Staphylococcus aureus bacteremia in patients with cardiac implantable electronic devices (CIEDs) is often associated with infective endocarditis (CIED-IE). The CIED-IE diagnosis is syndromic. Diagnostic uncertainty is common. Frequently, these patients are classified as having possible CIED-IE, resulting in guideline-noncompliant treatment and heterogeneous outcomes. Improved outcomes require accurate diagnoses. In these patients, we evaluated whether metagenomic sequencing of microbial cell-free DNA (mcfDNA) in serial plasma specimens could improve diagnostic precision.MethodsWe studied 16 patients with staphylococcal bacteremia who were classified with definite or possible CIED-IE and recommended for device removal, if there was a positive blood culture within 7 days and no concurrent deep infection. Plasma specimens obtained at consent, before extraction, and during 96 hours after extraction underwent metagenomic sequencing and quantification of staphylococcal mcfDNA.ResultsIn 10 of 11 patients with definite CIED-IE, mcfDNA persisted during antibiotic therapy for prolonged durations (median, 11 days [interquartile range {IQR}, 7.5–15 days]). In these cases, mcfDNA concentration in plasma obtained early after lead extraction increased significantly and thereafter decreased rapidly. In 5 cases of possible CIED-IE, mcfDNA was undetectable after 6 days (IQR, 5.5–7.5 days) of antibiotic therapy and remained undetectable after CIED extraction. These mcfDNA patterns differ significantly (P = .001), suggesting 2 distinct patient populations: 1 with definite CIED-IE and 1 without lead infection.ConclusionsIf confirmed, these mcfDNA patterns can serve as biomarkers, together with clinical features, to improve precision in diagnosing or rejecting S. aureus CIED-IE. Strategically timed mcfDNA testing before and after CIED extraction may aid in planning therapy.

Bedaquiline (BDQ) resistance presents a critical challenge in the fight against tuberculosis (TB), particularly multidrug-resistant (MDR) strains. The emergence of resistance to BDQ, a key drug in treating MDR-TB, poses significant threats to TB treatment effectiveness.MethodsThe National Institute of Tuberculosis and Respiratory Diseases in Delhi and the Médecins Sans Frontières clinic in Mumbai provide BDQ, delamanid, and carbapenem-based regimens for patients with suspected or confirmed treatment failure. BDQ phenotypic drug-susceptibility testing (DST) was performed for all BDQ-exposed patients. Treatment regimens were individualized based on exposure history, comorbidities, drug interactions, prior adverse drug reactions, and DST results.ResultsOf 117 BDQ-exposed patients from December 2020–December 2022, 42 (36%) exhibited a BDQ-resistant strain. Median (IQR) age was 24 (22–32) years, with 63 (54%) females and 94% with pulmonary TB. Patients with a BDQ-resistant strain were older (median age: 27 vs 23 years; P = .04), more likely to have lung cavities (risk ratio [RR]: 1.8; 95%-CI: 1.1–3.1; P = .02), and be resistant to clofazimine (RR: 2.3; 95%-CI: 1.5–3.6; P = .001). Overall, 102 patients initiated treatment. Patients with BDQ-resistance had higher risk of unfavorable outcomes compared with BDQ-susceptible patients (RR:2.1; 95%-CI: 1.5–2.8; P < .001). Overall, 87% (33/38) of patients with BDQ-resistance experienced unfavorable treatment outcomes: 15 (40%) died, 15 (40%) had treatment failure, and 3 (8%) were lost-to-follow-up.ConclusionsThe study highlights a concerning rate of BDQ-resistance among previously treated patients, resulting in poor treatment outcomes. To prevent treatment failure, we recommend implementing BDQ-DST, developing affordable and accurate rapid tests for BDQ-resistance, and intensifying research and development efforts for newer TB drugs.

Staphylococcus aureus bacteraemia presents a substantial clinical burden, with high rates of morbidity and mortality. Despite its severity, therapeutic advancements have been small in the past decade,...