Infectious Diseases — New This Month — Aug 29

A dense pull spanning two journals. In CID, a meta-analysis of C/T vs C/A for MDR/DTR Pseudomonas finds clinical cure advantage for ceftolozane-tazobactam (OR 1.82), the GAMES registry quantifies ICH risk from baseline anticoagulation in infective endocarditis (aRR 1.83; combined AC+APT worst at 2.45), and a Vanderbilt cohort confirms MRSA PCR nasal swab NPV is preserved even after universal mupirocin decolonization in the ICU. A comprehensive complement inhibitor infection risk review arrives as these agents expand beyond PNH. Four TB diagnostic studies push non-sputum and near-point-of-care testing. In OFID, a striking D+/R− heart transplant case demonstrates fulminant GI toxoplasmosis with secondary HLH after stopping prophylaxis, and the BATMO protocol shows 5-year safety data for FQ-free HSCT prophylaxis. 4 Anki cards minted (3 CID, 1 OFID).

Clinical Infectious Diseases

Major studies & new antimicrobials

CIDMajor Study · AMRHigh yield · ID

Ceftolozane-Tazobactam vs Ceftazidime-Avibactam for MDR/DTR Pseudomonas: Meta-Analysis

For MDR/DTR Pseudomonas aeruginosa infections, does ceftolozane-tazobactam or ceftazidime-avibactam achieve higher clinical cure?

Key findingSystematic review and meta-analysis of 6 observational studies (n = 1161). C/T: higher clinical cure — OR 1.82 (95% CI 1.10–2.99), I² = 25.3%. No differences in microbiological failure, 90-day resistance development, or 30-day mortality. MechanismCeftolozane has intrinsic anti-Pseudomonal activity independent of tazobactam; ceftazidime DEPENDS on avibactam PK — avibactam’s faster renal elimination may create subtherapeutic windows with normal/augmented renal clearance. Fellow implicationBoth agents are IDSA first-line for MDR/DTR Pseudomonas. This is the first pooled adjusted comparison suggesting C/T may have a clinical cure advantage. All data are observational; no RCTs exist.

Clinical takeaway. Both C/T and C/A are IDSA first-line for MDR/DTR Pseudomonas, but this is the first pooled adjusted comparison and it favors C/T for clinical cure. The mechanistic explanation matters: ceftolozane has intrinsic anti-Pseudomonal activity regardless of its partner, while ceftazidime depends entirely on avibactam PK — and avibactam clears renally faster. All data are observational; an RCT may never happen, so this meta-analysis is likely the best comparative evidence we get.

Anki: ✅ carded — new antimicrobial comparison (CID::Review_Article + Subject::Infectious_Disease)

CIDMajor Study · EndocarditisHigh yield · ID

Baseline Antithrombotic Therapy and Intracranial Hemorrhage in Infective Endocarditis (GAMES)

In patients with left-sided IE, does baseline anticoagulation increase ICH risk compared with no antithrombotic therapy?

Key findingProspective multicenter cohort (n = 3236). ICH 30-day rate 5.6%. AC: aRR 1.83 (1.16–2.91). Combined AC+APT: aRR 2.45 (1.55–3.87) — highest risk. APT alone: NOT associated with ICH. Ischemic stroke rates similar across groups. Fellow implicationDirectly informs risk stratification at IE diagnosis. Patients on baseline AC (especially combined with APT) should be flagged for early neuroimaging. APT alone is reassuring. Independent ICH risk factors: S. aureus, Candida, extracranial embolism, prior CVD, septic shock.

Clinical takeaway. This is the largest prospective cohort to quantify the antithrombotic–ICH relationship in IE. The numbers are immediately useful at the bedside: anticoagulation at diagnosis roughly doubles ICH risk, and combined AC+APT is the worst combination (nearly 2.5-fold). APT alone is safe, which matters for patients on aspirin who develop IE. Use antithrombotic status alongside organism (S. aureus, Candida) and septic shock for early neuroimaging triage.

Anki: ✅ carded — changes management/risk stratification (CID::Major_Study + Subject::Infectious_Disease)

CIDMajor Study · DiagnosticsHigh yield · ID

MRSA PCR Nasal Swab NPV Preserved After Mupirocin Decolonization in ICU

In ICU patients receiving universal mupirocin decolonization, does the NPV of MRSA PCR nasal swab testing remain reliable for guiding vancomycin de-escalation?

Key findingRetrospective cohort (n = 1034, Vanderbilt). NPV of MRSA PCR nasal swab 0–7 days after starting mupirocin was noninferior to pre-decolonization (difference +0.3%, 1-sided 95% CI −0.9%). Even >7 days after mupirocin: no clinically meaningful NPV reduction. Fellow implicationClinicians can trust a negative MRSA nares PCR for vancomycin de-escalation in ICUs with universal mupirocin decolonization. Testing within 7 days of mupirocin start is reliable.

Clinical takeaway. The question this answers is one that comes up in practice: “My ICU patient got mupirocin on admission — can I still trust the MRSA nares swab I just ordered?” Yes. NPV was noninferior even within 7 days of mupirocin start. This is a single-center retrospective, but the result is clean enough and the clinical scenario common enough that it can guide vancomycin de-escalation decisions now.

Anki: ✅ carded — diagnostic changes testing practice (CID::Major_Study + Subject::Infectious_Disease)

CIDReview · ImmunocompromisedHigh yield · ID

Strategies to Mitigate Infection Risk in Complement Inhibitor Therapy

How should infections be prevented and managed in patients starting systemic complement inhibitors?

Key pointsAll systemic complement inhibitors (C5: eculizumab, ravulizumab, crovalimab; proximal: pegcetacoplan, iptacopan, danicopan) carry increased risk of encapsulated bacterial infection — meningococcal disease 0.31–0.83 per 100 PY with eculizumab despite vaccination. Vaccinate MenACWY + MenB + PCV + Hib ≥2 weeks before initiation. Antibiotic prophylaxis when therapy cannot be delayed. Intravitreal complement inhibitors (Syfovre for AMD) and avacopan (C5aR, not C5) do NOT carry the same boxed warning. Fellow implicationAs complement inhibitor use expands beyond PNH/aHUS (IgA nephropathy, C3G, NMOSD, AMD), ID consultations for pre-treatment vaccination and infection mitigation will increase.

Clinical takeaway. The expanding use of complement inhibitors beyond PNH/aHUS — now into IgA nephropathy, C3 glomerulopathy, NMOSD, and AMD — means ID fellows will see more pre-treatment vaccination consults. The key distinction: intravitreal pegcetacoplan (Syfovre) and avacopan (C5a receptor, not C5 itself) do NOT carry the meningococcal boxed warning. All systemic C5 and proximal inhibitors do — and meningococcal disease still occurs at 0.31–0.83/100 PY despite vaccination.

Anki: not carded — narrative review of existing guidance, no new data threshold

Notable · structured key-takeaways

HIV/STINotable · confirmatory

Population-Level Impact of Doxy-PEP on Syphilis in King County, WA

ITS analysis: syphilis −52.3% (absolute −3031 cases) after March 2023 doxy-PEP implementation. Cisgender women saw a −46.9% reduction (indirect effect). But congenital syphilis rose from 0 to 23. Confirms SF data in a second US jurisdiction.

Not carded — ecological ITS; principle already established from prior RCTs

MycologyNotable · single-center

Histoplasma Antigen Persistence Varies by Immune Status

Single-center (n = 83). Transplant (20.3 mo) and biologic (14.6 mo) patients cleared antigen far slower than immunocompetent (6.8 mo) or PLWH (12.9 mo). At 1 year: 55% of immunocompromised still antigen-positive vs 19% immunocompetent. Persistent antigenuria in transplant/biologic patients does NOT necessarily mean treatment failure.

Not carded — single-center n=83, hypothesis-generating

AMRNotable · single-center

Cefepime vs Piperacillin-Tazobactam for Pseudomonas Pneumonia

Single-center retrospective (n = 204). 30-day mortality: pip-tazo 23.1% vs cefepime 11.5% (OW OR 2.38, p = .04). Mechanism: cefepime has better ELF penetration. Warrants multicenter confirmation.

Not carded — single-center, small n

Reviews

DiagnosticsNotable · framework

Role of mNGS in Culture-Negative Cardiovascular Infections

Narrative review. Plasma mcfDNA-NGS (Karius) identified pathogens in 60.6% of culture-negative IE vs 39.4% by conventional microbiologic testing (Mayo Clinic, n = 66). Key caveat: 28.6% of non-IE patients had positive mcfDNA — a positive alone does NOT confirm endocarditis. Proposed adjudication framework for cardiovascular infections.

Not carded — narrative review, framework for clinical use

Randomized controlled trials

AP-HP FLUO — Recombinant vs standard influenza vaccine in severe obesity (n = 206). GMT ratios favored RIV at Day 28 for 3/4 strains, but no differences by Day 180. Surrogate-only. DOI
SUPLA — Direct initiation of LA CAB/RPV in viremic PWH (n = 45 analyzed). Viral suppression 88% vs 55% (p = .026). First RCT evidence, but small n and off-label. DOI
VESTED secondary — HTN in DTG vs EFV-based ART in pregnancy (n = 626). 49% developed some degree of hypertension; no between-arm differences. DOI
IMPOWER-24 — Islatravir monthly PrEP. Stopped early (lymphocyte reductions). Safety data only; efficacy could not be assessed. Islatravir no longer in PrEP development. DOI

TB & Joint diagnostics

LyocartE MTB — Near-point-of-care TB assay (n = 689, China). Sputum: sensitivity 95.2%, specificity 98.6%. Tongue swab: sensitivity 84.1%, specificity 99.7%. Completes in 27 minutes. Comparable to Xpert Ultra. DOI
Rapid PCR on tongue swabs for sputum-scarce TB patients (n = 625, China). Sensitivity 79.9%, specificity 99.5%. Simulation: tongue-swab strategy outperforms sputum-only Xpert when >10% of patients are sputum-scarce. DOI
Xpert TB/LTBI blood-based assay (n = 214, Uganda/Vietnam). AUC 0.92 for active TB; sensitivity 93.5%, specificity 76.3%. Cannot distinguish active TB from LTBI. RUO only. DOI
BioFire BJI Panel for septic arthritis (n = 475, 9 US EDs). PCR sensitivity 89.2%, specificity 95.3%. Detected N. gonorrhoeae in 12 vs 4 by culture. Turnaround 1 hour. DOI

Also in CID this issue

Ceftriaxone SAEs including deaths — CDC multistate investigation (31 cases, 12 deaths); no product tampering or new safety signal identified • PCT and CAP antibiotic duration — real-world PCT testing: −0.32 days antibiotic duration (modest effect) • Outpatient stewardship at Mayo — LDAP metric, −12 pp long-duration prescribing in targeted departments • Remdesivir in renal/hepatic comorbidities — mortality benefit extends (HR 0.75 renal, 0.76 hepatic); Gilead-funded • Indirect influenza VE — meta-analysis of 12 RCTs: pooled IVE only 13.7%; individual vaccination remains the reliable strategy • HIV frailty and HRQoL (3 editorials + 2 observational) • RSV immunization and AOM (editorial + companion) • Doxy-PEP/syphilis editorials • LA CAB/RPV editorial • Transfusion-transmitted dengue • Photo quizzes (infant rigidity; invasive infection in trauma) • Telehealth ID consultations • +15 more (pediatric, cost-effectiveness, PK, epidemiologic, operational)

Open Forum Infectious Diseases

OFIDCase · Transplant IDHigh yield · ID

Gastrointestinal Toxoplasmosis in a Heart Transplant Recipient

In a D+/R− heart transplant recipient who stopped Toxoplasma prophylaxis, what atypical presentation should raise suspicion for disseminated toxoplasmosis?

Key learning38-year-old D+/R− heart transplant, 6 months after stopping 1 year of atovaquone. Subacute diarrhea and 20-lb weight loss → fulminant dissemination with ARDS, distributive shock (ECMO), rhabdomyolysis, and secondary HLH (ferritin >1500, H-score >98%). T. gondii PCR 8 million copies/mL. Tissue cysts on GI biopsy. Treated with high-dose TMP-SMX + anakinra + IVIG; remarkable recovery (off ECMO day 17, discharged day 86). Fellow implicationGI toxoplasmosis on the differential for unexplained diarrhea in D+/R− SOT after stopping prophylaxis. Optimal prophylaxis duration undefined; some experts advocate lifelong in D+/R− heart transplant. Even fulminant disease with HLH can respond to prompt treatment.

Clinical takeaway. The teaching points are durable: D+/R− heart transplant is the highest-risk serostatus for Toxoplasma reactivation (donor heart carries the highest tissue-cyst burden of any transplanted organ), GI presentation can precede dissemination by weeks, and stopping prophylaxis after only 1 year left this patient vulnerable. The secondary HLH (H-score >98%, ferritin >1500) responded to anakinra + IVIG — a recovery that argues against therapeutic nihilism even in fulminant disease.

Anki: ✅ carded — durable transplant ID teaching point (OFID::Major_Study + Subject::Infectious_Disease)

Notable studies

MycologyNotable · confirmatory

Challenging the Concept of Uncomplicated Candidemia for Shorter Antifungal Therapy

Retrospective (n = 314 episodes). Only 33% qualify as “uncomplicated.” A 7-day trial would need n = 1103 across 31–36 centers. Tempers enthusiasm for short-course candidemia therapy; the standard 14-day course remains well-supported.

Not carded — confirmatory of current practice

StewardshipNotable · single-center

FQ-Free Prophylaxis in Allo-HSCT: 5-Year BATMO Follow-Up

Before-after (n = 323). Removing levofloxacin prophylaxis increased 30-day GN BSI (24% vs 15%, P = .03) but OS and NRM were similar. FQ-resistant E. coli dropped from 100% to 46% (P = .003). Carbapenem use did not increase. Strengthens the case for stewardship-driven FQ withdrawal in HSCT.

Not carded — single-center retrospective, confirmatory of emerging trend

MycologyNotable · observational

Unclassifiable IPA in the ICU: ASPIRE Multicenter Cohort

48 French ICUs (n = 371). 19% of treated patients not classifiable by EORTC or FUNDICU. 90-day mortality 62%, driven by age/SOFA/frailty — not IPA classification. Don’t rely solely on formal IPA definitions to guide ICU antifungal decisions.

Not carded — no direct management change; observational awareness

HIV/HepatologyNotable · small n

HBV Risk After Withdrawal of Anti-HBV-Active ART in PWH

Retrospective (n = 166, Japan). 5 HBV-related events (0.70/100 PY; 1.28/100 PY in anti-HBs-negative). All events in anti-HBs-negative patients. Three events after switching to CAB+RPV. As non-anti-HBV ART regimens expand, verify HBV serologies before switching and monitor for reactivation.

Not carded — single-center, small n (5 events)

TB DiagnosticsNotable · single-center

BAL Lipoarabinomannan as Rapid TB Rule-Out

Prospective (n = 219, Thailand). BALF-LAM: NPV 92.2%, sensitivity 45.8%, specificity 74.9%. Rapid and low-cost adjunct in resource-limited settings but modest performance limits utility where Xpert is available. Needs multicenter validation.

Not carded — single-center, modest performance

Also in OFID this issue

Hypertension in REPRIEVE — 36% of PWH had HTN, 31% undiagnosed; 1.8-fold MACE risk • Rapid ART in Memphis — Connextion program halved time to viral suppression • Population HIV viremia in sub-Saharan Africa — declining viremia, concentrated in undiagnosed • Chikungunya reinfection in SLE — 2 SLE patients with documented prior CHIKV reinfected • Measles susceptibility in PrEP cohort — 4.5% susceptible by neutralization • “A Duty to Act” — multi-journal editorial (15 journals) on public health advocacy • CMV treatment preferences post-HCT — DCE/MCDA: physicians preferred maribavir • hMPV in children <5 — substantial burden in Scotland; RSV still 4–8× higher

Anki cards — quality-gated

4 cards minted (hard ceiling 25; four-gate bar governs; yield bar = ID-fellow):
1. C/T vs C/A for MDR/DTR Pseudomonas — CID::Review_Article + Subject::Infectious_Disease
2. Antithrombotic/ICH in IE (GAMES) — CID::Major_Study + Subject::Infectious_Disease
3. MRSA PCR NPV after mupirocin — CID::Major_Study + Subject::Infectious_Disease
4. GI toxoplasmosis in D+/R− heart transplant — OFID::Major_Study + Subject::Infectious_Disease

79 items summarized only — below the four-gate card bar (confirmatory, single-center, observational, surrogate-only, stopped, operational, or pediatric).

Original paraphrase — all figures verified against archived full text. DOI links point to the publisher. This digest is personal study material; it does not reproduce copyrighted text and is not a substitute for reading the source articles.
Generated Sep 6, 2026 — CID & OFID Biweekly Digest.