José Ramón Hernández
University of Seville
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Clinical Infectious Diseases | 2006
Jesús Rodríguez-Baño; M.D. Navarro; Luisa Romero; Miguel A. Muniain; Marina de Cueto; Maria Rios; José Ramón Hernández; Álvaro Pascual
BACKGROUND Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, particularly those producing CTX-M types of ESBL, are emerging pathogens. Bacteremia caused by these organisms represents a clinical challenge, because the organisms are frequently resistant to the antimicrobials recommended for treatment of patients with suspected E. coli sepsis. METHODS A cohort study was performed that included all episodes of bloodstream infection due to ESBL-producing E. coli during the period from January 2001 through March 2005. Data on predisposing factors, clinical presentation, and outcome were collected. ESBLs were characterized using isoelectric focusing, polymerase chain reaction, and sequencing. RESULTS Forty-three episodes (8.8% of cases of bacteremia due to E. coli) were included; 70% of the isolates produced a CTX-M type of ESBL. The most frequent origins of infection were the urinary (46%) and biliary tracts (21%). Acquisition was nosocomial in 21 cases (49%), health care associated in 14 cases (32%), and strictly community acquired in 8 cases (19%). Thirty-eight percent and 25% of patients had obstructive diseases of the urinary and biliary tracts, respectively, and 38% had recently received antimicrobials. Nine patients (21%) died. Compared with beta-lactam/beta-lactamase-inhibitor and carbapenem-based regimens, empirical therapy with cephalosporins or fluoroquinolones was associated with a higher mortality rate (9% vs. 35%; P=.05) and needed to be changed more frequently (24% vs. 78%; P=.001). CONCLUSIONS ESBL-producing E. coli is a significant cause of bloodstream infection in hospitalized and nonhospitalized patients in the context of the emergence of CTX-M enzymes. Empirical treatment of sepsis potentially caused by E. coli may need to be reconsidered in areas where such ESBL-producing isolates are present.
Clinical Infectious Diseases | 2010
Jesuús Rodríguez-Baño; Encarnación Picón; Paloma Gijón; José Ramón Hernández; Maite Ruíz; Carmen Peña; M. Almela; Benito Almirante; Fabio Grill; Javier Colomina; Monserrat Giménez; Antonio Oliver; Juan Pablo Horcajada; Gemma Navarro; Ana Coloma; Álvaro Pascual
BACKGROUND There is little clinical information about community-onset bloodstream infections (COBSIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBLEC). We investigated the prevalence and risk factors for COBSI due to ESBLEC, and described their clinical features and the impact of COBSI caused by ESBLEC on 14-day mortality. METHODS Risk factors were assessed using a multicenter case-control-control study. Influence of ESBL production on mortality was studied in all patients with COBSI due to E. coli. Isolates and ESBLs were microbiologically characterized. Statistical analysis was performed using multivariate logistic regression. Thirteen tertiary care Spanish hospitals participated in the study. RESULTS We included 95 case patients with COBSI due to ESBLEC, which accounted for 7.3% of all COBSI due to E. coli. The ESBL in 83 of these (87%) belonged to the CTX-M family of ESBL, and most were clonally unrelated. Comparison with both control groups disclosed association with health care (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.8), urinary catheter use (OR, 3.1; 95% CI, 1.5-6.5), and previous antimicrobial use (OR, 2.7; 95% CI, 1.5-4.9) as independent risk factors for COBSI due to ESBLEC. Mortality among patients with COBSI due to ESBLEC was lower among patients who received empirical therapy with beta-lactam/beta-lactam inhibitor combinations or carbapenems (8%-12%) than among those receiving cephalosporins or fluoroquinolones (24% and 29%, respectively). Mortality among patients with COBSI due to E. coli was associated with inappropriate empirical therapy irrespective of ESBL production. CONCLUSIONS ESBLEC is an important cause of COBSI due to E. coli. Clinicians should consider adequate empirical therapy with coverage of these pathogens for patients with risk factors.
Clinical Infectious Diseases | 2006
Jesús Rodríguez-Baño; M.D. Navarro; Luisa Romero; Miguel A. Muniain; Evelio J. Perea; Ramón Pérez-Cano; José Ramón Hernández; Álvaro Pascual
BACKGROUND Extended-spectrum beta-lactamase (ESBL)-producing members of the Enterobacteriaceae family are important nosocomial pathogens. Escherichia coli producing a specific family of ESBL (the CTX-M enzymes) are emerging worldwide. The epidemiology of these organisms as causes of nosocomial infection is poorly understood. The aims of this study were to investigate the clinical and molecular epidemiology of nosocomial infection or colonization due to ESBL-producing E. coli in hospitalized patients, consider the specific types of ESBLs produced, and identify the risk factors for infection and colonization with these organisms. METHODS All patients with nosocomial colonization and/or infection due to ESBL-producing E. coli in 2 centers (a tertiary care hospital and a geriatric care center) identified between January 2001 and May 2002 were included. A double case-control study was performed. The clonal relatedness of the isolates was studied by repetitive extragenic palindromic-polymerase chain reaction and pulsed-field gel electrophoresis. ESBLs were characterized by isoelectric focusing, polymerase chain reaction, and sequencing. RESULTS Forty-seven case patients were included. CTX-M-producing E. coli were clonally unrelated and more frequently susceptible to nonoxyimino-beta-lactams. Alternately, isolates producing SHV- and TEM-type ESBL were epidemic and multidrug resistant. Urinary catheterization was a risk factor for both CTX-M-producing and SHV-TEM-producing isolates. Previous oxyimino-beta-lactam use, diabetes, and ultimately fatal or nonfatal underlying diseases were independent risk factors for infection or colonization with CTX-M-producing isolates, whereas previous fluoroquinolone use was associated with infection or colonization with SHV-TEM-producing isolates. CONCLUSIONS The epidemiology of ESBL-producing E. coli as a cause of nosocomial infection is complex. Sporadic CTX-M-producing isolates coexisted with epidemic multidrug-resistant SHV-TEM-producing isolates. These data should be taken into account for the design of control measures.
Antimicrobial Agents and Chemotherapy | 2005
José Ramón Hernández; Luis Martínez-Martínez; Rafael Cantón; T. M. Coque; Álvaro Pascual
ABSTRACT Clonal dissemination of extended-spectrum β-lactamases (ESBL) in 170 Escherichia coli isolates and 70 Klebsiella pneumoniae isolates from a nationwide study of 40 Spanish centers in 2000 was not observed in most centers. The most prevalent ESBL were CTX-M-9 (27.3%), SHV-12 (23.9%), and CTX-M-14 (20.5%) for E. coli and TEM-3 (16.7%) and TEM-4 (25%) for K. pneumoniae. A new ESBL, TEM-133, with mutations L21F, E104K, and R164S, was identified.
Journal of Clinical Microbiology | 2010
Jesús Rodríguez-Baño; Encarnación Picón; Paloma Gijón; José Ramón Hernández; José Miguel Cisneros; Carmen Peña; M. Almela; Benito Almirante; Fabio Grill; Javier Colomina; Sonia Molinos; Antonio Oliver; Carlos Fernández-Mazarrasa; Gemma Navarro; Ana Coloma; Lorena López-Cerero; Álvaro Pascual
ABSTRACT Extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli (ESBLEC) is an increasing cause of community and nosocomial infections worldwide. However, there is scarce clinical information about nosocomial bloodstream infections (BSIs) caused by these pathogens. We performed a study to investigate the risk factors for and prognosis of nosocomial BSIs due to ESBLEC in 13 Spanish hospitals. Risk factors were assessed by using a case-control-control study; 96 cases (2 to 16% of all nosocomial BSIs due to E. coli in the participating centers) were included; the most frequent ESBL was CTX-M-14 (48% of the isolates). We found CTX-M-15 in 10% of the isolates, which means that this enzyme is emerging as a cause of invasive infections in Spain. By repetitive extragenic palindromic sequence-PCR, most isolates were found to be clonally unrelated. By multivariate analysis, the risk factors for nosocomial BSIs due to ESBLEC were found to be organ transplant (odds ratio [OR] = 4.8; 95% confidence interval [CI] = 1.4 to 15.7), the previous use of oxyimino-β-lactams (OR = 6.0; 95% CI = 3.0 to 11.8), and unknown BSI source (protective; OR = 0.4; 95% CI = 0.2 to 0.9), and duration of hospital stay (OR = 1.02; 95% CI = 1.00 to 1.03). The variables independently associated with mortality were a Pitt score of >1 (OR = 3.9; 95% CI = 1.2 to 12.9), a high-risk source (OR = 5.5; 95% CI = 1.4 to 21.9), and resistance to more than three antibiotics, apart from penicillins and cephalosporins (OR = 6.5; 95% CI = 1.4 to 30.0). Inappropriate empirical therapy was not associated with mortality. We conclude that ESBLEC is an important cause of nosocomial BSIs. The previous use of oxyimino-β-lactams was the only modifiable risk factor found. Resistance to drugs other than penicillins and cephalosporins was associated with increased mortality.
Antimicrobial Agents and Chemotherapy | 2006
M. de Cueto; L. López; José Ramón Hernández; Concepción Morillo; Álvaro Pascual
ABSTRACT The agar dilution, broth microdilution, and disk diffusion methods were compared to determine the in vitro susceptibility of 428 extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae to fosfomycin. Fosfomycin showed very high activity against all ESBL-producing strains. Excellent agreement between the three susceptibility methods was found for E. coli, whereas marked discrepancies were observed for K. pneumoniae.
Clinical Microbiology and Infection | 2010
Lorena López-Cerero; E. Picón; C. Morillo; José Ramón Hernández; F. Docobo; J. Pachón; J. Rodríguez-Bañ; Álvaro Pascual
A significant inoculum-size effect has been observed with piperacillin-tazobactam, and has been associated with beta-lactamase production in extended-spectrum beta-lactamase (ESBL) producers. This association has not been previously studied in the case of amoxycillin-clavulanate. Piperacillin-tazobactam and amoxycillin-clavulanate were compared, using high inocula of susceptible strains either harbouring ESBLs or not. Two non-ESBL-producing and 15 amoxycillin-clavulanate-susceptible and piperacillin-tazobactam-susceptible ESBL-producing Escherichia coli isolates, and their respective transconjugants, were tested in dilution susceptibility tests using standard and 100-fold higher inocula. Three ESBL-producing strains and E. coli ATCC 25922 were selected for time-kill studies using standard and high initial inocula. At high inocula, MICs of piperacillin increased >eight-fold for non-ESBL-producing strains, and MICs of piperacillin-tazobactam (8:1 ratio or with tazobactam fixed at 4 mg/L) increased>eight-fold for all ESBL-producing strains. However, amoxycillin MICs were not affected by a high inoculum with non-ESBL-producing strains, whereas the MICs of amoxycillin-clavulanate (2:1 and 4:1) increased <or=four-fold for ESBL producers, using the broth and agar dilution methods. In kinetic studies at a high inoculum, amoxycillin and amoxycillin-clavulanate were bactericidal against E. coli ATCC 25922, whereas piperacillin and piperacillin-tazobactam yielded decreases of <1 log(10) CFU/mL. Similarly, at a high inoculum, only amoxycillin-clavulanate was able to maintain bactericidal rates of killing over 24 h against the ESBL-positive E. coli isolates. The stability of amoxycillin-clavulanate and the contrasting results obtained with piperacillin-tazobactam against high inocula of ESBL-non-producing and ESBL-producing E. coli strains appear to be related to aspects other than the amount of beta-lactamase production.
Enfermedades Infecciosas Y Microbiologia Clinica | 2009
Miguel Ángel Díaz; José Ramón Hernández; Luis Martínez-Martínez; Jesús Rodríguez-Baño; Álvaro Pascual
INTRODUCTION During the year 2000, the 1st nationwide project (GEIH-BLEE Project 2000) on Escherichia coli and Klebsiella pneumoniae producing extended-spectrum ss-lactamases (ESBL) was carried out in Spain. The 2nd nationwide study was developed in 2006 to investigate the evolution of this problem. METHODS A prospective multicenter study was designed, including all ESBL-producing E. coli and K. pneumoniae strains isolated at 44 Spanish hospitals between February and March 2006. Identification was verified at the coordinating centre and ESBL production was confirmed following CLSI guidelines. RESULTS A total of 1021 E. coli and 162 K. pneumoniae strains were collected. ESBL-producing E. coli strains were isolated in all the participating hospitals, whereas ESBL-producing K. pneumoniae were isolated in 34. The overall percentage (range) of ESBL production among E. coli and K. pneumoniae was 4.04% (0.4-20.3) and 5.04% (0-30), respectively. In ESBL E. coli (Ec) cases, acquisition was considered community-acquired in 32%, related to health care in 36%, and nosocomial in 30%; and in ESBL K. pneumoniae (Kp) cases, acquisition by these routes was 10%, 18%, and 68% respectively. The samples most commonly showing these microorganisms were urine (77% Ec and 48.2% Kp) and wound exudate (8.6% Ec and 14.8% Kp). CONCLUSIONS Since 2000, the percentage of ESBL-producing strains among E. coli and K. pneumoniae isolates in Spain has increased 8-fold and 2-fold, respectively. The increase in ESBL-producing E. coli mainly occurred in isolates from outpatients, and most commonly in urine samples.
Enfermedades Infecciosas Y Microbiologia Clinica | 2009
Miguel Ángel Díaz; José Ramón Hernández; Luis Martínez-Martínez; Jesús Rodríguez-Baño; Álvaro Pascual
INTRODUCTION During the year 2000, the 1st nationwide project (GEIH-BLEE Project 2000) on Escherichia coli and Klebsiella pneumoniae producing extended-spectrum ss-lactamases (ESBL) was carried out in Spain. The 2nd nationwide study was developed in 2006 to investigate the evolution of this problem. METHODS A prospective multicenter study was designed, including all ESBL-producing E. coli and K. pneumoniae strains isolated at 44 Spanish hospitals between February and March 2006. Identification was verified at the coordinating centre and ESBL production was confirmed following CLSI guidelines. RESULTS A total of 1021 E. coli and 162 K. pneumoniae strains were collected. ESBL-producing E. coli strains were isolated in all the participating hospitals, whereas ESBL-producing K. pneumoniae were isolated in 34. The overall percentage (range) of ESBL production among E. coli and K. pneumoniae was 4.04% (0.4-20.3) and 5.04% (0-30), respectively. In ESBL E. coli (Ec) cases, acquisition was considered community-acquired in 32%, related to health care in 36%, and nosocomial in 30%; and in ESBL K. pneumoniae (Kp) cases, acquisition by these routes was 10%, 18%, and 68% respectively. The samples most commonly showing these microorganisms were urine (77% Ec and 48.2% Kp) and wound exudate (8.6% Ec and 14.8% Kp). CONCLUSIONS Since 2000, the percentage of ESBL-producing strains among E. coli and K. pneumoniae isolates in Spain has increased 8-fold and 2-fold, respectively. The increase in ESBL-producing E. coli mainly occurred in isolates from outpatients, and most commonly in urine samples.
Enfermedades Infecciosas Y Microbiologia Clinica | 2010
José Ramón Hernández; María del Carmen Conejo; Álvaro Pascual
INTRODUCTION The effect of porin loss and inoculum size on the comparative activity of ertapenem against either extended-spectrum beta lactamase-producing (ESBL) or plasmid-mediated AmpC beta lactamase-producing (pACBL) Klebsiella pneumoniae strains was evaluated. METHODS Microdilution using 2 different bacterial inocula. RESULTS Imipenem, amikacin, ertapenem, and cefepime were the most active agents under standard conditions. Ertapenem was more highly affected by porin loss than imipenem. CONCLUSIONS Ertapenem showed high activity against K. pneumoniae strains expressing ESBL, pACBL or both. Strains deficient in porins showed decreased susceptibility to beta lactams. The inoculum effect had a greater impact on imipenem than on ertapenem.