Co-infections and superinfections complicating COVID-19 in cancer patients: A multicentre, international study.

BACKGROUND: We aimed to describe the epidemiology, risk factors, and clinical outcomes of co-infections and superinfections in onco-hematological patients with COVID-19. METHODS: International, multicentre cohort study of cancer patients with COVID-19. All patients were included in the analysis of co-infections at diagnosis, while only patients admitted at least 48 h were included in the analysis of superinfections. RESULTS: 684 patients were included (384 with solid tumors and 300 with hematological malignancies). Co-infections and superinfections were documented in 7.8% (54/684) and 19.1% (113/590) of patients, respectively. Lower respiratory tract infections were the most frequent infectious complications, most often caused by Streptococcus pneumoniae and Pseudomonas aeruginosa. Only seven patients developed opportunistic infections. Compared to patients without infectious complications, those with infections had worse outcomes, with high rates of acute respiratory distress syndrome, intensive care unit (ICU) admission, and case-fatality rates. Neutropenia, ICU admission and high levels of C-reactive protein (CRP) were independent risk factors for infections. CONCLUSIONS: Infectious complications in cancer patients with COVID-19 were lower than expected, affecting mainly neutropenic patients with high levels of CRP and/or ICU admission. The rate of opportunistic infections was unexpectedly low. The use of empiric antimicrobials in cancer patients with COVID-19 needs to be optimized.

Impact of the Inclusion of an Aminoglycoside to the Initial Empirical Antibiotic Therapy for Gram-Negative Bloodstream Infections in Hematological Neutropenic Patients: a Propensity-Matched Cohort Study (AMINOLACTAM Study).

To test the hypothesis that the addition of an aminoglycoside to a ß-lactam antibiotic could provide better outcomes than ß-lactam monotherapy for the initial empirical treatment of hematological neutropenic patients with subsequently documented Gram-negative bacillus (GNB) bloodstream infection (BSI), a multinational, retrospective, cohort study of GNB BSI episodes in hematological neutropenic patients in six centers (2010 to 2017) was conducted. Combination therapy (ß-lactam plus aminoglycoside) was compared to ß-lactam monotherapy. The primary endpoint was the case fatality rate, assessed at 7 and 30 days from BSI onset. Secondary endpoints were nephrotoxicity and persistent BSI. Propensity score (PS) matching was performed. Among 542 GNB BSI episodes, 304 (56%) were initially treated with combination therapy, with cefepime plus amikacin being most common (158/304 [52%]). Overall, Escherichia coli (273/304 [50.4%]) was the main etiological agent, followed by Pseudomonas aeruginosa, which predominated in the combination group (76/304 [25%] versus 28/238 [11.8%]; P < 0.001). Multidrug resistance rates were similar between groups (83/294 [28.2%] versus 63/233 [27%]; P = 0.95). In the multivariate analysis, combination therapy was associated with a lower 7-day case fatality rate (odds ratio [OR], 0.37; 95% CI, 0.14 to 0.91; P = 0.035) with a tendency toward lower mortality at 30 days (OR, 0.56; 95% CI, 0.29 to 1.08; P = 0.084). After PS matching, these differences remained for the 7-day case fatality rate (OR, 0.33; 95% CI, 0.13 to 0.82; P = 0.017). In addition, aminoglycoside use was not significantly associated with renal function impairment (OR, 1.12; 95% CI, 0.26 to 4.87; P = 0.9). The addition of an aminoglycoside to the initial empirical therapy regimen for febrile neutropenic hematological patients should be considered.

Clinical Predictive Model of Multidrug Resistance in Neutropenic Cancer Patients with Bloodstream Infection Due to Pseudomonas aeruginosa.

We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens. Of a total of 1,217 episodes of BSI due to P. aeruginosa, 309 episodes (25.4%) were caused by MDR strains. The rate of multidrug resistance increased significantly over the study period (P = 0.033). Predictors of MDR P. aeruginosa BSI were prior therapy with piperacillin-tazobactam (odds ratio [OR], 3.48; 95% confidence interval [CI], 2.29 to 5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65 to 3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92 to 4.64), underlying hematological disease (OR, 2.09; 95% CI, 1.26 to 3.44), and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65 to 3.91), whereas older age (OR, 0.98; 95% CI, 0.97 to 0.99) was found to be protective. Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDR P. aeruginosa The application of this model using a web-based calculator may be a simple strategy to identify high-risk patients who may benefit from the early administration of broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at a low risk of resistance development.

Roles of the multiplex real-time PCR assay and ß-D-glucan in a high-risk population for intra-abdominal candidiasis (IAC).

Multiplex quantitative real-time PCR (MRT-PCR) using blood can improve the diagnosis of intra-abdominal candidiasis (IAC). We prospectively studied 39 patients with suspected IAC in the absence of previous antifungal therapy. Blood cultures, MRT-PCR, and ß-D-glucan (BDG) in serum were performed in all patients. IAC was defined according to the 2013 European Consensus criteria. For MRT-PCR, the probes targeted the ITS1 or ITS2 regions of ribosomal DNA. Candidaemia was confirmed only in four patients (10%), and IAC criteria were present in 17 patients (43.6%). The sensitivity of MRT-PCR was 25% but increased to 63.6% (P = .06) in plasma obtained prior to volume overload and transfusion; specificity was above 85% in all cases. BDG performance was improved using a cutoff > 260 pg/ml, and improvement was not observed in samples obtained before transfusion. In this cohort of high risk of IAC and low rate of bloodstream infection, the performance of non-culture-based methods (MRT-PCR or BDG) was moderate but may be a complementary tool given the limitations of diagnostic methods available in clinical practice. Volume overload requirements, in combination with other factors, decrease the accuracy of MRT-PCR in patients with IAC.

Aerosolized Lipid Amphotericin B for Complementary Therapy and/or Secondary Prophylaxis in Patients with Invasive Pulmonary Aspergillosis: A Single-Center Experience.

BACKGROUND: Experience with aerosolized lipid amphotericin B (aeLAB) as therapy or secondary prophylaxis in patients with invasive pulmonary aspergillosis (IPA) is anecdotal. METHODS: We performed a single-center retrospective cohort study to evaluate the efficacy of systemic antifungal therapy with and without aeLAB in patients with proven or probable IPA. Complete or partial response at 3 months was the primary end-point. Clinical response and mortality at 12 months, occurrence of adverse drug reactions and respiratory fungal colonization were secondary end-point. RESULTS: Eleven patients (39%) received aeLAB in addition to systemic antifungal therapy (group A), and 22 (61%) received systemic antifungal therapy only (group B). The use of aeLAB was not standardized. Amphotericin B lipid complex was used in all patients but one, who received liposomal amphotericin B. Five patients received aeLAB as antifungal complementary therapy and 6 received it as secondary prophylaxis. Except for the requirement of inhaled corticosteroids and home oxygen therapy, more frequent in group A, both groups were similar in baseline conditions. A better (nonsignificant) clinical outcome was observed at 3 months in patients receiving aeLAB. Only uncontrolled baseline condition was associated with one-year mortality in univariate analysis (p = 0.002). A multivariate Cox regression analysis suggests that aeLAB, corrected for uncontrolled underlying disease, reduces mortality at 12 months (HR 0.258; 95% CI 0.072-0.922; p = 0.037). CONCLUSION: Although no significant difference was observed in the main variable (3-month clinical response) and in spite of methodological limitations of the study, the possible survival benefit of aeLAB, adjusted for the control of the underlying disease, could justify the performance of well-controlled studies with a greater number of patients.

Changes in tuberculosis in human immunodeficiency virus infected patients in a Spanish tertiary hospital (1995-2013).

OBJECTIVE: Although the incidence of human immunodeficiency virus (HIV)-associated tuberculosis (TB) has decreased, changes in other characteristics of the disease are largely unknown. To describe the trends in TB in patients infected with HIV from 1995 to 2013. METHODS: We review all cases of TB in a tertiary hospital in Madrid, Spain. RESULTS: Among 1,284 patients diagnosed of TB, 298 (23%) were coinfected with HIV. The prevalence of HIV infection during the period of study has decreased from 40% to 14% (p for the trend < 0.001). Clinical presentation has also changed. Although pulmonary and extrapulmonary TB has remained unchanged, miliary presentation has significantly decreased (from 36% to 22%, p = 0.005). The 4-drug regimen was the preferable scheme, with higher implementation at the end of the study period (82% from 1995-1999 to 95% in 2010-2013, p = 0.43). Factors such as treatment failure (OR: 11.7; CI 95%: 3.12-44.1) and miliary form (OR: 2.8; CI 95%; 1.09-7.3) were independently associated with TB related mortality, while the longer duration of treatment was as a protective factor (OR 0.7; CI 95%: 0.6-0.8). CONCLUSIONS: HIV has decreased very significantly as a risk factor for the development of TB. Despite improvement in the treatment of both TB and HIV, and in overall mortality, deaths attributable to the disease in this population remain high mostly in miliary and relapsing forms.

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.

Clinical efficacy of ß-lactam/ß-lactamase inhibitor combinations for the treatment of bloodstream infection due to extended-spectrum ß-lactamase-producing Enterobacteriaceae in haematological patients with neutropaenia: a study protocol for a retrospective observational study (BICAR).

INTRODUCTION: Bloodstream infection (BSI) due to extended-spectrum ß-lactamase-producing Gram-negative bacilli (ESBL-GNB) is increasing at an alarming pace worldwide. Although ß-lactam/ß-lactamase inhibitor (BLBLI) combinations have been suggested as an alternative to carbapenems for the treatment of BSI due to these resistant organisms in the general population, their usefulness for the treatment of BSI due to ESBL-GNB in haematological patients with neutropaenia is yet to be elucidated. The aim of the BICAR study is to compare the efficacy of BLBLI combinations with that of carbapenems for the treatment of BSI due to an ESBL-GNB in this population. METHODS AND ANALYSIS: A multinational, multicentre, observational retrospective study. Episodes of BSI due to ESBL-GNB occurring in haematological patients and haematopoietic stem cell transplant recipients with neutropaenia from 1 January 2006 to 31 March 2015 will be analysed. The primary end point will be case-fatality rate within 30 days of onset of BSI. The secondary end points will be 7-day and 14-day case-fatality rates, microbiological failure, colonisation/infection by resistant bacteria, superinfection, intensive care unit admission and development of adverse events. SAMPLE SIZE: The number of expected episodes of BSI due to ESBL-GNB in the participant centres will be 260 with a ratio of control to experimental participants of 2. ETHICS AND DISSEMINATION: The protocol of the study was approved at the first site by the Research Ethics Committee (REC) of Hospital Universitari de Bellvitge. Approval will be also sought from all relevant RECs. Any formal presentation or publication of data from this study will be considered as a joint publication by the participating investigators and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE). The study has been endorsed by the European Study Group for Bloodstream Infection and Sepsis (ESGBIS) and the European Study Group for Infections in Compromised Hosts (ESGICH).

Management of cytomegalovirus infection in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Cytomegalovirus (CMV) infection remains a major complication of solid organ transplantation. Because of management of CMV is variable among transplant centers, in 2011 the Spanish Transplantation Infection Study Group (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) developed consensus guidelines for the prevention and treatment of CMV infection in solid organ transplant recipients. Since then, new publications have clarified or questioned the aspects covered in the previous document. For that reason, a panel of experts revised the evidence on CMV management, including immunological monitoring, diagnostics, prevention, vaccines, indirect effects, treatment, drug resistance, immunotherapy, investigational drugs, and pediatric issues. This document summarizes the recommendations.

Propensity Score Analysis of the Role of Initial Antifungal Therapy in the Outcome of Candida glabrata Bloodstream Infections.

Candida glabrata isolates have reduced in vitro susceptibility to azoles, which raises concerns about the clinical effectiveness of fluconazole for treating bloodstream infection (BSI) by this Candida species. We aimed to evaluate whether the choice of initial antifungal treatment (fluconazole versus echinocandins or liposomal amphotericin B [L-AmB]-based regimens) has an impact on the outcome of C. glabrata BSI. We analyzed data from a prospective, multicenter, population-based surveillance program on candidemia conducted in 5 metropolitan areas of Spain (May 2010 to April 2011). Adult patients with an episode of C. glabrata BSI were included. The main outcomes were 14-day mortality and treatment failure (14-day mortality and/or persistent C. glabrata BSI for ≥48 h despite antifungal initiation). The impact of using fluconazole as initial antifungal treatment on the patients' prognosis was assessed by logistic regression analysis with the addition of a propensity score approach. A total of 94 patients with C. glabrata BSI were identified. Of these, 34 had received fluconazole and 35 had received an echinocandin/L-AmB-based regimen. Patients in the echinocandin/L-AmB group had poorer baseline clinical status than did those in the fluconazole group. Patients in the fluconazole group were more frequently (55.9% versus 28.6%) and much earlier (median time, 3 versus 7 days) switched to another antifungal regimen. Overall, 14-day mortality was 13% (9/69) and treatment failure 34.8% (24/69), with no significant differences between the groups. On multivariate analysis, after adjusting for baseline characteristics by propensity score, fluconazole use was not associated with an unfavorable evolution (adjusted odds ratio [OR] for 14-day mortality, 1.16, with 95% confidence interval [CI] of 0.22 to 6.17; adjusted OR for treatment failure, 0.83, with 95% CI of 0.27 to 2.61). In conclusion, initial fluconazole treatment was not associated with a poorer outcome than that obtained with echinocandins/L-AmB regimens in patients with C. glabrata BSI. (This study has been registered at ClinicalTrials.gov under registration no. NCT01236261.).

Galactomannan in bronchoalveolar lavage fluid for diagnosis of invasive aspergillosis in non-hematological patients.

BACKGROUND: The role of galactomannan (GM) in serum or bronchoalveolar lavage fluid (BALF) for the diagnosis of invasive pulmonary aspergillosis (IPA) has been extensively evaluated in hematological patients, however its performance in non-hematological patients is not well established. METHODS: We performed a multicenter retrospective study in 3 university hospitals in Madrid, Spain between 2010 and 2014. The study population comprised patients with chronic obstructive pulmonary disease (COPD) and patients with immunosuppressive conditions in whom IPA was suspected and for whom BALF GM was available. Patients with hematological disorders were excluded. RESULTS: A total of 188 patients (35 with COPD and 153 with immunosuppressive conditions) were analyzed, and 31 cases of IPA (proven or probable) were identified. The global sensitivity of BALF GM (optical density index [ODI] ≥ 1.0) was 77.4%; sensitivity was higher in patients with immunosuppressive conditions than in patients with COPD (81.8% vs 66.7%; p: 0.38). In COPD patients, the best performance was obtained for BALF GM (ODI ≥ 0.5), although sensitivity (88.9%) was similar to that of BALF fungal culture (88.9%). The sensitivity of GM in serum was very poor in both populations (36.4% and 11.6%, respectively). CONCLUSIONS: In the present series, the diagnostic performance of BALF GM was good for IPA in non-hematological patients, especially in patients with immunosuppressive conditions.

Effect of long-term prophylaxis in the development of cytomegalovirus-specific T-cell immunity in D+/R- solid organ transplant recipients.

BACKGROUND: This study aimed to characterize the dynamics of acquisition of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) in CMV donor positive/recipient negative solid organ transplant (SOT) patients receiving long-term antiviral prophylaxis, and to determine whether development of CMI confers protection against CMV disease. METHODS: A prospective multicenter study was conducted in Spain from September 2009 to September 2012. Whole blood specimens were prospectively collected at 30, 90, 120, 200, and 365 days after SOT, and CMI was determined by enumeration of CMV pp65 and IE-1-specific CD69(+) /interferon-γ-producing CD8(+) and CD4(+) T cells by flow cytometry for intracellular cytokine staining. As part of a simultaneous clinical trial, patients received either early prophylaxis (in the first 3 days after transplantation) in the first period of the study or delayed prophylaxis (initiated at day 14) during the second period of the study. The impact of the dynamics of acquisition of CMV-specific CMI on the incidence of CMV disease was evaluated by Kaplan-Meier survival analysis. RESULTS: A total of 95 SOT recipients were recruited. CMV infection and disease occurred in 38 (40%) and 26 (27.4%) patients, respectively. The proportion of patients achieving any detectable CMV-specific CMI response at each of the different monitoring points was higher in liver transplant recipients, as compared to kidney or heart transplant recipients. The presence of any detectable response at day 120 or 200 was protective against the development of CMV disease (positive predictive values 92% and 93%, respectively). CONCLUSIONS: The rate of acquisition of CMV-specific CMI in SOT recipients undergoing antiviral prophylaxis differed significantly between different SOT populations. Patients developing any detectable CMI response were protected against the occurrence of CMV disease.

Effect of delaying prophylaxis against CMV in D+/R- solid organ transplant recipients in the development of CMV-specific cellular immunity and occurrence of late CMV disease.

OBJECTIVES: Evaluate the protective effect against late CMV disease of delaying antiviral prophylaxis initiation in D+/R- patients receiving solid organ transplant (SOT). METHODS: Prospective multicenter study in D+/R- SOT recipients in Spain (Sept/09-Sept/12). Whole blood specimens were prospectively collected after Tx for CMV-specific cell-mediated immunity (CMI) determination. Two prophylaxis strategies were compared: early prophylaxis (EP; starting within the first 3 days after Tx) and delayed prophylaxis (DP; starting 14 days after Tx). Risk factors for the occurrence of CMV disease were determined by survival analysis and proportional risk Cox regression models. RESULTS: We included 95 patients (50 EP V 45 DP). Twenty six patients (27.4%) developed CMV disease: 32.7% EP vs. 20% DP; (p = 0.2). No cases of CMV disease were reported previously to beginning delayed prophylaxis. The percentage of individuals with detectable CMI response was higher in patients with DP although differences did not reach statistic significance (42% vs 29.6% at day 200 after Tx; p = 0.4). There was a clear trend towards less end-organ CMV disease in patients receiving DP (18.2% EP vs 5% DP; p = 0.09) and DP was the only protective factor in the multivariate analysis (HR: 0.26; CI: 0.05-1.2; p = 0.09). CONCLUSIONS: A 14-day delay in CMV prophylaxis in D+/R- SOT recipients is safe and may reduce the incidence of late CMV end-organ disease although correlation of this effect with CMI responses was not complete.

Clinical validation of a multiplex real-time PCR assay for detection of invasive candidiasis in intensive care unit patients.

BACKGROUND: New techniques, such as those based on multiplex quantitative real-time PCR (MRT-PCR), can improve the detection of invasive candidiasis (IC). METHODS: We prospectively studied 63 intensive care unit patients with suspected IC and 40 healthy controls. Blood cultures and MRT-PCR were performed at day 0 and +2, +7, +14 and +21 days in all patients. In addition, ß-d-glucan (BDG) and Candida albicans germ tube antibody (CAGTA) were quantified. RESULTS: IC was confirmed in 27 patients. Colonization was significantly higher in patients with IC (96% versus 64%, P = 0.002). The sensitivity, specificity, positive predictive value and negative predictive value of MRT-PCR for the diagnosis of IC were 96.3%, 97.3%, 92.8% and 98.7%, respectively. The positive predictive value and specificity were significantly higher for MRT-PCR than for BDG and CATGA. MRT-PCR performed very well, especially in deep-seated IC (sensitivity 90.9% versus 45.4% for blood culture; P = 0.06). As regards the most appropriate clinical sample for DNA amplification, in this study whole blood and serum presented similar results. CONCLUSIONS: MRT-PCR appears to be a useful test for confirming a diagnosis of IC in critically ill patients, especially in those with deep-seated disease. Its high sensitivity and positive predictive value make it a much more efficient tool for the management of IC than other diagnostic procedures and clinical scores.

Daptomycin is safe and effective for the treatment of gram-positive cocci infections in solid organ transplantation.

INTRODUCTION: Infections caused by resistant gram-positive cocci (GPC), especially to glycopeptides, are difficult to treat in solid organ transplant (SOT) recipients as a result of lower effectiveness and high rates of renal impairment. The aim of this study was to evaluate the use of daptomycin in this population. METHODS: Over a 2-year period (March 2008-2010) in 9 Spanish centers, we enrolled all consecutive recipients who received daptomycin to treat GPC infection. The study included 43 patients, mainly liver and kidney transplant recipients. RESULTS: The most frequent infections were catheter-related bacteremia caused by coagulase-negative staphylococci (23.2%), skin infection caused by Staphylococcus aureus (11.5%), and intra-abdominal abscess caused by Enterococcus faecium (20.9%). The daily daptomycin dose was 6 mg/kg in 32 patients (74.4%). On day 7 of daptomycin treatment, median estimated area under the curve was 1251 µg/mL/h. At the end of follow-up, analytical parameters were similar to the values at the start of therapy. No changes were observed in tacrolimus levels. No patient required discontinuation of daptomycin because of adverse effects. Clinical success at treatment completion was achieved in 37 (86%) patients. Three patients died while on treatment with daptomycin. CONCLUSION: In summary, daptomycin was a safe and useful treatment for GPC infection in SOT recipients.

Extra-pulmonary tuberculosis: differential aspects and role of 16S-rRNA in urine.

BACKGROUND: Early diagnosis of extra-pulmonary tuberculosis (EPTB) is important for successful treatment. METHODS: All cases of EPTB diagnosed at Ramon y Cajal Hospital, Madrid, Spain, from 1997 to 2008 were analysed and compared with pulmonary tuberculosis (PTB) patients to identify differential parameters that could serve to predict the presence of EPTB at initial presentation. Different microbiological techniques were analysed, including amplification of 16S-rRNA in urine. RESULTS: During the study period, 814 cases of TB were diagnosed at our centre; 330 (40.5%) were EPTB. Concomitant PTB was detected in 45% of EPTB cases. The main clinical forms of EPTB were lymphadenitis (86, 26%), miliary TB (60, 18%), and multifocal TB (43, 13%). Variables independently associated with EPTB were human immunodeficiency virus (HIV) infection (OR 3.6, 95%CI 2.4-5.4), older age (>60 years) (OR 3.7, 95%CI 2.5-5.6) and mortality (OR 2.9, 95%CI 1.3-6.3). 16S-rRNA in urine was performed in 82 EPTB patients (25%), among whom a positive result was obtained in 70%; in the PTB group, a positive result was found in 5 of 28 patients (18%) (P <0.001). CONCLUSIONS: HIV infection and older age appear to be the main risk factors associated with EPTB. In this study, mortality was significantly higher in patients with EPTB. A positive 16S-rRNA test result in urine is a useful marker of EPTB.

Extra-pulmonary tuberculosis: a biomarker analysis.

INTRODUCTION: Studies on biomarkers in tuberculosis are focused on pulmonary forms of this disease (PTB), and only limited information is currently available on biomarkers of extra-pulmonary tuberculosis (EPTB). METHODS: Serum samples from 24 patients with PTB, 29 patients with EPTB and 27 healthy controls were obtained, and the levels of interferon-gamma, chemokine ligand 9, mannose-binding lectin (MBL), tumor marker Ca-125 and adenosine deaminase were determined. RESULTS: The circulating levels of all tested biomarkers in the serum were significantly higher in PTB and EPTB patients than in controls. However, there were no significant differences in the levels of the biomarkers between patients with PTB and EPTB, with the exception of serum levels of MBL which were significantly higher in patients with EPTB than in patients with PTB (p = 0.01). In patients with EPTB, no significant differences were observed in biomarker levels among patients with or without concomitant PTB involvement. Based on MBL serum levels, ROC curve analysis showed an AUC of 0.85 for EPTB versus non-EPTB. The optimal cut-off value of MBL serum levels for EPTB versus non-EPTB was 1,000 µg/ml, with a sensitivity and specificity of 79.3 and 78.0 %, respectively. CONCLUSIONS: Biomarkers usually present as acute phase reactants and do not enable pulmonary forms to be differentiated from more serious or extra-pulmonary forms. MBL may be an exception.

Infective endocarditis in congenital heart disease: a frequent community-acquired complication.

BACKGROUND: Infective endocarditis (IE) is a severe complication in patients with congenital heart disease (CHD). Epidemiology, etiology, and outcome in this group are different to those of patients with acquired heart disease. METHODS: We reviewed all cases of proven and probable IE (Duke's criteria) diagnosed in our center during the last two decades. RESULTS: We observed 45 cases of IE in patients with CHD (age range 8 months to 35 years); these represented 5.5 % of all the episodes of IE in our institution during the study period. The most frequent CHD were ventricular septal defect (31 %), tetralogy of Fallot (19 %), and atrioventricular septal defect (11 %). Twenty cases of IE (44 %) were recorded in patients with non-corrected native-valve CHD. Of the 24 patients with prosthetic-valve IE, post-operative acquisition during the first 6 months was confirmed in 11 patients (range 4-110 days). IE was community-acquired in 62 % of cases. Streptococcus spp. were the most frequent etiologic agents (33 %), followed by Staphylococcus spp. (32 %). Surgery was required to treat IE in 47 % of patients (52 % in prosthetic-valve IE and 41 % in native-valve IE, p = ns). In comparison to native-valve IE, prosthetic-valve IE was significantly more nosocomial-acquired (61 vs. 14 %, p = 0.002), presented a higher heart failure rate at diagnosis (39 vs. 9 %, p = 0.035), and developed more breakthrough bacteremia episodes (19 vs. 0 %, p = 0.048). Global mortality was 24 % (75 % in patients with prosthetic-valve IE who required surgery and 0 % in patients with native-valve IE who required surgery, p = 0.001). Multivariate analysis excluding breakthrough bacteremia (100 % mortality in this condition) confirmed that nosocomial IE [odds ratio (OR), 23.7; 95 % confidence interval (CI), 2.3-239.9] and the presence of heart failure at diagnosis of IE (OR, 25.9; 95 % CI, 2.5-269.6) were independent factors associated with mortality. CONCLUSION: Half of all cases of IE in patients with CHD occurred in patients with non-corrected native-valve CHD and two-thirds were community-acquired. Streptococcus spp. were the most frequent etiological agents. Patients with prosthetic-valve IE present a worse outcome, especially those requiring surgery. Breakthrough bacteremia, nosocomial IE, and heart failure are independent factors of mortality in patients with CHD presenting IE.

Emerging trends in candidemia: a higher incidence but a similar outcome.

The clinical presentation and outcome of candidemia has changed in recent years. We compared two 5-year periods (2000-2004 and 2005-2009) in a single institution. We recorded 419 candidemia episodes during the study period (124 in the first period and 295 in the second period). We observed a significant increase in the number of cases per 1000 admissions per year, from 0.57 in 2000 to 1.52 in 2009 (χ(2) LT <0.001). Candida albicans was the most frequently isolated species (42.2%), followed by Candida parapsilosis (34.4%) and Candida glabrata (12.9%). In the second period, episodes were associated with higher comorbidity and were more commonly nosocomial, with a more frequent catheter-related source and an increased rate of C. glabrata infection. No significant differences were observed in susceptibility by species during the study period. According to multivariate analysis, the independent factors associated with higher mortality were shock, age >50 years, elevated comorbidity score (Charlson index >6), and source of candidemia other than catheter. In contrast to the increase in comorbid conditions observed in recent years, mortality remained similar during both periods (~37% during the first month). This finding could be attributed to a significant increase in catheter-related candidemia and better outcome, as well as to a potential improvement in the management of antifungal therapy in recent years.

Pandemic influenza A(H1N1) virus infection in solid organ transplant recipients: impact of viral and non-viral co-infection.

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 3.7 years, 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 <90 days and pneumonia. In conclusion, pandemic influenza A can cause significant direct and indirect effects in SOTR, especially in the early post-transplant period, and should be treated early. Clinicians should be aware of the possibility of non-viral co-infection, mainly in diabetic patients and severe cases. An effort should be made to prevent influenza with immunization of the patient and the environment.