Mario Fernández-Ruiz

Seasonal and Pandemic A (H1N1) 2009 influenza vaccination coverage and attitudes among health-care workers in a Spanish University Hospital

Abstract Influenza vaccination coverage among health-care workers (HCWs) remains the lowest compared with other priority groups for immunization. Little is known about the acceptability and compliance with the pandemic (H1N1) 2009 influenza vaccine among HCWs during the current campaign. Between 23 December 2009 and 13 January 2010, once the workplace vaccination program was over, we conducted a cross-sectional, questionnaire-based survey at the University Hospital 12 de Octubre (Madrid, Spain). Five hundred twenty-seven HCWs were asked about their influenza immunization history during the 2009–2010 season, as well as the reasons for accepting or declining either the seasonal or pandemic vaccines. Multiple logistic-regression analysis was preformed to identify variables associated with immunization acceptance. A total of 262 HCWs (49.7%) reported having received the seasonal vaccine, while only 87 (16.5%) affirmed having received the pandemic influenza (H1N1) 2009 vaccine. “Self-protection” and “protection of the patient” were the most frequently adduced reasons for acceptance of the pandemic vaccination, whereas the existence of “doubts about vaccine efficacy” and “fear of adverse reactions” were the main arguments for refusal. Simultaneous receipt of the seasonal vaccine (odds ratio [OR]: 0.27; 95% confidence interval [95% CI]: 0.14–0.52) and being a staff (OR: 0.08; 95% CI: 0.04–0.19) or a resident physician (OR: 0.16; 95% CI: 0.05–0.50) emerged as independent predictors for pandemic vaccine acceptance, whereas self-reported membership of a priority group was associated with refusal (OR: 5.98; 95% CI: 1.35–26.5). The pandemic (H1N1) 2009 influenza vaccination coverage among the HCWs in our institution was very low (16.5%), suggesting the role of specific attitudinal barriers and misconceptions about immunization in a global pandemic scenario.

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.

Initial Use of Echinocandins Does Not Negatively Influence Outcome in Candida parapsilosis Bloodstream Infection: A Propensity Score Analysis

BACKGROUND Concerns have arisen regarding the optimal antifungal regimen for Candida parapsilosis bloodstream infection (BSI) in view of its reduced susceptibility to echinocandins. METHODS The Prospective Population Study on Candidemia in Spain (CANDIPOP) is a prospective multicenter, population-based surveillance program on Candida BSI conducted through a 12-month period in 29 Spanish hospitals. Clinical isolates were identified by DNA sequencing, and antifungal susceptibility testing was performed by the European Committee on Antimicrobial Susceptibility Testing methodology. Predictors for clinical failure (all-cause mortality between days 3 to 30, or persistent candidemia for ≥72 hours after initiation of therapy) in episodes of C. parapsilosis species complex BSI were assessed by logistic regression analysis. We further analyzed the impact of echinocandin-based regimen as the initial antifungal therapy (within the first 72 hours) by using a propensity score approach. RESULTS Among 752 episodes of Candida BSI identified, 200 (26.6%) were due to C. parapsilosis species complex. We finally analyzed 194 episodes occurring in 190 patients. Clinical failure occurred in 58 of 177 (32.8%) of evaluable episodes. Orotracheal intubation (adjusted odds ratio [AOR], 2.81; P = .018) and septic shock (AOR, 2.91; P = .081) emerged as risk factors for clinical failure, whereas early central venous catheter removal was protective (AOR, 0.43; P = .040). Neither univariate nor multivariate analysis revealed that the initial use of an echinocandin-based regimen had any impact on the risk of clinical failure. Incorporation of the propensity score into the model did not change this finding. CONCLUSIONS The initial use of an echinocandin-based regimen does not seem to negatively influence outcome in C. parapsilosis BSI.

Bacillus Calmette-Guérin (BCG) Infection Following Intravesical BCG Administration as Adjunctive Therapy For Bladder Cancer: Incidence, Risk Factors, and Outcome in a Single-Institution Series and Review of the Literature

AbstractBacillus Calmette-Guérin (BCG) is the most effective intravesical immunotherapy for superficial bladder cancer. Although generally well tolerated, BCG-related infectious complications may occur following instillation. Much of the current knowledge about this complication comes from single case reports, with heterogeneous diagnostic and therapeutic approaches and no investigation on risk factors for its occurrence. We retrospectively analyzed 256 patients treated with intravesical BCG in our institution during a 6-year period, with a minimum follow-up of 6 months after the last instillation. We also conducted a comprehensive review and pooled analysis of additional cases reported in the literature since 1975. Eleven patients (4.3%) developed systemic BCG infection in our institution, with miliary tuberculosis as the most common form (6 cases). A 3-drug antituberculosis regimen was initiated in all but 1 patient, with a favorable outcome in 9/10 cases. There were no significant differences in the mean number of transurethral resections prior to the first instillation, the time interval between both procedures, the overall mean number of instillations, or the presence of underlying immunosuppression between patients with or without BCG infection. We included 282 patients in the pooled analysis (271 from the literature and 11 from our institution). Disseminated (34.4%), genitourinary (23.4%), and osteomuscular (19.9%) infections were the most common presentations of disease. Specimens for microbiologic diagnosis were obtained in 87.2% of cases, and the diagnostic performances for acid-fast staining, conventional culture, and polymerase chain reaction (PCR)-based assays were 25.3%, 40.9%, and 41.8%, respectively. Most patients (82.5%) received antituberculosis therapy for a median of 6.0 (interquartile range: 4.0–9.0) months. Patients with disseminated infection more commonly received antituberculosis therapy and adjuvant corticosteroids, whereas those with reactive arthritis were frequently treated only with nonsteroidal antiinflammatory drugs (p < 0.001 for all comparisons). Attributable mortality was higher for patients aged ≥65 years (7.4% vs 2.1%; p  = 0.091) and those with disseminated infection (9.9% vs 3.0%; p = 0.040) and vascular involvement (16.7% vs 4.6%; p = 0.064). The scheduled BCG regimen was resumed in only 2 of 36 patients with available data (5.6%), with an uneventful outcome. In the absence of an apparent predictor of the development of disseminated BCG infection after intravesical therapy, and considering the protean variety of clinical manifestations, it is essential to keep a high index of suspicion to initiate adequate therapy promptly and to evaluate carefully the risk-benefit balance of resuming intravesical BCG immunotherapy.

Aspergillus tracheobronchitis: report of 8 cases and review of the literature.

AbstractAspergillus tracheobronchitis (AT) is an infrequent but severe form of invasive pulmonary aspergillosis in which the fungal infection is entirely or predominantly confined to the tracheobronchial tree. We reviewed 8 cases of AT diagnosed in our tertiary care center during an 18-year period, as well as 148 cases previously reported in the English literature from 1985 to July 2011. The demographic, clinical, imaging, bronchoscopic, and outcome characteristics of every eligible patient were excerpted, and predictors of inhospital mortality were identified by logistic regression. Solid organ transplantation (SOT) (44.2%), hematologic malignancy (21.2%), neutropenia (18.7%), and chronic obstructive pulmonary disease (15.4%) were the most common underlying conditions reported. Most cases occurred in patients receiving long-term corticosteroid treatment (71.8%) or chemotherapy (25.0%). Fever and respiratory complaints (cough, dyspnea, stridor, or wheezing) were the most frequent symptoms; one-third of patients developed acute respiratory distress at presentation, and 15.1% were asymptomatic at the time of diagnosis. Initial imaging studies were not informative in 47.4% of the cases. Aspergillus fumigatus was the predominant species (74.4%). The pseudomembranous form was the most commonly observed (31.9% of cases) and was more frequent in neutropenic patients (p = 0.007), whereas ulcerative AT (31.2%) was associated with SOT (p = 0.001). The most frequent antifungal monotherapy regimens were amphotericin B deoxycholate (23.1%) and itraconazole (18.6%), whereas combined therapy was administered in 35.9% of the cases. Overall inhospital mortality was 39.1%, with neutropenia (odds ratio [OR], 20.47; p < 0.001) and acute respiratory distress at presentation (OR, 9.54; p = 0.002) as independent prognostic factors. Our pooled analysis of the literature shows that AT remains a rare opportunistic infection with a nonspecific presentation and a variable course depending on the nature of the predisposing factor.

Monitoring of immunoglobulin levels identifies kidney transplant recipients at high risk of infection.

We aimed to analyze the incidence, risk factors and impact of hypogammaglobulinemia (HGG) in 226 kidney transplant (KT) recipients in which serum immunoglobulin (Ig) levels were prospectively assessed at baseline, month 1 (T1), and month 6 (T6). The prevalence of IgG HGG increased from 6.6% (baseline) to 52.0% (T1) and subsequently decreased to 31.4% (T6) (p < 0.001). The presence of IgG HGG at baseline (odds ratio [OR] 26.9; p = 0.012) and a positive anti‐HCV status (OR 0.17; p = 0.023) emerged as risk factors for the occurrence of posttransplant IgG HGG. Patients with HGG of any class at T1 had higher incidences of overall (p = 0.018) and bacterial infection (p = 0.004), bacteremia (p = 0.054) and acute pyelonephritis (p = 0.003) in the intermediate period (months 1–6). Patients with HGG at T6 had higher incidences of overall (p = 0.004) and bacterial infection (p < 0.001) in the late period (>6 month). A complementary log–log model identified posttransplant HGG as an independent risk factor for overall (hazard ratio [HR] 2.03; p < 0.001) and bacterial infection (HR 2.68; p < 0.0001). Monitoring of humoral immunity identifies KT recipients at high risk of infection, offering the opportunity for preemptive immunoglobulin replacement therapy.

Impact of hepatitis C virus infection on the risk of infectious complications after kidney transplantation: data from the RESITRA/REIPI cohort.

Background. There is scarce information regarding the role of hepatitis C virus (HCV) infection in the development of infectious complications after kidney transplantation (KT). Methods. We prospectively analyzed all KT recipients included in the Spanish Network for the Research of Infection in Transplantation cohort from September 2003 to February 2005 with a posttransplant follow-up of 3 years and compared the incidence of both overall and specific infections according to the pretransplant anti-HCV antibody status. Results. Of 1302 analyzed recipients, 105 (8.1%) were anti-HCV positive. These patients presented a higher rate of previous transplant (P<0.001), had a lower donor age (P=0.055), higher transfusion requirements (P=0.037), and more frequently received induction therapy with antithymocyte antibodies (P=0.005). We found no differences between anti-HCV-positive and -negative recipients in the overall incidence rate of infection (0.82 vs. 0.74 episodes per 1000 transplant-days, respectively). Nevertheless, anti-HCV-positive recipients had a higher cumulative incidence of bloodstream (P=0.01) and upper urinary tract infections (P=0.037). Anti-HCV status emerged by logistic regression as an independent risk factor only for bloodstream infection (odds ratio, 3.14; 95% confidence interval, 1.19–8.24; P=0.020). Anti-HCV-positive recipients also experimented a higher rate of recurrent acute rejection (P=0.045) and retransplantation (P=0.017), with no differences in overall mortality. Conclusions. According to the results of the Spanish Network for the Research of Infection in Transplantation cohort, the incidence of some potentially severe posttransplant infections may be increased in anti-HCV-positive KT recipients.

Splenic abscess: A review of 22 cases in a single institution

PURPOSE To describe the demographics, clinical features, etiology, imaging findings, bacteriologic profile, treatment and outcome in patients presenting splenic abscess in a European tertiary hospital. METHODS Review of the medical charts of patients in whom splenic abscess was diagnosed at a tertiary hospital in Madrid (Spain) within a nine-year period. RESULTS Twenty-two cases (13 males, 9 females) were found. Mycobacterium tuberculosis was the most frequent causative microorganism, accounting for 8 cases, and immunosuppression the main predisposing factor (in 63.6% of the patients). Symptoms were quite unspecific, leading to a long, median time until diagnosis (17 days). The overall mortality rate was 18.2% and it was 25% in patients with tuberculosis and 14.28% in patients with other causes of splenic abscesses (p=0.6). CONCLUSIONS Immunosuppressed states are the predisposing condition for splenic abscess in almost two thirds of the patients. We found a higher percentage of M. tuberculosis than that previously reported in the English literature.

Streptococcus bovis bacteraemia revisited: Clinical and microbiological correlates in a contemporary series of 59 patients

OBJECTIVE To characterise the clinical features, associations and outcome in a contemporary series of patients with Streptococcus bovis bacteraemia (SBB). METHODS Retrospective analysis of all episodes of SBB at the University Hospital 12 de Octubre (Madrid, Spain) between January 1997 and November 2008 was performed. Patient data were reviewed, focusing on clinical and microbiological associations with the different biotypes of S. bovis. RESULTS Fifty-nine episodes of SBB were documented in 59 adult patients (30 males; mean age: 70.9 ± 15.0 years). Chronic liver disease was identified in 20 patients (33.9%). Sixteen patients (27.1%) presented infective endocarditis (IE) and 14 (23.7%) had a biliary source of bacteraemia. Thirty-three patients (55.9%) underwent colonic evaluation, adenomatous polyps being the most common finding (21 patients). Malignancy was diagnosed following SBB in 9 cases, including 6 patients with colorectal carcinoma (18.2% of those who underwent colonic evaluation). Of 22 isolates biotyped, 12 were S. bovis biotype I and 10 were S. bovis biotype II. IE was more frequent among patients with S. bovis biotype I (P =0.010), whereas bacteraemia due to biotype II species was more likely to be of biliary origin (P=0.078). CONCLUSIONS S. bovis biotyping identifies some clinically relevant associations.

Nocardia Infection in Solid Organ Transplant Recipients: A Multicenter European Case-control Study

BACKGROUND Nocardiosis is a rare, life-threatening opportunistic infection, affecting 0.04% to 3.5% of patients after solid organ transplant (SOT). The aim of this study was to identify risk factors for Nocardia infection after SOT and to describe the presentation of nocardiosis in these patients. METHODS We performed a retrospective case-control study of adult patients diagnosed with nocardiosis after SOT between 2000 and 2014 in 36 European (France, Belgium, Switzerland, the Netherlands, Spain) centers. Two control subjects per case were matched by institution, transplant date, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors for nocardiosis. RESULTS One hundred and seventeen cases of nocardiosis and 234 control patients were included. Nocardiosis occurred at a median of 17.5 (range, 2-244) months after transplant. In multivariable analysis, high calcineurin inhibitor trough levels in the month before diagnosis (odds ratio [OR], 6.11; 95% confidence interval [CI], 2.58-14.51), use of tacrolimus (OR, 2.65; 95% CI, 1.17-6.00) and corticosteroid dose (OR, 1.12; 95% CI, 1.03-1.22) at the time of diagnosis, patient age (OR, 1.04; 95% CI, 1.02-1.07), and length of stay in the intensive care unit after SOT (OR, 1.04; 95% CI, 1.00-1.09) were independently associated with development of nocardiosis; low-dose cotrimoxazole prophylaxis was not found to prevent nocardiosis. Nocardia farcinica was more frequently associated with brain, skin, and subcutaneous tissue infections than were other Nocardia species. Among the 30 cases with central nervous system nocardiosis, 13 (43.3%) had no neurological symptoms. CONCLUSIONS We identified 5 risk factors for nocardiosis after SOT. Low-dose cotrimoxazole was not found to prevent Nocardia infection. These findings may help improve management of transplant recipients.