José Miguel Cisneros

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.

Tuberculosis after Solid-Organ Transplant: Incidence, Risk Factors, and Clinical Characteristics in the RESITRA (Spanish Network of Infection in Transplantation) Cohort

BACKGROUND It is necessary to clarify the incidence of and risk factors for tuberculosis (TB) among solid-organ transplant (SOT) recipients as well as changes in the chronology, clinical presentation, and prognosis of the disease. METHODS A total of 4388 SOT recipients were monitored prospectively at 16 transplant centers included in the Spanish Network for Research in Infectious Diseases (REIPI). TB episodes were studied, and the incidence rate was calculated. Certain variables were analyzed, by Cox regression analysis, as potential risk factors for TB. RESULTS Among the 4388 SOT recipients, 21 cases of TB were reported (0.48%). The median duration of follow-up was 360 days (range, 0-720 days). The global incidence of TB was 512 cases per 10(5) patients per year (95% confidence interval [CI], 317-783), which was higher than that in the general population in Spain (18.9 cases per 10(5) inhabitants per year; relative risk [RR], 26.6). The highest incidence (2072 cases per 10(5) patients per year; 95% CI, 565-5306) was observed among lung transplant recipients (RR, 73.3). Of the TB cases, 95% occurred within the first year after transplant, and 76% were pulmonary forms. Crude mortality was 19.0%, and attributable mortality was 9.5%. Multivariate analysis identified recipient age (RR, 1.05; 95% CI, 1.0-1.1) and receipt of a lung transplant (RR, 5.6; 95%, 1.9-16.9) as independent risk factors. CONCLUSIONS TB incidence is increased among SOT recipients. The risk factors identified were age and receipt of a lung transplant. TB-attributable mortality (9.5%) is still high.

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.

CLINICAL FEATURES AND EPIDEMIOLOGY OF ACINETOBACTER BAUMANNII COLONIZATION AND INFECTION IN SPANISH HOSPITALS

OBJECTIVE To investigate the clinical features and the epidemiology of Acinetobacter baumannii in Spanish hospitals. DESIGN Prospective multicenter cohort study. SETTING Twenty-seven general hospitals and one paraplegic center in Spain. METHODS All cases of A. baumannii colonization or infection detected by clinical samples during November 2000 were included. Isolates were identified using phenotypic and genotypic methods. The molecular relatedness of the isolates was assessed by pulsed-field gel electrophoresis. RESULTS Twenty-five (89%) of the hospitals had 221 cases (pooled rate in general hospitals, 0.39 case per 1,000 patient-days; range, 0 to 1.17). The rate was highest in intensive care units (ICUs). Only 3 cases were pediatric. The mean age of the patients in the general hospitals was 63 years; 69% had a chronic underlying disease and 80% had previously received antimicrobial treatment. Fifty-three percent of the patients had an infection (respiratory tract, 51%; surgical site, 16%; and urinary tract, 11%). Crude mortality was higher in infected than in colonized patients (27% vs 10%; relative risk, 1.56; 95% confidence interval, 1.2 to 2.0; P = .003). Molecular analysis disclosed 79 different clones. In most hospitals, a predominant epidemic clone coexisted with other sporadic clones. Imipenem resistance was present in 39% of the hospitals. CONCLUSIONS A. baumannii was present in most participating Spanish hospitals (particularly in ICUs) with different rates among them. The organisms mainly affected predisposed patients; half of them were only colonized. Epidemic and sporadic clones coexisted in many centers.

Risk Factors and Prognosis of Nosocomial Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase-Producing Escherichia coli

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.

Pneumonia after lung transplantation in the RESITRA Cohort: a multicenter prospective study.

The aim of the present study is to evaluate the epidemiology, etiology and prognosis of pneumonia in lung transplant (LT) recipients. This is a prospective, multicenter study of a consecutive cohort of LT recipients in Spain. From September 2003 to November 2005, 85 episodes of pneumonia in 236 LT recipients were included (incidence 72 episodes per 100 LT/year). Bacterial pneumonia (82.7%) was more frequent than fungal (14%) and viral pneumonia (10.4%). The most frequent microorganisms in each etiological group were Pseudomonas aeruginosa (n = 14, 24.6%), CMV (n = 6, 10.4%) and Aspergillus spp. (n = 5, 8.8%). Incidence of Aspergillus spp. and CMV pneumonia is lower than previously reported, probably due to the spread of universal prophylaxis. Pneumonia caused by viruses appeared significantly later than pneumonia due to gram‐negative bacilli, fungi and those without known etiology (p < 0.01, p = 0.03 and p = 0.02, respectively). The routine use of ganciclovir has changed the natural history of CMV infection, so that pneumonia appears later, once prophylaxis is suspended. The probability of survival during the first year of follow‐up was significantly higher in the multivariate analysis in LT recipients who did not have a pneumonia episode compared with those that had at least one episode (p < 0.01).

Progress on the development of rapid methods for antimicrobial susceptibility testing

Antimicrobial susceptibility testing is essential for guiding the treatment of many types of bacterial infections, especially in the current context of rising rates of antibiotic resistance. The most commonly employed methods rely on the detection of phenotypic resistance by measuring bacterial growth in the presence of the antibiotic being tested. Although these methods are highly sensitive for the detection of resistance, they require that the bacterial pathogen is isolated from the clinical sample before testing and must employ incubation times that are sufficient for differentiating resistant from susceptible isolates. Knowledge regarding the molecular determinants of antibiotic resistance has facilitated the development of novel approaches for the rapid detection of resistance in bacterial pathogens. PCR-based techniques, mass spectrometry, microarrays, microfluidics, cell lysis-based approaches and whole-genome sequencing have all demonstrated the ability to detect resistance in various bacterial species. However, it remains to be determined whether these methods can achieve sufficient sensitivity and specificity compared with standard phenotypic resistance testing to justify their use in routine clinical practice. In the present review, we discuss recent progress in the development of methods for rapid antimicrobial susceptibility testing and highlight the limitations of each approach that still remain be addressed.

Prophylaxis With Caspofungin for Invasive Fungal Infections in High-Risk Liver Transplant Recipients

Objective. The aim of this prospective, multicenter, noncomparative, open-label trial was to evaluate the prophylactic use of caspofungin in adult liver transplant recipients at high risk of developing invasive fungal infections (IFI). Methods. Patients received caspofungin for at least 21 days. A successful treatment outcome was defined as the absence of breakthrough IFI during the first 100 days after the onset of caspofungin. Results. According to study design, 71 patients were included. In the modified intention-to-treat analysis, successful treatment outcome was obtained in 88.7%. Two patients developed IFI: a Mucor and a Candida albicans surgical wound infections, respectively. Six more patients discontinued caspofungin because of drug-related altered liver function. No clinical side effects were related to caspofungin. Altered analytical data compatible with grade IV toxicity, irrespective of caspofungin attribution, were observed in 27.7% of patients at the end of caspofungin prophylaxis and in 15.4% of patients in safety visit (14 days after ending caspofungin administration) (P=0.13). Eight patients died, six during caspofungin administration and two during follow-up period, but none were attributed to IFI or caspofungin toxicity. Conclusion. These results show that caspofungin could be considered an efficacious and well-tolerated drug as antifungal prophylaxis in high-risk liver transplant recipients.

GESITRA-SEIMC/REIPI recommendations for the management of cytomegalovirus infection in solid-organ transplant patients

Cytomegalovirus infection remains a major complication of solid organ transplantation. In 2005 the Spanish Transplantation Infection Study Group (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) developed consensus guidelines for the prevention and treatment of CMV infection in solid organ transplant recipients. Since then, numerous publications have clarified or questioned the aspects covered in the previous document. These aspects include the situations and populations who must receive prophylaxis and its duration, the selection of the best diagnosis and monitoring technique and the best therapeutic strategy. For these reasons, we have developed new consensus guidelines to include the latest recommendations on post-transplant CMV management based on new evidence available.

Risk Factors for Fluconazole-Resistant Candidemia

ABSTRACT Previous studies have sought to determine the risk factors associated with candidemia caused by non-albicans Candida spp. or with potentially fluconazole-resistant Candida spp. (C. glabrata and C. krusei). Non-albicans Candida strains are a heterogeneous group that includes species with different levels of virulence, and only a limited number of C. glabrata isolates are resistant to fluconazole. We set out to identify the risk factors associated with microbiologically proven fluconazole-resistant candidemia. A prospective study including adult patients with candidemia was performed. Data were collected on patient demographics; underlying diseases; exposure to corticosteroids, antibiotics, or fluconazole; and invasive procedures. Risk factors associated either with non-albicans Candida spp. or potentially fluconazole-resistant Candida spp. (C. glabrata or C. krusei) or with Candida spp. with microbiologically confirmed fluconazole resistance were assessed using logistic regressions. We included 226 candidemia episodes. Non-albicans Candida isolates accounted for 53.1% of the fungal isolates, but only 18.2% of the cases were caused by potentially fluconazole-resistant organisms. Thirty isolates exhibited microbiologically confirmed fluconazole resistance. The multivariate analysis revealed that independent predictors associated with fluconazole-resistant Candida spp. were neutropenia (odds ratio [OR] = 4.94; 95% confidence interval [CI] = 1.50 to 16.20; P = 0.008), chronic renal disease (OR = 4.82; 95% CI = 1.47 to 15.88; P = 0.01), and previous fluconazole exposure (OR = 5.09; 95% CI = 1.66 to 15.6; P = 0.004). Independently significant variables associated with non-albicans Candida bloodstream infection or with potentially fluconazole-resistant Candida spp. did not include previous fluconazole exposure. We concluded that prior fluconazole treatment is an independent risk factor only for candidemia caused by microbiologically confirmed fluconazole resistant species. Our findings may be of value for selecting empirical antifungal therapy.