Infectious Diseases — New This Week

A week with more depth than headlines. The standouts are durable rather than newsworthy: a CID State-of-the-Art review on CSF shunt infections that makes the case for two-stage hardware exchange and explains why the CSF can look normal; a reminder that a single negative blood culture does not exclude candidemia; the subtype-specific oseltamivir-resistance mutations in avian influenza; adult neurologic Mycoplasma pneumoniae with 3-month disability data; and Campylobacter bacteremia that relapses in humoral immunodeficiency against a 75% fluoroquinolone-resistance background. Real-world lenacapavir and RSV burden in younger high-risk adults round out the practice-shaping tier. On the vaccine side, 2-year data on the pentavalent meningococcal ACWYX conjugate confirm outstanding serogroup X durability but weaker serogroup C persistence than MenACWY-TT.

Clinical Infectious Diseases

CIDVaccines · RandomizedNotable · surrogate

Persistence of Serum Bactericidal Antibody 2 Years After Pentavalent Meningococcal ACWYX Vaccine in Malian Infants and Toddlers

Two years out, does the pentavalent A/C/W/Y/X conjugate (NmCV-5) hold antibody as well as MenACWY-TT in African infants and toddlers?

What changedWHO recommended pentavalent meningococcal conjugate for routine infant/toddler immunization in the African meningitis belt in 2024 on short-term data only. This supplies the missing 2-year persistence data. Key figures1200 Malian children randomized; 92% completed day 181 and 90% day 730; no study-related serious adverse events. Serogroup A comparable to MenACWY-TT throughout. Serogroup C declined faster with NmCV-5 — fewer maintained responses at day 181 and day 730 in both age groups (all P ≤ .003). W and Y comparable in older toddlers; in younger infants NmCV-5 was lower for Y at day 181 (92.6% vs 100%) and W at day 730 (57.4% vs 76.8%). Serogroup X was the differentiator — 97–99% persistence at 2 years, significantly above MenACWY-TT at every comparison (all P < .0001). Fellow implicationNmCV-5's unique value is durable serogroup X protection, which no other licensed conjugate covers — and X has driven meningitis-belt outbreaks. The trade-off is less durable serogroup C antibody than MenACWY-TT, especially in the youngest infants; that is what booster-schedule debates will turn on. Immunogenicity endpoints only — no disease outcomes.

CIDResearch methods · ReviewNotable · methods

Artificial Intelligence Across the Vaccine Clinical Trial Lifecycle: Evidence, Readiness, and Guardrails

Where in a vaccine trial is AI actually ready to use, and where is it still unvalidated?

Key conclusionsEvidence is strongest for operational uses — recruitment, eligibility screening, trial matching, and risk-based monitoring. Applications to immune-response interpretation, correlates of protection, and safety surveillance remain less prospectively validated. Vaccine trials are distinctive: high safety expectations in healthy participants, evolving pathogen exposure and baseline immunity, incomplete correlates of protection, and intense public scrutiny. Fellow implicationUseful framing for anyone on a trial team or IRB: the defensible current use is operational triage, not immunogenicity or pharmacovigilance interpretation, with human scientific and safety judgment preserved.

CIDNeuro-ID · ReviewHigh yield · ID

State-of-the-Art Review: Infections in Patients With Cerebrospinal Fluid Shunts

In a suspected CSF shunt infection, what actually drives cure — and why can the CSF look normal?

What changedConsolidates the evidence that hardware strategy, not antibiotic choice alone, determines outcome — and names the diagnostic traps that delay recognition. Key figuresTwo-stage replacement (remove the shunt, externalize to an EVD, treat, then reimplant) achieves success >85% — 88% and 96% in two series — versus 65% for single-stage exchange. Dominant organisms: coagulase-negative staphylococci and S. aureus, with gram-negatives and Cutibacterium acnes regionally important. CoNS and C. acnes elicit only minimal CSF inflammation, so pleocytosis, high protein, and low glucose are each individually insensitive; C. acnes is recovered mainly on prolonged incubation. Fellow implicationDon't let a bland CSF profile talk you out of the diagnosis; ask the lab to hold cultures when C. acnes is plausible; push for two-stage exchange absent a specific reason not to.

Clinical takeaway. The single most consequential decision in shunt infection is surgical, and the review's numbers are lopsided enough to argue the point for you at the bedside. The diagnostic half is just as useful: the organisms that cause most of these infections are precisely the ones that produce an unimpressive CSF and grow slowly.

CIDDiagnostics · Brief ReportHigh yield · ID

Utility of Repeating Blood Cultures in Candidemia

If the first blood culture is negative but candidemia is still suspected, is it worth repeating?

What changedQuantifies, across two large EHR repositories, how much candidemia a single negative set misses. Key figureAmong 1386 candidemia episodes, repeat cultures after an initial negative detected 23% of episodes at Houston Methodist and 45% in MIMIC-IV. Fellow implicationA single negative blood culture does not exclude candidemia. With high pretest suspicion — colonization, vasopressors, indwelling lines — re-culture rather than de-escalate.

Clinical takeaway. Blood cultures are already known to be insensitive for invasive candidiasis; this puts a number on the practical corollary. Between a quarter and nearly half of episodes would have been missed by stopping at one negative set.

Also new in CID. Screened out — two corrections, one correspondence and one letter reply on valve strands in infective endocarditis. Backlog — the Vol. 83(1) assignment resurfaced ~70 older online-first articles (LLM-assisted CAUTI surveillance, gonorrhea diagnosis and treatment, fatal B virus encephalitis, rising Candidozyma auris resistance); these were scoped out by online date and remain available for a future pickup.

Open Forum Infectious Diseases

OFID

Avian influenza · Review High yield · ID

Oseltamivir Resistance in Human Influenza A(H5N1) and A(H7N9) Infections

When avian influenza develops oseltamivir resistance, which mutations do you expect — and does treatment still work?

What changedConsolidates the human-case literature and shows resistance emerges in a subtype-specific pattern. Key figuresA(H5N1) → H274Y and N294S; A(H7N9) → R292K. Mutations arose rapidly on therapy, and most cases of both subtypes had serious outcomes or died despite oseltamivir. Fellow implicationIn suspected avian influenza failing oseltamivir, send neuraminidase sequencing and expect the subtype-typical substitution. The poor outcomes argue for combination or non-NA-inhibitor strategies, not dose escalation alone.

Clinical takeaway. Two facts worth holding: which mutation goes with which subtype, and that oseltamivir has not rescued most human H5N1/H7N9 cases even when susceptible. Timely against the ongoing H5N1 situation.

OFID

Bacterial / Neuro High yield · ID

Neurological Manifestations of Mycoplasma pneumoniae in Hospitalized Adults

How often does M. pneumoniae cause neurologic disease in adults, what does it look like, and does it resolve?

What changedPuts adult numbers and 3-month outcomes on an association usually taught from pediatric case reports. National MYCADO cohort, 1309 adults hospitalized in the 2023–2024 French epidemic. Key figures28 patients (2.1%) — 19 CNS (encephalitis 8, isolated meningitis 6, myelitis 3, encephalomyelitis 2, cerebral vasculitis 1) and 9 PNS (Guillain-Barré 6, polyneuropathy 2, multifocal neuropathy 1). Median age 35; onset a median 7 days after infection. 46.4% needed intensive care. Longer stay (13 vs 9 days), more invasive ventilation (35.7% vs 4.2%), more rehab transfers (42.8% vs 4.3%); all P < .001. At 3 months, sequelae persisted in 36.8% of CNS cases and in all GBS cases. Fellow implicationRare but not benign. Keep M. pneumoniae on the differential for encephalitis, aseptic meningitis, myelitis, and GBS in a young adult with a recent respiratory illness — and counsel early that disability often persists.

Clinical takeaway. The board association is real and, in adults, carries an ICU rate near 50% and durable disability. The 3-month follow-up is what elevates this above the usual case series.

OFID

Bacterial · Multinational cohort High yield · ID

Campylobacter spp Bloodstream Infections in Immunocompetent vs Immunodeficient Patients

Who relapses after Campylobacter bacteremia, and what should you treat it with?

What changedA multinational retrospective cohort (261 episodes, 2009–2024) separates the course by the type of immune defect rather than lumping "immunocompromised." Key figures172/261 (65.9%) episodes were in immunodeficient patients; 104 (60.5%) of those had humoral immunodeficiency, 42 (24.4%) a primary immunodeficiency. Relapse or reinfection: 8.0% overall but 18.3% of humoral-immunodeficient patients, 57.9% of whom had a PID. Resistance: fluoroquinolones 75%, macrolides 14.5%. 30-day mortality 9.9% overall, and lower in humoral-ID (4.8%) than immunocompetent patients (13.5%; P = .05) — a younger, less comorbid group. Fellow implicationRecurrent Campylobacter bacteremia should trigger an immunoglobulin workup for hypogammaglobulinemia/PID. With 75% fluoroquinolone resistance, a macrolide is the safer empiric choice pending susceptibilities.

Clinical takeaway. Two actionable items in one paper: relapse points at the antibody compartment, and ciprofloxacin is the wrong reflex. Note the mortality inversion is confounded by age and comorbidity, not evidence that immunodeficiency protects.

OFID

Transplant ID High yield · ID

Refractory Mucocutaneous HSV in Hematopoietic Cell Transplant Recipients

When mucocutaneous HSV fails a week of appropriate therapy post-HCT, how often is it truly acyclovir-resistant?

Key figures125 adults, 7 US centers. Acyclovir resistance confirmed in 85/104 (81.7%) tested. 110 (88%) needed second-line therapy — foscarnet 94, IV cidofovir 6, topical 21. Complete healing in only 55.2%, at a median 38 days. Nephrotoxicity during 40.4% of foscarnet and 50.0% of cidofovir courses; 39.1% of healed patients recurred within a year. Fellow implicationIn post-HCT mucocutaneous HSV not improving after ~7 days of adequate acyclovir, resistance is the rule, not the exception. Send susceptibility testing, move to foscarnet early, and expect renal toxicity in ~40% and relapse in ~40%.

OFID

HIV · New antimicrobial Notable · confirmatory

Virologic Outcomes With Lenacapavir: A Multicenter Real-World Study

Outside CAPELLA, does lenacapavir suppress heavily treatment-experienced people with HIV?

Key figures70 PWH at 6 clinics, median follow-up 12 months; 26% multidrug-resistant, 54% viremic at baseline. Of 38 viremic patients, 34 (89%) reached VL <200 copies/mL; none of the 32 already-suppressed rebounded. Regimen potency improved and pill burden fell from 2 tablets to 1 (both P < .00005). Injection-site reactions in 30%, one discontinuation. Fellow implicationSupports lenacapavir as salvage in heavily treatment-experienced/MDR HIV, with ISRs common but rarely treatment-limiting. Small and retrospective — consistent with CAPELLA rather than extending it.

OFID

Viral · Prevention Notable · observational

Incidence of RSV Acute Respiratory Infection in Adults 18–64 With High-Risk Conditions

How much RSV lower-respiratory disease do younger adults with high-risk conditions actually get?

Key figuresMultistate prospective community cohort, Oct 2022–Sep 2024. Among 3375 adults with ≥1 high-risk condition: RSV-ARI 17.9 vs 14.8 per 1000 person-years, RSV-LRTD 10.0 vs 5.7. Asthma, congenital immunodeficiency, and immunosuppressive medications raised both; solid organ transplant and CKD raised LRTD. Adjusted, ≥1 high-risk condition carried a 62% higher RSV-LRTD risk — 117% in adults 18–49. Fellow implicationThe RSV-LRTD signal is strongest in the youngest high-risk adults — useful when asked about RSV vaccination in transplant, CKD, or immunosuppressed patients under 60.

Also new this week. Cryptococcosis — in 743 HIV-negative patients, mortality was 1.4% at 2 weeks, 8.4% at 10 weeks, 12.2% at 1 year; the higher Western early mortality tracks with solid organ transplant, malignancy, and older age rather than the organism (ofag410). Metabolic syndrome and CDI — risk rose with metabolic syndrome (OR 1.94), obesity (1.14), and type 2 diabetes (1.11), but only diabetes tracked with worse outcomes including recurrence and death (ofag419). Influenza antivirals — only ~54% of higher-risk outpatients under 65 were dispensed an antiviral across 549 424 encounters; same-day dispensing 91.1% commercial vs 81.4% Medicaid (ofag439). Patients vs short courses — 60.4% of 1475 US adults preferred a ≥7-day antibiotic course, rating longer courses safer and more effective (ofag407). TB care delays — median 65.5 days from symptom onset to treatment in Kenya and Uganda; longer after pharmacy care-seeking, shorter with HIV (ofag392). BNT162b2 in people with HIV — well tolerated, with binding and neutralizing responses sustained 6 months; surrogate endpoints only (ofag310). N-acetylcysteine for dengue liver injury — >95% of adults have transaminitis, 12% exceed 400 IU/L and 2% exceed 1000 IU/L; NAC remains unproven and a platform trial is under way (ofag421). LLM-assisted evidence synthesis — a randomized crossover trial found extraction 7.9 minutes faster with an LLM, but not significantly so (P = .099), with 100% accuracy in both arms (ofag401). Pediatric RSV — the two post-pandemic Atlanta waves fell outside the normal season and were less severe (ofag215).

Summaries are original paraphrases prepared for educational use; figures are drawn from the published full text. Read the full articles at the DOIs linked above — Clinical Infectious Diseases requires a subscription; Open Forum Infectious Diseases is open access. Pull window July 16–24, 2026 (19 articles archived: 4 CID, 15 OFID). Citations: Clin Infect Dis 2026;83(1) and Open Forum Infect Dis 2026;13(7). DOIs: 10.1093/cid/ciag449, 10.1093/cid/ciag445, 10.1093/cid/ciag269, 10.1093/cid/ciag216, 10.1093/ofid/ofag393, 10.1093/ofid/ofag406, 10.1093/ofid/ofag380, 10.1093/ofid/ofag377, 10.1093/ofid/ofag425, 10.1093/ofid/ofag391, 10.1093/ofid/ofag410, 10.1093/ofid/ofag419, 10.1093/ofid/ofag439, 10.1093/ofid/ofag407, 10.1093/ofid/ofag392, 10.1093/ofid/ofag310, 10.1093/ofid/ofag421, 10.1093/ofid/ofag401, 10.1093/ofid/ofag215.