In Infectious Disease Puscast #88, Drs. Daniel Griffin and Sarah Dong review recent infectious disease literature. Key topics include the alarmingly low RSV immunization rates among US infants despite new preventive options, the non-inferiority of bictegravir-based therapy for virally suppressed HIV patients in Haiti, and the efficacy of interferon-alpha nasal spray in reducing COVID-19 incidence in cancer patients.
They also discuss a study suggesting increased severity of infections in women on suppressive antibiotics for recurrent urinary tract infections, the evidence against treating asymptomatic bacteriuria in most kidney transplant recipients, and the increasing incidence of leptospirosis in the US. Further discussions cover the promise of tongue swabs for pediatric tuberculosis diagnosis, proposed criteria for defining uncomplicated candidemia to guide shorter therapy, outcomes of Trypanosoma cruzi screening in military blood donors, and case reports of cutaneous acanthamoebiasis. The episode concludes with a look at linezolid's association with optic nerve disorders, particularly at high cumulative doses, and its extreme pharmacokinetic variability in critically ill patients, advocating for therapeutic drug monitoring.
Infectious Disease Puscast #88: Key Literature Review (August 19-27, 2025)
0:00 Introduction & Labor Day Banter: Daniel Griffin and Sarah Dong discuss their Labor Day activities and set the stage for reviewing recent infectious disease literature.
Details: A cross-sectional analysis (Oct 2023-Mar 2024) revealed only 29% of US infants received recommended RSV immunization (nirsevimab or maternal vaccine), with state-specific coverage ranging from 11% to 53%.
Key Takeaway: Despite safe and effective tools to prevent the leading cause of infant hospitalization, uptake is significantly low, indicating critical needs for improved education, access, and supply.
5:00 HIV Second-Line Therapy Switch (Haiti Trial):
Details: A non-inferiority trial in Haiti found that switching virally suppressed HIV patients on second-line boosted protease inhibitor (PI) regimens to a once-daily bictegravir-based therapy (bictegravir, emtricitabine, and tenofovir alafenamide) was non-inferior to continuing the PI regimen, even in the presence of high baseline NRTI resistance.
Key Takeaway: Bictegravir-based therapy offers a safe and effective simplification for virally suppressed HIV patients, including those with NRTI resistance, reinforcing its role as a preferred treatment option.
8:11 Interferon-alpha Nasal Spray for COVID-19 Prophylaxis in Cancer Patients:
Details: A randomized, double-blinded, placebo-controlled trial demonstrated that once-daily interferon-alpha nasal spray reduced COVID-19 incidence by 40% (8.3% vs 14.4%) in cancer patients. Efficacy was particularly noted in younger individuals, females, and vaccinated patients. It was well-tolerated, but showed no difference for other respiratory viruses.
Key Takeaway: Interferon-alpha nasal spray shows promise as a safe and effective COVID-19 prophylaxis in vulnerable populations like cancer patients, meriting further investigation for broader clinical use.
11:10 Recurrent UTI and Suppressive Antibiotic Therapy:
Details: A retrospective cohort study observed that women with recurrent UTIs on continuous suppressive antibiotic therapy (≥6 months) had a higher incidence of severe infections (12.6%) compared to those treated episodically (6.4%). Pyelonephritis and septicemia showed the largest differences, and surprisingly, COVID-19 severity was also higher.
Key Takeaway: While suppressive antibiotics reduce UTI recurrences, they may increase the severity of subsequent infections when they do occur. This finding challenges current treatment paradigms and warrants a re-evaluation of recommendations and underlying mechanisms.
14:30 Asymptomatic Bacteriuria in Kidney Transplant Recipients:
Details: A systematic review and meta-analysis of four randomized controlled trials concluded that routine screening and treatment of asymptomatic bacteriuria in kidney transplant recipients is not supported by current evidence. It did not reduce symptomatic UTIs or improve graft outcomes and may contribute to the selection of resistant organisms. An exception might be the first 1-2 months post-transplant in profoundly immunosuppressed patients or those with indwelling catheters.
Key Takeaway: This review reinforces the guideline not to routinely treat asymptomatic bacteriuria in most kidney transplant recipients, advocating for a more judicious use of antibiotics in this population.
18:10 Leptospirosis Trends in the United States (2014–2020):
Details: Since its reinstatement as a notifiable condition in 2014, leptospirosis cases in the US have been increasing, with an average annual gain of 13 cases, peaking in late summer/early fall. 85% of cases resulted in hospitalization and 10% in death. Risk factors included contact with animals/bodily fluids (77%) and fresh water/mud (71%), often from avocational activities. Hotspots include Guam, Puerto Rico, Hawaii, Virgin Islands, Washington D.C., and New York City.
Key Takeaway: Leptospirosis is a serious, increasing, and potentially under-recognized public health concern in the US, with high rates of severe outcomes.
20:30 Tongue Swabs for Tuberculosis Diagnosis in Hospitalized Children <5:
Details: A prospective observational study in South African hospitals evaluated Expert MTB/RIF Ultra testing on tongue swabs from high-risk children under 5. For confirmed TB, sensitivity was 17% and specificity 89%. Tongue swabs detected MTB in 10.9% of children previously categorized as "unlikely TB," increasing overall confirmed cases by a fifth. Its sensitivity was similar to gastric aspirate testing. The interpretation of "trace" results (common) and potential for cross-contamination are ongoing challenges.
Key Takeaway: Tongue swabs offer a promising, less invasive, and comparably sensitive alternative to gastric aspirates for TB diagnosis in young children, potentially improving case detection in a challenging diagnostic population.
24:30 Towards Shorter Therapy for Candidemia: Defining Uncomplicated Candidemia:
Details: A Lancet ID review proposed criteria to define "uncomplicated candidemia" in adults, aiming to identify patients who might benefit from shorter antifungal therapy durations. The criteria involve candidate clearance in blood, documented appropriate source control, clinical response within 5 days, and specific patient/microbiological characteristics (e.g., no immunosuppression, no resistant species, no prolonged bloodstream infection, no IV drug use). This is a conceptual framework to inform future trials, not current clinical guidance.
Key Takeaway: This proposal represents a significant step towards developing a more nuanced approach to candidemia treatment, potentially moving away from a universal long-duration therapy by identifying a subset of patients suitable for shorter courses.
28:10Trypanosoma cruzi Antibody Screening in Military Blood Donors:
Details: A review of military blood donors at Joint Base San Antonio found a low reactive screening rate for T. cruzi antibodies (0.055%). Of these, only 8% were confirmed positive, and none met clinical criteria for Chagas disease. Reactive screening led to donor deferral, often without clear pathways for re-entry into the donor pool.
Key Takeaway: While T. cruzi screening is essential for blood safety, a significant number of false positives or indeterminate results can lead to unnecessary donor deferrals and logistical hurdles, especially in regions with vector presence but low human disease.
Details: Two cases in immunocompromised patients (lupus/pancytopenia and lymphoma on idelalisib) presented with skin nodules/ulcerations. Biopsies showed variable histopathologic inflammatory changes, but trophozoites and cysts were identified with special stains.
Key Takeaway: Cutaneous acanthamoebiasis should be considered in immunocompromised patients presenting with skin nodules, emphasizing the need for vigilant pathological examination due to its variable presentation and the ease with which organisms can be overlooked.
Details: A pharmacovigilance analysis of the US FDA adverse event reporting system identified a signal for optic nerve disorders exclusively associated with linezolid (not tedizolid). Risk factors included younger age (<60) and high cumulative doses (adjusted odds ratio ~8), suggesting a dose-dependent adverse effect.
Key Takeaway: Clinicians should monitor for optic nerve disorders, particularly in younger patients receiving high cumulative doses or prolonged courses of linezolid (e.g., for multi-drug resistant tuberculosis).
36:10 Extreme Variability in Linezolid Concentrations in the ICU:
Details: A case report detailed an ICU patient who experienced sub-therapeutic linezolid concentrations on standard dosing (leading to persistent VRE) followed by supra-therapeutic levels and adenuric toxicity with continuous infusion. The drug's clearance was highly variable and unrelated to renal function, suggesting non-linear elimination and alternative metabolic pathways.
Key Takeaway: Linezolid exhibits extreme pharmacokinetic variability in critically ill patients, underscoring the potential utility of routine therapeutic drug monitoring (TDM) to ensure optimal dosing and prevent both treatment failure and toxicity.
Summary of Linked Resources:
Viral
Respiratory Syncytial Virus Immunization Coverage Among Infants: This CDC MMWR report details the low immunization coverage for RSV among US infants, highlighting the need for increased uptake of nirsevimab and maternal vaccination.
Bictegravir, emtricitabine, and tenofovir alafenamide versus ritonavir-boosted protease inhibitor-based antiretroviral therapy in people with HIV and viral suppression: A Lancet HIV trial demonstrates the non-inferiority and effectiveness of switching to a bictegravir-based regimen for virally suppressed HIV patients on second-line therapy in Haiti.
Interferon-α Nasal Spray Prophylaxis Reduces COVID-19 in Cancer Patients: A CID study presents findings from a randomized trial showing that interferon-alpha nasal spray can reduce COVID-19 incidence in cancer patients.
Bacterial
Exposure to suppressive antibiotic therapy in women with recurrent urinary tract infections and severity of infections: A BMJ Open cohort study explores the relationship between suppressive antibiotic use for recurrent UTIs and the severity of subsequent infections.
Effectiveness and safety of antibiotics in kidney transplant recipients with asymptomatic bacteriuria: An OFID systematic review and meta-analysis concludes that routine antibiotic treatment for asymptomatic bacteriuria in kidney transplant recipients is not supported by evidence.
Epidemiological, temporal, and geographic trends of leptospirosis in the United States, 2014–2020: A PLoS Neglected Tropical Diseases article details the increasing incidence, geographical distribution, and outcomes of leptospirosis cases in the US.
Performance of Tongue Swabs for Tuberculosis Diagnosis in Hospitalized Children Under 5 Years of Age: An OFID study evaluates the diagnostic utility of tongue swabs for tuberculosis in young hospitalized children in South Africa.
Fungal
The Last of US Season 2: This YouTube link refers to a season of a TV show and is not a scientific paper.
Towards shorter therapy for candidaemia: defining uncomplicated candidaemia in adults: A Lancet Infectious Diseases review proposes criteria to define "uncomplicated candidaemia" to guide future research on shorter treatment durations in adults.
Parasitic
Outcomes of Military Blood Donors at Joint Base San Antonio with Reactive Trypanosoma cruzi Antibody Screening: An OFID study examines the low rate of confirmed T. cruzi infections among military blood donors who initially screened reactive, and the implications for donor deferral.
Cutaneous acanthamoebiasis: Two Cases Highlighting Diverse Histopathologic Findings: A Journal of Cutaneous Pathology article describes two cases of cutaneous acanthamoebiasis in immunocompromised patients, emphasizing the varied histological presentations.
Miscellaneous
Linezolid-related Optic Nerve Disorders: Insight from a Pharmacovigilance Analysis of the U.S. FDA Adverse Event Reporting System: An OFID pharmacovigilance analysis identifies linezolid as a risk factor for optic nerve disorders, particularly with high cumulative doses.
Extreme variability in linezolid concentrations in the ICU: A case for routine therapeutic drug monitoring: An American Journal of Health-System Pharmacy case report illustrates the profound pharmacokinetic variability of linezolid in critically ill patients, suggesting a need for therapeutic drug monitoring.