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Bacterial prostatitis, acute or chronic, is one of the most prevalent urogenital infections in men. Its diagnosis requires the application of a careful methodology. Gram-negative bacilli are the most frequent causative agents, and in recent years, an increase in the frequency of multiresistant bacteria has been detected. The choice of the optimal antimicrobial treatment requires the selection of drugs with proven in vitro activity associated with good penetration into the prostatic tissue, especially in chronic forms of infection.The aim of this article is to summarize the current evidence regarding the pathogenesis, etiology, empirical and definitive antimicrobial therapy, and new pharmacotherapeutic interventions to improve the prognosis of bacterial acute or chronic prostatitis.Bacterial prostatitis requires the application of an accurate diagnostic protocol to identify the causative agent and establish the optimal antimicrobial treatment. The structural and biochemical characteristics of prostatic tissue result in poor penetration of antimicrobials; therefore, in the choice of treatment, it is essential to select agents with proven antimicrobial activity and pharmacokinetic characteristics that ensure good and sustained concentrations in this area. Patients with chronic forms of infection require prolonged treatment, and relapses of the infectious process are frequent.

Dysplasia; Screening; HIV-infected Displasia; Cribado; Infectado por el VIH Displàsia; Cribratge; Infectat pel VIH Background: HIV-infected men who have sex with men (MSM) are at high risk to develop human papilloma virus (HPV)-related oropharyngeal cancer. The aim of our study was to assess the usefulness of a pilot oral dysplasia screening program and its correlation with an anal dysplasia screening program. Methods: This was a prospective study with HIV-infected MSM. Oral and anal screenings were performed based on HPV determination, liquid cytology, direct and microscopy oral examinations, high-resolution anoscopy and biopsies, if necessary. Results: A total of 103 patients were included. The mean age of the patients was 44.6 years, 55.3% were smokers, and 57.3% had a history of previous anal high-grade squamous intraepithelial lesions (HSILs). The prevalence of oral HPV infections was 14% (9% HPV-high risk), the prevalence of abnormal cytology was 25.2%, and in 4.8% of the patients, oral examinations showed suspicious HSILs. Oral microscopy did not detect additional lesions that visual inspection. Five oral biopsies were performed and the results were normal. No risk factors for oral HPV infections were identified. The prevalence of anal HPV infections was 88.3% (76.7% HPV-high risk), 52.9% of the patients had altered cytology, and in 45.6% anoscopy showed changes suggestive of HSILs. Seventy-two anal biopsies were performed, detecting 25 cases of HSILs (24.3%). A poor correlation was observed between oral and anal HPV infections (κ = 0.037). Conclusions: The prevalence of oral HPV infections, abnormal cytology and lesions in HIV-infected MSM was low, and their correlation with anal HPV-related lesions was slight. These results confirm the current barriers to oral dysplasia screening techniques. Study funded by program MISP of MSD (Merck HPV Investigator Study Program). MISP project code 58237.

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.

Objectives To assess the clinical and immunovirological outcomes among naive patients with advanced HIV presentation starting an antiretroviral regimen in real-life settings. Methods This was a multicentre, prospective cohort study. We included all treatment-naive adults with advanced HIV disease (CD4+ T cell count Results We included 1594 patients with advanced HIV disease [median CD4+T cell count of 81 cells/mm3and 371 (23.3%) with AIDS-defining illness] and with a median follow-up of 4.44 years. The most common ART used was an integrase strand transfer inhibitor (InSTI) regimen (46.9%), followed by PI (35.7%) and NNRTI (17.4%), with adjusted mortality rates at 3 years of 3.1% (95% CI 1.8%–4.3%), 4.7% (95% CI 2.2%–7.1%) and 7.6% (95% CI 5.4%–9.7%) (P = 0.001), respectively. Factors associated with increased mortality included older age and history of injection drug use, whilst treatment with an InSTI regimen was a protective factor [HR 0.5 (95% CI 0.3–0.9)]. A sensitivity analysis with propensity score procedure confirms these results. Patients who started an InSTI achieved viral suppression and CD4+ T cell count above 350 cells/mm3significantly earlier. Conclusions In this large real-life prospective cohort study, a significant lower mortality, earlier viral suppression and earlier immune reconstitution were observed among patients with advanced HIV disease treated with InSTIs.

BACKGROUND: We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19.METHODS: In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978.FINDINGS: Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90.INTERPRETATION: Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19.FUNDING: US National Institutes of Health and Operation Warp Speed.

Community-acquired pneumonia (CAP) is a common infection with a constantly evolving etiological spectrum. This changing etiology conditions the adequate selection of optimal therapeutic regimens, both in empirical and definitive treatments. In recent years, new antimicrobials have been approved by regulatory authorities for use in CAP, although it is necessary to continue incorporating new antimicrobial agents that improve the activity profile in relation to the appearance of bacterial resistance in certain pathogens, such as pneumococcus, Staphylococcus aureus or Pseudomonas aeruginosa. Delafloxacin, omadacycline and lefamulin are the most recently approved antibiotics for CAP. These three antibiotics have shown non-inferiority to their comparators for the treatment of CAP with an excellent safety profile. However, in the 2019 ATS/IDSA guidelines, it has been considered that more information is needed to incorporate these new drugs into community-based treatment. New antimicrobials, such as solithromycin and nemonoxacin, are currently being studied in Phase III clinical trials. Both drugs have shown non-inferiority against the comparators and an acceptable safety profile; however, they have not yet been approved by the regulatory authorities. Several drugs are being tested in Phase I and II clinical trials. These include zabofloxacin, aravofloxacin, nafithromycin, TP-271, gepotidacin, radezolid, delpazolid, and CAL02. The preliminary results of these clinical trials allow us to assure that most of these drugs may play a role in the future treatment of CAP.

A higher incidence of malignancies has been described in patients with HIV infection compared to the general population.Observational retrospective study in patients with HIV infection followed up at the Vall d'Hebron University Hospital (Barcelona, Spain) between 2009 and 2017. The objective of this research was to estimate the incidence of malignancies in HIV patients and their surveillance. Age and sex-adjusted incidence was compared to the incidence calculated by the Spanish Cancer Registry network (REDECAN) in 2015.We included 2,773 patients (41,238 patients-year). Two hundred and eleven malignancies were diagnosed in 182 patients. Non-AIDS defining cancers accounted for 78.2% of the malignancies. The global incidence of cancer was 485 cases per 100,000 person-years. Twenty-year mortality rate was 31.2% in patients with cancer and 7.8% in patients without cancer. In men, adjusted for age, the incidence of malignancies was higher than the incidence in the general population (978.4 vs. 641 cases per 100,000 person-years, P.001). The most common malignancies in men were lung cancer, Kaposi sarcoma and Hodgkin lymphoma. In women, the incidence of malignancies was not higher than in the general population (340.6 vs. 404.7 cases per 100,000 person-years, P=.27). The most common malignancies among women were lung cancer, head and neck cancer, cervical cancer and Hodgkin's lymphoma.Men with HIV infection showed a statistically significant higher incidence of malignancies compared to the general Spanish population. Lung cancer was the most common non-AIDS defining cancer.

Resumen Introduccion Se ha descrito una mayor incidencia de neoplasias en los pacientes con infeccion por VIH en comparacion con la poblacion general. Pacientes y metodos Estudio observacional retrospectivo de la poblacion infectada por VIH en seguimiento en el Hospital Vall d’Hebron (Barcelona) entre 2009 y 2017. El objetivo de este estudio fue estimar la incidencia de neoplasias en estos pacientes con infeccion por VIH y su supervivencia. Se comparo la incidencia ajustada por edad y sexo en dicha poblacion con la calculada por la Red Espanola de Registros de Cancer (REDECAN) en 2015. Resultados Se incluyeron 2.773 pacientes (41.238 pacientes-ano). Se diagnosticaron 211 canceres en 182 pacientes. El 78,2% de las neoplasias fueron no definitorias de sida (NNDS). La tasa global de incidencia de cancer fue 485 neoplasias por 100.000 pacientes-ano. La mortalidad a 20 anos en pacientes con cancer fue del 31,2%, y del 7,8% en pacientes sin cancer. En varones, ajustada por edad, la incidencia de neoplasias fue mayor que en la poblacion general (978,4 vs. 641 por 100.000 pacientes-ano, p Conclusiones Los varones con infeccion por VIH presentaron una incidencia significativamente mayor de cancer que la poblacion espanola del mismo sexo. Los carcinomas pulmonares fueron las NNDS mas frecuentes.

Direct-acting antivirals (DAAs) for HCV treatment have improved tolerance and efficacy among adults, but experience in vertical transmission is scarce. In our vertically HIV/HCV co-infected youth cohort of 58 patients, DAA achieved excellent rates of cure among naïve and pretreated individuals. Treating vertically infected seems important as 29.6% displayed advanced fibrosis at treatment initiation.

Acute bacterial prostatitis; Antibiotic resistance; Relapse Prostatitis bacteriana aguda; Resistencia a los antibióticos; Recaída Prostatitis bacteriana aguda; Resistència als antibiòtics; Recaiguda The aim of the study was to analyze the risk factors for relapse in patients with acute bacterial prostatitis (ABP), focusing on the impact of different antibiotic regimens. We conducted an observational study of all patients diagnosed with ABP (irritative and/or obstructive urinary symptoms, temperature of >37.8°C, and the presence of bacteriuria in urine culture, in the absence of data suggesting pyelonephritis) from January 2017 to December 2018. The main outcome was relapse. We performed a multivariate analysis to identify the risk factors associated with relapse. A propensity score with inverse weighting was applied to attenuate antibiotic selection bias. We included 410 patients. The mean age was 68 years; 28.8% had diabetes mellitus, and 61.1% benign prostatic hyperplasia. The most common isolated bacteria were Escherichia coli (62.4%) and Klebsiella spp. (10%). The overall resistance rate was 39.5% to quinolones. The mortality rate was 1.2%, and the relapse rate was 6.3%. The only independent risk factor for relapse was inadequate antibiotic therapy (odds ratio [OR] 12.3; 95% confidence interval [95% CI], 3.5 to 43.1). When the antibiotic was modified according to the susceptibility pattern, the rates of relapse were 1.8% in those treated with ciprofloxacin, 3.6% with intravenous beta-lactam, 9.3% with co-trimoxazole, and 9.8% with oral (p.o.) beta-lactam (P = 0.03). Treatment with oral beta-lactam (OR, 5.3; 95% CI, 1.2 to 23.3) and co-trimoxazole (OR, 4.9; 95% CI, 1.1 to 23.2) were associated with a risk of relapse. In this large real-life observational study, a significantly higher relapse rate was observed when antibiotic treatment was inadequate. When the antibiotic was tailored, quinolones and intravenous beta-lactams had a lower relapse rate than co-trimoxazole and oral beta-lactams. IMPORTANCE In the manuscript, we report a large series of acute bacterial prostatitis cases and describe data about the etiology, antibiotic resistance rate, and outcome, specially focused on the risk factors for relapse. We found high rates of resistance to the most frequently used antibiotics and a high relapse rate in patients whose treatment was not adjusted according to their microbiological susceptibility. We did not observe differences, though, in mortality or relapse according to appropriate or inappropriate empirical treatment. What is new in this article is the different relapse rates observed depending upon the definitive adequate antibiotic used. Quinolones and intravenous (i.v.) beta-lactam have lower rates of relapse (1.8% and 3.6%, respectively) compared to co-trimoxazole and oral (p.o.) beta-lactam (3.3% and 9.8%, respectively). Clinicians should carefully choose an adequate antibiotic for definitive ABP treatment depending on the results of microbiological isolation, using quinolones as the first option. Whenever quinolones cannot be administered, i.v. beta-lactams seem to be the second-best option. The Spanish Network for Research in Infectious Diseases is supported by AGAUR grant 2017 SGR 1055, Generalitat de Catalunya. No other financial support was received for this work.

Hospital-acquired pneumonia (HAP) is a potentially serious infection that primarily affects older patients. The number of patients affected by multidrug-resistant (MDR) bacteria is increasing, including infection from strains of Staphylococcus aureus, Enterobacteriaceae, and Pseudomonas aeruginosa.This article focuses specifically on HAP, excluding patients afflicted by ventilator-associated pneumonia (VAP). The pathogenesis and clinical features of HAP in the elderly are discussed as well as specific drug pharmacokinetic and pharmacodynamic considerations in elderly patients. The current recommended guidelines for the management of HAP are also discussed. Finally, the authors provide evidence on the empirical therapy used for the treatment of HAP and widely consider specific-pathogen treatment of HAP in elderly patients.In patients not at risk of MDR organism infection, antibiotics including piperacillin-tazobactam, cefepime, carbapenems or fluorquinolones are recommended. However, the emergence of MDR organisms as causal agents of HAP makes it necessary to accurately assess risk factors to these pathogens and revise our knowledge on specific antimicrobial susceptibility patterns from each institution. The authors believe that broader-spectrum empiric antibiotic therapies that target P. aeruginosa and methicillin-resistant S. aureus are best recommended in elderly patients at risk of HAP infection by MDR strains.

OBJECTIVES The aim of the study was to investigate the dynamics of cytomegalovirus (CMV) replication and CMV-specific immune response recovery after antiretroviral treatment (ART) initiation in patients with advanced HIV infection. METHODS A prospective observational study of patients with HIV infection and CD4 counts of

SUMMARY To inform on the correlates of protection against SARS-CoV-2, we studied T cell functions, migration patterns and apoptosis associated with antigen responses in three groups of patients during acute infection. T cell functional profiles against SARS-CoV-2 depended on the targeted viral protein and clinical outcome. Hospitalization and disease severity were associated with predominant IFNg and IL-4 responses, as well as increased responses against S peptides and apoptosis, while non-hospitalized patients were characterized by IL-10 secretion, to which a particular subset expressing high levels of CCR7 contributed abundantly. Importantly, lung-resident memory T cells were strongly detected in convalescent patients, in which contemporary blood did not reflect tissue resident profiles. Our results suggest that a balanced anti-inflammatory antiviral response promoted by non-spike proteins may be key to favor infection resolution without major complications. Still, these immune responses can migrate and establish in the lung as resident memory T cells, affecting future protection.

Introduction: Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are prevalent nosocomial infections with a worrisomely increasing prevalence of multidrug-resistant causative organisms, including those with resistance to carbapenems. The addition of relebactam, a β-lactamase inhibitor, to imipenem treatment restores the antimicrobial activity against the most of multidrug-resistant Gram-negative bacteria, including some carrying β‐lactamase enzyme-type carbapenemases. Areas covered: The aim of this article is to summarize the current evidence regarding imipenem/relebactam for the treatment of HAP/VAP. The authors discuss its chemistry, pharmacokinetics/pharmacodynamics, microbiology, tolerance and clinical efficacy. The results of clinical trials have demonstrated an efficacy of imipenem/relebactam similar to that of its comparator for the treatment of patients with HAP/VAP. Different studies have also shown its good safety profile, which is better than that of the combination of other β‐lactams with other antibiotics. Expert opinion: This drug should be incorporated as a new therapeutic option for the treatment of patients with HAP/VAP, especially as an alternative treatment in patients with confirmed infections caused by multidrug-resistant Gram-negatives.

The performance of an immunofluorescence-based Streptococcus pneumoniae antigen detection test in pleural fluid (IF-PF) was evaluated. For proven and possible pneumococcal pneumonias global sensitivity and specificity were 92.6 (95 CI 76.6-97.9) and 80 (95 CI 62.7-90.5), respectively, with no significant differences between children and adults. Global diagnostic accuracy of IF-PF was 86% (74.2-93.7), and a substantial k index of concordance with culture/RT-PCR of 0.716 (0.535-0.896). IF-PF might be useful as a rapid complementary test for the etiologic diagnosis of pneumococcal pneumonia.

We aimed to study the prevalence, characteristics and risk factors of asymptomatic sexually transmitted infections (STIs) in HIV-infected men who have sex with men (MSM). We conducted a prospective cross-sectional study, including asymptomatic HIV-infected MSM attending regular visits between December 2014 and December 2017. Of the 301 patients included, 60 patients (19.9%) presented at least one STI. The most common STI was syphilis (33 of 69 STIs), followed by chlamydia (19 of 69), gonorrhoea (10 of 69), hepatitis C virus (4 of 69) and lymphogranuloma venereum (3 of 69). Illicit drug use during sex was the only variable significantly associated with the presence of an STI on multivariate analysis (OR 2.13; 95% CI 1.17–3.89). We were unable to identify a subgroup of patients where we could potentially avoid STI screening. Our findings support current guidelines that recommend routine screening for all HIV-infected MSM regardless of their self-reported sexual history.

Ceftolozane-tazobactam is a combination of a new cephalosporin, with activity similar to that of ceftazidime, and a known inhibitor of beta-lactamases. This compound shows excellent activity against most gram-negative organisms causative of hospital-acquired pneumonia (HAP) or ventilator-acquired pneumonia (VAP), including extended spectrum beta-lactamase (ESBL)-producing Enterobacterales and multidrug-resistant (MDR)This article reviews the spectrum of activity, the main pharmacokinetic and pharmacodynamic characteristics and the clinical efficacy and safety of ceftolozane-tazobactam in the treatment of HAP/VAP in adult patients.The results of a randomized clinical trial have demonstrated an efficacy and safety profile of ceftolozane-tazobactam similar to that of its comparator for the treatment of patients with HAP/VAP. Several retrospective studies have shown good efficacy of the drug for the treatment of respiratory infections caused by MDR

Lefamulin is a novel antibiotic that belongs to the pleuromutilin class with excellent activity against all microorganisms, including atypical pathogens, that cause community-acquired pneumonia (CAP).This article reviews the spectrum of activity, the main pharmacokinetic and pharmacodynamic characteristics of lefamulin as well as its clinical efficacy and safety in the treatment of CAP in adult patients.The clinical efficacy of lefamulin in patients with non severe CAP has been demonstrated in 2 randomized clinical trials. Precisely one of the limitations of the phase 3 trials is that the proportion of severe CAP cases is very low. Its particular mechanism of action, affecting ribosomal protein synthesis, provides a low probability of cross-resistance to other commonly used antibiotics in CAP. These findings, together with the antimicrobial activity of lefamulin, its pharmacokinetic parameters and safety profile make it a good alternative for outpatient treatment of CAP. In patients hospitalized with CAP, lefamulin can be used as a potential oral step-down agent after an intravenous regimen with beta-lactams, or as a therapeutic alternative in patients with β-lactam allergies.

BACKGROUND Trichloroacetic acid (TCA) and electrocautery ablation (ECA) are 2 of the main treatment options for anal high-grade squamous intraepithelial lesion (HSIL). Our aim was to compare the efficacy and tolerance of TCA vs. ECA for HSIL. METHODS Retrospective uncontrolled study of HIV-infected men who have sex with men who had an anal HSIL treated with TCA or ECA. On-treatment effectiveness was evaluated at 6-8 weeks after treatment. A complete response was defined as resolution of HSIL, a partial response as regression to low-grade lesion, and recurrence as biopsy-proven HSIL during follow-up. A propensity-score analysis was used to adjust efficacy to potential confounding. RESULTS From May 2009 to March 2018, 182 and 56 cases of anal HSIL were treated with ECA and TCA, respectively. Comparing ECA with TCA, a complete response was observed in 33.5% (95% confidence interval: 25.8 to 41.6) vs. 60.7% (50.0 to 74.8) and a partial response in 28.0% (20.3 to 36.0) vs. 23.2% (12.5 to 37.3), respectively (P < 0.001). These differences were maintained in the propensity-score analyses. Side effects were common in both treatment, but tolerance was reported as good in 80.6% (74.2 to 89.2) and 82.6% (73.9 to 93.9) of cases treated with ECA and TCA, respectively, and no serious events were described. Recurrence cumulative incidence for the first 12 months was 14.6% (9.1 to 23.1) for ECA episodes and 27.6% (11.5 to 57.7) for TCA (P = 0.183). CONCLUSIONS Our study showed a higher efficacy of TCA than ECA with similar rates of side effects. In our opinion, considering the benefits of TCA, it should be considered as a first-line therapy for most anal HSIL management.

Ceftobiprole is a novel broad-spectrum cephalosporin with excellent activity against a broad range of pathogens that are important in community-acquired pneumonia (CAP), including drug-resistant pneumococci, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa. Areas covered: This article reviews the spectrum of activity, the main pharmacological and pharmacodynamic characteristics of ceftobiprole as well its clinical efficacy and safety in the treatment of CAP in adult patients. Expert opinion: Taking into account that the current treatment guidelines for CAP recommend the use of an adequate empirical therapy to improve its prognosis, ceftobiprole shows a profile of antimicrobial activity that would cover most etiological agents in patients with risk factors for infection caused by multidrug resistant organisms. The results of the pivotal clinical trial of patients hospitalized with CAP treated with ceftobiprole showed a high rate of clinical cure. The clinical tolerance of ceftobiprole in clinical trials was generally very good. These findings make ceftobiprole a good parenteral therapeutic alternative for the empirical treatment of CAP that requires hospitalization, especially in patients with risk factors for CAP caused by resistant microorganisms.

The Sofia Pneumococcal FIA® test is a recently introduced immunofluorescent assay automatically read aimed to detect Streptococcus pneumoniae antigen in urine. The aim of this study was to evaluate the usefulness of SofiaFIA® urinary antigen test (UAT) in comparison with classical immunochromatographic BinaxNOW® test for the diagnosis of pneumococcal pneumonia (PP). Observational study was conducted in the Hospital Universitari Vall d'Hebron from December 2015 to August 2016. Consecutive adult patients diagnosed of pneumonia and admitted to the emergency department in whom UAT was requested were prospectively enrolled. Paired pneumococcal UAT was performed (BinaxNOW® and SofiaFIA®) in urine samples. To assess the performance of both tests, patients were categorized into proven PP (isolation of S. pneumoniae in sterile fluid) or probable PP (isolation of S. pneumoniae in respiratory secretion). Sensitivity, specificity, and concordance were calculated. A total of 219 patients with pneumonia were enrolled, of whom 14% had a proven or probable PP, 22% a non-pneumococcal etiology, and 64% an unidentified pathogen. Concordance between tests was good (κ = 0.81). Sensitivity of SofiaFIA® and BinaxNOW® UAT was 78.6 and 50% for proven PP (p = 0.124), and 74.2 and 58% for proven/probable PP (p = 0.063). Specificity for both tests was 83.3 and 85.5% for proven and proven/probable PP. In patients without an identified pathogen, SofiaFIA® test was positive in 33 (23.6%) cases and BinaxNOW® in 25 (17.8%), so Sofia Pneumococcal FIA® detected 32.6% more cases than BinaxNOW® (p = 0.001). Sofia Pneumococcal FIA® test showed an improved sensitivity over visual reading of BinaxNOW® test without a noticeable loss of specificity.

Objective To assess the oncogenic human papillomavirus (HPV) determination and the cotesting HPV and anal cytology value to detect high-grade anal intraepithelial neoplasia (HGAIN) in a cohort of HIV-MSM. Design and methods Prospective study of HIV-infected MSM who underwent screening for anal dysplasia. Screening program includes anal cytology, HPV testing, and high-resolution anoscopy (HRA) at each visit. Histological samples were obtained if suspicious lesions were revealed by HRA. Sensitivity and specificity of the different tests were calculated by using histological results of HRA-guided biopsy as the reference test for HGAIN diagnosis. Results From May 2009 to August 2016, 692 HIV-infected MSM underwent 1827 anal cytologies, 1841 HRA examinations, and 1607 HPV testing. At first screening visit, anal cytology results were abnormal in 418 (60.4%) of 692 patients, and oncogenic HPV genotypes were found in 482 (79.5%) of 606 patients. Anal cytology showed a sensitivity of 89.2% [95% confidence interval (CI); 80.7-94.2] and a specificity of 44.2% (95% CI; 40.2-48.2) to detect HGAIN. Oncogenic HPV testing had 90.4% sensitivity (95% CI; 82-86.8) and 24.4% specificity (95% CI; 20.8-28.3). Cotesting showed a 97.4% sensitivity (95% CI; 91-99.3) and 14% specificity (95% CI; 11.2-17.3). In patients with atypical squamous cells of uncertain significance on cytology, oncogenic HPV testing had 91.3% sensitivity and 28.3% specificity to detect HGAIN. Conclusion Abnormal cytology and oncogenic HPV determination showed similar sensitivity for detecting HGAIN. The two tests used together improved the sensitivity but with lowered specificity. In our opinion, HPV testing does not improve HGAIN detection and should not replace anal cytology as a standard screening test for HIV-infected MSM.

Objective To assess risk factors of high-grade anal intraepithelial neoplasia (HGAIN) recurrence in a cohort of HIV-infected MSM. Design and methods Consecutive HIV-infected 100 MSM with a history of successfully treated intra-anal HGAIN with electrocautery were followed with anal cytology, human papillomavirus (HPV) determination, and high-resolution anoscopy (HRA) at 3-6-month intervals. HGAIN recurrence was analyzed using Kaplan-Meier analysis. Risk factors of recurrence were assessed using Cox proportional hazards regression. The value of different tests for detecting recurrence was also assessed. Results After a mean follow-up of 17.6 months, 39 of the 100 patients [39%, 95% confidence interval (CI): 29-49] developed recurrent HGAIN, 24 at the previously treated site, and 15 at a different site. The probability of recurrence was 23.5% at 12 months (95% CI: 13.9-33.1) and 53.3% at 24 months (95% CI: 34.3-72.7). Risk factors of recurrence were presence of hepatitis C antibodies (hazard ratio 2.79; 95% CI: 1.04-7.53), nadir CD4 cell count less than 200 cells/μl (hazard ratio 2.61; 95% CI: 1.06-6.44), and HGAIN lesions affecting at least two octants of anal circumference (hazard ratio 8.27; 95% CI: 1.1-62). Infection by at least two HPV oncogenic strains increased the risk of recurrence (hazard ratio 2.3; 95% CI: 0.98-5.42). HRA, anal cytology, and oncogenic HPV determination test showed a sensitivity of 100, 79.4, and 86.7%, and a specificity of 57.7, 36.6, and 34.7%, respectively, for detecting HGAIN recurrence. Conclusion The risk of HGAIN recurrence in HIV-infected MSM is high. Regular posttreatment follow-up of these patients is mandatory, and performing direct HRA appears to be the best strategy.

Background Organizing pneumonia (OP) is a rare complication of influenza virus infection but scarce data are available. The recognition of this entity is important because require appropriate treatment. Methods We report two cases and perform a systematic review on PubMed database. Only cases with histological confirmation of OP and influenza virus positive laboratory test were included. Results We collected 16 patients. Median age was 52 year, 20% of patients were smokers and 43.8% had not any comorbidity. Influenza A virus infection was diagnosed in 75%. Clinical manifestation consisted on a respiratory deterioration with a median time of appearance of 14 days. Radiological pattern observed was ground-glass opacities with consolidations. Survival was observed in 12 patients (75%). All three patients who did not receive steroid treatment died. Conclusion Physicians must be aware that patients with influenza infection with a torpid course could be developing OP and prompt corticoid therapy should be instaured.

In this study we attempt to assess the utility of a simplified step-wise diagnostic algorithm to determinate the aetiology of encephalitis in daily clinical practice and to describe the main causes in our setting. This was a prospective cohort study of all consecutive cases of encephalitis in adult patients diagnosed between January 2010 and March 2015 at the University Hospital Vall d'Hebron in Barcelona, Spain. The aetiological study was carried out following the proposed step-wise algorithm. The proportion of aetiological diagnoses achieved in each step was analysed. Data from 97 patients with encephalitis were assessed. Following a simplified step-wise algorithm, a definite diagnosis was made in the first step in 53 patients (55 %) and in 12 additional cases (12 %) in the second step. Overall, a definite or probable aetiological diagnosis was achieved in 78 % of the cases. Herpes virus, L. monocytogenes and M. tuberculosis were the leading causative agents demonstrated, whereas less frequent aetiologies were observed, mainly in immunosuppressed patients. The overall related mortality was 13.4 %. According to our experience, the leading and treatable causes of encephalitis can be identified in a first diagnostic step with limited microbiological studies. L. monocytogenes treatment should be considered on arrival in some patients. Additional diagnostic effort should be made in immunosuppressed patients.

HIV and antiretroviral therapy affect lipid metabolism. Lipidomics quantifies several individual species that are overlooked using conventional biochemical analyses, outperforming traditional risk equations. We aimed to compare the plasma lipidomic profile of HIV patients taking efavirenz (EFV) or rilpivirine (RPV). Patients &ge, 18 years old on EFV co-formulated with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) with HIV-RNA &lt, 50 copies/mL for &ge, 6 months were randomized to continue EFV/FTC/TDF (n = 14) or switch to RPV/FTC/TDF (n =15). Lipidomic analyses conducted by mass spectrometry (MS) were performed at baseline and after 12 and 24 weeks. OWLiver&reg, Care and OWLiver&reg, tests were performed to estimate the presence of fatty liver disease (NAFLD). No significant differences (83% male, median age 44 years, 6 years receiving EFV/FTC/TDF, CD4+ count 740 cells/mm3, TC 207 [57 HDL-C/133 LDL-C] mg/dL, TG 117 mg/dL) were observed between the groups at baseline. Significant reductions in plasma lipids and lipoproteins but increased circulating bilirubin concentrations were observed in patients who switched to RPV/FTC/TDF. Patients on RPV/FTC/TDF showed a decrease in the global amount of storage lipids (-0.137 log2 [fold-change] EFV vs. 0.059 log2 [fold-change] RPV) but an increase in lysophosphatidylcholines (LPCs) and total steroids. Compared with EFV, RPV increased metabolites with anti-inflammatory properties and reduced the repository of specific lipotoxic lipids.

The aim of the study was to assess the rates of discontinuation of integrase inhibitor regimens because of any neuropsychiatric adverse event (NPAE) and the factors associated with discontinuation.A population-based, prospective, multicentre cohort study was carried out. Treatment-naïve subjects starting therapy with a regimen containing integrase inhibitors, or those switching to such a regimen, with plasma HIV-1 RNA 50 HIV-1 RNA copies/mL in 14 hospitals in Catalonia or the Balearic Islands (Spain) were included in the study. Every discontinuation because of adverse events (AEs) was double-checked directly with treating physicians. Multivariable Cox models identified factors correlated with discontinuation.A total of 4165 subjects (37% treatment-naïve) started regimens containing dolutegravir (n = 1650; 91% with abacavir), raltegravir (n = 930) or elvitegravir/cobicistat (n = 1585). There were no significant differences among regimens in the rate of discontinuation because of any AE. Rates of discontinuation because of NPAEs were low but higher for dolutegravir/abacavir/lamivudine [2.1%; 2.9 (95% confidence interval (CI) 2.0, 4.2) discontinuations/100 patients/year] versus elvitegravir/cobicistat (0.5%; 0.8 (95% CI 0.3, 1.5) discontinuations/100 patients/year], with significant differences among centres for dolutegravir/abacavir/lamivudine and NPAEs (P = 0.003). We identified an association of female gender and lower CD4 count with increased risk of discontinuation because of any AE [Incidence ratio (IR) 2.3 (95% CI 1.4, 4.0) and 1.8 (95% CI 1.1, 2.8), respectively]. Female gender, age 60 years and abacavir use were not associated with NPAE discontinuations. NPAEs were commonly grade 1-2, and had been present before and improved after drug withdrawal.In this large prospective cohort study, patients receiving dolutegravir, raltegravir or elvitegravir/cobicistat did not show significant differences in the rate of discontinuation because of any toxicity. The rate of discontinuations because of NPAEs was low, but was significantly higher for dolutegravir than for elvitegravir/cobicistat, with significant differences among centres, suggesting that greater predisposition to believe that a given adverse event is caused by a given drug of some treating physicians might play a role in the discordance seen between cohorts.

Advanced HIV disease, defined as a CD4 cell count below 200 cells/μl or the presence of an AIDS-defining illness, remains common among HIV-infected individuals who first present for medical care. In developed countries, nearly 30% of new HIV diagnoses occurred at advanced stages of the disease, and it is important because advanced HIV disease has been associated with worse clinical outcomes, including lower rates of virological response, higher morbidity, and higher mortality. However, there are scarce data regarding which is the best antiretroviral regimen in these patients. Nowadays, integrase inhibitor-based regimens are widely recommended as the best initial therapy for treatment-naïve HIV-infected patients by all international guidelines. However, these guidelines hardly mention the recommended regimens in individuals with advanced HIV disease. Otherwise, recent data indicating a higher risk of immune reconstitution inflammatory syndrome associated to the use of integrase inhibitors have raised concerns on the use of these drugs in patients with advanced HIV disease. The aim of this article is to review the available evidence from randomized clinical trials for the best treatment in patients with advanced HIV disease.

Our objective was to describe the pharmacokinetic (PK) parameters of total and unbound darunavir and ritonavir concentrations in HIV-hepatitis C virus (HCV)-coinfected patients with cirrhosis, as ritonavir-boosted darunavir is mainly metabolized in the liver, and hepatic cirrhosis might modify darunavir-ritonavir concentrations. This was a prospective, case-control, and unicenter study. HIV-HCV-coinfected patients with compensated cirrhosis (cases) and HIV-monoinfected patients with normal liver function (controls) were included. Darunavir-ritonavir was given at 800/100 mg once daily. Patients were followed for 24 weeks to assess safety and efficacy. A steady-state 12-h PK study was performed. Total and unbound concentrations were determined by liquid chromatography-tandem mass spectrometry. The unbound fraction was obtained by ultrafiltration. The plasma area under the concentration-time curve (AUC) and oral clearance (CL/F) were assessed by noncompartmental models. Thirty patients (20 cases and 10 controls) were included. Among cirrhotic patients, the Child-Pugh score was C in 4 cases, B in 1 case, and A in 15 cases; the median (interquartile range) transient elastography values were 20 kPa (14 to 26 kPa), and 5 patients had prior clinical decompensations. There were no significant differences in the darunavir PK parameters between cases and controls except for longer time to maximum plasma concentrations ( T max ) and half-lives in the cirrhotic patients. There were no significant differences in ritonavir total concentrations, but the unbound concentrations were higher in cirrhotic patients. There were significant correlations between the darunavir total and unbound concentrations in both cirrhotic patients and controls. There were no differences in PK parameters based on Child-Pugh score, liver elasticity, gender, or use of concomitant medications. In conclusion, in HIV-HCV-coinfected patients with clinically compensated cirrhosis receiving darunavir-ritonavir at 800/100 mg once daily, the darunavir total and unbound concentrations are similar to those observed in noncirrhotic patients, and dose adjustments are not necessary.

Background Our objective was to assess the therapeutic noninferiority of dual therapy with darunavir/ritonavir and lamivudine compared to triple therapy with darunavir/ritonavir plus 2 nucleos(t)ides for maintenance of human immunodeficiency virus type 1 (HIV-1) suppression. Methods This was a multicenter, open-label, noninferiority trial (margin 12%). Patients with HIV-1 RNA

Introduction The incidence of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients after an episode of Pneumocystis jirovecii pneumonia (PJP) seems to be lower than with other opportunistic infections. We conducted an observational study in order to determine the incidence, clinical characteristics and outcome of patients diagnosed with PJP-related IRIS. Methods We conducted an observational study of HIV patients diagnosed with PJP-related IRIS from January 2000 to November 2015. We analyzed epidemiological and clinical characteristics as well as laboratory findings. We also carried out a systematic review of published cases. Results Six cases of IRIS out of 123 (4.9%) HIV-infected patients with PJP who started ART were diagnosed. All six cases were men with a median age of 34 (IQR: 8) years. The six patients developed paradoxical IRIS. Subjects younger than 40 years old (p = 0.084) and with an HIV-RNA viral load >100 000 copies/ml (p = 0.081) at diagnosis showed a tendency to develop IRIS. Thirty-seven published cases of PJP-related IRIS were identified. Although 51% of cases involved respiratory failure, no deaths were reported. Conclusions PJP-related IRIS is rare condition compared to other opportunistic infections. It can lead to a severe respiratory failure in a significant proportion of cases, although no deaths have been reported.

Objectives Maximizing ART efficiency is of growing interest. This study assessed the efficacy, safety, pharmacokinetics and economics of a darunavir dose-reduction strategy. Methods This was a multicentre, randomized, open-label clinical trial in HIV-infected patients with plasma HIV-1 RNA 50 copies/mL or discontinuation of study treatment by week 48. The study was registered at https://www.clinicaltrialsregister.eu (trial number 2011-006272-39). Results Fifty participants were allocated to each arm. The mean (SD) CD4+ T cell count at baseline was 562 (303) cells/mm3 and HIV-1 RNA had been Conclusions The efficacy of a darunavir daily dose of 600 mg seemed to be similar to the efficacy of the standard 800 mg dose in virologically suppressed HIV-infected patients on triple ART. This strategy can potentially translate to substantial savings in the cost of care of HIV-infected patients.

Objectives The aim of the study was to investigate liver fibrosis outcome and the risk factors associated with liver fibrosis progression in hepatitis C virus (HCV)/HIV-coinfected patients. Methods We prospectively obtained liver stiffness measurements by transient elastography in a cohort of 154 HCV/HIV-coinfected patients, mostly Caucasian men on suppressive antiretroviral treatment, with the aim of determining the risk for liver stiffness measurement (LSM) increase and to identify the predictive factors for liver fibrosis progression. To evaluate LSM trends over time, a linear mixed regression model with LSM level as the outcome and duration of follow-up in years as the main covariate was fitted. Results After a median follow-up time of 40 months, the median increase in LSM was 1.05 kPa/year [95% confidence interval (CI) 0.72–1.38 kPa/year]. Fibrosis stage progression was seen in 47% of patients, and 17% progressed to cirrhosis. Aspartate aminotransferase (AST) levels and liver fibrosis stage at baseline were identified as independent predictors of LSM change. Patients with F3 (LSM 9.6–14.5 kPa) or AST levels ≥ 64 IU/L at baseline were at higher risk for accelerated LSM increase (ranging from 1.45 to 2.61 kPa/year), whereas LSM change was very slow among patients with both F0−F1 (LSM ≤ 7.5 kPa) and AST levels ≤ 64 IU/L at baseline (0.34 to 0.58 kPa/year). An intermediate risk for LSM increase (from 0.78 to 1.03 kPa/year) was seen in patients with F2 (LSM 7.6–9.5 kPa) and AST baseline levels ≤ 64 IU/L. Conclusions AST levels and liver stiffness at baseline allow stratification of the risk for fibrosis progression and might be clinically useful to guide HCV treatment decisions in HIV-infected patients.

BACKGROUND The 13-valent pneumococcal conjugate vaccine (PCV13) has recently been approved for use in immunocompromised adults. However, it is unclear whether there is an association between specific underlying conditions and infection by individual serotypes. The objective was to determine the prevalence of serotypes covered by PCV13 in a cohort of patients with invasive pneumococcal disease of respiratory origin and to determine whether there are specific risk factors for each serotype. METHODS An observational study of adults hospitalized with invasive pneumococcal disease in 2 Spanish hospitals was conducted during the period 1996-2011. A multinomial regression analysis was performed to identify conditions associated with infection by specific serotypes (grouped according their formulation in vaccines and individually). RESULTS A total of 1094 patients were enrolled; the infecting serotype was determined in 993. In immunocompromised patients, 64% of infecting serotypes were covered by PCV13. After adjusting for age, smoking, alcohol abuse, and nonimmunocompromising comorbidities, the group of serotypes not included in either PCV13 or PPV23 were more frequently isolated in patients with immunocompromising conditions and cardiopulmonary comorbidities. Regarding individual serotypes, 6A, 23F, 11A, and 33F were isolated more frequently in patients with immunocompromise and specifically in some of their subgroups. The subgroup analysis showed that serotype10A was also associated with HIV infection. CONCLUSIONS Specific factors related to immunocompromise seem to determine the appearance of invasive infection by specific pneumococcal serotypes. Although the coverage of serotypes in the 13-valent conjugate pneumococcal vaccine (PCV13) was high, some non-PCV13-emergent serotypes are more prevalent in immunocompromised patients.

An HIV-infected patient treated with tenofovir disoproxil fumarate/emtricitabine/elvitegravir/cobicistat developed severe acute ischaemia of both legs during a migraine episode. After being interrogated he admitted taking an ergotamine-containing preparation. Ergotism due to interaction between ergotics and cobicistat was diagnosed. We describe the first reported case of this interaction.