ZIKV is potentially sexually transmitted and persists in male genital secretions for a prolonged period after symptom onset. PROSPERO systematic review registration number CRD42016041475.

Objective: To analyse cases of blood culture negative endocarditis (BCNE) seen at St Thomas ' Hospital, London, between 1975 and. Methods: Data on all episodes of endocarditis with negative blood cultures seen at St Thomas' Hospital between 1975 and 2000 were collected prospectively and analysed retrospectively. Results: Sixty three patients with BCNE were seen during the study period: 48 (76%) with native and 15 (24%) prosthetic valve infection. BCNE accounted for 12.2% of the 516 cases of endocarditis seen at St Thomas' Hospital. The diagnosis of endocarditis was clinically definite by the Duke criteria in only 21% (7 of 34) of cases of pathologically proven native valve endocarditis but in 62% (21 of 34) of cases by the St Thomas' modifications of the criteria. Comparable figures for the 11 cases of pathologically proven prosthetic valve endocarditis were 45% and 73%. Despite negative blood cultures a causative organism was identified in 31 (49%) of the 63 cases: in 15 by serology (8 Coxiella burnetii, 6 Bartonella species, and 1 Chlamydia psittaci); in 9 cases by culture of the excised valve; in 3 by microscopy of the excised valve, on which large numbers of Gram positive cocci were seen although the culture was sterile; and in the other 4 by isolation from a site other than the excised valve (2 respiratory specimens, 1 from the pacemaker tip, and 1 from an excised embolus). In addition 5 of the 6 cases of Bartonella infection were confirmed by polymerase chain reaction study of the excised valve. Two thirds of the 32 patients for whom no pathogen was identified had received antibiotics before blood was cultured. Thus truly "negative" endocarditis was very uncommon (6% of the cases). Conclusion: If blood cultures are negative in definite or suspected endocarditis, serum should be analysed for Bartonella, Coxiella, and Chlamydia species antibodies, and the excised valve or (rarely) embolus should be analysed by microscopy, culture, histology, and relevant polymerase chain reaction. Other specimens may be relevant. The Duke criteria performed poorly in BCNE; St Thomas' additional minor criteria gave more definite diagnoses.

We appreciate the thoughtful comments of Drs Almonedro-Delia, Galvez-Acebal, and Rodriguez-Bano regarding our recent publication, "Association Between Surgical Indications, Operative Risk, and Clinical Outcome in Infective Endocarditis: a Prospective Study From the International Collaboration on Endocarditis." 1 These authors raise important issues for evaluating the impact of surgery on patient outcomes, particularly survival. We strongly agree that treatment selection bias and survivor bias are major issues when evaluating the impact of surgery on mortality and that the use of appropriate statistical methodologies is necessary to quantify an unbiased and causal association of the effect of surgical treatment on outcome. In our previous studies on the impact of surgery on mortality, we have used such methods, including propensity scores, 2 to account for selection bias and Cox proportional hazards models with surgery entered as a time-dependent covariate 3,4 for survivor bias adjustment. However, the objective of the current study was to evaluate the differences in clinical characteristics comparing patients treated with and without cardiac surgery for infective endocarditis, and to evaluate the relationship between surgical indications, operative risk (by using the Society of Thoracic Surgeons operative risk score), and outcome. Our results emphasize the relevance of specific surgical indications in treatment decisions in infective endocarditis, and the relationship between the Society of Thoracic Surgeons operative risk score and outcome, as well. The purpose of our study was not to determine the prognostic influence of surgery in comparison with medical therapy alone in infective endocarditis.

Sporotrichosis is a fungal infection of man and animals caused by Sporothrix complex. It usually presents as a lymphocutaneous form, but disseminated disease may occur. Given the paucity of data about HIV/AIDS and sporotrichosis co-infection, a systematic review of reported cases of HIV-associated sporotrichosis found via Pubmed (1984-2013) was done. A total of 39 papers were included, and 58 patients' data analyzed. Thirty-three (56.9 %) cases were from Brazil and 18 (31 %) from the USA. Patients' mean age was 37.8 ± 10.4 years; males predominated (84.5 %). The median CD4(+) cell count was 97 cells/mm(3). The most common clinical forms were disseminated and disseminated cutaneous with 33 (56.9 %) and 10 (17.5 %) patients, respectively. There was a correlation between CD4(+) count and clinical categories (p = 0.002). Mortality was 30 % and there was a correlation between central nervous system involvement and death (p < 0.001).

We analyzed 50 cases of bicuspid aortic valve endocarditis in patients who presented to St. Thomas' Hospital from 1970 through 1998. These represented 12.3% of the 408 cases of native valve endocarditis (NVE). All patients were male, and their mean age was 39 years. Forty-five of the 50 cases were pathologically proven; 47 were clinically definite according to the Duke criteria and 49 according to our modifications of the Duke criteria. Viridans streptococci and staphylococci accounted for 72% of cases. The prevalences of clinical features were similar to those seen in NVE: fever (temperature >/=38 degrees C, 74%) and malaise (70%), although dyspnea was more frequent (36%). There was a high incidence of serious complications (72% heart failure; 30% periannular abscesses). Surgery was required during the initial admission in 82% of cases. Overall mortality was 14%, and surgical mortality was 9%. Few patients knew they had a "heart condition," and a bicuspid aortic valve was detected in only 35% of echocardiograms performed before surgery.

We analyzed 118 consecutive cases of pathologically proven infective endocarditis (100 cases of native valve endocarditis [NVE] and 18 cases of prosthetic valve endocarditis [PVE]) with use of the Beth Israel criteria, the Duke criteria, and our suggested modifications of the Duke criteria; we found improved diagnostic sensitivity with our modifications. These modifications included the following additional minor criteria: the presence of newly diagnosed clubbing, splenomegaly, splinter hemorrhages, and petechiae; a high erythrocyte sedimentation rate; a high C-reactive protein level; and the presence of central nonfeeding lines, peripheral lines, and microscopic hematuria. Analysis of the pathologically proven cases of NVE showed that 64% were probable by the Beth Israel criteria, 83% were definite by the Duke criteria, and 94% were definite by our modified Duke criteria. For the pathologically proven cases of PVE, 50% were probable by the Beth Israel criteria, 50% were definite by the Duke criteria, and 89% were definite by our modified Duke criteria. All cases of NVE and PVE rejected by the Duke criteria remained rejected by our modifications. Therefore, our modifications improved diagnostic sensitivity while retaining specificity.

BackgroundHost 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 ResultsUsing 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.ConclusionsSix‐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.

o Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis. Candida infective endocarditis (CIE) accounts for only 1 to 2% of all cases of infective endocarditis (IE) (1). This infection is important because it is associated with an exceptionally high mortality rate ranging from 30 to 80% (1-5). In addition, rates of fungemia have increased significantly in recent years, resulting in a growing number of patients at risk for this disease (2, 6).Due to its rarity, our understanding of the clinical features, treatment, and mortality of CIE has been derived predominantly from retrospective reviews of case series, case reports, and several small prospective series (1, 2, 7). The standard-ofcare treatment for CIE has historically been an amphotericin B-based regimen coupled with adjunctive surgical therapy. However, the options for treating invasive Candida infections changed with the development of the echinocandins. Echinocandins have fungicidal activity and exert their effect by inhibiting beta-glucan synthesis and disrupting the fungal cell wall. In 2003, caspofungin, the first echinocandin, was approved as therapy for invasive candidiasis, and since that time there has been a small but growing body of literature regarding echinocandin use in CIE (1,2,(8)(9)(10)(11)(12)(13). This has resulted in the addi...