JAC Advance Access originally published online on November 16, 2007
Journal of Antimicrobial Chemotherapy 2008 61(1):222-224; doi:10.1093/jac/dkm439
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Research letters |
Antibiotic-resistant Klebsiella pneumoniae in Spain: analyses of 718 invasive isolates from 35 hospitals and report of one outbreak causedby an SHV-12-producing strain
1 Antibiotic Laboratory, Bacteriology Service, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain 2 Microbiology Department, Hospital Infanta Cristina, Badajoz, Spain 3 Consejo Superior de Investigaciones Científicas, Madrid, Spain
* Corresponding author. Tel: +34-91-822-3650; Fax: +34-91-509-7966; E-mail: jcampos{at}isciii.es
Keywords: antibiotic resistance , blood infections , K. pneumoniae
Klebsiella pneumoniae is a well-recognized nosocomial pathogen causing blood, urinary tract and respiratory tract infections. Since the early 1990s, extended-spectrum β-lactamase (ESBL)-producing and multiresistant K. pneumoniae isolates have rapidly emerged. 1
The European Antimicrobial Resistance Surveillance System (EARSS) is an international network of national surveillance systems that attempts to collect reliable and comparable antimicrobial resistance data on invasive pathogens. 2,3 Recently, K. pneumoniae has been included as one of the EARSS indicator organisms.
The goals of this surveillance study were to determine the antibiotic resistance prevalence of K. pneumoniae causing blood infections in Spain and to describe the spread of an SHV-12-producing strain in a Spanish hospital.
The selection of the 35 participating hospitals was done according to EARSS criteria. 2,3 All the first blood infections per patient obtained between October 2005 and March 2007 were included. To assess the comparability of susceptibility test results, a quality assurance exercise (UK National External Quality Assessment Scheme) was performed. By definition, patients with community-acquired infections were those who had a positive culture of K. pneumoniae at the time of or within 48 h of hospitalization.
Of the 718 consecutive blood infections caused by K. pneumoniae, 424 (59.1%) were from males, 411 cases (57.2%) were from patients >64 years old and 434 (62.8%) were considered nosocomial infections. According to hospital department distribution, 195 cases (27.2%) were from Internal Medicine, 167 (23.3%) from Emergency Room, 127 (17.7%) from ICUs, 69 (9.6%) from Surgery and 160 (22.3%) from other departments.
Resistance to co-trimoxazole, ciprofloxacin, tobramycin, gentamicin, piperacillin/tazobactam, amikacin and imipenem was found at rates of 12.4%, 9.9%, 5.6%, 5.2%, 5.2%, 0.7% and 0%, respectively. ESBL producers accounted for 65 (9.1%) of all strains tested; 56 (86.2%) and 50 (76.9%) of them were resistant or intermediate to cefotaxime and ceftazidime, respectively. The ESBL production detected in this study is higher than the 2.7% found in an earlier Spanish nationwide study, which was conducted during 2000 and included invasive and non-invasive K. pneumoniae clinical isolates. 4 Nationwide studies in other south European countries described ESBL production values of 10.2% (Italy, 2003) 5 and 9.4% (France, 1998). 6
Only 6 of the 65 (9.2%) ESBL-producing K. pneumoniae in this study were considered as community-acquired, 5 of them were cefotaxime-resistant but ceftazidime-susceptible. The prevalence of antimicrobial resistance according to gender, nosocomial or community origin, ESBL production and isolation from ICU or non-ICU departments is shown in Table 1. Of the 566 (78.8%) isolates tested for simultaneous susceptibility to ciprofloxacin, gentamicin, co-trimoxazole and cefotaxime, resistance to three or more of these antibiotics was present in 28 (4.9%) isolates; the most prevalent resistance phenotype was ciprofloxacin–gentamicin–cefotaxime, detected in eight isolates (28.6% of multiresistant isolates and 1.4% of isolates overall).
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The 65 blood infections due to ESBL-positive K. pneumoniae came from 23 of the 35 participating hospitals (mean: 2.83 ± 3.02; CI 95%: 1.52–4.13; range: 1–15). Fifteen of them were detected in the Hospital Infanta Cristina of Badajoz (South-West Spain), a 463 bed hospital covering a population of 260 000. All 15 isolates were resistant to cefotaxime (>16 mg/L), ceftazidime (>32 mg/L) and tobramycin, but susceptible to co-trimoxazole (
1 mg/L), ciprofloxacin (0.06–1 mg/L) and imipenem (0.5 mg/L). Four and three of the isolates exhibited resistance to gentamicin and amikacin, respectively. Profiles of aminoglycoside resistance were compatible with the presence of the aminoglycoside-modifying enzyme gene aac(6')-1b detected by PCR and sequencing in the nine blood isolates tested. After further analysis, it was observed that in this hospital a total of 61 ESBL-producing K. pneumoniae had been isolated between June 2005 and June 2007, peaking in March and May 2006 with nine cases each. Forty-eight (78.7%) isolates were from males; 31 (50.8%) were from ICU departments, 21 (34.4%) were isolated from the respiratory tract and 15 (24.6%) from blood cultures. The mean age of the infected patients was 56.3 years (range: 19–77). Eighteen of the 61 isolates, 9 from blood and 9 from other non-invasive samples (respiratory tract, 6; wounds, 2; catheter, 1) were subjected to further molecular studies. After total DNA digestions with XbaI, PFGE revealed that all 18 isolates belonged to one unique PFGE profile. Standard PCR conditions were used to amplify the genes bla TEM, bla SHV, bla CTX-M and bla OXA; 7 sequence analysis of PCR products obtained with bla SHV- and bla TEM-specific primers identified SHV-12 and TEM-1 β-lactamases in all 18 isolates; no PCR products were obtained using the bla CTX-M and bla OXA primers. In a nationwide study carried out in Spain in 2000, 4 seven of the 24 unrelated ESBL-producing K. pneumoniae studied were of the SHV-type, although SHV-12 was detected only in three strains from three different geographical areas, none of them belonging to the Hospital Infanta Cristina area. 4
This surveillance study reports on 718 Spanish invasive infections caused by K. pneumoniae; the most significant resistance problems found were resistance to ciprofloxacin (10.4%) and ESBL production (13.7%) in nosocomial isolates. An outbreak of SHV-12-positive K. pneumoniae was detected in one of the participating hospitals. As antibiotic resistance is continually evolving, properly conducted surveillance systems are essential for the early detection of these variations and to apply effective prevention programmes.
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Funding |
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EARSS is funded by the European Commission, DG Sanco (Agreement SI2.123794). This study was supported by a research grant from the Dirección General de Salud Pública, Ministry of Health, Spain (reference 1429/05-11).
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Transparency declarations |
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None to declare.
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Footnotes |
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Spanish members of EARSS are listed in the Acknowledgements section. 
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Acknowledgements |
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Spanish Group of the European Antimicrobial Resistance Surveillance System: E. Garduño (H. Infanta Cristina), C. Miranda and M. D. Rojo (H. U. Virgen de la Nieves), A. Delgado-Iribarren (Fundación Hospital de Alcorcón), D. Fontanals (Corporació Sanitària Parc Taulí), P. López and G. Royo (H. G. U. de Elche), J. Calvo and L. Martínez (H. Marqués de Valdecilla), P. Álvarez, V. Pulian and M. García-Campello (Complejo Hospitalario de Pontevedra), F. J. Vasallo-Vidal (H. do Meixoeiro), A. Pinedo (H. Virgen de la Victoria), L. Marco and M. J. Revillo (H. Miguel Servet), I. Wilhemi (H. Severo Ochoa), M. F. Brezmes and J. Rodríguez-Hernández (H. Virgen de la Concha), B. Fernández and A. Tinajas (Complexo Hospitalario de Ourense), R. Moreno (H. C. de Castellón), A. Fleites (H. G. de Asturias), M. M. Pérez-Moreno and I. Buj (H. Verge de la Cinta), N. Gonzalo (H. Vega Baja), N. Montiel (H. Costa del Sol), P. Teno (H. San Pedro de Alcántara), G. Megías-Lobón and E. Ojeda (H. General Yagüe), P. Berdonces (H. Galdakao), M. D. Crespo and J. J. Palomar (Complejo Hospitalario de Albacete), J. Lite and J. Garau (H. Mutua de Terrassa), I. Cuesta (H. Ciudad de Jaén), J. C. Alados (H. de Jerez), A. Tinajas (H. G. Cristal Piñor), C. Raya and C. Fuster (H. del Bierzo), Á. Campos and T. Nebreda (H. de Soria), E. Martín (H. Valme), J. A. Lepe (H. Río Tinto), C. Amores (H. San Agustín), E. Loza and F. Baquero (H. Ramón y Cajal), M. Menéndez-Rivas (H. Infantil del Niño Jesús), M. T. Cabezas (H. de Poniente), A. Yagüe (H. La Plana), V. Gallardo (Consejería de Salud de la Junta de Andalucía).
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References |
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1 Gaynes R, Edwards JR. National Nosocomial Infections Surveillance System. Overview of nosocomial infections caused by Gram-negative bacilli. Clin Infect Dis (2005) 41:848–54.[CrossRef][Web of Science][Medline]
2 Oteo J, Lázaro E, de Abajo FJ, et al. Antimicrobial-resistant invasive Escherichia coli, Spain. Emerg Infect Dis (2005) 11:546–53.[Web of Science][Medline]
3 European Antimicrobial Resistance Surveillance System. http://www.rivm.nl/earss/ (8 July 2007, date last accessed).
4
Hérnandez JR, Martínez-Martínez L, Cantón R, et al. Nationwide study of Escherichia coli and Klebsiella pneumoniae producing extended-spectrum β-lactamases in Spain. Antimicrob Agents Chemother (2005) 49:2122–5.
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Luzzaro F, Mezzatesta M, Mugnaioli C, et al. Trends in production of extended-spectrum β-lactamases among enterobacteria of medical interest: report of the second Italian nationwide survey. J Clin Microbiol (2006) 44:1659–64.
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De Champs C, Sirot D, Chanal C, et al. A 1998 survey of extended-spectrum β-lactamases in Enterobacteriaceae in France. Antimicrob Agents Chemother (2000) 44:3177–9.
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Oteo J, Navarro C, Cercenado E, et al. High-level of cefotaxime and ceftazidime resistance in Escherichia coli: spread of clonal and unrelated isolates between the community, long-term care facilities, and hospital institutions. J Clin Microbiol (2006) 44:2359–66.
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