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Background Immune-based therapies are standard-of-care treatment for coronavirus disease 2019 (COVID-19) patients requiring hospitalization. However, safety concerns related to the potential risk of secondary infections may limit their use. Methods We searched OVID Medline, Ovid EMBASE, SCOPUS, Cochrane Library, clinicaltrials.gov, and PROSPERO in October 2020 and updated the search in November 2021. We included randomized controlled trials (RCTs). Pairs of reviewers screened abstracts and full studies and extracted data in an independent manner. We used RevMan to conduct a meta-analysis using random-effects models to calculate the pooled risk ratio (RR) and 95% CI for the incidence of infection. Statistical heterogeneity was determined using the I2 statistic. We assessed risk of bias for all studies and rated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation methodology. We conducted a meta-regression using the R package to meta-explore whether age, sex, and invasive mechanical ventilation modified risk of infection with immune-based therapies. The protocol is registered with PROSPERO (CRD42021229406). Results This was a meta-analysis of 37 RCTs including 32 621 participants (mean age, 60 years; 64% male). The use of immune-based therapy for COVID-19 conferred mild protection for the occurrence of secondary infections (711/15 721, 4.5%, vs 616/16 900, 3.6%; RR, 0.82; 95% CI, 0.71–0.95; P = .008; I2 = 28%). A subgroup analysis did not identify any subgroup effect by type of immune-based therapies (P = .85). A meta-regression revealed no impact of age, sex, or mechanical ventilation on the effect of immune-based therapies on risk of infection. Conclusions We identified moderate-certainty evidence that the use of immune-based therapies in COVID-19 requiring hospitalization does not increase the risk of secondary infections.

Objectives Ceftolozane/tazobactam is a cephalosporin/β-lactamase inhibitor combination with activity against Gram-negative bacilli. We report the use of ceftolozane/tazobactam in Canada using a national registry. Methods The CLEAR registry uses REDCapTM (Research Electronic Data Capture) (online survey, https://is.gd/CLEAR_ceftolozanetazobactam) to capture details associated with clinical use of ceftolozane/tazobactam. Results Data from 51 patients treated in 2020 with ceftolozane/tazobactam are available. Infections treated included hospital-acquired bacterial pneumonia (37.3% of patients), ventilator-associated bacterial pneumonia (15.7%), bone/joint infection (11.8%), complicated intra-abdominal infection (7.8%) and complicated skin and skin structure infection (7.8%). 17.6% of patients had bacteremia and 47.1% were in intensive care. Ceftolozane/tazobactam was primarily used as directed therapy for Pseudomonas aeruginosa infections (92.2% of patients). Ceftolozane/tazobactam was used because of resistance to (86.3%), failure of (11.7%), or adverse effects from (2.0%) previously prescribed antimicrobials. Ceftolozane/tazobactam susceptibility testing was performed on isolates from 88.2% of patients. Ceftolozane/tazobactam was used in combination with another antimicrobial active versus Gram-negative bacilli in 39.2% of patients (aminoglycosides [15.7%], fluoroquinolones [7.8%] and colistin/polymyxin B [7.8%]). The dosage regimen was customized in all patients based on their creatinine clearance. Treatment duration was primarily >10 days (60.8% of patients) with microbiological success in 60.5% and clinical success in 64.4% of patients. 7.8% of patients had adverse effects not requiring drug discontinuation. Conclusions In Canada, ceftolozane/tazobactam is used as directed therapy to treat a variety of severe infections caused MDR P. aeruginosa. It is commonly used in combination with other antimicrobials with relatively high microbiological/clinical cure rates, and an excellent safety profile.

Background Cytomegalovirus (CMV) is the most common opportunistic pathogen, following solid organ transplantation (SOT), that leads to direct and indirect effects. The aim of this study was to assess the impact of CMV exposure at transplantation on the rate of posttransplant thrombotic events (TEs). Methods We conducted a retrospective cohort study of patients transplanted at the University of Alberta Hospital between July 2005 and January 2018. We included adult SOT CMV-seronegative recipients at transplantation who received an allograft from either a seropositive donor (D+/R-) or a seronegative donor (D-/R-). Results A total of 392 SOT recipients were included: 151 (39%) liver, 188 (48%) kidney, 45 (11%) pancreas, and 8 (2%) other transplants. The mean age was 47 years, 297 (76%) were males, and 181 (46%) had a CMV D+/R- donor. Patients in the CMV D+/R- cohort were slightly older (51 years versus 48 years in the D-/R- cohort; P = .036), while other variables, including cardiovascular risk factors and pretransplant TEs, were not different between groups. Overall, TEs occurred in 35 (19%) patients in the CMV D+/R- group, versus 21 (10%) in the CMV D-/R- group, at 5 years of follow-up (P = .008); the incidence rates per 100 transplant months were 5.12 and 1.02 in the CMV D+/R- and CMV D-/R- groups, respectively (P = .003). After adjusting for potential confounders with a Cox regression model, a CMV D+/R- transplantation was independently associated with an increased risk of a TE over 5 years (adjusted hazard ratio, 3.027; 95% confidence interval, 1.669–5.488). Conclusions A CMV D+/R- transplantation is associated with an increased risk of a TE posttransplantation.

We report the effect of prospective audit and feedback (PAF) on inpatient fluoroquinolone (FQN) prescriptions. During the PAF period, FQN use decreased from 39.19 to 29.58 days of therapy per 1,000 patient days (P < .001) and appropriateness improved from 68% to 88% (P < .001). High-yield indications to target included noninfectious urinary tract and respiratory presentations.

Direct-acting antivirals have proved to be highly efficacious and safe in monoinfected liver transplant (LT) recipients who experience recurrence of hepatitis C virus (HCV) infection. However, there is a lack of data on effectiveness and tolerability of these regimens in HCV/HIV-coinfected patients who experience recurrence of HCV infection after LT. In this prospective, multicenter cohort study, the outcomes of 47 HCV/HIV-coinfected LT patients who received DAA therapy (with or without ribavirin [RBV]) were compared with those of a matched cohort of 148 HCV-monoinfected LT recipients who received similar treatment. Baseline characteristics were similar in both groups. HCV/HIV-coinfected patients had a median (IQR) CD4 T-cell count of 366 (256-467) cells/mu L. HIV-RNA was

Background HHV-8/Kaposi Sarcoma herpesvirus has been associated with a broad spectrum of diseases in solid organ transplant (SOT) recipients. Primary donor-derived infection can be associated with severe and rapidly fatal non-neoplastic disease, and diagnosis is made with high HHV-8 DNAemia. Methods We carried out an international survey to investigate the current approach to HHV-8 screening, and management in SOT since a protocol has not been established by international guidelines. Results A total of 51 transplant centers from 15 countries filled out the survey. HHV-8-associated diseases in SOT have been diagnosed during the previous 5 years in 67% of centers. Pretransplant serological screening is performed in 17 centers (33%), and posttransplant HHV-8 nucleic acid testing (NAT) monitoring is performed in 21 centers (41%). Performing HHV-8 NAT monitoring and serological screening were found associated with having diagnosed in the previous 5 years a non-malignant HHV-8-associated disease. Conclusions Serological pretransplant screening of donors and recipients and post-transplant HHV-8 NAT monitoring recommendations should be standardized. Even though serological assays are not optimal, they could contribute to increasing knowledge on epidemiology and management of HHV-8-associated diseases after SOT.

Purpose Respiratory viral infection (RVI) in lung transplant recipients (LTR) have variably been associated with poor outcomes. Our center uses systemic corticosteroids (orally or intravenous) in some RVI cases to treat inflammation based on clinical judgment, but evidence for this is limited. Methods We reviewed all adult LTR diagnosed with RVI (via nasopharyngeal swab or bronchoscopy) between 2017 and 2019. The primary outcome was recovery of lung function (forced expiratory volume in 1 second [FEV1]) at next stable visit between 1- and 12-months post-infection, expressed as a ratio between stable, representative FEV1 at follow up divided by stable FEV1 prior to infection (FEV1 recovery ratio). We modelled the association between steroid use and FEV1 recovery ratio using linear regression, adjusting for age, sex, transplant type, FEV1 presentation ratio (FEV1 at time of viral infection divided by stable FEV1 prior), hospitalization, coexistent bacterial or fungal infection, time post-transplant and CLAD status at infection. Results 158 patients were diagnosed with RVI, 62 (39%) of whom received corticosteroids. 9 patients (6%) died prior to any follow-up lung function, including two deaths attributed to infection and two to bronchiolitis obliterans. Baseline characteristics were similar between steroid treated and untreated, but steroid-treated patients had a lower FEV1 presentation ratio (0.90 vs. 1.00, p=0.0094) and were more likely to have CLAD at infection (26% vs. 10%, p=0.0268). Mean FEV1 recovery ratio was 1.00 (SD 0.20) with no relationship to specific virus type. Steroid treatment was not associated with FEV1 recovery ratio either unadjusted (p=0.3709) or adjusted (p=0.4498). Conclusion Treatment with systemic corticosteroids was not associated with improved FEV1 recovery in our cohort even after adjustment for presentation severity and other factors. This suggests systemic steroids have limited utility in the management of RVI in this population.

FOSIMI Investigators., This work was supported by the Ministerio de Sanidad y Consumo of Spain (Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Madrid, Spain, Grant #EC0800190). JMP received a “Rio Hortega” Research Grant (CM14/00135; 2015-16) from Instituto de Salud Carlos III and the Ministerio de Economia and Competitividad, Madrid (Spain) and the ESCMID/FEMS Research Fellowship 2016. JMM received a personal 80:20 research grant from the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–19.

Background: Daptomycin is an optimal choice for outpatient parenteral antibiotic therapy (OPAT) because of its safety, once-daily administration and its activity against Gram-positive bacteria. Although daptomycin is increasingly being used in OPAT, limited information about its safety in this scenario is available. Methods: We performed a prospective multicentre pilot study to evaluate the safety of daptomycin in outpatients with proved or suspected Gram-positive infections (DAPTODOM). The primary objective was to evaluate the safety and the secondary objective to evaluate the efficacy in OPAT. We also looked at the development of daptomycin resistance in those cases with microbiological failure. Results: We included 54 patients from 12 Spanish hospitals, 67% male with a mean age of 67.1 years. Most patients (87%) had chronic underlying diseases. The main reason for inclusion was skin and soft-tissue infections in 52%, followed by bacteremia or endocarditis in 34%. Staphylococcus aureus accounted for 44% of the isolates (24% were methicillin-resistant), coagulase-negative staphylococci 15% and enterococci 7%. Two patients (4%) had to be readmitted because of complications; only one patient had an adverse effect related to daptomycin (increase in serum creatine kinase levels), which disappeared after discontinuation (2%). At the end of follow-up, 96% of patients had good outcome and only 4% of patients did not have a clinical or microbiological cure. The use of a 2-minute bolus in 18 cases was not associated with adverse effects. Conclusions: Daptomycin was safe and efficacious in outpatients with Gram-positive bacterial infections and can be administered in 2-minute bolus infusion.

Background Valganciclovir (VGCV) prophylaxis in solid-organ transplant patients (SOT) is limited by myelotoxicity. We aimed to analyze the impact of VGCV prophylaxis on myelotoxicity and risk factors for its occurrence. Methods Retrospective single-center cohort study of adult CMV-seronegative recipients transplanted between July 2005 and November 2017. CMV D+/R− recipients received 3 to 6 months of VGCV prophylaxis whereas CMV D-/R- received no VGCV. Definitions: leukopenia < 3.5 × 109/L, significant neutropenia < 1.0 × 109/L and significant thrombocytopenia < 50 × 109/L. Results A total of 363 SOT recipients were included, 169 (47%) CMV D+/R− and 194 (53%) CMV D−/R−, with a mean age of 49.5 years and 275 (76%) males; types of organ transplant: 133 (37%) liver, 181 (50%) kidney, 37 (10%) simultaneous kidney-pancreas and 12 (3%) other. Although there was no difference in the incidence of significant neutropenia or thrombocytopenia per transplant type, leukopenia in the first year was more common in liver transplant patients (P < 0.001). New onset leukopenia post-SOT, significant neutropenia (Figure 1) and significant thrombocytopenia in the first year were more common in patients receiving VGCV: 116 D+/R− (69%) vs. 52 D−/R− (31%), P < 0.001; 86 (91%) vs. 9 (9%), P < 0.001; 8 (80%) vs. 2 (20%), P = 0.050; respectively. G-CSF was used more frequently in patients receiving prophylaxis (60% CMV D+/R− vs. 10% CMV D−/R−, P < 0.001). Significant neutropenia had no impact on long-term mortality adjusted by age and transplant type (HR 1.1, 95% CI 0.6–2.1, P = 0.709). Significant neutropenia led to decrease immunosuppression in 90% of patients (vs. 46%, P < 0.001) and was associated with increased risk of rejection (HR 8.5, P < 0.001). In multivariate analysis for significant neutropenia in the first year, VGCV prophylaxis was the only predictor of this outcome after adjusting for confounders (HR 15.1, 95% CI 7.5–30.1, P < 0.001). Conclusion VGCV prophylaxis increased the risk of significant neutropenia by 15-fold post-SOT. No other clinical variables were useful to predict this complication. Therefore, complete blood count monitoring is still needed for all SOT recipients receiving VGCV prophylaxis. Disclosures All authors: No reported disclosures.

BACKGROUND Scedosporium species and Lomentospora prolificans (S/L) are the second most common causes of invasive mold infections following Aspergillus in lung transplant recipients. METHODS We assessed the current practices on management of S/L colonization/infection of the lower respiratory tract before and after lung transplantation in a large number of lung transplant centers through an international practice survey from October 2016 to March 2017. RESULTS A total of 51 respondents from 45 lung transplant centers (17 countries, 4 continents) answered the survey (response rate 58%). S/L colonization was estimated to be detected in candidates by 48% of centers. Only 18% of the centers used a specific medium to detect S/L colonization. Scedosporium spp. colonization was a contraindication to transplantation in 10% of centers whereas L prolificans was a contraindication in 31%; 22% of centers declared having had 1-5 recipients infected with S/L in the past 5 years. CONCLUSIONS This survey gives an overview of the current practices regarding S/L colonization and infection in lung transplant centers worldwide and underscores the need of S/L culture procedure standardization before implementing prospective studies.

Background and aims Cirrhosis is associated with dysbiosis, but its functional consequences are still largely unknown. Short-chain fatty acids (SCFAs) account for physiological interactions between the gut microbiota and host. Our aim was to assess the impact of cirrhotic dysbiosis on the production of SCFAs. Methods Seventeen patients with cirrhosis and 17 controls were selected. Microbiota composition in faecal samples was assessed by next-generation 16S rRNA gene sequencing. SCFAs were measured with GC-MS in faecal samples and after in vitro batch fermentations using arabinoxylan, resistant starch, pectin, and lactulose as substrates. Results Among the 17 cirrhotic patients (mean age 58, eight males), six, nine and two were, respectively, Child-Pugh class A, B and C. Eleven patients were on oral antibiotics, 11 on lactulose and 13 on proton pump inhibitors. Cirrhotic patients showed marked differences in the composition and diversity of gut microbiome when compared to controls, that were more pronounced with increased severity. Stool samples from cirrhotic patients showed lower SCFAs content and reduced capacity to produce SCFAs in batch fermentations, with butyrate production being the most abnormal. These functional aberrancies were more pronounced with greater liver disease severity. Abundance of Ruminococcus faecis (in family Ruminococcaceae), Faecalicatena fissicatena and Fusicatenibacter saccharivorans (in family Lachnospiraceae) was positively correlated with the SCFAs production. Conclusion Cirrhotic dysbiosis is associated with a decreased capacity to ferment non-digestible carbohydrates into SCFAs, especially into butyrate. These functional abnormalities are more pronounced as disease progresses. These results might inform the design of gut-targeted therapies for cirrhosis.

Urinary tract infections are common after transplantation and the most frequent infectious complication of kidney transplant recipients. The prevalence of UTI post renal transplantation ranges from 23-85%, but this is less know for other solid organ transplants. Risk factors for UTI are similar to those described in the general population, and usually involves invasive procedures after surgery. The requirement of ureteric stents and post-transplant urinary obstruction are specific risk factors for kidney transplant patients that partially explains the high incidence of UTI in this setting. UTI are classified into lower (cystitis) and upper (pyelonephritis) tract infections according to clinical symptoms. Lower UTI are usually treated with oral antibiotics and usually has minor or absent impact in the allograft. Upper UTI require intravenous antibiotics and hospital admission in most cases and in kidney transplant patients can deteriorate the function of the allograft and patient’s survival. In kidney transplant patients, asymptomatic bacteriuria should only be treated during the first 1-2 months post-transplantation. After this period of time, monitoring urine cultures is controversial and has not shown significant benefits. Some kidney transplant patients develop recurrent UTI which usually worsen the quality of life. To decide antibiotic prophylaxis for recurrent UTI we should take into account the clinical impact of previous UTI, the kidney allograft function, antibiotic sensitivities of previous isolated uropathogens and colonization with multi-drug resistant bacteria.

Background Universal antiviral prophylaxis is the preferred preventive strategy for lung transplant recipients (LTRs) at risk of CMV infection. We compared the risk of CMV infection between CMV D+/R + and D-/R + LTRs after 3 months of prophylaxis. Methods This was a retrospective review of CMV R + LTRs transplanted between 2005 and 2013. Patients dying before completing 3 months, or receiving >180 days of prophylaxis were excluded. The primary outcome was proportion of LTRs who developed CMV infection and clinically significant CMV infection defined as CMV infection leading to preemptive therapy or CMV disease. Results We analyzed 90 D+/R + and 72 D-/R + with a median follow up of 730 days. CMV infection and disease was more common in D+/R + compared to D-/R+ (CMV infection 66% vs 40%; P = 0.001; CMV disease 13% vs 4% P = 0.045). Fifty-nine patients developed at least one episode of clinically significant CMV infection (41/90 [46%] D+/R + and 18/72 [25%] D-/R + P=0.007) with recurrence occurring in 29 LTRs (49% of patients with previous CMV infection), of which 22 (76%) were CMV D+/R+. Thirty percent had side effects related to CMV therapy. Conclusion Three months prophylaxis in D+/R + LTRs was associated with high rates of clinically significant CMV infection and recurrences.

To evaluate the course of left-sided infective endocarditis (LsIE) in patients with liver cirrhosis (LC) analyzing its influence on mortality and the impact of surgery.Prospective cohort study, conducted from 1984 to 2013 in 26 Spanish hospitals.A total of 3.136 patients with LsIE were enrolled and 308 had LC: 151 Child-Pugh A, 103 B, 34 C and 20 were excluded because of unknown stage. Mortality was significantly higher in the patients with LsIE and LC (42.5% vs. 28.4%; p0.01) and this condition was in general an independent worse factor for outcome (HR 1.51, 95% CI: 1.23-1.85; p0.001). However, patients in stage A had similar mortality to patients without cirrhosis (31.8% vs. 28.4% p = NS) and in this stage heart surgery had a protective effect (28% in operated patients vs. 60% in non-operated when it was indicated). Mortality was significantly higher in stages B (52.4%) and C (52.9%) and the prognosis was better for patients in stage B who underwent surgery immediately (mortality 50%) compared to those where surgery was delayed (58%) or not performed (74%). Only one patient in stage C underwent surgery.Patients with liver cirrhosis and infective endocarditis have a poorer prognosis only in stages B and C. Early surgery must be performed in stages A and although in selected patients in stage B when indicated.

Background International guidelines recommend 4 weeks of treatment with ampicillin plus gentamicin (A+G) for uncomplicated native valve Enterococcus faecalis infective endocarditis (EFIE) and 6 weeks in the remaining cases. Ampicillin plus ceftriaxone (A+C) is always recommended for at least 6w, with no available studies assessing its suitability for 4w. We aimed to investigate differences in the outcome of EFIE according to the duration (4 versus 6 weeks) of antibiotic treatment (A+G or A+C). Methods Retrospective analysis from a prospectively collected cohort of 78 EFIE patients treated with either A+G or A+C. Results 32 cases (41%) were treated with A+G (9 for 4w, 28%) and 46 (59%) with A+C (14 for 4w, 30%). No significant differences were found in 1-year mortality according to the type of treatment (31% and 24% in A+G and A+C, respectively; P = 0.646) or duration (26% and 27% at 4 and 6w, respectively; P = 0.863). Relapses were more frequent among survivors treated for 4w than in those treated for 6w (3/18 [17%] at 4w and 1/41 [2%] at 6w; P = 0.045). Three out of 4 (75%) relapses occurred in cirrhotic patients. Conclusions A 4-week course of antibiotic treatment might not be suitable neither for A+G nor A+C for treating uncomplicated native valve EFIE.

β-Lactam/β-lactamase inhibitors (BLBLIs) were compared to carbapenems in two cohorts of hematological neutropenic patients with extended-spectrum-β-lactamase (ESBL) bloodstream infection (BSI): the empirical therapy cohort (174 patients) and the definitive therapy cohort (251 patients). The 30-day case fatality rates and other secondary outcomes were similar in the two therapy groups of the two cohorts and also in the propensity-matched cohorts. BLBLIs might be carbapenem-sparing alternatives for the treatment of BSI due to ESBLs in these patients., We thank the ESGBIS and the ESGICH study groups for supporting the study. This study was supported by Ministerio de Economía y Competitividad, Instituto de Salud Carlos III—cofinanced by European Development Regional Fund “A way to achieve Europe” EDRF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015).

Enterococci are the third most common etiologic agent of infective endocarditis worldwide after staphylococci and streptococci and cause 10% to 15% of cases.1 Enterococcal infections are increasingly relevant, especially among the elderly and patients with comorbid conditions in the healthcare setting.2,3 Approximately 90% of cases of enterococcal endocarditis are caused by Enterococcus faecalis , with 3-month history of symptoms before diagnosis.4 The gentamicin dose schedule (3 mg/kg per 24 hours IV …

Clostridium difficile-associated disease (CDAD) is the most common cause of nosocomial diarrhea. Information about CDAD in solid organ transplant (SOT) recipients is scarce. To determine its epidemiology and risk factors, we conducted a cohort study in which 4472 SOT patients were prospectively included in the RESITRA/REIPI (Spanish Research Network for the Study of Infection in Transplantation) database between July 2003 and July 2006. Forty-two episodes of CDAD were diagnosed in 36 patients. The overall incidence was 0.94%. Median onset of infection was 31.5 days (range 6–741); in half the cases, onset occurred during the first month after transplantation. In 26% of cases, there was no previous antibiotic use. Independent risk factors for CDAD using Cox regression analysis were previous use of first- and second-generation cephalosporins (HR 3.68; 95%CI 1.8–7.52; P

Mammalian target of rapamycin inhibitors (mTORi) prevents cytomegalovirus (CMV) infection in kidney transplant (KT) patients. From May 2010 to December 2013, all KT recipients were retrospectively analysed. Maintenance immunosuppression regimen was divided into mTORi or calcineurin inhibitors (CNI)-based regimen. Since June 2011, CMV-seropositive recipients (R+) treated with high-intensity immunosuppression and mTORi did not receive anti-CMV prophylaxis. We analysed 350 consecutive patients, of which 95 (27%) received mTORi and 255 (73%) CNI-based immunosuppression. A Cox-regression multivariate analysis showed that the use of mTORi-based immunosuppression during all follow-up reduced the risk of CMV infection (HR 0.36, 95% CI 0.15-0.89, P = 0.028) and confirmed in a propensity score-matched cohort (HR 0.4, 95% CI 0.1-0.9, P = 0.047). Early discontinuation of mTORi increased the risk of CMV infection (HR 3.2; 95% CI 1.7-6.0) in univariate analysis. The incidence of CMV infection was not higher among CMV R+ patients on mTORi and requiring high-intensity immunosuppression when CMV prophylaxis was not given. The use of mTORi protected for CMV infection in KT patients, allowing to avoid antiviral prophylaxis for R+ patients receiving high-intensity immunosuppression. The increased risk of CMV infection after early discontinuation of mTORi warrants further research.

Background Host factors and complications have been associated with higher mortality in infective endocarditis ( IE ). We sought to develop and validate a model of clinical characteristics to predict 6‐month mortality in IE . Methods and Results Using a large multinational prospective registry of definite IE (International Collaboration on Endocarditis [ ICE ]–Prospective Cohort Study [ PCS ], 2000–2006, n=4049), a model to predict 6‐month survival was developed by Cox proportional hazards modeling with inverse probability weighting for surgery treatment and was internally validated by the bootstrapping method. This model was externally validated in an independent prospective registry ( ICE ‐ PLUS , 2008–2012, n=1197). The 6‐month mortality was 971 of 4049 (24.0%) in the ICE ‐ PCS cohort and 342 of 1197 (28.6%) in the ICE ‐ PLUS cohort. Surgery during the index hospitalization was performed in 48.1% and 54.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE , causative organism, left‐sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6‐month mortality, and surgery was associated with a lower risk of mortality (Harrell's C statistic 0.715). In the validation model, these variables had similar hazard ratios (Harrell's C statistic 0.682), with a similar, independent benefit of surgery (hazard ratio 0.74, 95% CI 0.62–0.89). A simplified risk model was developed by weight adjustment of these variables. Conclusions Six‐month mortality after IE is ≈25% and is predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality but is performed less frequently in the highest risk patients. A simplified risk model may be used to identify specific risk subgroups in IE .

Information regarding liver retransplantation in HIV-infected patients is scant. Data from 14 HIV-infected patients retransplanted between 2002 and 2011 in Spain (6% retransplantation rate) were analyzed and compared with those from 157 matched HIV-negative retransplanted patients. In HIV-infected patients, early (≤30 days) retransplantation was more frequently indicated (57% vs. 29%; p = 0.057), and retransplantation for HCV recurrence was less frequently indicated (7% vs. 37%; p = 0.036). Survival probability after retransplantation in HIV-positive patients was lower than in HIV-negative patients, 42% versus 64% at 3 years, although not significantly (p = 0.160). Among HIV-infected patients, those with undetectable HCV RNA at retransplantation and those with late (>30 days) retransplantation showed better 3-year survival probability (80% and 67%, respectively), similar to that in their respective HIV-negative counterparts (72% and 70%). In HIV-infected and HIV-negative patients, 3-year survival probability in those with positive HCV RNA at retransplantation was 22% versus 65% (p = 0.008); in those with early retransplantation, 3-year survival probability was 25% versus 56% (p = 0.282). HIV infection was controlled with antiretroviral therapy after retransplantation. In conclusion, HIV-infected patients taken as a whole have unsatisfactory survival after liver retransplantation, although patients with undetectable HCV RNA at retransplantation or undergoing late retransplantation show a more favorable outcome.

Candida peritonitis is a potentially life-threatening infection after abdominal transplantation, although there is scant information regarding its incidence and outcome. We analysed the incidence rate and outcome of Candida peritonitis in 717 liver or pancreas transplant recipients. Five cases of Candida peritonitis were diagnosed, representing the second most frequent cause of invasive fungal infection in the cohort. The incidence rate of Candida peritonitis during the first 30 days after transplantation was 6.5 cases/10 000 transplant days in pancreas recipients and 1.2 cases/10 000 transplant days in liver recipients (P = 0.035). Four of the five patients received an echinocandin in combination with other antifungal. All patients were alive and with good graft function at 1-year follow-up. In our series, Candida peritonitis in liver and pancreas transplant recipients was not uncommon and had a good prognosis.

Antiretroviral therapy has been immensely successful in reducing the incidence of opportunistic infections and death after HIV infection. This has resulted in heightened interest in noninfectious comorbidities including kidney disease. Although HIV-associated nephropathy, the most ominous kidney disease related to the direct effects of HIV, may be prevented and treated with antiretrovirals, kidney disease remains an important issue in this population. In addition to the common risk factors for kidney disease of diabetes mellitus and hypertension, HIV-infected individuals have a high prevalence of other risk factors, including hepatitis C and exposure to antiretrovirals and other medications. Therefore, the differential diagnosis is vast. Early identification (through efficient screening) and prompt treatment of kidney disease in HIV-infected individuals are critical to lead to better outcomes. This review focuses on clinical and epidemiological issues, treatment strategies (including dialysis and kidney transplantation), and recent advances among kidney disease in the HIV population.

Daptomycin is a cyclic lipopeptide with a rapid bactericidal effect against Gram-positive bacteria. The pharmacokinetic properties of this drug allow once-daily intravenous infusion as the best posology (including a 2-minute bolus). Because of its ease of administration and excellent safety profile, daptomycin is a first-line agent for use as outpatient antimicrobial parenteral therapy (OPAT). The best evidence supporting this indication exists for the treatment of complicated and uncomplicated skin and soft tissue infections, as well as osteoarticular infections caused by Gram-positive bacteria. For the remaining indications, the use of daptomycin as OPAT should be analyzed in each patient. Information from the EUCORE Registry in Spain indicates that daptomycin has high rates of treatment success in both hospitalized patient and in those included in OPAT programs.

Solid organ transplant recipients (SOTR) are at risk of serious influenza-related complications. The impact of respiratory co-infection in SOTR with 2009 pandemic influenza A(H1N1) is unknown. A multicentre prospective study of consecutive cases of pandemic influenza A(H1N1) in SOTR was carried out to assess the clinical characteristics and outcome and the risk factors for co-infection. Overall, 51 patients were included. Median time from transplant was 3.7years, 5.9% of the cases occurred perioperatively and 7.8% were hospital-acquired. Pneumonia was diagnosed in 15 (29.4%) patients. Ten cases were severe (19.6%): 13.7% were admitted to intensive care units, 5.9% suffered septic shock, 5.9% developed acute graft rejection and 7.8% died. Co-infection was detected in 15 patients (29.4%): eight viral, six bacterial and one fungal. Viral co-infection did not affect the outcome. Patients with non-viral co-infection had a worse outcome: longer hospital stay (26.2±20.7 vs. 5.5±10.2) and higher rate of severe diseases (85.7% vs. 2.3%) and mortality (42.8% vs. 2.3%). Independent risk factors for non-viral co-infection were: diabetes mellitus and septic shock. Other factors associated with severe influenza were: delayed antiviral therapy, diabetes mellitus, time since transplantation

This study was partially financed by the CIBER de Enfermedades Respiratorias (CIBERES) from the ISCIII (CB06/06/0058) and by Fundación BBVA-FundacioóCarolina (research fellowship of Maricela Valerio)., Muñoz, P; Kestler, M; De Alarcon, A; Miro, JM; Bermejo, J; Rodriguez-Abella, H; Farinas, MC; Belaustegui, MC; Mestres, C; Llinares, P; Goenaga, M; Navas, E; Oteo, JA; Tarabini, P; Bouza, E.

Information about infections unrelated to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV)-infected liver recipients is scarce. The aims of this study were to describe the prevalence, clinical characteristics, time of onset, and outcomes of bacterial, viral, and fungal infections in HIV/hepatitis C virus (HCV)-coinfected orthotopic liver transplant recipients and to identify risk factors for developing severe infections. We studied 84 consecutive HIV/HCV-coinfected patients who underwent liver transplantation at 17 sites in Spain between 2002 and 2006 and were followed until December 2009. The median age was 42 years, and 76% were men. The median follow-up was 2.6 years (interquartile range = 1.25-3.53 years), and 54 recipients (64%) developed at least 1 infection. Thirty-eight (45%) patients had bacterial infections, 21 (25%) had cytomegalovirus (CMV) infections (2 had CMV disease), 13 (15%) had herpes simplex virus infections, and 16 (19%) had fungal infections (7 cases were invasive). Nine patients (11%) developed 10 opportunistic infections with a 44% mortality rate. Forty-three of 119 infectious episodes (36%) occurred in the first month after transplantation, and 53 (45%) occurred after the sixth month. Thirty-six patients (43%) had severe infections. Overall, 36 patients (43%) died, and the deaths were related to severe infections in 7 cases (19%). Severe infections increased the mortality rate almost 3-fold [hazard ratio (HR) = 2.9, 95% confidence interval (CI) = 1.5-5.8]. Independent factors for severe infections included a pretransplant Model for End-Stage Liver Disease (MELD) score >15 (HR = 3.5, 95% CI = 1.70-7.1), a history of AIDS-defining events before transplantation (HR = 4.0, 95% CI = 1.9-8.6), and non-tacrolimus-based immunosuppression (HR = 2.5, 95% CI = 1.3-4.8). In conclusion, the rates of severe and opportunistic infections are high in HIV/HCV-coinfected liver recipients and especially in those with a history of AIDS, a high MELD score, or non-tacrolimus-based immunosuppression.

Despite recent advances in prevention and treatment, cytomegalovirus (CMV) is still a major complication in transplant patients. This study sought to analyze the incidence of CMV disease and its impact on patient and graft survival.Between June 2003 and December 2009, we included all kidney, liver, heart, and double transplant patients who underwent solid organ transplantation. They had 1-year posttransplant follow-up.Among the 1427 patients who received kidney (n = 661), liver (n = 494), heart (n = 89), or double (n = 183) transplants, 103 (7.2%) displayed CMV disease. The incidence by type of transplant was: heart (n = 17, 19%), liver (n = 35, 7%), kidney (n = 41, 6.2%), or double transplant (n = 10, 5.5%; P.001). In 59% of cases, the infection developed during the first 3 months after transplantation. CMV infections ranged from viral syndrome (n = 47, 45%) to tissue-invasive disease (n = 56, 55%), including 38% with gastrointestinal involvement. Relapsing episodes occurred in 12 patients (11%). Discordant donor/recipient CMV serology was present in 151 patients (donor positive/receptor negative), including 34 (22.5%) who developed primary CMV disease (P.001). Coinfections mostly bacterial, were diagnosed in 38% of patients. An acute rejection episode was present in 31% of patients with CMV disease compared to 20% without this complication (P = .017). Crude mortality was significantly higher among patients with CMV disease (n = 18 patients [18%] vs 92 patients [7%]; P.001).Our data confirmed that CMV disease was associated with worse transplant outcomes, with higher incidences of acute rejection episodes and mortality.

The guidelines on the treatment of invasive fungal disease by Aspergillus spp. and other fungi issued by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) are presented. These recommendations are focused on four clinical categories: oncology-haematology patients, solid organ transplant recipients, patients admitted to intensive care units, and children. An extensive review is made of therapeutical advances and scientific evidence in these settings. These guidelines have been prepared according the SEIMC consensus rules by a working group composed of specialists in infectious diseases, clinical microbiology, critical care medicine, paediatrics and oncology-haematology. Specific recommendations on the prevention of fungal infections in these patients are included.

Background Information concerning the risk factors and outcome of late infection (LI) after solid organ transplantation (SOT) still remains scarce. Methods We prospectively analyzed all patients undergoing SOT from July 2003 to March 2008, who survived the ¢rst 6 months after surgery and with a minimum 1-year follow-up. Risk factors associated with the development of bacterial and cytomegalovirus (CMV) LI and survival were identi¢ed. Results Overall, 942 SOT recipients (491 kidney, 280 liver, 65 heart, and 106 double transplants) were included. During the study period 147 patients (15.6%) developed 276 episodes of LI (incidence rate, 0.43 per 1000 transplantation-days). Bacteria were the most prevalent etiology (88.0%). Primary sources of infection included urinary tract (36.9%), intra-abdominal (16.7%), and sepsis without source (13.4%). Independent risk factors for late bacterial infection were: age (hazard ratio (HR) (per year) 1.0; 95% con¢dence interval (CI): 1.0^1,0), female gender (HR 1.7; 95%CI: 1.1^2.6), anti-hepatitis C virus (HCV) positive serostatus (HR 1.8; 95%CI: 1.1^3.0), chronic allograft dysfunction (HR 3.2; 95%CI: 1.7^6.1), early CMV disease (HR 2.2; 95%CI 1.2^4.1), and early bacterial infection (HR 2.5; 95%CI 1.6^3.8). The occurrence of chronic allograft dysfunction was an independent risk factor for late CMVd isease (HR 6.5; 95%CI: 1.7^24.6), whereas immunosuppression based on mammalian target of rapamycin inhibitors protected against the development of late CMV disease (HR 0.3; 95%CI: 0.1^1.0). Cox model selected anti-HCV positive serostatus (adjusted HR (aHR) 2.67; 95%CI: 1.27^5.59), age (aHR (per year) 1.06; 95%CI: 1.02^1.10), and the occurrence of LI (aHR 9.12; 95%CI: 3.90^21.33) as independent factors for mortality. Conclusions LI did not constitute an uncommon complication in our cohort, and patients at risk may bene¢t from close clinical monitoring.

The rate of compliance with antifungal drug use guidelines by transplant physicians is mostly unknown. We performed a nationwide electronic survey to assess antifungal use by different types of transplant physicians. Sixty-one percent (53/87) of the transplant programs responded (accounting for 85% of heart transplant procedures, 65% of kidney transplantations, and 71.5% of liver transplantations). Antifungal prophylaxis was used in 41.5% programs (liver 93.3%, heart 30.8%, and kidney 16%). Prophylaxis was universal in 32% of the programs and targeted only to selected patients in 68%, mainly indicated after re-transplantation (73.3%), re-intervention (66.7%) and hemodialysis (60%). Main drugs for universal prophylaxis were fluconazole and itraconazole (42.9% each), while fluconazole (60%), L-amphotericin B (AMB), and caspofungin (13.4% each) were preferred for targeted prophylaxis. Overall, 84.9% of the programs used galactomannan for the diagnosis of invasive aspergillosis (only 34% in BAL) and 66.6% used voriconazole as first-line monotherapy. Combination first-line therapy for invasive aspergillosis was used by 31.3%, mainly with voriconazole with caspofungin (40%) or anidulafungin (26.7%) or L-AMB-caspofungin (26.7%). Adherence of transplant physicians to current recommendations on antifungal treatment and prophylaxis is poor. An international consensus that responds to differences in patients and centers and emphasizes patient safety is clearly needed.

Since the introduction of combined antiretroviral therapy (cART), solid organ transplantation (SOT) has become a therapeutic option for the HIV-positive population. In contrast with liver and kidney transplantation, only three simultaneous pancreas-kidney transplants (SPKT) have been reported among HIV-infected patients. Herein we have reported the first SPKT in an HIV-infected patient in Spain. The pancreas graft failed at 2 weeks and the patient died at 9 months because of a Pseudomonas aeruginosa infection. The three recipients reported in the literature lived, despite the failure of both the pancreas and kidney grafts in one subject. Despite the poor outcome of our case, HIV-1 infection was controlled after transplantation (stable CD4(+) cells and no AIDS-related events), and the kidney graft functioned with no episodes of rejection. The cART regimen used in the pretransplant period was switched at the time of transplantation to raltegravir and two nucleoside reverse transcriptase inhibitors (NRTI). Raltegravir has no interactions with immunosuppressive drugs. Target plasma levels of tacrolimus were achieved at a dose similar to that used in HIV-negative transplant recipients. The most adequate antiretroviral regimen for HIV-infected SOT recipients has not yet been established; however, one may consider switching protease inhibitors or non-NRTI-based regimens for a raltegravir-based regimen at the time of transplantation.

We aimed to determine the epidemiology, risk factors, and impact of bacterial infection on pancreatic function after pancreas transplantation. Data for pancreas transplant recipients were retrospectively reviewed between 2000 and 2014 for at least 1 year. We collected and analyzed post-transplant data for bacterial infection, morbidity, and mortality. During the study period, 312 pancreas transplants were performed. In total, 509 episodes of bacterial infection were diagnosed in 191 patients (61%). Multidrug-resistant (MDR) organisms were present in 173 of the 513 isolated microorganisms (33%). Risk factors independently associated with bacterial infection were acute allograft rejection (OR 1.7, 95%CI 1.1-3), the need for post-transplant hemodialysis, (OR 5.3, 95%CI 1.8-15.7) and surgical re-intervention (OR 2.8, 95%CI 1.5-5.1), which was also considered a risk factor for infections caused by MDR bacteria. Graft survival was associated with the occurrence of one or more episodes of bacterial infection (log-rank test = 0.009). Surgical re-intervention was independently associated with graft loss (OR 2.5, 95%CI 1.3-4.7). To conclude, pancreas recipients frequently experienced bacterial infections associated with the need for hemodialysis or surgical re-intervention. Infection by MDR organisms is a growing concern in these patients and was related to graft survival. Graft loss was independently associated with surgical re-intervention.

BACKGROUND Pre-transplant cytomegalovirus (CMV) serostatus has been associated with lung transplant patient survival. We retrospectively analyzed the relationship between pre-transplant donor/recipient CMV serostatus and long-term mortality in a cohort of lung transplant recipients at our center. METHOD Adult (Age >17 years) lung recipients transplanted between July 1985-December 2015 were analyzed. Variables included age, sex, pre-transplant donor (D)/recipient (R) serostatus [D-/R-, D-/R+, D+/R+, D+/R-], CMV infection within 2 years of transplant and transplant eras divided by changes in CMV prevention strategies: Era 1 (pre-ganciclovir, July 1985-April 1998), Era 2 (oral ganciclovir, May 1998-December 2004), Era 3 (valganciclovir, January 2005-December 2015). Survival analysis and Cox regression were performed at 10 years. RESULTS A total of 652 lung recipients were analyzed. Twenty percent were CMV mismatched pre-transplant and 45% had CMV infection within 2 years post-transplant. Survival at 10 years appeared worse in D+ transplants (P = 0.027). D-/R- lungs did not have significantly different survival across eras (P = 0.76), but survival of D-/R+, D+/R+, D+/R- lungs improved (P

J.Fortun,P.Martin-Davila,J.Pascual,C.Cervera,A.Moreno,J.Gavalda,J.M.Aguado,P.Pereira,M.Gurgu|¤,J.Carratala,M.Fogueda,M. Montejo, F. Blasco, G. Bou, J.Torre-Cisneros; RESITRATransplantNetwork. Immunosuppressive therapy and infection afterkidneytransplantation.TransplInfectDis2010:12:397^405.AllrightsreservedAbstract: Background.The role of immunosuppressive drugs inthedevelopmentof infection intransplant recipients hasbeen poorlyanalyzed.Objective.To evaluate the possible associationbetween infection andimmunosuppressionregimensinalarge cohortof renaltransplantrecipients.Methods. AllrenaltransplantrecipientsincludedintheRESITRAprospectivecohort from August2003toFebruary2005withaminimum follow-up of 3 monthswere studied. An intention-to-treatanalysiswas performed and patientswere analyzed in groupsaccording tothetype ofinductionandinitialmaintenancetherapy.V|ral,bacterial,andfungalinfectionsoccurringduring thisperiodwere evaluated.Results. Atotalof1398renaltransplant recipientswerestudied.Amaintenance regimen containing sirolimuswas independentlyassociatedwithalower riskofcytomegalovirus(CMV)infection(oddsratio [OR],0.16; 95%con¢dence interval [CI],0.05^0.54) andwith ahigher rate of surgical site infection (OR,3.21; 95%CI,1.26^8.21).Excludingtreatmentusedforacuterejectionepisodes,nootherfactorsrelatedtotheimmunosuppression regimenswereassociatedwiththedevelopmentofbacteremia,urinaryinfections,pneumonia,orotherinfections.Conclusion.The use of sirolimus as maintenance therapy in kidneyrecipientsisassociatedwithalow rate ofCMVinfectionandwithahigher riskofsurgicalsite infection.2009, accepted for publication 22 December 2009Correspondence to:Madrid, SpainIn recentyears,ashifthasbeenobservedtowardtheroutineuse of induction therapy with antibody preparations andmaintenancetherapywithamammaliantargetofrapamycin(mTOR) inhibitor (sirolimus or everolimus) to avoid the ne-phrotoxicityassociatedwithcalcineurin inhibitors(1).Calcineurin inhibitors are still the main cause ofimmunosuppression in the maintenance regimens takenby kidney recipients.Tacrolimus is the agent of choice andisincreasingly used:470%ofpatients are receiving tacro-limus at discharge compared with 20% who receive cyclo-sporine (1).The use of mycophenolate mofetil (MMF), themost frequently prescribed antiproliferative agent, is alsoincreasing: approximately 80% of patients are taking thisdrug at discharge (1). Calcineurin inhibitor-sparing regi-mensincludingsirolimusandMMFcombinedwithcortico-steroids have been proposed as a less nephrotoxicalternative. However, the results obtained with thiscombination have been questioned (2), and the potentiale⁄cacyof sirolimus as the main immunosuppressive druginthe combination needsto bebalanced against its safetypro¢le.Major progress has been made in the development andclinical application of novel immunosuppressive drugs toprevent acute rejection. However, few protocols includemonitoring of infectious diseases (3). Althoughthe associ-ation between immunosuppressive drugs and infection iswell known, the speci¢c contribution of diierent drugs totheseinfectionshasbeenpoorlyanalyzed.

The therapeutic options available for central nervous system (CNS) infections due to resistant Gram-positive cocci remain limited. We report an unusual case of community-acquired methicillin-resistant Staphylococcus aureus meningitis complicated by cerebral infarction in the middle cerebral artery territory in a previously healthy young male. After an initial vancomycin-based regimen, treatment was completed with a seven-week course of linezolid and levofloxacin. The potential role of such a combination and, particularly, linezolid as a first-line therapy in serious CNS infections is also discussed.

Staphylococcus aureus is one of the most common causative pathogens of bloodstream infections (BSIs). In approximately one-half of patients with S. aureus BSI, no portal of entry can be documented. This group of patients has a high risk of developing septic metastases. Similarly, patient populations at high risk of S. aureus BSI and BSI-associated complications include patients receiving hemodialysis, injection drug users, patients with diabetes, and patients with preexisting cardiac conditions or other comorbidities. One of the most severe complications of S. aureus BSI is infective endocarditis, and S. aureus is now the most common cause of infective endocarditis in the developed world. Patients with methicillin-resistant S. aureus BSI or infective endocarditis have higher rates of mortality, compared with patients with methicillin-susceptible S. aureus infection. Nasal carriage is the most important source of S. aureus BSI. Better eradication and control strategies, including nasal decolonization and more-active antibiotics, are needed to combat S. aureus BSIs.

Background. Incisional surgical site infections (ISSIs) are common bacterial infections in heart transplantation (HT). The purpose of this study was to determine the incidence, etiology, timing, and risk factors for ISSIs. Methods. A prospective study was performed, which included all heart transplants carried out in the participating hospitals (pertaining to the Spanish National Hospital Network RESITRA) between August 2003 and February 2005. A population of 292 consecutive patients was included (84.9% males). The definition of ISSI used in the study was based on the Centers for Disease Control criteria. Results. Seventeen episodes of ISSIs were recorded in 14 patients (4.8%; confidence interval [CI] 95% 2.7–7.7%). The median time from transplant to ISSI was 14 days (range 3–75). Two patients (14%) died; fatality was related to ISSI (mediastinitis) in 1 patient (7%). Coagulase-negative staphylococci (7 cases), methicillin-resistant Staphylococcus aureus (3 cases), Proteus mirabilis, extended-spectrum β-lactamase-producing Escherichia coli, Candida albicans, and Candida glabrata, 1 case each, were the isolated pathogens. The duration of extracorporeal circulation was longer in patients with ISSI, although the difference did not reach statistical significance. Antibiotic prophylaxis with ciprofloxacin alone (odds ratio, 15.8; 95% CI, 1.2–216.9) was independently associated with the development of ISSI. Conclusions. ISSIs in HT are frequently caused by resistant bacteria and Candida, but are associated with good prognosis.

Increasing prevalence of infections caused by multiresistant gram-negative enteric bacilli due to synthesis of extended-spectrum beta-lactamase (ESBL) or to desrepressed chromosomic AmpC beta-lactamase (AmpC) is a major concern in the hospitalized patient population. Renal transplant recipients are especially susceptible to these infections. A cohort observational study in a 3-year period was performed. ESBL-production was determined by phenotypic analysis based on the CLSI recommendations. A multi-variate logistic regression analysis was performed to identify independent variables associated with multi-resistant gram-negative bacilli infection. The study included 417 patients (61 double kidney-pancreas recipients). The incidence of ESBL-producing and desrepressed chromosomic AmpC beta-lactamase resistance was 11.8% (49 patients). The most frequent bacteria isolated was E. coli (35/60 isolations), followed by Klebsiella spp(12/60 isolations). Double kidney-pancreas transplantation(OR 3.5, CI95% 1.6-7.8), previous use of antibiotics(OR 2.1,CI95% 1.1-4.1), posttransplant dialysis requirement (OR 3.1, CI95% 1.5-6.4) and posttransplant urinary obstruction (OR 5.8, CI95% 2.2-14.9) were independent variables associated with these multiresistant gram-negative enteric bacilli infections. The incidence of ESBL-producing and desrepressed AmpC beta-lactamase gram-negative enteric bacilli infection in our population was high. These infections are associated with significant morbidity after renal transplantation.

Community-acquired pneumonia (CAP) is a serious lower respiratory tract infection associated with significant morbidity and mortality in immunocompromised patients. The present study evaluated the clinical spectrum of CAP in immunocompromised hosts and the role of respiratory viruses, as well as the yield of viral diagnostic methods. Conventional microbiological tests were routinely performed in immunocompromised patients with CAP. Nasopharyngeal swabs were processed for respiratory viruses by indirect immunofluorescence assay, cell culture and PCR. Four groups were defined according to aetiology of CAP, as follows: group 1 (nonviral), group 2 (mixed, nonviral and viral), group 3 (only viral) and group 4 (unknown aetiology). Over a 1-yr period, 92 patients were included. An aetiological diagnosis was achieved in 61 (66%) patients: 38 (41%), group 1; 12 (13%), group 2; and 11 (12%), group 3. The most frequent pathogen detected was Streptococcus pneumoniae (n = 29, 48%), followed by rhinovirus (n = 11, 18%). PCR identified 95% of respiratory viruses. Clinical characteristics could not reliably distinguish among the different aetiological groups. Respiratory viruses represent a substantial part of the aetiologies of community-acquired pneumonia in immunocompromised patients and its routine assessment through PCR in nasopharyngeal swabs should be considered in the clinical care of these patients.

Background. Cytomegalovirus (CMV) infection causes morbidity in solid organ transplant (SOT) recipients, either by direct injury or in association with chronic allograft rejection or other opportunistic infections. Ganciclovir is the treatment of choice, but this agent requires intravenous administration, which affects its feasibility for long-term use. Valganciclovir, which has an oral bioavailability of 60%, has proven to be useful for prophylaxis of CMV infection in high-risk SOT recipients and for treating retinitis in persons with acquired immunodeficiency syndrome. Objective. To compare the efficacy of valganciclovir (alone or as sequential therapy after a regimen of intravenous ganciclovir) with intravenous ganciclovir alone for preemptive therapy or treatment of CMV disease (viral syndrome or focal disease) in SOT recipients and to determine the incidence of adverse effects and relapses. Methods. In this 2-year prospective, comparative cohort study, 376 episodes of preemptive therapy or treatment of CMV disease were recorded among 334 of 3467 SOT recipients included in the Spanish Network for Research on Infection in Transplantation (RESITRA) database. Intravenous ganciclovir was the first-line treatment in 170 episodes; valganciclovir followed by intravenous ganciclovir was administered in 82 episodes, and valganciclovir alone was administered in 112 episodes. Results. Valganciclovir was used as preemptive therapy or treatment for CMV disease in 84 and 28 episodes, respectively. Duration of treatment was longer in valganciclovir recipients than in ganciclovir recipients for both preemptive therapy (21 vs. 15 days; P

The best immunosuppressive regimen in HIV-infected renal transplant recipients has not been established. Thymoglobulin has been associated with an increased risk of serious bacterial infections in HIV-negative patients and, for this reason, there is some concern over its use in the HIV-infected population. We describe three consecutive HIV-infected renal transplant recipients who received thymoglobulin as induction therapy, and we compared their progress with a cohort of 23 HIV-negative recipients. Median follow-up was 24 and 11 months, respectively. Nadir lymphocytopenia was observed at 1 week in both groups, and their absolute lymphocyte count recovery was similar. An early and deep (

Infection can lead to graft loss and death in patients undergoing kidney and double kidney-pancreas transplantation. In this review, the prophylactic measures, the post-transplant timeline for the development of infections, and the most frequent infectious complications in patients with kidney and pancreas transplantation are described. Although great advances have been achieved in the prevention of infections, new problems have developed. Nosocomial bacterial infection with multidrug-resistant bacteria is an emerging complication. Cytomegalovirus is still the most frequent viral infection despite the advances in prevention measures. Moreover, in recent years polyomavirus type BK infection has been recognized as a major cause of renal graft loss. Knowledge of the infectious complications associated with these transplants and the risk factors for their occurrence will allow optimal therapeutic management of this patient population.

Background & Aims: The aim of this study was to evaluate the results of treatment with pegylated interferon and ribavirin for the recurrence of hepatitis C after liver transplantation in HCV/ HIV-coinfected patients. Methods: This was a prospective, multicentre cohort study, including 78 HCV/HIV-coinfected liver transplant patients who received treatment for recurrent hepatitis C. For comparison, we included 176 matched HCV-monoinfected patients who underwent liver transplantation during the same period of time at the same centres and were treated for recurrent hepatitis C. Results: Antiviral therapy was discontinued prematurely in 56% and 39% (p = 0.016), mainly because of toxicity (22% and 11%, respectively; p = 0.034). Sustained virological response (SVR) was achieved in 21% of the coinfected patients and in 36% of monoinfected patients (p = 0.013). For genotype 1, SVR rates were 10% and 33% (p = 0.002), respectively; no significant differences were observed for the other genotypes. A multivariate analysis based on the whole series identified HIV-coinfection as an independent predictor of lack of SVR (OR, 0.17; 95% CI, 0.06-0.42). Other predictors of SVR were donor age, pretreatment HCV viral load, HCV genotype, and early virological response. SVR was associated with a significant improvement in survival: 5-year survival after antiviral treatment was 79% for HCV/HIV-coinfected patients with SVR vs. 43% for those without (p = 0.02) and 92% vs. 60% in HCV-monoinfected patients (p < 0.001), respectively. Conclusions: The response to pegylated interferon and ribavirin was poorer in HCV/HIV-coinfected liver recipients, particularly those with genotype 1. However, when SVR was achieved, survival of coinfected patients increased significantly. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

International audience; Background : Nearly half of patients require cardiac surgery during the acute phase of infective endocarditis (IE). We describe the characteristics of patients according to the type of valve replacement (mechanical or biological), and examine whether the type of prosthesis was associated with in-hospital and 1-year mortality.Methods and results : Among 5591 patients included in the International Collaboration on Endocarditis Prospective Cohort Study, 1467 patients with definite IE were operated on during the active phase and had a biological (37%) or mechanical (63%) valve replacement.Patients who received bioprostheses were older (62 vs 54 years), more often had a history of cancer (9% vs 6%), and had moderate or severe renal disease (9% vs 4%); proportion of health care-associated IE was higher (26% vs 17%); intracardiac abscesses were more frequent (30% vs 23%). In-hospital and 1-year death rates were higher in the bioprosthesis group, 20.5% vs 14.0% (p = 0.0009) and 25.3% vs 16.6% (p < .0001), respectively.In multivariable analysis, mechanical prostheses were less commonly implanted in older patients (odds ratio: 0.64 for every 10 years), and in patients with a history of cancer (0.72), but were more commonly implanted in mitral position (1.60).Bioprosthesis was independently associated with 1-year mortality (hazard ratio: 1.298).Conclusions :Patients with IE who receive a biological valve replacement have significant differences in clinical characteristics compared to patients who receive a mechanical prosthesis. Biological valve replacement is independently associated with a higher in-hospital and 1-year mortality, a result which is possibly related to patient characteristics rather than valve dysfunction.

International audience; Background - The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. Methods - Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. Results - EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). Conclusions - In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

Information regarding the processes leading to death in patients with invasive aspergillosis (IA) is lacking. We sought to determine the causes of death in these patients, the role that IA played in the cause, and the timing of death. The factors associated with IA-related mortality are also analyzed. We conducted a multicenter study (2008-2011) of cases of proven and probable IA. The causes of death and whether mortality was judged to be IA-related or IA-unrelated were determined by consensus using a six-member review panel. A multivariate analysis was performed to determine risk factors for IA-related death. Of 152 patients with IA, 92 (60.5%) died. Mortality was judged to be IA-related in 62 cases and IA-unrelated in 30. The most common cause of IA-related death was respiratory failure (50/62 patients), caused primarily by Aspergillus infection, although also by concomitant infections or severe comorbidities. Progression of underlying disease and bacteremic shock were the most frequent causes of IA-unrelated death. IA-related mortality accounted for 98% and 87% of deaths within the first 14 and 21 days, respectively. Liver disease (HR 4.54; 95% CI, 1.69-12.23) was independently associated with IA-related mortality, whereas voriconazole treatment was associated with reduced risk of death (HR 0.43; 95% CI, 0.20-0.93). In conclusion, better management of lung injury after IA diagnosis is the main challenge for physicians to improve IA outcomes. There are significant differences in causes and timing between IA-related and IA–unrelated mortality and these should be considered in future research to assess the quality of IA care.