Clinical features and prognosis of prosthetic valve endocarditis due to Staphylococcus aureus.

PURPOSE: Staphylococcus aureus prosthetic valve endocarditis (SAPVE) is a serious infection with high mortality. The main objective of this study was to identify factors associated with in-hospital mortality. METHODS: From January 2008 to December 2021, consecutive patients from a Spanish cohort of infective endocarditis with a definitive diagnosis of SAPVE were analyzed. RESULTS: During the study period, 219 cases of definitive SAPVE were diagnosed, which accounted for 16.7% of a total of 1309 cases of definitive prosthetic valve endocarditis (PVE). Patients presented advanced age and marked comorbidity. There was a higher incidence of persistent bacteremia, septic shock, stroke, and acute kidney injury than in cases of PVE caused by other microorganisms. Methicillin resistance was not associated with differences in clinical presentation, echocardiographic findings, or mortality. Only 50.6% of the patients with surgical indications (88 patients) underwent surgery. Overall, in-hospital mortality was 47.9%. The variables associated with in-hospital mortality were age (OR:1.03, 95% CI: 1.00-1.05; p = 0.016), heart failure (OR:2.86, 95% CI: 1.53-5.32; p = 0.001), acute kidney injury (OR:2.42, 95%CI:1.28-4.58; p = 0.006), stroke (OR:3.53, 95%CI:1.79-6.96; p < 0.001) and surgery indicated but not performed (OR:2.01, 95%CI:1.06-3.8; p = 0.030). On the other hand, the performance of surgery per se in patients with SAPVE, regardless of whether there was a surgical indication according to the guidelines, was not associated with a reduction in in-hospital mortality. CONCLUSIONS: SAPVE is characterized by high mortality, which is more marked in patients who present a surgical indication but do not undergo surgery.

A phase III randomized controlled trial of plitidepsin, a marine derived compound, in hospitalized adults with moderate COVID-19.

BACKGROUND: Plitidepsin has shown potent preclinical activity against SARS-CoV-2 and was generally well tolerated in a Phase I trial of hospitalized patients with COVID-19. NEPTUNO, a Phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients. METHODS: Included patients had documented SARS-CoV-2 infection, required oxygen therapy, and had adequate organ function. The planned sample size was 609 patients. Patients were randomized 1:1:1 to at least 3 days of dexamethasone plus either plitidepsin (1.5 mg/day or 2.5 mg/day, for 3 days) or standard of care (control). The primary endpoint was the time to sustained withdrawal of supplemental oxygen. Secondary endpoints included time to sustained hospital discharge, clinical status, duration of oxygen support, percentage of patients requiring admission to the intensive care unit, and safety. FINDINGS: After randomizing 205 patients, NEPTUNO was discontinued due to a notable drop in COVID-19-related hospitalizations. Available data suggest a 2-day improvement in the median time to sustained oxygen therapy discontinuation (5 vs 7 days) favoring both plitidepsin arms (hazard ratio [HR] 1.37, 95% confidence interval [CI] 0.96-1.96, p=0.08 for plitidepsin 1.5 mg vs control; HR 1.06, 95% CI 0.73-1.53, p=0.78 for plitidepsin 2.5 mg vs control). Plitidepsin was generally well tolerated. INTERPRETATION: Despite the trial limitations, these results suggest that plitidepsin may have a positive benefit-risk ratio in the management of patients requiring oxygen therapy. Further studies with plitidepsin, including those in immunosuppressed patients, are warranted. FUNDING: This trial has been funded by Pharmamar, S.A. (Madrid, Spain).

Safety and Immunogenicity of the Nonavalent Human Papillomavirus Vaccine in Women Living with HIV.

BACKGROUND: The objectives were to evaluate the safety and immunogenicity of the nonavalent human papillomavirus (nHPV) vaccine in adult Spanish women living with HIV (WLHIV); the prevalence of anal and cervical dysplasia and nHPV vaccine genotypes in the anus and cervix; and risk factors for high-risk HPV (HR-HPV) infection in anal mucosa. METHODS: In this single-center, open-arm, non-randomized clinical trial, the nHPV vaccine was administered at 0, 2, and 6 months to WLHIV enrolled between February 2020 and November 2023, measuring vaccine antibody titers pre-vaccination and at 2, 6, and 7 months after the first dose. Cervical and anal cytology and HPV PCR genotyping studies were performed. Women with abnormal cytology and/or anal or cervical HPV infection at baseline underwent high-resolution anoscopy and/or colposcopy. RESULTS: A total of 122 participants were included with mean age of 49.6 years: 52.5% smoked; 10.7% had anal-genital condylomatosis; 38.5% were infected by HR-HPV in the anus and 25.4% in the cervix, most frequently HPV 16; 19.1% had anal intraepithelial neoplasia 1-(AIN1); and 3.1% had cervical intraepithelial neoplasia 1 and 2 (CIN1/CIN2). Vaccine administration did not modify viral-immunological status (CD4 [809 ± 226.8 cells/uL vs. 792.35 ± 349.95; p = 0.357]) or plasma HIV load (3.38 ± 4.41 vs. 1.62 ± 2.55 cop/uL [log]; p = 0.125). Anti-HPV antibodies ([IQR: 0-0] vs. 7.63 nm [IQR: 3.46-19.7]; p = 0.0001) and seroconversion rate (8.2% vs. 96.7% [p = 0.0001]) were increased at 7 versus 0 months. There were no severe vaccine-related adverse reactions; injection-site pain was reported by around half of the participants. HR-HPV infection in the anus was solely associated with a concomitant cervix infection (HR 5.027; 95% CI: 1.009-25.042). CONCLUSIONS: nHPV vaccine in adult WLHIV is immunogenic and safe.

Infective Endocarditis Due to Corynebacterium jeikeium: Four Case Reports and Narrative Review of the Literature.

Corynebacterium jeikeium, a pleomorphic Gram-positive bacillus, is a common component of the cutaneous microbiota, usually considered as a contaminant, with little pathogenic potential. However, its role in various types of infections, such as bacteremia, sepsis, endocarditis (IE) and infection of prosthetic material is gradually being proven. Few cases of IE due to Corynebacterium jeikeium have been described in the literature. The aim of this article was to describe four cases of IE due to Corynebacterium jeikeium diagnosed in our hospital between May 2021 and April 2022, as well as to conduct a narrative review of the literature on this entity. After analysis, we highlight that 65.6% were men, 81.3% were valve or intravascular device carriers, and IE cases presented early, before one year after surgery. The most affected valve was the aortic valve (68.8%), followed by the mitral valve (21.1%). Valve replacement was performed in 65.6% of cases, and the most commonly used antibiotic was vancomycin (68.8%) at a dose of 15 mg/kg/12 h. With respect to prognosis, the overall mortality rate was 21.9%. The comparative results between our series and the literature review were similar except for a higher mortality rate (50%) and the use of dalbavancin in the treatment. We go on to review previously reported cases, along with four cases described in our hospital, of C. jeikeium endocarditis and will discuss various aspects of C. jeikeium infection, focusing on microbiology, pathophysiology, and treatment.

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-International Society for Cardiovascular Infectious Diseases (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 polymerase chain reaction of the 16S rRNA gene and sequencing (16SPCR) was evaluated. RESULTS: Of 6692 episodes of IE, 67 (1%) were caused by Cutibacterium spp. with 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 of 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. CONCLUSIONS: 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.

Bictegravir/emtricitabine/tenofovir alafenamide as first-line treatment in naïve HIV patients in a rapid-initiation model of care: BIC-NOW clinical trial.

OBJECTIVE: Multiple strategies have been utilised to reduce the incidence of HIV, including PrEP and rapid antiretroviral therapy initiation. The study objectives were to evaluate the efficacy, safety, satisfaction, treatment adherence, and system retention obtained with rapid initiation of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in naïve patients. METHODS: This phase IV, multicenter, open-label, single-arm, 48-week clinical trial enrolled patients between January 2020 and June 2022. Adherence to treatment was evaluated with the SMAQ questionnaire and patient satisfaction with the EQ-5D. RESULTS: Two hundred eight participants were enrolled with mean age of 35.6 years; 87.6% were males; mean CD4 count was 393.5 cells/uL (<200 cells/uL in 22.1%); viral load log was 5.6 (VL>100 000 cop/mL in 43.3%); 22.6% had AIDS, and 4.3% were coinfected with HBV. BIC/FTC/TAF was initiated on the day of their first visit to the HIV specialist in 98.6% of participants, and 9.6% were lost to follow-up. The efficacy at week 48 was 84.1 % by intention-to- treat (ITT), 94.6% by modified ITT, and 98.3% by per protocol analysis. The regimen was discontinued in two subjects (0.9%) during week 1 for grade 3 adverse events. Treatment adherence (weeks 4 [90%, IQR: 80-99%] vs. 48 [90%, IQR: 80-95%; P = 0.49]) and patient satisfaction (weeks 4 [90%, IQR: 80-99%] vs. 48 [90%, IQR: 80-95 P = 0.49]) rates were very high over the 48- week study period. CONCLUSIONS: BIC/FTC/TAF is an appropriate option for rapid ART initiation in naïve HIV patients, offering high efficacy, safety, durability, treatment adherence, retention in the healthcare system, and patient satisfaction. Number Clinical Trial registration: NCT06177574.

The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers.

BACKGROUNDPersistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure.METHODSThe characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq).RESULTSPCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONSThese results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.FUNDINGInstituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation.

DOLAMA 200: Effectiveness and Safety of a Dual Therapy with Dolutegravir Plus Lamivudine in Treatment-Experienced HIV-1 Infected Real World Participants in Spain.

The continuous pharmacological advances in antiretroviral treatment (ART) and the increasing understanding of HIV drug resistance has led to a change in the paradigm of ART optimization in the setting of the viral suppression of treatment-experienced patients with the emerging evidence of the effectiveness and safety of dual therapies. The aim of this study is to determine the antiviral efficacy and safety of switching to Dolutegravir + Lamivudine in people living with HIV, and to analyze the rate of patients with virologic failure (VF). A total of 200 patients were included with a median age of 51 years, 189 cells/µL of nadir CD4+, 13 years on ART and four previous ART regimens. Among the 168 patients who completed a follow-up at 48 weeks, a total of five VFs occurred, resulting in a 2.98% (5/168) VF rate. The results of the intention-to-treat analysis were a VF rate of 2.54% (5/197), and the rate of patients/year with viral suppression was 98.3% (298/303) in the observed data analysis. We observed a significant improvement in mean CD4 lymphocytes, the CD4/CD8 ratio and lipid profiles. The optimization of ART to DTG plus 3TC is a cost-effective switch option for treatment-experienced HIV patients, and also improves their lipid profiles.

Aislamiento de Haemophilus no ducreyi en muestras del aparato genital de varones: relación con la clínica / Isolation of Haemophilus no ducreyi in samples from the genital tract of men: Its clinical relationship

Introducción: Con el avance de los métodos microbiológicos, cada vez es más frecuente el aislamiento de patógenos menos típicos en cuadros de infección uretral y rectal, además de los agentes etiológicos clásicos. Uno de ellos está formado por especies de Haemophilus no ducreyi (HND). El objetivo de este trabajo es describir la frecuencia, la sensibilidad antibiótica y las características clínicas de las uretritis y proctitis por HND en varones. Pacientes y métodos: Se realizó un estudio observacional descriptivo y retrospectivo, a partir de los resultados emitidos por el Laboratorio de Microbiología del Hospital Universitario Virgen de las Nieves de Granada, de los aislamientos, entre 2016 y 2019, de HND en episodios infecciosos genitales y rectales de varones adultos. Resultados: Se aisló HND en 135 (7%) episodios. La especie más frecuente fue H. parainfluenzae (34/45; 75,6%). Los síntomas más frecuentes de las proctitis fueron: tenesmo rectal (31,6%) y adenopatías (10,5%); en aquellos con uretritis, fueron disuria (71,6%), supuración uretral (46,7%) y lesiones en el glande (27%), siendo manifestaciones similares a las infecciones provocadas por los genitopatógenos habituales. Un 43% de los pacientes eran VIH positivos. Las tasas de resistencia a antibióticos de H. parainfluenzae fueron elevadas a levofloxacino, ampicilina, tetraciclina y azitromicina. Conclusión: Las especies de HND deberían tenerse en cuenta como posibles agentes etiológicos en episodios de infección uretral y rectal en varones, sobre todo en los casos con pruebas de detección negativas para agentes productores habituales de infecciones de transmisión sexual. Su detección microbiológica es fundamental para la instauración de un tratamiento efectivo dirigido. (AU)

Introduction: With the advancement of microbiological methods, the isolation of less typical pathogens in cases of urethral and rectal infection is more frequent, apart from the classic etiological agents. One of them is formed by species of Haemophilus no ducreyi (HND). The objective of this work is to describe frequency, susceptibility to antibiotics, and clinical features of HDN urethritis and proctitis in adult males. Patients and methods: This is an observational retrospective descriptive study of the results obtained by the Microbiology laboratory of the Virgen de las Nieves University Hospital on the isolates of HND in genital and rectal samples from males between 2016 and 2019. Results: HND was isolated in 135 (7%) of the genital infection episodes diagnosed in men. H. parainfluenzae was the most commonly isolated (34/45; 75.6%). The most frequent symptoms in men with proctitis were rectal tenesmus (31.6%) and lymphadenopathy (10.5%); in those with urethritis, dysuria (71.6%), urethral suppuration (46.7%) and gland lesions (27%), so differentiating it from infections caused by other genitopathogens is difficult. 43% of patients were HIV positive. Antibiotic resistance rates for H. parainfluenzae were high to quinolons, ampicillin, tetracycline and macrolides. Conclusion: HND species should be considered as possible etiologic agents in episodes of urethral and rectal infection in men, especially in cases with negative screening tests for agents that cause sexually transmitted infections (STIs). Its microbiological identification is essential for the establishment of an effective targeted treatment. (AU)

Ceft-to-Ceft Study: Real-Life Experience with Ceftaroline and Ceftobiprole in Treatment of the Principal Infectious Syndromes in a Spanish Multicenter Hospital Cohort.

BACKGROUND: To compare the real-life effectiveness and safety of ceftaroline fosamil (ceftaroline-F) and ceftobiprole medocaril (ceftobiprole-M) for infections in hospitalized patients. METHODS: This comparative, observational, retrospective, and multicenter Spanish study included patients receiving outpatient parenteral antimicrobial therapy (OPAT) and hospitalized patients treated for at least 48 h with ceftaroline-F or ceftobiprole-M between their first incorporation in the clinical protocol of each hospital and 31 July 2022. RESULTS: Ceftaroline-F was administered to 227 patients and ceftobiprole-M to 212. In comparison to the latter, ceftaroline-F-treated participants were younger (63.02 vs. 66.40 years, OR 1.1; 95%CI: 1.001-1.05) and had higher rates of septic shock (OR 0.27; 95%CI: 0.09-0.81) and higher frequencies of targeted (57.7 vs. 29.7%; OR: 0.35; 95%CI: 0.18-0.69) and combined (89.0 vs. 45.8%, OR: 0.13; 95%CI: 0.06-0.28) therapies that were second line or more (82.4% vs. 64.6%%; OR 0.35; 95%CI: 0.18-0.69), and higher rates of infections due to Gram-positive cocci (92.7 vs. 64.7%, p = 0.001), bacteremia (51.9 vs. 21.7%, p = 0.001), infective endocarditis (24.2 vs. 2.4%, p = 0.0001), and mechanical ventilation-associated pneumonia (8.8 vs. 2.4%, p = 0.0001). Ceftobiprole-M was more frequently administered against polymicrobial infections (38.1 vs. 14.0%, p = 0.001), those produced by Gram-negative bacilli (19.7 vs. 6.0%, p = 0.0001), nosocomial pneumonia (33 vs. 10.6%, p = 0.0001), and skin and soft-tissue infections (25.4 vs. 10.1%, p = 0.0001). Patients treated with ceftaroline-F had a longer hospital stay (36 (IQR: 19-60) vs. 19.50 (IQR: 12-30.75, p = 0.0001) days), with no difference in infection-related mortality at 14 (13.2 vs. 8.0%, p = 0.078) or 28 (4.8 vs. 3.3%, p = 0.415) days or in dropout rate for adverse effects (2.2 vs. 0.9%; p = 1). CONCLUSIONS: The fifth-generation cephalosporins, ceftaroline-F and ceftobiprole-M, are safe and effective in real life, with no difference between them in health outcomes.

Switching to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat in heavily antiretroviral-experienced, virologically suppressed HIV-infected adults receiving complex regimens.

OBJECTIVES: To evaluate the efficacy and safety of the two-pill regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat as a switching strategy in heavily treatment-experienced people living with HIV (PLWH). METHODS: Multicentre, prospective, single-arm pilot clinical trial. Participants were virologically suppressed adults receiving a stable antiretroviral regimen of at least three pills from at least three drug families due to previous virological failures and/or toxicities with no documented resistance to integrase strand transfer inhibitors or darunavir (≥15 points, Stanford). Clinical and laboratory assessments were performed at 0, 4, 12, 24, 36 and 48 weeks. HIV-1 proviral DNA was amplified and sequenced by Illumina at baseline. Plasma bictegravir concentrations were determined in 22 patients using UHPLC-MS/MS. The primary study endpoint was viral load (VL)< 50 copies/mL at Week 48 (ITT). RESULTS: We enrolled 63 participants (92% men) with median baseline CD4 count of 515 cells/mm3 (IQR: 334.5-734.5), 24 years on ART (IQR: 15.9-27.8). The median number of pills was 4 (range: 3-10). At baseline, proviral DNA was amplified in 39 participants: 33/39 had resistance mutations. Three participants discontinued owing to toxicity. At 48 weeks, 95% had VL < 50 copies/mL by ITT and 100% by PP analysis. A modest increase was observed in the bictegravir plasma concentration, and a significant decrease in estimated glomerular filtration rate was observed only at Week 4, probably related to interaction with renal transporters. CONCLUSIONS: Our data suggest that BIC/FTC/TAF + darunavir/cobicistat is an effective, well-tolerated regimen that may improve convenience and, potentially, long-term success in stable heavily pre-treated PLWH.

Expert Opinion on Dose Regimen and Therapeutic Drug Monitoring for Long-Term Use of Dalbavancin: Expert Review Panel.

BACKGROUND: Dalbavancin is a lipoglycopeptide with a long elimination half-life and is currently licensed for the treatment of acute bacterial skin and skin structure infections in adults. Dalbavancin's potential in treating off-label complex Gram-positive infections is promising and real-world experience in treating such infections is growing. However, clear guidance on extended dosing regimens is lacking. OBJECTIVES: This study aimed to provide clear expert opinion based on recent pharmacokinetic literature and expert and real-world experience in infection areas that require > 2 weeks of treatment. METHODS: A single face-to-face meeting was held in September 2022 to collate expert opinion and present safety data of dalbavancin use in these clinical indications. A survey was completed by all authors on their individual experience with dalbavancin, which highlighted the heterogeneity in the regimens that were used. RESULTS: After review of the survey data and recent literature, this study presents expert panel proposals that accommodate different healthcare settings and resource availability, and centre around the length of treatment duration including up to or exceeding 6 weeks. To achieve adequate dalbavancin concentrations for up to 6 weeks, 3000 mg of dalbavancin should be given over 4 weeks for the agreed complex infections requiring > 2 weeks of treatment. Therapeutic drug monitoring (TDM) is advised for longer treatment durations and in cases of renal failure. Specific dosing recommendations for other special populations require further investigation. CONCLUSIONS: These proposals based on expert opinion have been defined to encourage best practice with dalbavancin, to optimise its administration beyond the current approved licenced dose across different healthcare settings.

Cefto Real-Life Study: Real-World Data on the Use of Ceftobiprole in a Multicenter Spanish Cohort.

BACKGROUND: Ceftobiprole is a fifth-generation cephalosporin that has been approved in Europe solely for the treatment of community-acquired and nosocomial pneumonia. The objective was to analyze the use of ceftobiprole medocaril (Cefto-M) in Spanish clinical practice in patients with infections in hospital or outpatient parenteral antimicrobial therapy (OPAT). METHODS: This retrospective, observational, multicenter study included patients treated from 1 September 2021 to 31 December 2022. RESULTS: A total of 249 individuals were enrolled, aged 66.6 ± 15.4 years, of whom 59.4% were male with a Charlson index of four (IQR 2-6), 13.7% had COVID-19, and 4.8% were in an intensive care unit (ICU). The most frequent type of infection was respiratory (55.8%), followed by skin and soft tissue infection (21.7%). Cefto-M was administered to 67.9% of the patients as an empirical treatment, in which was administered as monotherapy for 7 days (5-10) in 53.8% of cases. The infection-related mortality was 11.2%. The highest mortality rates were identified for ventilator-associated pneumonia (40%) and infections due to methicillin-resistant Staphylococus aureus (20.8%) and Pseudomonas aeruginosa (16.1%). The mortality-related factors were age (OR: 1.1, 95%CI (1.04-1.16)), ICU admission (OR: 42.02, 95%CI (4.49-393.4)), and sepsis/septic shock (OR: 2.94, 95%CI (1.01-8.54)). CONCLUSIONS: In real life, Cefto-M is a safe antibiotic, comprising only half of prescriptions for respiratory infections, that is mainly administered as rescue therapy in pluripathological patients with severe infectious diseases.

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.

[Isolation of Haemophilus no ducreyi in samples from the genital tract of men: Its clinical relationship]. / Aislamiento de Haemophilus no ducreyi en muestras del aparato genital de varones: relación con la clínica.

INTRODUCTION: With the advancement of microbiological methods, the isolation of less typical pathogens in cases of urethral and rectal infection is more frequent, apart from the classic etiological agents. One of them is formed by species of Haemophilus no ducreyi (HND). The objective of this work is to describe frequency, susceptibility to antibiotics, and clinical features of HDN urethritis and proctitis in adult males. PATIENTS AND METHODS: This is an observational retrospective descriptive study of the results obtained by the Microbiology laboratory of the Virgen de las Nieves University Hospital on the isolates of HND in genital and rectal samples from males between 2016 and 2019. RESULTS: HND was isolated in 135 (7%) of the genital infection episodes diagnosed in men. H. parainfluenzae was the most commonly isolated (34/45; 75.6%). The most frequent symptoms in men with proctitis were rectal tenesmus (31.6%) and lymphadenopathy (10.5%); in those with urethritis, dysuria (71.6%), urethral suppuration (46.7%) and gland lesions (27%), so differentiating it from infections caused by other genitopathogens is difficult. 43% of patients were HIV positive. Antibiotic resistance rates for H. parainfluenzae were high to quinolons, ampicillin, tetracycline and macrolides. CONCLUSION: HND species should be considered as possible etiologic agents in episodes of urethral and rectal infection in men, especially in cases with negative screening tests for agents that cause sexually transmitted infections (STIs). Its microbiological identification is essential for the establishment of an effective targeted treatment.

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.

The Challenge of Bacteremia Treatment due to Non-Fermenting Gram-Negative Bacteria.

Nosocomial infections caused by non-fermenting Gram-negative bacteria are a real challenge for clinicians, especially concerning the accuracy of empirical treatment. This study aimed to describe the clinical characteristic, empirical antibiotic therapy, accuracy of these prescriptions for appropriate coverage and risk factor for clinical failure of bloodstream infections due to non-fermenting Gram-negative bacilli. This retrospective, observational cohort study was conducted between January 2016 and June 2022. Data were collected from the hospital's electronic record. The statistic tests corresponding to each objective were applied. A multivariate logistic regression was performed. Among the total 120 patients included in the study, the median age was 63.7 years, and 79.2% were men. Considering the appropriate empirical treatment rate by species, inappropriate treatment for S. maltophilia was 72.4% (p = 0.088), for A. baumanii 67.6% and 45.6% for P. aeruginosa. Clinical success was achieved in 53.3%, and overall, 28-day mortality was 45.8%. ICU admission, sepsis or shock septic, age, previous antibiotic treatment and contact with healthcare facilities were independently associated with clinical failure. In conclusion, bloodstream infection produced by multidrug-resistant non-fermenting Gram-negative bacteria is a significant therapeutic management challenge for clinicians. The accuracy of empirical treatment is low due to the fact that it is not recommended to cover these microorganisms empirically, especially S. maltophilia and A. baumanii.

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.