneumoniae isolates causing bacteremia. Clin Infect Dis 2000;30:473–8. [11] Rodr´ıguez-Mart´ınez JM. Mechanisms of plasmid-mediated resistance to quinolones. Enferm Infecc Microbiol Clin 2005;23:25–31 [in Spanish]. [12] Jacoby GA, Mills DM, Chow N. Role of beta-lactamases and porins in resistance to ertapenem and other beta-lactams in Klebsiella pneumoniae. Antimicrob Agents Chemother 2004;48:3203–6. [13] Mart´ınez-Mart´ınez L, Pascual A, Hern´andez-Alles S, et al. Roles of beta-lactamases and porins in activities of carbapenems and cephalosporins against Klebsiella pneumoniae. Antimicrob Agents Chemother 1999;43:1669–73.