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Objective: To demonstrate that a 7-day course of antibiotic therapy for Enterobacteriaceae bacteremia reduces patients’ exposure to antibiotics while ensuring clinical efficacy comparable to that of a 14-day course of treatment.

Methods: A randomized clinical trial was conducted. Adult patients with Enterobacteriaceae bacteremia and a confirmed source of infection were randomized to receive either 7 or 14 days of treatment and were followed up for up to 28 days after the end of treatment. If necessary, antibiotic therapy was resumed. The primary endpoint was the number of days of treatment at the end of follow-up. Clinical endpoints included clinical cure, recurrence of bacteremia, and recurrence of fever. The superiority threshold for the primary endpoint was set at 3 days, and a 10% non-inferiority margin was used for the clinical endpoints. A post-hoc sensitivity analysis evaluating the benefit of the shortened treatment and the risk of reduced efficacy was performed using a DOOR/RADAR analysis (desirability of response level adjusted for duration of antibiotic therapy).

Results: 248 patients were randomized to a 7-day treatment duration (n = 119) or a 14-day treatment duration (n = 129). In the ITT analysis, the median number of days of antibiotic therapy at the end of follow-up was 7 and 14 days (difference: 7 days, 95% CI: 7 to –7). Non-inferiority was also demonstrated for the clinical endpoints, except for recurrence of fever (–0.2%, 95% CI: –10.4 to 10.1). The DOOR/RADAR analysis showed that a 7-day course of antibiotics had a 77.7% probability of yielding better outcomes than a 14-day course.

Conclusion: A 7-day course of antibiotic therapy reduced antibiotic exposure in patients with Enterobacteriaceae bacteremia while ensuring a cure rate similar to that of a 14-day course of antibiotic therapy. The possibility of a febrile relapse in a limited number of patients — which had no impact on clinical outcomes at day 28— should not be overlooked, but this was offset by the benefit of a shorter treatment duration.

Introduction: NNRTs have been associated with an increased risk of cardiovascular complications. We investigated the impact of initiating ARV therapy with NIs in ARV-naive HIV patients on the occurrence of cardiovascular events using a methodology similar to a randomized clinical trial, thereby reducing the risk of selection bias or bias related to confounding factors.

Methods: We included participants from the Swiss HIV Cohort Study who were ARV-naive as of May 2008, when NIs became available in Switzerland. Participants were classified according to their first ARV regimen (with or without NIs) and were followed from the start of ARV treatment until the first cardiovascular event (myocardial infarction, stroke, invasive cardiovascular procedure), loss to follow-up, death, or the last follow-up visit. We calculated hazard ratios and risk differences using pooled logistic regression models with inverse probability of treatment and weighted censoring.

Results: Among the 5,362 participants (median age 38 years, 21% women, 15% of African descent), 1,837 (34.3%) initiated their first ARV treatment with an NNRTI. After 4.9 years (IQR 2.4 to 7.4), 116 cardiovascular events occurred. Initial treatment with INIs was not associated with an increased risk of cardiovascular events (HRa = 0.80; 95% CI: 0.46 to 1.39). The adjusted risk differences between individuals who started treatment with INIs and those who did not were –0.17% (95% CI: –0.37 to 0.19) after 1 year, –0.61% (–1.54 to 0.22) after 5 years, and –0.71% (–2.16 to 0.94) after 8 years.

Conclusion: In this simulated clinical trial, we found no difference in the short- or long-term risk of cardiovascular events between HIV-naive patients initiating ARV therapy with or without INIs.

Introduction: The administration of beta-lactam therapy via continuous infusion is an important optimization strategy. The available data on the impact of this continuous infusion strategy on clinical outcomes are based primarily on clinical cure and mortality in patients in intensive care or with resistant microorganisms. The potential benefits of continuous infusion extend to other clinical scenarios, and further studies on patient outcomes with this strategy are needed.

Methods: A retrospective study of adult patients who received cefepime, piperacillin/tazobactam, or meropenem for Gram-negative bacteremia via intermittent or continuous infusion. Patients were matched 1:1 based on the drug, severity of sepsis, admission to the intensive care unit (ICU) or not, source of bacteremia, and the microorganism. The outcome measures were time to clinical stabilization, treatment failure rate, mortality, relapse, and length of stay.

Results: 268 patients were included. Baseline characteristics were identical between the groups. 42% of patients were hospitalized in the intensive care unit at the time of bacteremia onset, and the primary pathogen was E. coli (41%). After adjusting for residual differences between the two groups, continuous beta-lactam infusion was independently associated with a shorter time to clinical stability (OR 0.32, 95% CI 0.22–0.47), afebrile status, and normalization of white blood cell count. Furthermore, continuous infusion was associated with lower rates of treatment failure, recurrence of bacteremia, and shorter length of hospital stay. There was no difference in mortality. These findings were consistent regardless of the setting of hospitalization (intensive care or non-intensive care), baseline renal function, the cause of bacteremia, and the specific beta-lactam antibiotics used.

Conclusion: Our results suggest that continuous infusion of beta-lactam antibiotics is an important strategy for improving outcomes in patients with Gram- negative bacteremia.

Introduction: There is a need for randomized clinical trials comparing tocilizumab and baricitinib in COVID-19. To this end, we conducted a randomized, controlled, open-label trial.

Methods: To demonstrate the non-inferiority of baricitinib versus tocilizumab, with an upper bound of the 95% two-sided confidence interval for the hazard ratio < 1.50. The primary endpoint was the need for mechanical ventilation or death at Day 28. Secondary endpoints included time to hospital discharge at Day 28 and change in the WHO severity score at Day 10.

Results: We randomized 251 patients with COVID-19 and a PaO₂/FiO₂ ratio < 200, at any time during their hospitalization, to receive tocilizumab 8 mg/kg IV (n = 126; 5 received a second dose at 48 hours) or baricitinib 4 mg/day for up to 14 days (n = 125), plus standard of care (dexamethasone 6 mg/day IV, remdesivir, anticoagulant prophylaxis with fondaparinux SC, and oxygen therapy based on FiO₂). The mean age of the patients was 72 years (IQR 61 to 83), and the median PaO₂/FiO₂ on Day 1 was 145. Baricitinib was non-inferior to tocilizumab on the primary endpoint at Day 28: progression to mechanical ventilation: 39.2% in the baricitinib group vs. 44.4% in the tocilizumab group (HR: 0.83; 95% CI: 0.56 to 1.21; p = 0.001). Baricitinib was non- inferior to tocilizumab on the secondary outcome of time to hospital discharge at Day 28, with 58.4% of patients discharged from the hospital in the baricitinib group versus 52.4% in the tocilizumab group (HR: 0.85; 95% CI: 0.61 to 1.18; p < 0.001). There was no difference between the two groups in the change in the WHO scale at Day 10 (0.00 vs. 0.00; p = 0.83).

Conclusion: In this trial, baricitinib was non-inferior to tocilizumab in terms of the primary endpoint — mechanical ventilation or death at Day 28— and the time to hospital discharge at Day 28, in patients with severe COVID-19.

Introduction: Clinical trials conducted in low- and middle-income countries suggest that early initiation of antiretroviral therapy in people living with HIV who have cryptococcal meningitis is associated with higher mortality. Little is known about the relationship between the time to initiation of antiretroviral therapy and mortality in high-income countries.

Methods: Data on ARV-naive HIV-positive patients diagnosed with cryptococcal meningitis between 1994 and 2012 were pooled from the COHERE, NA- ACCORD, and CNIS HIV collaborative cohorts in Europe and North America. Follow-up was conducted from the date of meningitis diagnosis until either death, the last follow-up visit, or the 6-month follow-up. We used structured marginal models to simulate a randomized trial comparing the effect of early (before Day 14) versus late (between Day 14 and Day 56) initiation of antiretroviral therapy on all-cause mortality, adjusting for potential confounding factors.

Results: Among 190 identified individuals, 33 (17%) had died by 6 months. At the time of diagnosis of cryptococcal meningitis, the median age was 38 years (IQR: 33–44), the median CD4 count was 19/mm³ (IQR: 10–56), and the median HIV RNA level was 5.3 log₁₀ copies/mL (IQR: 4.9–5.6). Most participants (83%) were men, and 76% initiated antiretroviral (ARV) therapy. In a simulation of a randomized clinical trial with 190 participants in each group, the number of deaths was 13 in the early ARV group (median time to initiation = 0 days) and 20 in the late ARV group (median time to initiation = 31 days). The unadjusted and adjusted hazard ratios comparing early versus late ARV initiation were 1.28 (95% CI %: 0.64 to 2.56) and 1.40 (95% CI: 0.66 to 2.95), respectively.

Conclusion: We found little evidence that early initiation of ARV treatment for cryptococcal meningitis was associated with higher mortality in high-income countries, but the confidence intervals were wide.

Introduction: Frailty is a phenotype associated with poor outcomes in older adults. Frailty has been assessed in the context of HIV infection primarily among middle-aged individuals. The French prospective multicenter ANRS EP66 SEPTAVIH study aimed to assess the prevalence and risk factors for frailty among people living with HIV aged 70 years or older who had been receiving antiretroviral therapy for at least 12 months

Methods: At enrollment, the following were collected: frailty phenotype according to Fried’s criteria, sociodemographic data, medical and HIV infection history, history of falls, and concomitant medications. We measured the prevalence of frailty and compared the characteristics of frail, pre-frail, and non- frail patients using univariate (Kruskal-Wallis test for continuous variables, chi-square test for categorical variables) and multivariate analyses.

Results: 510 people living with HIV (81.4% men, median age 73 years) were included. The median duration of HIV infection and antiretroviral therapy was 22.7 years and 15.7 years, respectively. The prevalence of frailty was 13.5% and that of pre-frailty was 63.3%. In the multivariate analysis, factors associated with frailty were: older age (odds ratio: 1.79 for every 5-year increase; 95% CI: 1.32 to 2.41), poor socioeconomic status (OR: 3.17; 95% CI: 1.76 to 5.70), and the presence of three or more comorbidities (OR: 2.09; 95% CI: 1.06 to 3.90).

Conclusion: Among people living with HIV aged 70 years or older, the prevalence of frailty was low (13.5%), with two-thirds of individuals being pre-frail. Age, socioeconomic status, and multiple comorbidities — but not HIV-related factors — were associated with frailty, suggesting the need to address these factors to support healthier aging in this population.

Objectives: We compared the clinical outcomes of patients with infectious endocarditis treated with intravenous (IV) therapy alone or with a switch to oral therapy following the implementation of new guidelines in facilities within the Los Angeles Department of Public Health.

Methods: We conducted a multicenter retrospective study of adults with confirmed or probable endocarditis treated with IV therapy alone versus those who received oral therapy as a follow-up regimen at three public hospitals in the Los Angeles area between December 2018 and June 2022. The primary outcome measure was clinical success at day 90, defined as the patient being alive and free of relapse of bacteremia or emerging infectious complications while on treatment.

Results: We identified 257 patients with infective endocarditis treated with IV therapy (n = 211) or with a switch to oral therapy (n = 46). The two groups were comparable for most demographic variables, but the IV cohort was older and more frequently had aortic valve involvement, was on hemodialysis, and had a central venous catheter. Conversely, the oral cohort had a higher prevalence of methicillin-resistant Staphylococcus aureus , tricuspid valve involvement, and patients who used intravenous drugs. Clinical success at Day 90 or at the last follow-up was not significantly different between the two groups (84.4% vs. 87% at Day 90 and 82% vs. 76.1% at the last follow-up, for the IV and oral groups, respectively). There was no difference in the rates of relapse of bacteremia (3.3% vs. 2.2% at Day 90) or hospital readmission. Patients treated with oral continuation therapy experienced significantly fewer adverse events. Adjusted multivariate analysis did not identify any factors associated with clinical success in either group.

Conclusion: These results demonstrate equivalent real-world success between IV therapy alone and therapy with an oral continuation regimen in infectious endocarditis, consistent with the results of published randomized trials and meta-analyses.

Introduction: Several studies have suggested that in patients with Staphylococcus aureus bacteremia, a PET scan improves prognosis. However, these studies have often ignored the potential for immortal time bias (if a patient dies early, they will not undergo a PET scan).

Methods: A prospective, multicenter study conducted at 2 university hospitals and 5 non-university hospitals, including all patients with Staphylococcus aureus bacteremia. PET scans were performed as part of standard care when clinically indicated. The primary endpoint was all-cause mortality at day 90. The impact of the PET scan on mortality was modeled using a proportional hazards Cox model, with the PET scan included as a time-dependent variable and adjusted for mortality confounders (age, Charlson score, persistent positive blood cultures, septic shock, and endocarditis). The secondary endpoint was infection- related mortality at 90 days (determined by an independent committee), analyzed using the same procedure. In a subgroup analysis, we assessed the impact of the PET scan in patients at high risk for secondary sites of infection.

Results: Among the 476 patients studied (survival > 48 hours after the first blood culture), 178 (37%) underwent a PET scan. The median time to PET scan was 9 days (range 6–13 days); no patients who underwent a PET scan died during the first week, compared with 24% of patients who did not undergo a PET scan who died during the first week. At day 90, all-cause mortality was 31% and infection-related mortality was 17 %. The hazard ratio adjusted for confounding factors for all-cause mortality was 0.50 (95% CI: 0.34 to 0.74) among patients who underwent a PET scan. Adjustment for immortal time bias altered the HRa, which was thus 1.00 (95% CI: 0.68 to 1.48); Similarly, after adjusting for immortal time bias, the PET scan had no impact on infection-related mortality (HRa: 1.30; 95% CI: 0.77 to 2.21), on all-cause mortality among high-risk patients (HRa: 1.07; 95% CI: 0.63 to 1.83), or on infection-related mortality in high-risk patients (HRa = 1.24; 95% CI: 0.67 to 2.28).

Conclusion: After adjusting for immortal time bias, PET scanning is not associated with 90-day mortality — whether all-cause or infection-related — in patients with Staphylococcus aureus bacteremia

Background: Antiretroviral (ARV) therapy halts HIV replication, reducing viremia below the detection threshold of clinically used tests. However, some individuals have persistent, unsuppressible viremia originating from CD4+ lymphocyte clones harboring infectious proviruses. Defective proviruses account for more than 90% of all proviruses persisting under ART and can express viral genes, but it is unknown whether they can contribute to persistent, unsuppressible viremia.

Methods: We conducted an in-depth characterization of the proviruses causing persistent, unsuppressible viremia in 4 individuals with optimal adherence and no ARV resistance. We determined the impact of the observed defects on the properties of the 5’ untranslated region of the RNA, on viral infectivity, and on gene expression. Integration site-specific assays were used to detect these proviruses over time and across different cellular subpopulations.

Results: Clones harboring proviruses with abnormalities in the 5’ untranslated region can lead to persistent, unsuppressible viremia at levels as high as 10³ copies/mL. These proviruses have small, often identical deletions or mutations in the major splice donor site, and exhibit partially reduced RNA dimerization and nucleocapsid binding. However, these proviruses are inducible and produce non-infectious virions containing viral RNA but no envelope.

Conclusion: These results show that proviruses with abnormalities in the 5’ untranslated region of the RNA in CD4+ lymphocyte clones may be responsible for persistent, unsuppressible viremia, posing a challenge for clinical monitoring. Sequencing of the 5’ untranslated region may help elucidate treatment failures in cases of persistent, unsuppressible viremia.

Introduction: In September 2015, the protein-based Group B meningococcal vaccine (4CMenB; Bexsero®) became available in Spain.

Methods: We conducted a nationwide matched case-control study to evaluate the effectiveness of 4CMenB in preventing invasive meningococcal infections in children. The study included all biologically confirmed cases of invasive meningococcal disease in children under 5 years of age between October 5, 2015, and October 6, 2019, in Spain. Each case was matched with four controls, who shared the same date of birth and were born and living in the same region as the cases. The 4CMenB vaccination status of cases and controls was compared using multivariate conditional logistic regression.

Results: We compared 306 cases (79.4% related to serogroup B) with 1,224 controls. A total of 35 cases (11.4%) and 298 controls (24.3%) had received at least one dose of 4CMenB. The protective efficacy of the complete 4CMenB vaccination series (defined as at least 2 doses, administered according to the manufacturer’s recommendations) was 76% (95% CI: 57 to 87) against invasive meningococcal infection regardless of serogroup, and that of partial vaccination was 54% (95% CI: 18 to 74). Complete vaccination had a protective efficacy of 71% (95% CI: 45 to 85) against invasive meningococcal infection of serogroup B. The protective efficacy with at least 1 dose of 4CMenB was 64% (95% CI: 41 to 78) against serogroup B and 82% (95% CI: 21 to 96) against non-B serogroups. Using the molecular typing system for meningococcal antigen, serogroup B strains covered by 4CMenB were detected in 44 of the cases; none of these children had been vaccinated.

Conclusion: Complete vaccination with 4CMenB is effective in preventing invasive meningococcal infection caused by serogroup B and non-B serogroups in children under 5 years of age.

Introduction: The optimal duration of antibiotic therapy for male urinary tract infections remains controversial.

Methods: To compare 7 days versus 10 days of antibiotic therapy for febrile urinary tract infections in men, this multicenter, randomized, controlled, double-blind, non-inferiority clinical trial enrolled 282 patients across 27 centers in France. Men were eligible if they presented with a febrile urinary tract infection and a urine culture identified a single pathogen. Participants initially received ofloxacin or a third-generation cephalosporin, then were randomized on days 3–4 to continue ofloxacin until day 7 or to continue ofloxacin until day 7 followed by placebo until day 14. The primary endpoint for treatment success was a negative urine culture with no fever and no resumption of antibiotic treatment between the end of treatment and the assessment at week 6. Secondary endpoints included the occurrence of a recurrent urinary tract infection at week 8 or week 12, rectal carriage of antibiotic-resistant Enterobacteriaceae, and treatment-related adverse events.

Results: 240 participants were randomized to receive 7 days (n = 115) or 14 days (n = 125) of antibiotics. In the ITT analysis, treatment success was observed in 55.7% and 77.6% of participants, respectively (risk difference –21.9; 95% CI: –33.3 to –10.1), demonstrating the inferiority of the 7-day regimen. Adverse events during antibiotic therapy occurred in 4 participants in the 7-day arm and 7 in the 14-day arm. The prevalence of rectal carriage of resistant Enterobacteriaceae did not differ between the two groups.

Conclusion: A 7-day course of ofloxacin is inferior to a 14-day course for febrile urinary tract infections in men and should not be recommended.

Introduction: Cabotegravir (CAB) + rilpivirine (RPV) administered intramuscularly every month or every 2 months is a long-acting regimen for maintenance therapy in virologically controlled HIV-1 patients. We report the results at S152 of the ATLAS-2M trial.

Methods: ATLAS-2M is a phase 3b, randomized, multicenter trial evaluating the efficacy and tolerability of CAB+RPV LA every 8 weeks (Q8S) or every 4 weeks (Q4S). Virologically suppressed HIV-1 patients (HIV-1 RNA < 50 c/ml) were randomized to CAB + RPV LA Q8S vs. Q4S. The endpoints were the proportion of participants with HIV-1 RNA ≥ 50 c/ml and < 50 c/ml, the incidence of confirmed virologic failure (2 consecutive HIV-1 RNA measurements ≥ 200 c/ml), tolerability, and safety.

Results: 1,045 participants were randomized, 522 to the Q8S group and 523 to the Q4S group. CAB+RPV: Q8S was non-inferior to Q4S in terms of efficacy; the proportion of patients with HIV-1 RNA ≥ 50 c/ml at week 152 was 2.7% (n = 14) and 1.0% (n = 5), respectively. The adjusted difference between the treatments was 1.7% (95% CI: 0.1 to 3.3), meeting the pre-specified non-inferiority criterion at a 4% threshold. At week 152, HIV-1 RNA was < 50 c/ml in 87% of patients in the Q8S group and 86% of patients in the Q4S group. In total, there were 12 (2.3%) confirmed virologic failures in the Q8S group and 2 (0.4%) in the Q4S group. Among these 14 virologic failures, the emergence of resistance mutations to RPV and integrase inhibitors was detected in 8 and 10 cases, respectively. Tolerability was comparable, with no new safety signals since week 48.

Conclusion: These data demonstrate the durability of the virologic response with CAB + RPV LA Q8S for approximately 3 years and confirm the efficacy, safety, and good tolerability of CAB + RPV LA as maintenance therapy in virologically controlled HIV-1 patients.

Introduction: Nirmatrelvir/ritonavir has been approved in many countries for the treatment of COVID-19. However, demand exceeds supply, warranting alternative options. VV116 is an oral antiviral with potent in vitro activity against SARS-CoV-2.

Methods: We conducted a phase 3, non-inferiority, randomized, investigator-blinded study during the surge caused by the B.1.1.529 (Omicron) variant. Symptomatic adults with mild or moderate COVID-19 and a high risk of disease progression were randomized to receive 5 days of VV116 or nirmatrelvir/ritonavir. The primary endpoint was the time to sustained clinical resolution at Day 28. Sustained clinical resolution was defined as improvement in all COVID-19-related symptoms with a total symptom score of 0 or 1 for 2 consecutive days (on an 11-symptom scale with scores ranging from 0 to 3). Non-inferiority was pre-specified as a lower bound of the two-sided 95% confidence interval for the hazard ratio > 0.8 (a hazard ratio > 1 indicating a shorter time to sustained clinical resolution with VV116 than with nirmatrelvir/ritonavir).

Results: 822 participants were randomized, and 771 received either VV116 (n = 384) or nirmatrelvir/ritonavir (n = 387). The non-inferiority of VV116 in terms of the time to sustained clinical resolution was demonstrated in the primary analysis (hazard ratio: 1.17; 95% CI: 1.01 to 1.35) and was confirmed in the final analysis (hazard ratio: 1.17; 95% CI: 1.02 to 1.36). In the final analysis, the time to sustained clinical resolution (a score of 0 for each of the 11 target symptoms for 2 consecutive days) and the time to the first negative SARS-CoV-2 test did not differ between the two groups. No participant died or progressed to severe COVID-19 at the Day 28 assessment. The incidence of adverse events was lower with VV116 than with nirmatrelvir/ritonavir (67.4% vs. 77.3%).

Conclusion: In adults with mild or moderate COVID-19 at risk of progression, VV1116 was non-inferior to nirmatrelvir/ritonavir in terms of the time to sustained clinical resolution, with fewer tolerability issues.

Background: Zinc supplementation has been considered a potential treatment for COVID-19. We evaluated the efficacy of zinc treatment in adult patients with COVID-19.

Methods: We conducted a multicenter, prospective, randomized, double-blind, placebo-controlled trial. Patients who tested positive for COVID-19 and did not have organ failure were randomized to receive oral zinc (n=231) or a placebo (n=239) for 15 days. The primary composite endpoint was death due to COVID-19 or admission to the intensive care unit within 30 days of randomization. Secondary endpoints included length of hospital stay for hospitalized patients and duration of COVID-19 symptoms, as well as COVID-19-related hospitalizations for outpatients.

Results: Among the enrolled patients, 190 (40.4%) were outpatients and 280 (59.6%) were hospitalized. Mortality at Day 30 was 6.5% in the zinc group and 9.2% in the placebo group (OR: 0.68; 95% CI: 0.34–1.35); the rate of admission to the intensive care unit was 5.2% and 11.3% (OR: 0.43; 95% CI: 0.21–0.87). The composite primary endpoint occurred less frequently in the zinc group than in the placebo group (OR: 0.58; 95% CI: 0.33–0.99). Consistent results were observed in the pre-specified subgroups of patients older than 65 years, those with comorbidities, or those requiring oxygen therapy at enrollment. The length of hospital stay was shorter in the zinc group than in the placebo group (difference: 3.5 days; 95% CI: 2.76–4.23); among outpatients, the duration of COVID-19 symptoms was shorter with zinc than with placebo (difference: 1.9 days; 95% CI: 0.62–2.6). There were no serious adverse events during the study.

Conclusion: Our results show that in patients with COVID-19, oral zinc may reduce 30-day mortality and intensive care unit admission and may shorten the duration of symptoms.

Introduction: The optimal duration of treatment for residual osteomyelitis following amputation for diabetic foot infection is uncertain, with inconsistent findings regarding the duration of antibiotic therapy prescribed in clinical practice. We evaluated whether there was a difference in clinical outcomes between long- and short-term antibiotic therapy in patients with a positive culture of the proximal bone specimen post-amputation.

Methods: In this single-center retrospective cohort study (Melbourne, Australia), we analyzed the duration of antibiotic therapy in patients who underwent amputation for diabetic foot infection and had a positive culture of proximal bone specimens over a 31-month period (January 2019–September 2021). The primary outcome measure was reamputation or reoperation at the same site or an adjacent site to the initial amputation within the following 6 months. Secondary outcome measures included rehospitalization and/or resumption of antibiotic therapy for diabetic foot infection at the same site or an adjacent site within the following 6 months.

Results: Among 92 patients (83% male, median age 67 years), 26 received antibiotics for less than 4 weeks (short-course antibiotic therapy) and 66 received antibiotics for 4 weeks or more (long-course antibiotic therapy). In the short-course antibiotic therapy group, the primary endpoint occurred in 9 patients (35%) compared with 15 patients (23%) in the long-course antibiotic therapy group (p=0.246). Secondary endpoints occurred in 12 patients (46 %) in the short-course antibiotic therapy group and 18 patients (27%) in the long-course antibiotic therapy group (p=0.086). The adjusted logistic regression analysis did not reveal a significant difference between short-course and long-course antibiotic therapy for the primary endpoint (OR 1.12; 95% CI % 0.38–3.31) or the secondary endpoints (OR 1.67; 95% CI 0.60–4.66).

Conclusion: This single-center study found no significant difference in outcomes between short- and long-term antibiotic therapy (< or 4 weeks) in patients with diabetic foot infection who had a positive proximal bone culture following amputation. These findings provide a rationale for conducting large- scale, international, randomized controlled trials to determine the optimal duration of treatment.

Objectives: Amoxicillin is the antibiotic of choice for the treatment of streptococcal and enterococcal infective endocarditis, but there are few data on the distribution of amoxicillin in infected heart valves. Here, we evaluated the valvular distribution of amoxicillin and the achievement of pharmacokinetic/pharmacodynamic targets in patients with infective endocarditis undergoing cardiac valve surgery.

Patients and Methods: This prospective 2-year study included patients with infectious endocarditis who were treated with continuous amoxicillin infusion and underwent valve replacement surgery. Amoxicillin concentrations were measured in both plasma and tissues on the day of surgery. Amoxicillin concentrations in plasma and in crushed heart valves were measured using liquid chromatography coupled with UV detection and mass spectrometry, respectively. The minimum inhibitory and minimum bactericidal concentrations of amoxicillin were determined for all available samples. The rate of obtaining PK/PD efficacy parameters was evaluated.

Results: A total of 22 heart valves were removed from 20 patients; the bacterial etiology was Streptococcus in 17 cases and Enterococcus in 3 cases. The mean dose of amoxicillin administered was 12 ± 3 g/day; the mean plasma concentration was 29 ± 21 mg/L (n = 15); and the mean tissue concentration was 23 15 mg/L (n = 22). The median rate of valvular diffusion was 62%. Patients achieved a target plasma concentration greater than 4 times the MIC in 13 cases. Tissue concentrations were bactericidal for all streptococcal endocarditis cases but not for those caused by enterococci.

Conclusion: Intravalvular measurements of amoxicillin in patients treated for infective endocarditis demonstrated significant penetration at the site of infection. These data are reassuring regarding in situ bactericidal concentrations, which are widely achieved in the management streptococcal endocarditis and reinforce the need for combination antibiotic therapy for enterococcal endocarditis.

Introduction: This Part 2b of a Phase 2-3 randomized clinical trial evaluated the efficacy and tolerability of ensitrelvir for mild to moderate COVID-19 during the Omicron surge

Methods: Patients were randomized 1:1:1 to receive oral ensitrelvir flumaric acid 125 mg (375 mg on Day 1) or 250 mg (750 mg on Day 1) or placebo once daily for 5 days. The primary and co-primary endpoints were the change from Day 0 in the SARS-CoV-2 viral load on Day 4 and the mean change over time, between Day 0 and the 120th hour, in the total score of 12 predefined COVID-19 symptoms. Tolerability was assessed by the occurrence of adverse events.

Results: A total of 341 patients (ensitrelvir 125 mg, n = 114; ensitrelvir 250 mg, n = 116; placebo, n = 111), 53.5% to 64.9% of whom were men, with a mean age of 35.3–37.3 years, were included in the efficacy analysis. The change in SARS-CoV-2 viral load between Day 0 and Day 4 was significantly greater with both doses of ensitrelvir than in the placebo group (difference from placebo: −0.41 log10 50% TCID/mL, p < 0.0001 for both groups). The total score for the 12 COVID-19 symptoms showed no significant differences between the ensitrelvir and placebo groups. The weighted mean change over time between Day 0 and the 120th hour was significantly greater with ensitrelvir than with placebo for several subtotals, notably acute symptoms and respiratory symptoms. Most adverse events were of moderate severity.

Conclusion: Treatment with ensitrelvir demonstrated favorable antiviral efficacy and potential clinical benefit with an acceptable safety profile

Introduction: We investigated the association between genetic markers associated with obesity and weight gain during antiretroviral therapy in HIV-positive patients.

Methods: Participants were patients on first-line antiretroviral therapy from the Spanish HIV Research Cohort who began antiretroviral therapy starting in 2014 and who had a DNA sample stored in the cohort’s biobank. The primary outcome measure was change in weight 96 weeks after the start of antiretroviral therapy. We determined the genotypes of 14 genetic markers associated with obesity based on a meta-analysis of GWAS data, as well as body mass index (BMI). Changes in weight and BMI over time were analyzed using an adjusted mixed-effects linear model.

Results: A total of 1,021 HIV patients were included. The mean weight gain at 96 weeks was 2.9 (95% CI: 2.54–3.26) kg. Factors associated with greater weight gain included female sex, birth in sub-Saharan Africa, a history of AIDS, a CD4 count < 200/mm³, a viral load > 100,000 copies/mL, HCV-negative serology, and the use of TAF. There was a significant association between increases in weight and BMI and the GG genotype of the ZC3H4 rs3810291 SNP, as well as the GG genotype of the BCDIN3D/FAIM2 rs7138803 SNP. The estimated mean adjusted weight gain was 4.26 (0.56) kg among carriers of the GG genotype of the ZC3H4 rs3810291 SNP, and 2.66 (0.19) kg among carriers of the AA/AG genotypes (p = 0.007). The estimated mean weight gain at 96 weeks was 3.35 (0.29 kg) among carriers of the GG genotype of the BCDIN3D/FAIM2 rs7138803 SNP, and 2.51 (0.24) kg among carriers of the AG/AA genotypes (p = 0.020).

Conclusion: Genetic factors may play a role in weight gain following initiation of antiretroviral therapy. Further studies are needed to confirm these findings and to understand how the identified genetic markers lead to greater weight gain in this context

Introduction: We compared RPR titers between the day of initial presentation and the day treatment for syphilis began to determine whether repeat RPR testing should be recommended in clinical practice.

Method: We conducted a retrospective study between March 1, 2011, and December 31, 2020, at the Melbourne Sexual Health Center in Australia among individuals with positive syphilis serology on the day of presentation and on the day of treatment, provided the interval between these two dates was less than 14 days. We calculated the percentage of individuals with a change in RPR antibody titer of at least a factor of 4, stratified by the time interval between initial presentation and treatment as well as the stage of syphilis.

Results: Among the 766 cases of syphilis, the median number of days between initial presentation and treatment was 6 (IQR = 5–7). 14.8% (n = 113) of cases experienced a more than fourfold increase or decrease in antibody titer between the day of initial presentation and the day of treatment. The number of cases with a more than fourfold increase or decrease in the RPR titer increased with the number of days between the day of initial presentation and the day of treatment, ranging from 4.1% (n = 6) for a delay of 1 to 3 days to 25.7% (n = 27) for a delay of 10 to 14 days (p < 0.0001). There was no significant difference in the number of cases with a more than 4-fold increase or decrease in the RPR titer according to the stage of syphilis (p = 0.37).

Conclusion: Our data support the recommendation to repeat the RPR test if the interval between initial presentation and treatment varies, even when treatment is initiated only a few days after initial presentation.