Cutibacterium species valvular and cardiac device-related infective endocarditis: contemporary data from the GAMES prospective cohort (2008-2023).

BACKGROUND: Information on infective endocarditis (IE) caused by Cutibacterium spp. is limited and new Duke-ISCVID criteria have not yet been properly assessed. We examined clinical characteristics, outcomes and performance of diagnostic tests for Cutibacterium valvular and cardiac implantable electronic device-related IE (CIED-IE). METHODS: Data corresponding to all episodes of Cutibacterium IE recorded from 2008 to 2023 in a prospective national cohort including 46 Spanish hospitals were examined. Possible IE cases were reassessed using the new criteria. The sensitivity of blood cultures, valvular and CIED cultures, and PCR of the 16SrRNA gene and sequencing (16SPCR) was evaluated. RESULTS: There were 67/6,692 (1%) episodes of IE caused by Cutibacterium spp., 85% affecting men. Of these, 50 were valve-related (45 prosthetic, 5 native) and 17 CIED-related. The new criteria identified 8 additional cases and reclassified 15 as definite IE. Intracardiac complications (abscess, pseudoaneurysm, perforation or intracardiac fistula) occurred in 23/50 (46%) valvular IE episodes, leading to 18% mortality, and up to 40% mortality if surgery was indicated but could not be performed. All CIED-IE cases underwent device removal and no deaths were recorded. Positive diagnosis rates for blood cultures, valve/device cultures and 16SPCR were 52%, 70% and 82%, respectively. CONCLUSION: Cutibacterium IE is a rare yet potentially life-threatening condition that warrants a high index of suspicion in men with endovascular prosthetic material. The new Duke-ISCVID criteria and molecular techniques are useful for its diagnosis. Considering a significant complication rate, cardiac surgery and removal of CIEDs play a key role in reducing mortality.

Prevalence and prognostic impact of stroke in a national cohort of infective endocarditis.

BACKGROUND: Stroke is a common complication of infective endocarditis (IE). Our aim was to describe the prevalence and prognostic impact of stroke in a national cohort of IE. METHODS: Consecutive inclusion at 46 Spanish hospitals between 2008 and 2021. RESULTS: Out of 5667 IE cases, 1125 had acute stroke (19.8%): 818 ischemic strokes (811 cardioembolic strokes (193 with hemorrhagic transformation), 4 transient ischemic attacks, 3 lacunar infarctions), 127 intracranial hemorrhages, and 27 other neurological complications (cerebral abscesses, encephalitis, and meningitis). Compared to patients without stroke, those with stroke had a similar mean age (69 years) but were more frequently female (68.2% vs 63.7%, p = 0.04) and had a higher incidence of intracardiac complications (35% vs 30%, p = 0.01), surgical indication (69.9% vs 65.9%, p = 0.001), in-hospital mortality (40.9% vs 22.0%, p < 0.001), and 1-year mortality (46.2% vs 27.9%, p < 0.001). The following variables were independently associated with stroke: mitral location (odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.34-1.8, p < 0.001), vascular phenomenon (OR = 2.9, 95% CI = 2.4-3.6, p = 0.0001), acute renal failure (OR = 1.2, 95% CI = 1.0-1.4, p = 0.021), septic shock (OR = 1.3, 95% CI = 1.1-1.6, p = 0.007), sepsis (OR = 1.3, 95% CI = 1.1-1.6, p = 0.005), surgery indicated but not performed (OR = 1.4, 95% CI = 1.2-1.7, p < 0.001), community-acquired IE (OR = 1.2, 95% CI = 1-1.4, p = 0.017), and peripheral embolization (OR = 1.6, 95% CI = 1.4-1.9, p < 0.001). Stroke was an independent predictor of in-hospital (OR = 2.1, 95% CI = 1.78-2.51, p < 0.001) and 1-year mortality (hazard ratio = 1.9, 95% CI = 1.6-2.5). CONCLUSION: One-fifth of patients with IE have concomitant stroke. Stroke is associated with mortality.

EN-DALBACEN 2.0 Cohort: real-life study of dalbavancin as sequential/consolidation therapy in patients with infective endocarditis due to Gram-positive cocci.

OBJECTIVES: Infective endocarditis (IE) has high mortality and morbidity and requires long hospital stays to deliver the antibiotic treatment recommended in clinical practice guidelines. We aimed to analyse the health outcomes of the use of dalbavancin (DBV) in the consolidation treatment of IEs caused by Gram-positive cocci and to perform a pharmacoeconomic study. MATERIALS AND METHODS: This observational, retrospective, Spanish multicentre study in patients with IE who received DBV as part of antibiotic treatment in consolidation phase were followed for at least 12 months. The study was approved by the Provincial Committee of the coordinating centre. RESULTS: The study included 124 subjects, 70.2% male, with a mean age of 67.4 years and median Charlson index of 4 (interquartile range: 2.5-6). Criteria for definite IE were met by 91.1%. Coagulase-negative staphylococci (38.8%), Staphylococcus aureus (22.6%), Enterococcus faecalis (19.4%), and Streptococcus Spp. (9.7%) were isolated more frequently, all susceptible to vancomycin. Before DVB administration, 91.2% had undergone surgery; 60.5% had received a second regimen for 24.5 d (16.6-56); and 20.2% had received a third regimen for 14.5 d (12-19.5). DBV was administered to facilitate discharge in 95.2% of cases. At 12 months, the effectiveness was of 95.9%, and there was 0.8% loss to follow-up, 0.8% IE-related death, and 3.2% relapse. Adverse events were recorded in 3.2%. The hospital stay was reduced by 14 d, and there was a mean savings of 5548.57 €/patient vs. conventional treatments. CONCLUSION: DBV is highly effective, safe, and cost-effective as consolidation therapy in patients with IE by Gram-positive cocci, with few adverse events.

HPV Infection of the Oropharyngeal, Genital and Anal Mucosa and Associated Dysplasia in People Living with HIV.

BACKGROUND: The main objectives were to describe the prevalence of HPV, its genotypes and HPV-associated dysplastic lesions in the oropharyngeal mucosa of PLHIV and related factors. MATERIAL AND METHODS: This cross-sectional prospective study consecutively enrolled PLHIV attending our specialist outpatient units. At visit, HIV-related clinical and analytical variables were gathered, and oropharyngeal mucosa exudates were taken to detect HPV and other STIs by polymerase chain reaction. Samples were also taken from the anal canal of all participants and from the genital mucosa of the women for HPV detection/genotyping and cytological study. RESULTS: The 300 participants had a mean age of 45.1 years; 78.7% were MSM and 21.3% women; 25.3% had a history of AIDS; 99.7% were taking ART; and 27.3% had received an HPV vaccine. HPV infection prevalence in the oropharynx was 13%, with genotype 16 being the most frequent (2.3%), and none had dysplasia. Simultaneous infection with Treponema pallidum (HR: 4.02 (95% CI: 1.06-15.24)) and a history of anal HSIL or SCCA (HR: 21.52 (95% CI: 1.59-291.6)) were risk factors for oropharyngeal HPV infection, whereas ART duration (8.8 vs. 7.4 years) was a protective factor (HR: 0.989 (95% CI: 0.98-0.99)). CONCLUSIONS: The prevalence of HPV infection and dysplasia was low in the oropharyngeal mucosae. A higher exposure to ART was protective against oral HPV infection.

Role of Low-Risk HPV PCR Monoinfection in Screening for HSIL and Anal Cancer in Men Who Have Sex with Men Living with HIV.

To determine the value of low-risk human papillomavirus (HPV) PCR to screen for "high-grade anal squamous intraepithelial lesion and anal cancer" (HSIL-plus), rate of patients with low-grade anal squamous intraepithelial lesion (LSIL) progressing to HSIL-plus, and progression-related factors. Prospective, longitudinal study of consecutive MSM-LHIV attended between May 2010 and December 2021 and followed for 43 months (IQR: 12-76). HIV-related variables were gathered at baseline, performing anal cytology for HPV detection/genotyping, thin-layer cytological study, and high-resolution anoscopy (HRA). Follow-up was annual when HRA was normal or LSIL, and post-treatment in cases of HSIL-plus, re-evaluating sexual behavior, viral-immunological status, and HPV infection of anal mucosa. The 493 participants had mean age of 36 years: CD4 nadir < 200 cells/uL in 23.1%, virological failure in 4.1%, and tetravalent HPV vaccine > 5 years earlier in 15%. HSIL-plus was ruled out in patients with monoinfection by low-risk HPV genotype and normal cytology (100% sensitivity, 91.9% specificity, PPV 2.9%, and NPV 100%). Progression from LISL to HSIL-plus occurred in 4.27% of patients within 12 months (IQR: 12-12): risk factors were acquisition of high-risk (HR: 4.15; 95% CI: 1.14-15.03) and low-risk (HR: 3.68 95% CI: 1.04-12.94) HPV genotypes, specifically genotype 6 (HR: 4.47, 95% CI: 1.34-14.91), and history of AIDS (HR: 5.81 95% CI: 1.78-18.92). Monoinfection by LR-HPV genotypes in patients with normal cytology is not associated with anal cancer or precursor lesions. Progression from LSIL to HSIL-plus, observed in <5% of patients, was related to acquisition of HR and LR HPV genotypes, especially 6, and a history of AIDS.

Incidence and Clearance of Anal Human Papillomavirus Infection in 16 164 Individuals, According to Human Immunodeficiency Virus Status, Sex, and Male Sexuality: An International Pooled Analysis of 34 Longitudinal Studies.

BACKGROUND: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized. METHODS: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants. RESULTS: Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection. CONCLUSIONS: This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.

Blood Culture-Negative Infective Endocarditis by Mycoplasma hominis: Case Report and Literature Review.

Mycoplasma hominis is a habitual colonizing microorganism of the lower genital tract but can exceptionally be the causal agent of blood culture-negative infective endocarditis (IE). Only 11 cases of this entity have been published to date. The study objectives were to describe the first case diagnosed in our center of IE by M. hominis on pacemaker lead and to carry out a narrative review. Among published cases of IE by this microorganism, 72.7% were male, with a mean age of 45 years and a history of valve surgery; the diagnosis was by culture (54.5%) or molecular technique (45.5%), and the prognosis was favorable in 72.7% of cases. The most frequently prescribed antibiotics were doxycycline, quinolones, and clindamycin.

Bartonella Endocarditis in Spain: Case Reports of 21 Cases.

Blood culture negative endocarditis (BCNE) is frequent in infective endocarditis (IE). One of the causes of BCNE is fastidious microorganisms, such as Bartonella spp. The aim of this study was to describe the epidemiologic, clinical characteristics, management and outcomes of patients with Bartonella IE from the "Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España (GAMES)"cohort. Here we presented 21 cases of Bartonella IE. This represents 0.3% of a total of 5590 cases and 2% of the BCNE from the GAMES cohort. 62% were due to Bartonella henselae and 38% to Bartonella quintana. Cardiac failure was the main presenting form (61.5% in B. hensalae, 87.5% in B. quintana IE) and the aortic valve was affected in 85% of the cases (76% in B. henselae, 100% in B. quintana IE). Typical signs such as fever were recorded in less than 40% of patients. Echocardiography showed vegetations in 92% and 100% of the patients with B. henselae and B. quintana, respectively. Culture was positive only in one patient and the remaining were diagnosed by serology and PCR. PCR was the most useful tool allowing for diagnosis in 16 patients (100% of the studied valves). Serology, at titers recommended by guidelines, only coincided with PCR in 52.4%. Antimicrobial therapy, in different combinations, was used in all cases. Surgery was performed in 76% of the patients. No in-hospital mortality was observed. One-year mortality was 9.4%. This article remarks the importance for investigating the presence of Bartonella infection as causative agent in all BCNE since the diagnosis needs specific microbiological tools and patients could benefit of a specific treatment.

Tenofovir Alafenamide Plasma Concentrations Are Reduced in Pregnant Women Living With Human Immunodeficiency Virus (HIV): Data From the PANNA Network.

BACKGROUND: Tenofovir alafenamide (TAF), a prodrug of tenofovir (TFV), is included in the majority of the recommended first-line antiretroviral regimens for patients living with human immunodeficiency virus (HIV), but there are limited data on TAF use in pregnant women. We aimed to examine the plasma pharmacokinetics of TAF and TFV in pregnant women from Europe. METHODS: Pregnant women living with HIV were included from treatment centers across Europe, and intensive pharmacokinetic sampling in the third trimester and postpartum was performed. Pharmacokinetic parameters of TAF and TFV were determined with noncompartmental analysis. The proportion of women with a TAF area under the curve (AUClast) below the target of 53.1 ng∗h/mL was determined. Clinical efficacy and safety outcome parameters were reported. RESULTS: In total, 20 pregnant women living with HIV were included. At the third trimester, geometric mean TAF AUClast and Cmax were decreased by 46% and 52%, respectively, compared with postpartum. TFV AUC0-24h, Cmax, and Ctrough decreased by 33%, 30%, and 34%, respectively. The proportion of women with a TAF AUClast < 53.1 ng∗h/mL was 6% at third trimester and 0% postpartum. One out of 20 women had a viral load > 50 copies/mL at third trimester and no mother-to-child transmission occurred. CONCLUSIONS: TAF plasma concentrations were reduced by about half in women living with HIV during third trimester of pregnancy but remained above the predefined efficacy target in the majority of the pregnant women. TFV concentrations were reduced by approximately 30% during third trimester. Despite the observed exposure decrease, high virologic efficacy was observed in this study.

Aspergillus endocarditis in the recent years, report of cases of a multicentric national cohort and literature review.

OBJECTIVES: (1) To describe the incidence, clinical characteristics, treatment and outcome of Aspergillus Endocarditis (AE) in a nationwide multicentric cohort (GAMES). (2) To compare the AE cases of the GAMES cohort, with the AE cases reported in the literature since 2010. (3) To identify variables related to mortality. METHODS: We recruited 10 AE cases included in the GAMES cohort (January 2008-December 2018) and 51 cases from the literature published from January 2010 to July 2019. RESULTS: 4528 patients with infectious endocarditis (IE) were included in the GAMES cohort, of them 10 (0.2%) were AE. After comparing our 10 cases with the 51 of the literature, no differences were found. Analysing the 61 AE cases together, 55.7% were male, median age 45 years. Their main underlying conditions were as follows: prosthetic valve surgery (34.4%) and solid organ transplant (SOT) (19.7%). Mainly affecting mitral (36.1%) and aortic valve (29.5%). Main isolated species were as follows: Aspergillus fumigatus (47.5%) and Aspergillus flavus (24.6%). Embolisms occurred in 54%. Patients were treated with antifungals (90.2%), heart surgery (85.2%) or both (78.7%). Overall, 52.5% died. A greater mortality was observed in immunosuppressed patients (59.4% vs. 24.1%, OR = 4.09, 95%CI = 1.26-13.19, p = .02), and lower mortality was associated with undergoing cardiac surgery plus azole therapy (28.1% vs. 65.5%, OR = 0.22, 95%CI = 0.07-0.72, p = .01). CONCLUSIONS: AE accounts for 0.2% of all IE episodes of a national multicentric cohort, mainly affecting patients with previous valvular surgery or SOT recipients. Mortality remains high especially in immunosuppressed hosts and azole-based treatment combined with surgical resection are related to a better outcome.

Real-world outcomes of COVID-19 treatment with remdesivir in a Spanish hospital.

ABSTRACT: Remdesivir is the only antiviral approved for lower respiratory tract infection produced by SARS-CoV-2. The main objective of this study was to determine the mortality rate, readmissions, mean hospital stay, need for higher levels of oxygen support, and adverse effect-induced abandonment rate in hospitalized patients diagnosed with COVID-19 and treated with remdesivir (RDSV). The secondary objective was to determine mortality-related risk factors in these patients.The study included a prospective cohort of patients admitted to a third level Spanish hospital between July 5, 2020 and February 3, 2021 for COVID-19 diagnosed by SARS-CoV-2 polymerase chain reaction and/or antigen test and treated with RDSV.Remdesivir was received by 185 patients (69.7% males) with a mean age of 62.5 years, median Charlson index of 3 (interquartile range [IQR]: 1-4), and median ambient air oxygen saturation of 91% (IQR: 90-93); 61.6% of patients had hyper-inflammatory syndrome at admission. Median time with symptoms before RDSV treatment was 5 days (IQR: 3-6) and the median hospital stay was 10 days (IQR: 7-15); 19 patients (10.3%) died after a median stay of 13.5 days (IQR: 9.7-24 days), 58 patients (12.9%) were admitted to ICU, 58 (31.4%) needed higher levels of oxygen support, 0.5% abandoned the treatment due to adverse effects, and there were no readmissions. The only mortality-related factor was the need for higher levels of oxygen support (odds ratio 12.02; 95% confidence interval 2.25-64.2).All studied patients were admitted to hospital with a diagnosis of COVID-19 and in respiratory failure, needing initial low-flow oxygen support, and all received RDSV within 1 week of symptom onset. The percent mortality was lower in these patients than was observed in all patients with severe COVID-19 admitted to our center (10.3% vs 20.3%, respectively). Despite receiving RDSV, 1 in 3 patients needed higher levels of oxygen support, the sole mortality-related factor.

Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies.

BACKGROUND: Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality. METHODS: We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models. FINDINGS: The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15-18 years and 28·8% (141 of 490) among those age 23-24 years (ptrend=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25-34 years and 22·8% (451 of 1979) among those age 55 and older (ptrend<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15-18 and 13·9% (166 of 1192) among those age 23-24 years (ptrend=0·0076); the prevalence plateaued thereafter (ptrend=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36-1·73), HPV16-positive HSIL+ (1·66, 1·36-2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04-1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age. INTERPRETATION: High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+. FUNDING: International Agency for Research on Cancer.

Outcomes and Risk Factors of Septic Shock in Patients With Infective Endocarditis: A Prospective Cohort Study.

BACKGROUND: Little is known about the characteristics and impact of septic shock (SS) on the outcomes of infective endocarditis (IE). We aimed to investigate the characteristics and outcomes of patients with IE presenting with SS and to compare them to those of IE patients with sepsis (Se) and those with neither Se nor SS (no-Se-SS). METHODS: This is a prospective cohort study of 4864 IE patients from 35 Spanish centers (2008 to 2018). Logistic regression analyses were performed to identify risk factors for SS and mortality. RESULTS: Septic shock and Se presented in 597 (12.3%) and 559 (11.5%) patients, respectively. Patients with SS were younger and presented significantly higher rates of diabetes, chronic renal and liver disease, transplantation, nosocomial acquisition, Staphylococcus aureus, IE complications, and in-hospital mortality (62.5%, 37.7% for Se and 18.2% for no-Se-SS, P < .001). Staphylococcus aureus (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.34-2.81; P < .001), Gram negative (OR, 2.21; 95% CI, 1.25-3.91; P = .006), nosocomial acquisition (OR, 1.44; 95% CI, 1.07-1.94; P = .015), persistent bacteremia (OR, 1.82; 95% CI, 1.24-2.68; P = .002), acute renal failure (OR, 3.02; 95% CI, 2.28-4.01; P < .001), central nervous system emboli (OR, 1.48; 95% CI, 1.08-2.01; P = .013), and larger vegetation size (OR, 1.01; 95% CI, 1.00-1.02; P. = 020) were associated with a higher risk of developing SS. Charlson score, heart failure, persistent bacteremia, acute renal failure, mechanical ventilation, worsening of liver disease, S aureus, and receiving aminoglycosides within the first 24 hours were associated with higher in-hospital mortality, whereas male sex, native valve IE, and cardiac surgery were associated with lower mortality. CONCLUSIONS: Septic shock is frequent and entails dismal prognosis. Early identification of patients at risk of developing SS and early assessment for cardiac surgery appear as key factors to improve outcomes.

Blood culture-negative infective endocarditis: a worse outcome? Results from a large multicentre retrospective Spanish cohort study.

BACKGROUND: To assess the impact of blood cultures negative infective endocarditis (BCNIE) on in-hospital mortality. METHODS: Prospective multicentre study with retrospective analysis of a Spanish cohort including adult patients with definite IE. Cardiac implantable devices infection were excluded. Comparisons between blood cultures positive and BCNIE groups were performed to analyse in-hospital mortality. RESULTS: 1001 cases were included of which 83 (8.3%) had BCNIE. Alternative microbiological diagnosis was achieved for 39 (47%) out 83 cases. The most frequent identifications were: Coxiella burnetii (11; 28.2%), Tropheryma whipplei (4; 10.3%), Streptococcus gallolyticus (4;10.3%) and Staphylococcus epidermidis (3; 7.7%). Surgery was performed more frequently in BCNIE group (57.8 vs. 36.9%, p < .001). All-cause in-hospital mortality rate was 26.7% without statistical difference between compared groups. BCNIE was not associated to worse mortality rate in Cox regression model (aHR = 1.37, 95% CI 0.90-2.07, p = .14). Absence of microbiological diagnosis was also not associated to worse in-hospital prognosis (aHR = 1.62, 95% CI 0.99-2.64, p = .06). CONCLUSIONS: In our cohort, BCNIE was not associated to greater in-hospital mortality based in multivariate Cox regression models. The variables most frequently associated with mortality were indicated but not performed surgery (aHR = 2.48, 95% CI 1.73-3.56, p < .001), septic shock (aHR = 2.24, 95% CI 1.68-2.99, p < .001), age over 65 years (aHR = 1.88, 95% CI 1.40-2.52, p < .001) and complicated endocarditis (aHR = 1.79, 95% CI 1.36-2.37, p < .001).

Risk factors for ≥high-grade anal intraepithelial lesions in MSM living with HIV and the response to topical and surgical treatments.

BACKGROUND: The objective of this study in MSM living with HIV was to determine the incidence of HSIL and ASCC, related factors, and the response to treatment. PATIENTS AND METHODS: Data were gathered in 405 consecutive HIV-infected MSM (May 2010-December 2018) at baseline and annually on: sexual behavior, anal cytology, and HPV PCR and/or high-resolution anoscopy results. They could choose mucosectomy with electric scalpel (from May 2010) or self-administration of 5% imiquimod 3 times weekly for 16 weeks (from November 2013). A multivariate logistic regression model was developed for ≥HSIL-related factors using a step-wise approach to select variables, with a significance level of 0.05 for entry and 0.10 for exit, applying the Hosmer-Lemeshow test to assess the goodness of fit. RESULTS: The study included 405 patients with a mean age of 36.2 years; 56.7% had bachelor´s degree, and 52.8% were smokers. They had a mean of 1 (IQR 1-7) sexual partner in the previous 12 months, median time since HIV diagnosis of 2 years, and mean CD4 nadir of 367.9 cells/uL; 86.7% were receiving ART, the mean CD4 level was 689.6 cells/uL, mean CD4/CD8 ratio was 0.77, and 85.9% of patients were undetectable. Incidence rates were 30.86/1,000 patient-years for ≥high squamous intraepithelial lesion (HSIL) and 81.22/100,000 for anal squamous cell carcinoma (ASCC). The ≥HSIL incidence significantly decreased from 42.9% (9/21) in 2010 to 4.1% (10/254) in 2018 (p = 0.034). ≥HSIL risk factors were infection with HPV 11 (OR 3.81; 95%CI 1.76-8.24), HPV 16 (OR 2.69, 95%CI 1.22-5.99), HPV 18 (OR 2.73, 95%CI 1.01-7.36), HPV 53 (OR 2.97, 95%CI 1.002-8.79); HPV 61 (OR 11.88, 95%CI 3.67-38.53); HPV 68 (OR 2.44, CI 95% 1.03-5.8); low CD4 nadir (OR1.002; 95%CI 1-1.004) and history of AIDS (OR 2.373, CI 95% 1.009-5.577). Among HSIL-positive patients, the response rate was higher after imiquimod than after surgical excision (96.7% vs 73.3%, p = 0.009) and there were fewer re-treatments (2.7% vs 23.4%, p = 0.02) and adverse events (2.7% vs 100%, p = 0.046); none developed ASCC. CONCLUSIONS: HSIL screening and treatment programs reduce the incidence of HSIL, which is related to chronic HPV infection and poor immunological status. Self-administration of 5% imiquimod as first-line treatment of HSIL is more effective than surgery in HIV+ MSM.

Characteristics and Outcome of Acute Heart Failure in Infective Endocarditis: Focus on Cardiogenic Shock.

BACKGROUND: Studies investigating the impact of cardiogenic shock (CS) on endocarditis are lacking. METHODS: Prospectively collected cohort from 35 Spanish centers (2008-2018). Logistic regression analyses were performed to identify risk factors for developing CS and predictors of mortality. RESULTS: Among 4856 endocarditis patients, 1652 (34%) had acute heart failure (AHF) and 244 (5%) CS. Compared with patients without AHF and AHF but no CS, patients with CS presented higher rates of surgery (40.5%, 52.5%, and 68%; P < .001) and in-hospital mortality (16.3%, 39.1%, and 52.5%). Compared with patients with septic shock, CS patients presented higher rates of surgery (42.5% vs 68%; P < .001) and lower rates of in-hospital and 1-year mortality (62.3% vs 52.5%, P = .008, and 65.3% vs 57.4%, P = .030). Severe aortic and mitral regurgitation (OR [95% CI], 2.47 [1.82-3.35] and 3.03 [2.26-4.07]; both P < .001), left-ventricle ejection fraction <60% (1.72; 1.22-2.40; P = .002), heart block (2.22; 1.41-3.47; P = .001), tachyarrhythmias (5.07; 3.13-8.19; P < .001), and acute kidney failure (2.29; 1.73-3.03; P < .001) were associated with higher likelihood of developing CS. Prosthetic endocarditis (2.03; 1.06 -3.88; P = .032), Staphylococcus aureus (3.10; 1.16 -8.30; P = .024), tachyarrhythmias (3.09; 1.50-10.13; P = .005), and not performing cardiac surgery (11.40; 4.83-26.90; P < .001) were associated with a higher risk of mortality. CONCLUSIONS: AHF is common among patients with endocarditis. CS is associated with high mortality and should be promptly identified and assessed for cardiac surgery.

Effectiveness of the Quadrivalent HPV Vaccine in Preventing Anal ≥ HSILs in a Spanish Population of HIV+ MSM Aged > 26 Years.

Anal squamous cell carcinoma is the most frequent virus-related non-AIDS-defining neoplasia among HIV-infected individuals, especially MSM. The objectives of this study were to analyze the effectiveness of the quadrivalent HPV (qHPV) vaccine to prevent anal ≥ high-grade squamous intraepithelial lesions (≥HSILs), external ano-genital lesions (EAGLs), and infection by qHPV vaccine genotypes in HIV+ MSM, and to study the immunogenicity of the vaccine and risk factors for ≥ HSILs. This study is nested within a randomized, double-blind, placebo-controlled trial of the qHPV vaccine, which enrolled participants between May 2012 and May 2014, with a 48-month follow-up. A vaccine or placebo was administered at 0, 2, and 6 months, and vaccine antibody titers were evaluated at 7, 12, 24, 36, and 48 months. Data were gathered at 12, 24, 36, and 48 months on sexual habits, CD4/CD8 cell/counts, HIV viral load, and the results of cytology (Thin Prep® Pap Test), HPV PCR genotyping (Linear Array HPV Genotyping Test), and high-resolution anoscopy (Zeiss 150 fc© colposcope). The study included 129 patients (mean age of 38.8 years, 40 [31%] with a history of AIDS, 119 [92.2%] receiving ART, and 4 [3.3%] with virological failure), 66 (51.2%) in vaccine arm and 63 (48.4%) in placebo arm. The vaccine and placebo groups did not differ in ≥ HSILs (14.1 vs. 13.1%, respectively, p = 0.98) or EAGL (11.1 vs. 6.8%, p = 0.4) rates during follow-up; however, a protective effect against HPV 6 was observed during the first year of follow-up in the vaccine versus placebo group (7.5% vs. 23.4%; p = 0.047). A between-arm difference (p = 0.0001) in antibodies against qHPV vaccine genotypes was observed at 7 months (76.9% in vaccine arm vs. 30.2% in placebo arm), 12 months (68.1% vs. 26.5%), 24 months (75% vs. 32.5%), 36 months (90% vs. 24.4%), and 48 months (87.2% vs. 30%). Finally, the factor associated with the risk of anal ≥ HSIL onset during the four-year follow-up was the receipt of the last dose of the vaccine less than 6 months earlier in comparison to those vaccinated for a longer period (82.4% vs. 17.6% (OR 0.869 [95% CI, 0.825-0.917]). Vaccine and placebo arms did not significantly differ in ≥ HSIL or EAGL rates or in protection against infection by HPV genotype vaccine except for HPV6 at 12 months after the first dose. A long-lasting immune response was observed in almost all the vaccinated men. The main protective factor against ≥ HSIL was to have completed the vaccination regimen more than 6 months earlier.

Prevalence of Colorectal Neoplasms Among Patients With Enterococcus faecalis Endocarditis in the GAMES Cohort (2008-2017).

OBJECTIVE: To investigate the rate of colorectal neoplasms (CRNs) in patients who have Enterococcus faecalis infective endocarditis (EFIE) with available colonoscopies and to assess whether this is associated with the identification of a focus the infection. PATIENTS AND METHODS: Retrospective analysis of data from a prospective multicenter study involving 35 centers who are members of the Grupo de Apoyo para el Manejo de la Endocarditis en España [Support Group for the Management of Infective Endocarditis in Spain] cohort. A specific set of queries regarding information on colonoscopy and histopathology of colorectal diseases was sent to each participating center. Four-hundred sixty-seven patients with EFIE were included from January 1, 2008, to December 31, 2017, from whom data on colonoscopy performance and results were available in 411 patients. RESULTS: One hundred forty-two (34.5%) patients had a colonoscopy close to the EFIE episode. The overall rate of colorectal diseases was 70.4% (100 of 142), whereas the prevalence of CRN (advanced adenomas and colorectal carcinoma) was 14.8% (21 of 142), with no significant differences between the group of EFIE of unknown focus and that with an identified focus. CONCLUSION: Our study adds to prior evidence suggesting a much higher rate of CRN among patients with EFIE than in the general population of the same age and sex. In addition, our findings suggest that this phenomenon might take place both in EFIE with an unknown and an identified source of infection.

The Effect of Pregnancy on the Pharmacokinetics of Total and Unbound Dolutegravir and Its Main Metabolite in Women Living With Human Immunodeficiency Virus.

BACKGROUND: Pharmacokinetic and efficacy data on dolutegravir in pregnant women living with human immunodeficiency virus (HIV) are still limited but needed to support its use as one of the preferred antiretroviral agents. METHODS: Within the multicenter Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women (PANNA) study, pregnant women living with HIV and using dolutegravir once daily (50 mg, with food) underwent 24-hour pharmacokinetic profiling in their third trimester and postpartum. Dolutegravir exposure in the third trimester was considered adequate if geometric mean unbound, pharmacologically active, minimal plasma concentrations (Cmin, unbound) and ≥90% of individual Cmin, unbound levels were >0.85 µg/L, the proposed 90% inhibitory concentration for unbound dolutegravir. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) for comparison of total and unbound pharmacokinetic parameters in the third trimester and postpartum were calculated, including the metabolic ratio for dolutegravir-glucuronide. Safety and virological data were collected. RESULTS: Seventeen women (76% black) were enrolled (25 evaluable pharmacokinetic profiles; 15 in the third trimester, 10 in postpartum). In the third trimester, geometric mean (coefficient of variation, %) Cmin, unbound was 2.87 (87) µg/L and 93% of individual Cmin, unbound levels were >0.85 µg/L. The GMR (90% CI) in the third trimester vs postpartum was 0.86 (.68-1.10) for area under the curve (AUC0-24h), and for Cmax, 0.93 (.77-1.13). GMR (90% CI) for the trough concentrations was 0.71 (.49-1.02), based on total dolutegravir concentrations. Four serious adverse events were reported, unlikely related to dolutegravir. The HIV polymerase chain reaction test was negative in 14/17 infants (result unknown for 3 infants). CONCLUSIONS: Pharmacokinetic changes for dolutegravir in late pregnancy are not clinically relevant and support the use of dolutegravir 50 mg once daily with food in pregnancy. CLINICAL TRIALS REGISTRATION: NCT00825929.

Genetic diversity of HIV in seminal plasma remains higher than in blood after short-term antiretroviral therapy.

OBJECTIVE: To provide insight on viral kinetics and genetic diversity of HIV in seminal plasma at baseline and 1 month after initiating antiretroviral therapy (ART). PATIENTS AND METHODS: Blood and seminal samples from patients with newly diagnosed HIV were obtained before ART initiation (T0) and 1 month after ART initiation (T1). HIV env genetic diversity was studied using deep sequencing Nextera and V3 chemistry in a MiSeq Illumina platform. The number of viral quasispecies (5% cut-off) and Shannon Index were used to analyse diversity. RESULTS: Forty-seven ART-naive patients were recruited between September 2016 and November 2018. At enrolment, the number of quasispecies in blood (median 4 (IQR 2-5)) was lower than in the seminal compartment (median 6, (IQR 4-8)) (p<0.01); the Shannon Index was also higher (p<0.001) in the seminal compartment than in blood (1.77 vs 0.64). At T1, for the 13 patients with detectable HIV in both blood/seminal plasma, viral diversity remained higher (p=0.139) in seminal plasma (median 2 (IQR 1-4.5)) than in blood (median 1 (IQR 1-1.5)) Integrase inhibitors (INI)-based regimens achieved higher levels of undetectability and led more frequently to lower variability (p<0.001) than protease inhibitors (PI) or non-nucleoside reverse transcriptase inhibitors (NNRTI). CONCLUSION: We provide here further evidence of a larger genetic diversity in seminal plasma, both at diagnosis and short term after ART initiation. Our results strengthen previous findings on HIV diversity in seminal plasma. In addition, INIs decrease variability more rapidly than PI and NNRTI in both blood and seminal plasma.