Background: Integrase strand transfer inhibitors (INSTIs) are increasingly used in patients living with HIV due to their safety, effectiveness and high genetic barrier. However, an association with weight gain has recently been suggested and several cases of diabetes mellitus have been reported with raltegravir and dolutegravir. The long-time metabolic impact of these recent molecules remains unclear.Objectives: To assess if an INSTI as a third agent is statistically associated with new-onset diabetes mellitus compared with an NNRTI or a PI.Patients and methods: Patients undergoing first-line combined ART (cART) without diabetes at baseline were retrospectively included from the Dat’AIDS French cohort study (ClinicalTrials.gov NCT02898987). Incident diabetes mellitus was defined as a notification of new diabetes in the medical history, a glycated haemoglobin (HbA1c) level superior to 7.5% or the start of a diabetes therapy following the initiation of ART.Results: From 2009 to 2017, 19 462 patients were included, among which 265 cases of diabetes mellitus occurred. Multivariate and survival analyses did not highlight an increase in new-onset diabetes in patients undergoing cART with an INSTI as a third agent compared with an NNRTI or a PI. BMI >30 kg/m2, age >37 years old (in survival analysis), black race or Hispanic ethnicity, arterial hypertension and AIDS were associated with a higher proportion of incident diabetes.Conclusions: INSTIs were not statistically associated with new-onset diabetes. However, clinicians should remain aware of this possible metabolic comorbidity, particularly in patients with a high BMI and older patients.

AmpC β-lactamase-hyperproducing Enterobacterales (ABLHE) bloodstream infections (BSI) are emerging and leading to therapeutic challenges worldwide. Prescriptions of carbapenems may lead to the emergence of resistance. This study aimed to compare cefepime with carbapenems for the treatment of third-generation cephalosporin-resistant ABLHE BSI. This retrospective multicenter study included patients with ABLHE BSI from two tertiary hospitals in France, between July 2017 and July 2022. Non-AmpC-producing Enterobacterales, extended-spectrum β-lactamase, and carbapenemase-producing Enterobacterales were excluded. Cefepime was prescribed only in case of minimal inhibitory concentration ≤1 mg/l. The primary outcome was 30-day in-hospital mortality from the date of index blood culture. Secondary outcomes were infection recurrence and treatment toxicity. An inverse probability of treatment weighting approach was used to balance the baseline characteristics between the two groups. We analyzed 164 BSI, which included 77 in the cefepime group and 87 in the carbapenem group. In the weighted cohort, the 30-day mortality rates were similar between the cefepime group (23.3%) and the carbapenem group (19.6%) with a relative risk of 1.19 (95% confidence interval, 0.61-2.33 P = 0.614). No significant difference in recurrence or toxicity was found between the two groups. This study adds evidence in favor of the use of cefepime for treating third-generation cephalosporin-resistant ABLHE BSI in case of minimal inhibitory concentration ≤ 1 mg/l, which could spare carbapenems.

Suppressive antibiotic therapy (SAT) is a long-term antibiotic strategy at times applied when an indicated surgical management of infective endocarditis (IE) is not possible. Our aim was to describe the characteristics and outcomes of patients having received SAT for IE. We conducted a retrospective, observational study at Strasbourg University Hospital, France between January 2020 and May 2023. We reviewed all medical files taken into consideration at weekly meetings of the local Multidisciplinary Endocarditis Team (MET) during the study period. We included patients having received SAT following the MET evaluation. The primary endpoint was all-cause mortality at most recent follow-up. Secondary endpoints included all-cause mortality at 3 and 6 months, infection relapse, and tolerance issues attributed to SAT. The MET considered 251 patients during the study time, among whom 22 (9 %) had received SAT. Mean age was 77.2 ± 12.3 years. Patients were highly comorbid with a mean Charlson index score of 6.6 ± 2.5. Main indication for SAT was surgery indicated but not performed or an infected device not removed (20/22). Fourteen patients had prosthetic valve IE, including 9 TAVIs. Six patients had IE affecting cardiac implantable electronic devices. Staphylococcus aureus and enterococci were the main bacteria involved (6/22 each). Median follow-up time was 249 days (IQR 95-457 days). Mortality at most recent follow-up was 23 % (5/22). Three patients (14 %) presented tolerance issues attributed to SAT, and two patients suffered late infectious relapse. Mortality at most recent follow-up was low and tolerance issues were rare for patients under SAT, which might be a palliative approach to consider when optimal surgery or device removal is not possible.

Background: PCRs targeting 16S ribosomal DNA (16S PCR) followed by Sanger’s sequencing can identify bacteria from normally sterile sites and complement standard analyzes, but they are expensive. We conducted a retrospective study in the Strasbourg University Hospital to assess the clinical impact of 16S PCR sequencing on patients’ treatments according to different sample types. Methods: From 2014 to 2018, 806 16S PCR samples were processed, and 191 of those were positive. Results: Overall, the test impacted the treatment of 62 of the 191 patients (32%). The antibiotic treatment was rationalized in 31 patients (50%) and extended in 24 patients (39%), and an invasive procedure was chosen for 7 patients (11%) due to the 16S PCR sequencing results. Positive 16S PCR sequencing results on cerebrospinal fluid (CSF) had a greater impact on patients’ management than positive ones on cardiac valves (p = 0.044). The clinical impact of positive 16S PCR sequencing results were significantly higher when blood cultures were negative (p < 0.001), and this difference appeared larger when both blood and sample cultures were negative (p < 0.001). The diagnostic contribution of 16S PCR was higher in patients with previous antibiotic treatment (p < 0.001). Conclusion: In all, 16S PCR analysis has a significant clinical impact on patient management, particularly for suspected CSF infections, for patients with culture-negative samples and for those with previous antibiotic treatments.

We describe bundle measures implemented to overcome a protracted carbapenem-resistant Acinetobacter baumannii (CRAB) outbreak in an 18-bed trauma Intensive Care Unit (ICU) at Strasbourg University Hospital, a tertiary referral center in France. Outbreak cases were defined by a positive CRAB sample with OXA-23 profile during or after ICU say. To sustain the capacity of the busy trauma ICU, infection control bundles were purposely selected to control the outbreak without closing the ICU. During the outbreak, from May 2015 to January 2019, 141 patients were contaminated by CRAB, including 91 colonized and 50 infected patients. The conventional infection and prevention control (IPC) measures implemented included weekly active surveillance of patients’ samples, enhancement of environmental cleaning, interventions to improve hand hygiene compliance and antibiotic stewardship with audits. Supplemental measures were needed, including environmental samplings, health care workers’ (HCWs) hand sampling, chlorhexidine body-washing, relocation of the service to implement Airborne Disinfection System (ADS), replication of crisis cells, replacement of big environmental elements and improvement of HCW organization at the patient’s bedside. The final measure was the cohorting of both CRAB patients and HCW caring for them. Only the simultaneous implementation of aggressive and complementary measures made it possible to overcome this long-lasting CRAB epidemic. Facing many CRAB cases during a rapidly spreading outbreak, combining simultaneous aggressive and complementary measures (including strict patients and HCW cohorting), was the only way to curb the epidemic while maintaining ICU capacity.

Introduction: Prevention of cardiovascular disease is a major issue in the current management of people living with HIV. Concern is growing about the metabolic impact of integrase strand transfer inhibitors (INSTIs), which could lead to an increased risk of diabetes, but the data are conflicting. This is an updated version of our previous analysis, with longer follow‐up and new molecules.Methods: We retrospectively evaluated the incidence of new‐onset diabetes in people living with HIV starting combined antiretroviral therapy with an INSTI compared with non‐nucleoside reverse transcriptase inhibitors and protease inhibitors. Data were collected from the Dat'AIDS cohort study, a collaboration of 30 HIV treatment centres in France. We used a propensity score‐based inverse probability of treatment weighting approach to adjust for baseline characteristics between the two groups (INSTI and non‐INSTI).Results: Between 2009 and 2021, a total of 12 150 people living with HIV were included. The incidence of diabetes was higher in the INSTI group than in the non‐INSTI group (hazard ratio 1.38; 95% confidence interval 1.07–1.77; p = 0.012). Regardless of the third drug, but to a greater extent for INSTIs, we observed a peak of new‐onset diabetes in the year following initiation of combined antiretroviral therapy.Conclusions: The incidence of diabetes was higher in people treated with integrase inhibitors than in those receiving other third agents. This increased risk occurred both during the first year of treatment and in the longer term.