The edition · Infectious Diseases
Testing everyone for TB on admission did not save lives
EXULTANT put sputum, stool and urine Xpert Ultra plus urine LAM into every HIV admission regardless of symptoms — and found no more confirmed tuberculosis started on treatment and no mortality benefit. Plus a shorter antibiotic course for endocarditis, and an oral option that may spare carbapenems.
The edition in brief
EXULTANT randomised 1,172 adults with HIV admitted to 11 hospitals in Tanzania and Mozambique to expanded tuberculosis testing — Xpert Ultra on sputum, stool and urine plus lateral flow urine lipoarabinomannan, irrespective of symptoms — or to symptom-triggered WHO standard care. Microbiologically confirmed tuberculosis started on treatment within 72 hours was 16.0% versus 15.3% (difference 0.7%, 95% CI -3.4 to 4.8). Eight-week mortality was 25.8% versus 28.8% (hazard ratio 0.86, 95% CI 0.69 to 1.07). Time to treatment was unchanged. Notably, only 60.6% of eligible control patients actually produced a sputum sample, so the comparison was against a standard of care that was already failing. POET II randomised 508 adults with stabilised left-sided infective endocarditis to stop antibiotics after 2 to 4 weeks or complete 4 to 6 weeks. Days alive without antibiotics rose by 13 (95% CI 12 to 13), and the safety composite of death, unplanned cardiac surgery or embolism was noninferior at 8.2% versus 10.7%. Relapse rose from 1.6% to 5.1% (p=0.04). On resistance, phase 1 work has selected a dose for oral ceftibuten plus avibactam tomilopil — 400 mg with 1200 mg every 8 hours — for phase 3 in complicated urinary tract infection. If it works, it is the first oral option for extended-spectrum beta-lactamase-producing Enterobacterales. RECOVER-VITAL randomised 959 patients with long COVID to 15 or 25 days of nirmatrelvir-ritonavir or placebo and found no benefit across cognitive, autonomic or exercise phenotypes. Regulatory: the FDA approved a generic fidaxomicin from Sandoz on 13 August.
EXULTANT: testing every HIV admission for tuberculosis did not improve detection or survival
Expanding tuberculosis testing to sputum, stool and urine in every HIV admission regardless of symptoms did not increase confirmed cases treated or reduce eight-week mortality — the gap is in earlier care, not in the assay menu.
POET II: stopping antibiotics early in stabilised endocarditis is safe on hard outcomes, but relapse triples
In stabilised left-sided endocarditis due to common organisms, stopping antibiotics after 2 to 4 weeks does not increase death, surgery or embolism at six months but raises relapse from about 2% to about 5% — only do it where follow-up is assured.
An oral avibactam prodrug moves to phase 3 as a possible carbapenem alternative
An oral ceftibuten plus avibactam prodrug combination has a phase 3 dose but no efficacy data yet — keep using culture-directed nitrofurantoin, fosfomycin or aminoglycosides to spare carbapenems in ESBL urinary infection.
Generic fidaxomicin approved, which should matter more than it will
A generic fidaxomicin has been approved in the US, which begins the price erosion that eventually makes a guideline-preferred C. difficile drug usable outside well-funded systems.
RECOVER-VITAL: an antiviral does not treat long COVID
Nirmatrelvir-ritonavir for up to 25 days gave no benefit in any long COVID phenotype — stop offering antivirals for this indication.
The ESBL urinary infection that does not need a carbapenem
For ESBL cystitis, use nitrofurantoin or fosfomycin rather than a carbapenem, but never for pyelonephritis or bacteraemia — and set a review date on every carbapenem you do start.
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