Jesús Rodríguez-Baño

Epidemiology and Clinical Features of Infections Caused by Extended-Spectrum Beta-Lactamase-Producing Escherichia coli in Nonhospitalized Patients

ABSTRACT Infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBLEC) in nonhospitalized patients seem to be emerging in different countries. Their incidence, epidemiology, and clinical impact in the community have not been studied. We describe the epidemiology and clinical features of infections caused by ESBLEC in nonhospitalized patients in Spain and the results of a case-control study performed to investigate the risk factors associated with the acquisition of these organisms. The clonal relatedness of the organisms was assessed by repetitive extragenic palindromic sequence PCR. The ESBLs and the genes encoding the ESBLs were initially characterized by isoelectric focusing and PCR, respectively. Forty-nine patients (76% with urinary tract infections, 22% with asymptomatic bacteriuria, and 2% with acute cholangitis) were included. Six patients were bacteremic. Diabetes mellitus (odds ratio, 5.5; 95% confidence interval, 1.6 to 18.7), previous fluoroquinolone use (odds ratio, 7.6; 95% confidence interval, 1.9 to 30.1), recurrent urinary tract infections (odds ratio, 4.5; 95% confidence interval, 1.3 to 15.1), a previous hospital admission (odds ratio, 18.2; 95% confidence interval, 5.3 to 61.1), and older age in male patients (odds ratio per year, 1.03; 95% confidence interval, 1.03 to 1.05) were identified as risk factors by multivariate analysis. The ESBLEC isolates were not clonally related. The ESBLs were characterized as members of the CTX-M-9 group, the SHV group, and the TEM group in 64, 18, and 18% of the isolates, respectively. ESBLEC is an emergent cause of urinary tract infections in nonhospitalized patients. There was no evidence of horizontal transmission of ESBLEC strains. Avoidance of fluoroquinolone use in high-risk patients should be considered whenever possible in order to avoid the selection of these organisms.

A Multinational Survey of Risk Factors for Infection with Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae in Nonhospitalized Patients

BACKGROUND Infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are increasing in frequency and are associated with high mortality rates. Circulation of CTX-M-type ESBLs in the community is of particular concern, because it may confound standard infection-control measures. METHODS We analyzed the results of epidemiologic studies of infection caused by ESBL-producing Enterobacteriaceae in nonhospitalized patients from 6 centers in Europe, Asia, and North America. Risk factors for infection with an ESBL-producing organism were identified by univariate and multivariate analyses. RESULTS A total of 983 patient-specific isolates were reviewed (890 [90.5%] of which were Escherichia coli, 68 [6.9%] of which were Klebsiella species, and 25 [2.5%] of which were Proteus mirabilis); 339 [34.5%] of the isolates produced ESBLs. CTX-M types were the most frequent ESBLs (accounting for 65%). Rates of co-resistance to ciprofloxacin among ESBL-producing isolates were high (>70%), but significant variation was seen among centers with respect to rates of resistance to gentamicin, amoxicillin-clavulanate, and trimethoprim-sulfamethoxazole. Similar risk factors for infection with an ESBL-producing organism were found in the different participating centers. Significant risk factors, identified by multivariate analysis, were recent antibiotic use, residence in a long-term care facility, recent hospitalization, age 65 years, and male sex (area under the receiver-operator characteristic [ROC] curve, 0.80). However, 34% of ESBL-producing isolates (115 of 336 isolates) were obtained from patients with no recent health care contact; the area under the ROC curve for the multivariate model for this group of patients was only 0.70, which indicated poorer predictive value. CONCLUSIONS Community-acquired ESBL-producing Enterobacteriaceae are now prevalent worldwide, necessitating international collaboration. Novel approaches are required to adequately address issues such as empirical treatment for severe community-acquired infection and infection control.

Community Infections Caused by Extended-Spectrum β-Lactamase–Producing Escherichia coli

BACKGROUND Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is an increasingly important group of community pathogens worldwide. These organisms are frequently resistant to many of the antimicrobial agents usually recommended for the treatment of infections caused by E coli, such as penicillins, cephalosporins, fluoroquinolones, and trimethoprim-sulfamethoxazole. Data concerning risk factors, clinical features, and therapeutic options for such infections are scarce. METHODS A case-control study was performed to investigate the risk factors for all types of community-acquired infections caused by ESBL-producing E coli in 11 Spanish hospitals from February 2002 to May 2003. Controls were randomly chosen from among outpatients with a clinical sample not yielding ESBL-producing E coli. The clinical features of these infections were investigated in the case patients. The efficacy of fosfomycin tromethamine and amoxicillin-clavulanate potassium was observationally studied in patients with cystitis. RESULTS A total of 122 cases were included. Risk factors selected by multivariate analysis included the following: age older than 60 years; female sex; diabetes mellitus; recurrent urinary tract infections (UTIs); previous invasive procedures of the urinary tract; follow-up in outpatient clinic; and previous receipt of aminopenicillins, cephalosporins, and fluoroquinolones. Urinary tract infections accounted for 93% of the cases; 6% of the patients were bacteremic and 10% needed hospitalization. The cure rate of patients with cystitis was 93% with fosfomycin therapy (all isolates were susceptible); among patients treated with amoxicillin-clavulanate, cure rates were 93% for those with susceptible isolates (minimum inhibitory concentration < or =8 microg/mL) and 56% for those with intermediate or resistant isolates (minimum inhibitory concentration > or =16 microg/mL) (P = .02). CONCLUSIONS In predisposed patients, ESBL-producing E coli is a notable cause of community-acquired infection, and particularly UTI. Fosfomycin and amoxicillin-clavulanate appear to be effective for cystitis caused by susceptible isolates.

Bacteremia Due to Extended-Spectrum β-Lactamase–Producing Escherichia coli in the CTX-M Era: A New Clinical Challenge

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.

β-Lactam/β-Lactam Inhibitor Combinations for the Treatment of Bacteremia Due to Extended-Spectrum β-Lactamase–Producing Escherichia coli: A Post Hoc Analysis of Prospective Cohorts

BACKGROUND Extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) is an important cause of invasive infections. Alternatives to carbapenems--considered the drugs of choice--are needed because of the emergence of carbapenemase-producing enterobacteria. The efficacy of ß-lactam/ß-lactam inhibitors (BLBLI) in such infections is controversial. METHODS The authors performed a post hoc analysis of patients with bloodstream infections due to ESBL-EC from 6 published prospective cohorts. Mortality and length of hospital stay in patients treated with an active BLBLI (amoxicillin-clavulanic acid [AMC] and piperacillin-tazobactam [PTZ]) or carbapenem were compared in 2 cohorts: the empirical therapy cohort (ETC) and the definitive therapy cohort (DTC). Confounding was controlled by multivariate analysis; for patients in the ETC, a propensity score for receiving carbapenem was also used. RESULTS The ETC included 103 patients (BLBLI, 72; carbapenem, 31), and the DTC included 174 (BLBLI, 54; carbapenem, 120). Mortality rates at day 30 for those treated with BLBLI versus carbapenems were 9.7% versus 19.4% for the ETC and 9.3% versus 16.7% for the DTC, respectively (P > .2, log-rank test). After adjustment for confounders, no association was found between either empirical therapy with BLBLI (adjusted hazard ratio [HR], 1.14; 95% confidence interval [CI], .29-4.40; P = .84) or definitive therapy (adjusted HR, 0.76; 95% CI, .28-2.07; P = .5) and increased mortality. Furthermore, BLBLI therapy, with respect to carbapenem, was not found to influence length of hospital stay. CONCLUSIONS These results suggest that AMC and PTZ are suitable alternatives to carbapenems for treating patients with bloodstream infections due to ESBL-EC if active in vitro and would be particularly useful as definitive therapy.

The global threat of antimicrobial resistance: science for intervention

In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies and the scientific community at large) to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. We summarize the views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance.

Clinical progression of hepatitis C virus–related chronic liver disease in human immunodeficiency virus–infected patients undergoing highly active antiretroviral therapy

Little is known about the natural history of liver disease in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)‐coinfected subjects under highly active antiretroviral therapy (HAART). The objectives of this study were to obtain information about the mortality, the incidence of hepatic decompensations, and the predictors thereof in this population. In a multicenter cohort study, the time to the first hepatic decompensation and the survival of 1,011 antiretroviral naïve, HIV/HCV‐coinfected patients who started HAART and who were followed prospectively were analyzed. After a median (Q1‐Q3) follow‐up of 5.3 (2.9–7.1) years, 59(5.83%) patients developed a hepatic decompensation and 69 (6.82%) died, 30 (43%) of them because of liver disease. The factors independently associated [HR (95% CI)] with the occurrence of hepatic decompensations were age older than 33 years [2.11 (1.18–3.78)], female sex [2.11 (1.07–4.15)], Centers for Disease Control stage C [2.14 (1.24–3.70)], a diagnosis of cirrhosis at baseline [10.86 (6.02–19.6)], CD4 cell gain lower than 100/mm3 [4.10 (2.18–7.69)] and less than 60% of the follow‐up with undetectable HIV viral load [5.23 (2.5–10.93)]. Older age [2.97 (1.18–7.50)], lack of HCV therapy [11.32 (1.44–89.05)], hepatitis D virus coinfection [16.15 (2.45–106.48)], a diagnosis of cirrhosis at recruitment [13.69 (5.55–34.48)], hepatic encephalopathy [62.5 (21.27–200)] and lower CD4 cell gain [3.63 (1.45–9.09)] were associated with mortality due to liver failure. Conclusion: End‐stage liver disease is the primary cause of death in HIV/HCV‐coinfected patients under HAART. Higher increase of CD4 cell counts, lack of markers of serious liver disease and therapy against HCV are factors associated with better hepatic outcome. (HEPATOLOGY 2007.)

Faecal carriage of extended-spectrum β-lactamase-producing Escherichia coli: prevalence, risk factors and molecular epidemiology

OBJECTIVES The aim of this study was to investigate the epidemiology of faecal carriage of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in the community. PATIENTS AND METHODS Faecal carriage with ESBL-producing E. coli was studied in 53 outpatients with urinary tract infection (UTI) due to these organisms, 73 household members, 32 non-household relatives and 54 unrelated patients. Clonal relatedness of the isolates was investigated using repetitive extragenic palindromic-PCR and PFGE, and ESBLs were characterized by PCR and sequencing. Multivariate analysis was performed to investigate risk factors for faecal carriage. RESULTS The prevalence of faecal carriage was 67.9% in patients with UTI, 27.4% in household members, 15.6% in non-household relatives and 7.4% in unrelated patients. Being a relative of a patient with UTI was independently associated with an increased risk of being a carrier. Among the relatives, multivariate analysis showed that those eating their main meal outside their own home >15 days during the previous month were less likely to be faecal carriers (OR = 0.2; 95% CI: 0.06-0.6; P = 0.007). The faecal isolates of patients with UTI were CTX-M-producers in 66.6% and SHV-producers in 33.3% of the cases, while the percentages for other population groups were 40% to 55.5% and 50% to 75%, respectively. Of the 19 families with >1 carrier member, 8 families had 2 members who shared clonally related isolates, 8 families had 2 members carrying different clones producing the same enzymes and there were 3 families where all members had different enzyme-producing clones. CONCLUSIONS Our results suggest that both acquisition from a common source and person-to-person transmission might contribute to ESBL dissemination.

Clinical and Molecular Epidemiology of Extended-Spectrum β -Lactamase—Producing Escherichia coli as a Cause of Nosocomial Infection or Colonization: Implications for Control

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.

Biofilm formation in Acinetobacter baumannii : associated features and clinical implications

Biofilm formation in 92 unrelated strains of Acinetobacter baumannii isolated in a multicentre cohort study was investigated using a microtitre plate assay. Fifty-six (63%) isolates formed biofilm. These isolates were less frequently resistant to imipenem or ciprofloxacin than were non-biofilm-forming isolates (25% vs. 47%, p 0.04; and 66% vs. 94%, p 0.004, respectively). All catheter-related urinary or bloodstream infections and the sole case of shunt-related meningitis were caused by biofilm-forming strains. Multivariate analysis revealed that treatment in an intensive care unit, ciprofloxacin resistance and isolation from a respiratory sample were associated with non-biofilm-forming isolates, while previous aminoglycoside use was associated with biofilm-forming isolates.