Infectious Diseases · In Review
Infectious Diseases — New This Week
July 1 – July 10, 2026 · Clinical Infectious Diseases & Open Forum Infectious Diseases
No new randomized trials in either journal this week — but three items are worth your time. Gepotidacin, the newly approved first-in-class oral antibacterial, turns out to have a larger advantage over nitrofurantoin precisely when the uropathogen is nitrofurantoin-nonsusceptible. A target-trial emulation across eight hospitals finds ~7 days is enough for uncomplicated enterococcal bacteremia. And an OFID meta-analysis quantifies what rapid blood-culture ID panels actually buy: 17 hours and a hospital day, but no mortality benefit. Also: a State-of-the-Art review reframes what "fever of unknown origin" even means, a negative pre-rash measles PCR is shown to miss ~1 in 5 cases, and third-party BK-virus T cells produce the first real signal of efficacy in PML.
Clinical Infectious Diseases
Gepotidacin vs Nitrofurantoin for Uncomplicated UTI, Including Nitrofurantoin-Nonsusceptible Uropathogens
In females ≥12 years with uncomplicated UTI, does gepotidacin vs nitrofurantoin improve therapeutic success — and does the benefit hold when the organism is not susceptible to nitrofurantoin?
- Population
- Pooled microbiological ITT population of two completed phase 3 trials, EAGLE-2 (NCT04020341) and EAGLE-3 (NCT04187144). Females ≥12 yr with uUTI, split into nitrofurantoin-susceptible (NTF-S) and nitrofurantoin-not-susceptible (NTF-NS = resistant, intermediate, or no interpretation).
- Intervention
- Gepotidacin 1500 mg orally twice daily × 5 days.
- Comparison
- Nitrofurantoin 100 mg orally twice daily × 5 days.
- Outcome
- Therapeutic success at test-of-cure (day 10–13; clinical + microbiological success). Treatment difference favoring gepotidacin: NTF-S +9.6% (95% CI 4.1–15.2); NTF-NS +20.8% (95% CI 9.2–32.4). Microbiological success +10.4% and +20.7%. The clinical-success component alone was not significant in either population (+2.8%, +10.3%). Benefit held across higher-resistance-risk subgroups (age >50, recurrent uUTI, diabetes, mild renal impairment, ESBL or fluoroquinolone-resistant isolates).
Major studies & new antimicrobials
7 vs 14 Days for Uncomplicated Monomicrobial Enterococcal Bloodstream Infection — A Target Trial Emulation
In uncomplicated monomicrobial enterococcal bacteremia, does ~7 days of antibiotics vs ~14 days change 30-day mortality?
•What changed. Enterococcal BSI had no duration evidence and no RCT. Eight Israeli hospitals (2013–2023), 485 analyzed patients, analyzed as a target trial emulation with a clone–censor–weight design to defeat immortal-time bias. •Key figure. 30-day mortality 21.6% (short, 7 ± 2 d) vs 21.3% (long, 14 ± 2 d); adjusted risk ratio 1.01 (95% CI 0.84–1.22). No difference in 90-day mortality, recurrence, length of stay, readmission, or C. difficile. •ID-fellow implication. ~7 days is defensible for uncomplicated enterococcal bacteremia in selected patients — extending the short-course movement into a gap where guidance was silent. Endocarditis and deep-seated foci were excluded by design, so this says nothing about complicated disease. Parienti's editorial explains the clone–censor–weight method; residual confounding by indication remains the limitation.Sensitivity of Measles rRT-PCR in Exposed, Symptomatic Persons Without Rash
During an outbreak, does a negative measles rRT-PCR in a symptomatic, exposed person who has not yet developed a rash rule out measles?
•What changed. Puts a number on a principle usually taught qualitatively: measles nucleic-acid detection is least sensitive in the prodromal (pre-rash) phase. 2024 Chicago outbreak; 120 tests in 117 exposed, symptomatic persons without rash. •Key figure. Sensitivity 78% — on only 7 true positives, so the estimate is imprecise. •ID-fellow implication. A negative pre-rash measles PCR does not exclude measles — roughly 1 in 5 true cases is missed if you test too early. Maintain suspicion, do not release from isolation or quarantine on that single negative, and repeat testing once the rash appears.State-of-the-Art Review: Contemporary Ambulatory Approach to Adult Fever of Unknown Origin
What actually separates the qualitative from the quantitative definition of classic FUO — and why does the choice change the causes you find?
•The quantitative definition is time-only: fever >38.3 °C on several occasions, illness >3 weeks, undiagnosed. The qualitative definition additionally requires that a minimum set of investigations be completed first — CBC with differential, CMP with calcium and LFTs, ESR, blood cultures, then clue-directed imaging. •Studies using qualitative criteria report a relative +15.3% (95% CI 2.3–28.3; P=0.021) higher proportion of undiagnosed FUO; the 11 quantitative (time-only) studies report +19.7% (95% CI 6.0–33.4; P=0.005) more infectious diagnoses. •The lesson: a time-only label sweeps in incompletely worked-up patients, inflating the apparent share of infection and shrinking the truly undiagnosed group. Reframes FUO as "a definition plus a workup standard," and (with the modified Delphi consensus and SNMMI recommendations) positions 18FDG-PET/CT for the clue-free patient whose minimum workup is already complete — not as a reflex early scan.Third-Party Allogeneic BK Virus–Specific T Cells for Progressive Multifocal Leukoencephalopathy
In PML — a uniformly fatal JC polyomavirus disease with no approved therapy — can off-the-shelf, partially HLA-matched BK virus–specific T cells clear virus and stabilize the patient?
•What changed. Exploits BKV/JCV antigenic cross-reactivity: donor BK-specific T cells recognize JC virus. Single-center, single-arm phase 2, n=37 (23 with hematologic malignancy), 2.0×105 cells/kg, median 2 doses. •Key figure. Overall response (virologic clearance + neurologic stabilization/improvement) in 21/37 (56.8%); complete response 43.2%; median time to response 23 days. 1-year overall survival 61.1% (95% CI 41.9–77.4). •ID-fellow implication. The most promising therapy yet for a disease whose only "treatment" is reversing immunosuppression. But there is no control arm; the headline 93.3%-vs-0% survival split is a responder analysis (responders must survive long enough to respond). Know it; it is not yet standard of care.Does a Prior Typhoid Episode Protect Against Recurrence? A Large Dhaka Cohort
Does natural typhoid infection protect against a recurrent episode — and how much does the control group you pick decide the answer?
•Key figure. Against 3,760 matched community controls, prior cases looked more likely to recur (adjusted HR 3.7, 95% CI 1.8–7.9). Against facility-based controls (febrile patients who also presented and were cultured), the effect vanished: adjusted HR 1.5 (95% CI 0.8–2.8; P=0.160). •ID-fellow implication. Natural typhoid confers no demonstrable protection against recurrence — a prior episode is not a reason to defer typhoid conjugate vaccination. The methodological lesson is the sharper one: the community-control result was an artifact of healthcare-utilization bias. The control group chose the answer.Open Forum Infectious Diseases · Vol. 13, No. 7
Multiplex PCR Blood-Culture Identification Panels: Systematic Review and Meta-Analysis
In adult inpatients with bloodstream infection, what do rapid blood-culture identification panels actually improve — and what do they not?
•Key figures (20 studies, 4,587 patients, US hospitals): time to appropriate antimicrobial therapy −17.28 hours (95% CI −24.00 to −10.56); hospital length of stay −1.25 days (95% CI −1.79 to −0.71); mortality OR 1.04 (95% CI 0.81–1.34, not significant); economic outcomes not significantly different. •What this corrects. Rapid organism ID reliably compresses time-to-appropriate-therapy and shortens stay — but on pooled data it does not move mortality and does not save money by itself. •ID-fellow implication. BCID is a diagnostic whose value is realized through the response attached to it — real-time notification and protocolized stewardship de-escalation. The authors say it plainly: "a timely clinical response is necessary." Deploying the panel without a response pathway is the standard implementation failure. Do not promise a mortality benefit when justifying the assay.Long-Term Follow-Up of Classic FUO Discharged Without a Definitive Diagnosis
What actually happens to the classic-FUO patient you send home without an answer?
•Key figures (739 patients, Peking Union Medical College Hospital): among 396 followed patients discharged undiagnosed, mortality was 3.3%. Concordance between discharge and follow-up diagnosis 93.0%. Among those who stayed undiagnosed, 31.8% remitted spontaneously and 36.4% after short-term anti-inflammatory therapy. Hospitalization cost was higher in the definitively diagnosed group. •ID-fellow implication. Undiagnosed classic FUO is not a dangerous holding pattern: mortality is low, the discharge working diagnosis is usually right, and about a third resolve on their own. Supports watchful waiting with structured follow-up over escalating invasive workup or reflex empiric therapy. Setting matters — a high-TB-prevalence tertiary referral center (empiric anti-TB "succeeded" in 79%), so that figure does not transfer to low-burden US practice. •Reads directly alongside this week's CID State-of-the-Art FUO review.Direct-Acting Antivirals and Long-Term Outcomes in Dialysis Patients With Hepatitis C
Among patients with ESKD on dialysis and HCV, is DAA therapy associated with better long-term survival?
•Key figures (TriNetX, 2015–2025; 1,458 propensity-matched pairs): all-cause mortality HR 0.68 (95% CI 0.59–0.77); kidney transplantation HR 1.42 (95% CI 1.12–1.80); no difference in incident cirrhosis or hepatocellular carcinoma over 5 years. •ID-fellow implication. Reinforces existing guidance to treat HCV on dialysis. Note the pattern: benefit tracked with survival and with getting transplanted, not with liver endpoints — hinting the survival gain is not purely hepatic, and that treatment improves transplant candidacy. Confounding by indication (healthier patients get offered DAAs) is what matching cannot fully remove.Vascular Graft Infections: Characteristics and Risk Factors for Mortality
In surgically managed vascular graft infection, which organisms dominate — and what actually predicts death?
•Key figures (129 patients, French reference center, 2020–2025): polymicrobial in 49%; Staphylococcus aureus the predominant pathogen at 16% of isolates; 85% extracavitary; 1-year mortality 43%. Independent predictors of infection-related death: age >75 (P=0.03) and ICU admission (P=0.045). •ID-fellow implication. Nearly half are polymicrobial, so empiric coverage must be broad and skin flora (coagulase-negative staphylococci, Cutibacterium acnes, corynebacteria) needed ≥2 concordant samples to count. Strikingly, once host factors were accounted for, neither the microbiological profile nor the surgical strategy independently predicted death — age and severity at presentation did.Secondary Oral Vancomycin Prophylaxis and C. difficile in Children and Young Adults With Cancer
After a first CDI episode, does oral vancomycin prophylaxis during broad-spectrum antibiotics prevent recurrence in young cancer patients?
•Key figures. Unadjusted, CDI was not significantly reduced (17.9% without OVP vs 7.4% with). After propensity matching — only 11 matched sets — adjusted OR 0.074 (95% CI 0.01–0.54). •ID-fellow implication. Extends the adult secondary-OVP literature into pediatric/young-adult oncology, but the null unadjusted comparison, 11 matched sets, and very wide CI make this a signal, not a practice change — exactly as the authors conclude.Summaries are original paraphrases prepared for educational use; all figures are drawn from the published full text and verified against it. Read the full articles at the DOI links (CID requires a subscription; OFID is open access). Window: 1–10 July 2026. No randomized controlled trials were newly posted in either journal this week; the gepotidacin item is a post hoc pooled subgroup analysis of two completed phase 3 RCTs (NCT04020341, NCT04187144) and the PML item is a single-arm phase 2 study (NCT02479698). CID DOIs: 10.1093/cid/ciag408 (editorial 10.1093/cid/ciag409), 10.1093/cid/ciag387 (editorial 10.1093/cid/ciag388), 10.1093/cid/ciag405, 10.1093/cid/ciag158, 10.1093/cid/ciag404, 10.1093/cid/ciag411, 10.1093/cid/ciag399, 10.1093/cid/ciag400, 10.1093/cid/ciag369. OFID DOIs (Vol. 13, No. 7): 10.1093/ofid/ofag370, 10.1093/ofid/ofag372, 10.1093/ofid/ofag389, 10.1093/ofid/ofag385, 10.1093/ofid/ofag365, 10.1093/ofid/ofag374, 10.1093/ofid/ofag378, 10.1093/ofid/ofag317.