Vicente Pintado

Visceral leishmaniasis in human immunodeficiency virus (HIV)-infected and non-HIV-infected patients. A comparative study.

Visceral leishmaniasis is an endemic infection in Mediterranean countries, where it has become a frequent complication of acquired immunodeficiency syndrome (AIDS). The incidence of visceral leishmaniasis is increasing in Spain due to human immunodeficiency virus (HIV)-related cases, but some aspects of its epidemiology, clinical features, and management remain unknown. In addition, no comparative clinical studies about the disease in HIV-infected and non-HIV-infected patients have been reported. During a 24-year period, 120 cases of visceral leishmaniasis were diagnosed at our institution and 80 (66%) were associated with HIV infection. The mean age at diagnosis was higher in HIV-infected that in non-HIV-infected patients (33.2 versus 23.2 yr; p = 0.002), but the male/female ratio was similar in both groups. The main risk factor for HIV infection was intravenous drug abuse (78.7%). The clinical presentation of leishmaniasis was similar in both groups, but HIV-infected patients had a lower frequency of splenomegaly than HIV-negative individuals (80.8% versus 97.4%; p = 0.02). HIV-infected patients had a greater frequency and degree of leukopenia, lymphocytopenia, and thrombocytopenia. Most of them were profoundly immunosuppressed (mean CD4+ lymphocyte count, 90 cells/mm3) at the time of diagnosis of leishmaniasis, and 53.7% had AIDS. The sensitivity of serologic studies for Leishmania was significantly lower in HIV-infected than in non-HIV-infected patients (50% versus 80%; p < 0.001), but the diagnostic yield of bone marrow aspirate (67.1% versus 79.4%) and bone marrow culture (62.9% versus 66.6%) was similar in both groups. After initial treatment, the response rate was significantly lower in HIV-infected than in non-HIV-infected individuals (54.8% versus 89.7%; p = 0.001). The relapse rate was 46.2% and 7.5%, respectively (p < 0.001). Secondary prophylaxis with antimonial compounds or amphotericin B seems to be useful in preventing relapses in HIV-infected patients. The mortality rate was higher (53.7% versus 7.5%; p < 0.001) and the median survival time shorter (25 versus > 160 mo; p < 0.001) in AIDS patients than in HIV-negative individuals. Although leishmaniasis could contribute to death in a significant number of HIV-infected patients, it was the main cause of death in only a few of them. The CD4+ lymphocyte count and the use of highly active antiretroviral therapy and secondary prophylaxis for leishmaniasis were the most significant prognostic factors for survival in AIDS patients. Visceral leishmaniasis behaves as an opportunistic infection in HIV-infected individuals and should be considered as an AIDS-defining disease.

High Rate of Intestinal Colonization with Extended-Spectrum-β-Lactamase-Producing Organisms in Household Contacts of Infected Community Patients

ABSTRACT Fecal carriage of extended-spectrum-β-lactamase (ESBL)-producing organisms was detected in 70% of index cases of patients (n = 40) with community-acquired infections due to ESBL producers and reached 16.7% in household contacts (n = 54). A total of 66% of ESBL-producing organisms from index cases were indistinguishable from isolates from household contacts by pulsed-field gel electrophoresis. Patients with community infections and members of their households represent a reservoir for ESBL producers, increasing dispersal of resistance in healthy people.

Complex Clonal and Plasmid Epidemiology in the First Outbreak of Enterobacteriaceae Infection Involving VIM-1 Metallo-β-Lactamase in Spain: Toward Endemicity?

BACKGROUND We report the emergence and spread of metallo-beta-lactamases (MBLs) among enterobacterial isolates at Ramón y Cajal University Hospital (Madrid, Spain). METHODS AND RESULTS During the period from March 2005 through September 2006, 25 patients (52% of whom were in the intensive care unit) were infected and/or colonized with single or different MBL-producing Enterobacteriaceae isolates (Klebsiella pneumoniae, 14 patients; Enterobacter cloacae, 12 patients; Escherichia coli, 1 patient; and/or Klebsiella oxytoca, 1 patient). Clonal analysis (XbaI pulsed-field gel electrophoresis) revealed that all K. pneumoniae isolates belonged to the same clone, but 6 patterns were found among the E. cloacae isolates. Carbapenems were affected to different degrees (minimum inhibitory concentration, < or = 1 to > 8 microg/mL), as were aminoglycosides and ciprofloxacin. The bla(VIM-1) MBL gene was present in all isolates; in addition, the bla(SHV-12) extended-spectrum beta-lactamase gene was detected in K. pneumoniae and E. coli isolates. The bla(VIM-1) gene was detected within a 4.0-kb class 1 integron (bla(VIM-1)-aacA4-dfrII-aadA1-catB2) in K. pneumoniae and E. coli and in a 2.5-kb class 1 integron (bla(VIM-1)-aacA4-aadA1) in E. cloacae and K. oxytoca isolates. The bla(VIM-1) gene was transferable (filter-mating) in 14 of 14 K. pneumoniae isolates, 4 of 11 E. cloacae isolates, and 1 of 1 E. coli isolate. A 60-kb plasmid belonging to the IncI1 group was detected in the epidemic VIM-1-K. pneumoniae clone. Plasmids of 300- or 435-kb belonging to IncH12 group were found among E. cloacae isolates. CONCLUSIONS K. pneumoniae-MBL monoclonal epidemics coexisted with E. cloacae-MBL multiclonal epidemics in our hospital. The spread of the bla(VIM-1) gene among Enterobacteriaceae was driven by clonal spread associated with intergeneric plasmid transfer with different class I integron platforms. Such complex epidemiology might anticipate endemicity and should be considered for the design of containment epidemiology strategies.

Intravenous colistin sulphomethate sodium for therapy of infections due to multidrug-resistant gram-negative bacteria

OBJECTIVE To assess the efficacy and toxicity of intravenous colistin in the treatment of infections due to multidrug-resistant gram-negative bacteria. METHODS Retrospective cohort study. RESULTS Sixty patients received colistin sulphomethate sodium (mean dose, 4.4mg/kg/day; median duration, 20days). The main infections were pneumonia or tracheobronchitis (63.3%), intra-abdominal (10%), urinary tract (8.3%), and surgical site infection (6.6%), primary bacteremia (5%), catheter infection (3.3%), meningitis (1.6%), and soft-tissue infection (1.6%). The responsible bacteria were Acinetobacter spp. (50%), P. aeruginosa (23.3%), K. pneumoniae (13.3%), Enterobacter spp. (10%), E. coli (1.6%), and S. maltophilia (1.6%). Eight patients (13%) received colistin monotherapy, and 52 (87%) received combination therapy with other antibiotics such as beta-lactams (15 cases), aminoglycosides (14), beta-lactams and aminoglycosides (15), or ciprofloxacin (8). A favourable response was observed in 43 cases (71.7%). Overall mortality was 26.7%. Despite the common use of combination therapy with aminoglycosides (48%), nephrotoxicity during colistin therapy was observed in only 10.9% of patients; most of them had previous renal failure. CONCLUSION Colistin appears to be an effective and safe drug for therapy of severe infections due to multidrug-resistant gram-negative bacteria. Despite the concomitant use of aminoglycosides in a high proportion of patients, renal toxicity was an uncommon adverse event.

Candidal Meningitis in HIV-Infected Patients: Analysis of 14 Cases

Five cases of candidal meningitis in human immunodeficiency virus (HIV)-infected patients have been diagnosed in our hospital. This article describes these cases and reviews another nine previously reported in the literature. Most patients (71%) had at least one well-known predisposing factor for candidiasis. Median CD4 cell count was 135/mm3. Headache and fever, in the absence of focal neurologic signs, were the predominant clinical features. The CSF analysis revealed mild pleocytosis and hypoglycorrachia, indistinguishable from those seen in tuberculous or cryptococcal meningitis. Twelve patients (92%) received amphotericin B for a median of 51 days, in combination with flucytosine in five cases. The overall mortality among treated patients was 31%. Although the risk of relapse of candidal meningitis is unknown, maintenance antifungal therapy was given to seven patients (63%), usually with fluconazole. Candida species must be kept in mind as a cause of chronic meningitis in HIV-infected patients who have a known predisposing factor.

Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study

BACKGROUND The best available treatment against carbapenemase-producing Enterobacteriaceae (CPE) is unknown. The objective of this study was to investigate the effect of appropriate therapy and of appropriate combination therapy on mortality of patients with bloodstream infections (BSIs) due to CPE. METHODS In this retrospective cohort study, we included patients with clinically significant monomicrobial BSIs due to CPE from the INCREMENT cohort, recruited from 26 tertiary hospitals in ten countries. Exclusion criteria were missing key data, death sooner than 24 h after the index date, therapy with an active antibiotic for at least 2 days when blood cultures were taken, and subsequent episodes in the same patient. We compared 30 day all-cause mortality between patients receiving appropriate (including an active drug against the blood isolate and started in the first 5 days after infection) or inappropriate therapy, and for patients receiving appropriate therapy, between those receiving active monotherapy (only one active drug) or combination therapy (more than one). We used a propensity score for receiving combination therapy and a validated mortality score (INCREMENT-CPE mortality score) to control for confounders in Cox regression analyses. We stratified analyses of combination therapy according to INCREMENT-CPE mortality score (0-7 [low mortality score] vs 8-15 [high mortality score]). INCREMENT is registered with ClinicalTrials.gov, number NCT01764490. FINDINGS Between Jan 1, 2004, and Dec 31, 2013, 480 patients with BSIs due to CPE were enrolled in the INCREMENT cohort, of whom we included 437 (91%) in this study. 343 (78%) patients received appropriate therapy compared with 94 (22%) who received inappropriate therapy. The most frequent organism was Klebsiella pneumoniae (375 [86%] of 437; 291 [85%] of 343 patients receiving appropriate therapy vs 84 [89%] of 94 receiving inappropriate therapy) and the most frequent carbapenemase was K pneumoniae carbapenemase (329 [75%]; 253 [74%] vs 76 [81%]). Appropriate therapy was associated with lower mortality than was inappropriate therapy (132 [38·5%] of 343 patients died vs 57 [60·6%] of 94; absolute difference 22·1% [95% CI 11·0-33·3]; adjusted hazard ratio [HR] 0·45 [95% CI 0·33-0·62]; p<0·0001). Among those receiving appropriate therapy, 135 (39%) received combination therapy and 208 (61%) received monotherapy. Overall mortality was not different between those receiving combination therapy or monotherapy (47 [35%] of 135 vs 85 [41%] of 208; adjusted HR 1·63 [95% CI 0·67-3·91]; p=0·28). However, combination therapy was associated with lower mortality than was monotherapy in the high-mortality-score stratum (30 [48%] of 63 vs 64 [62%] of 103; adjusted HR 0·56 [0·34-0·91]; p=0·02), but not in the low-mortality-score stratum (17 [24%] of 72 vs 21 [20%] of 105; adjusted odds ratio 1·21 [0·56-2·56]; p=0·62). INTERPRETATION Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to CPE. Combination therapy was associated with improved survival only in patients with a high mortality score. Patients with BSIs due to CPE should receive active therapy as soon as they are diagnosed, and monotherapy should be considered for those in the low-mortality-score stratum. FUNDING Spanish Network for Research in Infectious Diseases, European Development Regional Fund, Instituto de Salud Carlos III, and Innovative Medicines Initiative.

A Multinational, Preregistered Cohort Study of β-Lactam/β-Lactamase Inhibitor Combinations for Treatment of Bloodstream Infections Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae

ABSTRACT The spread of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether β-lactam/β-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.)

Clinical study of 44 cases of Staphylococcus aureus meningitis

Abstract.In order to describe the clinical features and outcome of Staphylococcus aureus meningitis, the charts of 44 cases seen at one teaching hospital during a 20-year period were retrospectively reviewed. Staphylococcus aureus was the fifth most common cause of bacterial meningitis (10.2% of cases). There were 28 (63%) cases of postoperative meningitis and 16 (37%) of spontaneous meningitis. Patients with postoperative meningitis were younger than patients with spontaneous meningitis (mean age, 40.3 vs. 59.3 years; P=0.04) and had a lower frequency of community-acquired infection (32.1% vs. 93.8%; P<0.01), severe underlying diseases (28% vs. 87%; P<0.01) and associated staphylococcal infection (35% vs. 75%; P=0.01). The clinical presentation was similar in both groups, but patients with postoperative meningitis had a lower frequency of altered mental status (39% vs. 75%; P=0.02), meningeal signs (28% vs. 62%; P=0.02), petechial rash (0% vs. 18%; P=0.04), bacteremia (7% vs. 75%; P<0.01), and septic shock (0% vs. 44%; P<0.01). Most patients were treated with cloxacillin or vancomycin, with or without rifampicin, for a mean period of 22.5 days (range, 1–100 days). Overall mortality was 27%, and the mortality rate was higher for cases of spontaneous than postoperative meningitis (50% vs. 14%; P=0.01). Mortality correlated significantly with advanced age, spontaneous meningitis, altered mental status, and the presence of severe underlying diseases, bacteremia, and septic shock.

Healthcare-associated, community-acquired and hospital-acquired bacteraemic urinary tract infections in hospitalized patients: a prospective multicentre cohort study in the era of antimicrobial resistance

The clinical and microbiological characteristics of community-onset healthcare-associated (HCA) bacteraemia of urinary source are not well defined. We conducted a prospective cohort study at eight tertiary-care hospitals in Spain, from October 2010 to June 2011. All consecutive adult patients hospitalized with bacteraemic urinary tract infection (BUTI) were included. HCA-BUTI episodes were compared with community-acquired (CA) and hospital-acquired (HA) BUTI. A logistic regression analysis was performed to identify 30-day mortality risk factors. We included 667 episodes of BUTI (246 HCA, 279 CA and 142 HA). Differences between HCA-BUTI and CA-BUTI were female gender (40% vs 69%, p <0.001), McCabe score II-III (48% vs 14%, p <0.001), Pitt score ≥2 (40% vs 31%, p 0.03), isolation of extended spectrum β-lactamase-producing Enterobacteriaciae (13% vs 5%, p <0.001), median hospital stay (9 vs 7 days, p 0.03), inappropriate empirical antimicrobial therapy (21% vs 13%, p 0.02) and mortality (11.4% vs 3.9%, p 0.001). Pseudomonas aeruginosa was more frequently isolated in HA-BUTI (16%) than in HCA-BUTI (4%, p <0.001). Independent factors for mortality were age (OR 1.04; 95% CI 1.01-1.07), McCabe score II-III (OR 3.2; 95% CI 1.8-5.5), Pitt score ≥2 (OR 3.2 (1.8-5.5) and HA-BUTI OR 3.4 (1.2-9.0)). Patients with HCA-BUTI are a specific group with significant clinical and microbiological differences from patients with CA-BUTI, and some similarities with patients with HA-BUTI. Mortality was associated with patient condition, the severity of infection and hospital acquisition.

Enterococcal meningitis: A clinical study of 39 cases and review of the literature

To describe the clinical features and outcome of enterococcal meningitis, we retrospectively reviewed the charts of 39 cases seen at 2 tertiary hospitals during a 25 years and collected 101 additional, previously reported cases for review. Among these 140 cases, there were 82 cases (59%) of postoperative meningitis and 58 cases (41%) of spontaneous meningitis. Eighty-six patients (61%) were adults and 54 (39%) were children. Patients with spontaneous meningitis had a higher frequency of community-acquired infection (50% versus 18%; p < 0.01), severe underlying diseases (67% versus 22%; p < 0.01), and associated enterococcal infection (29% versus 8%; p < 0.01) than patients with postoperative meningitis. The clinical presentation was similar in both groups, but patients with spontaneous infection had a higher frequency of bacteremia (58% versus 12%; p < 0.01), and a lower frequency of mixed infection (9% versus 29%; p < 0.01). Spontaneous meningitis in children was associated with a significantly lower frequency of fever, altered mental status, headache, and meningeal signs (p < 0.01), probably explained by the high proportion of neonates in this age-group. Most infections were caused by Enterococcus faecalis, which accounted for 76% of the isolates identified at the species level. Fifteen of the 25 cases due to Enterococcus faecium were produced by vancomycin-resistant strains. Most patients were treated with ampicillin, penicillin, or vancomycin, with or without aminoglycosides, for a median period of 18 days (range, 1–85 d). Overall mortality was 21%. The mortality rate was higher in spontaneous than in postoperative meningitis (33% versus 12%; p < 0.01), but was similar in patients treated with beta-lactams (18%), glycopeptides (14%), or other antibiotics (25%), as well as in patients treated with monotherapy (16%) or combination therapy (22%). An adverse outcome correlated significantly with advanced age, the presence of severe underlying diseases, associated enterococcal infection, bacteremia, septic shock, and the absence of fever at presentation. Shunt removal was associated with a lower mortality. Multivariate analysis showed that the presence of severe underlying diseases was the only prognostic factor associated with mortality (odds ratio = 6.8, 95% confidence intervals = 2.7–17.5, p < 0.01).