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Abstract:
This episode of the Infectious Disease Puscast (Episode 78) reviews recent significant literature and developments in infectious diseases. Key topics include a critical re-evaluation and call to abandon the Milwaukee Protocol for rabies treatment due to lack of proven efficacy. The potential protective effect of the live attenuated herpes zoster vaccine against dementia development is highlighted, based on a natural experiment study in Wales. Updated European guidelines for CMV management in post-transplant and T-cell therapy patients are discussed, emphasizing letermovir for prophylaxis and maribavir for resistant cases. Evidence suggesting prior Epstein-Barr virus (EBV) infection precedes Crohn's disease development is presented. Bacterial topics cover the FDA approval of jepotidacin (Blue Jepida), a new oral antibiotic class for uncomplicated UTIs, and a Danish trial (Induti) comparing individualized versus standard 10-day antibiotic courses for pediatric febrile UTIs, which found increased recurrence with shorter duration but less antibiotic exposure. The episode also examines the low actual risk of myasthenia gravis exacerbations with fluoroquinolones and azithromycin, the significant cost barrier of blood cultures in low- and middle-income countries, and trends in anaplasmosis based on Mayo Clinic data. Fungal discussions include a critique of inadequate fungal disease coverage in medical textbooks, a case report of the emerging pathogen Kazakhstania, and the utility of plasma microbial cell-free DNA sequencing (like Karius) for diagnosing invasive fungal diseases, noting high specificity. Parasitic disease updates feature case reports of fatal Naegleria fowleri linked to a splash pad and Acanthamoeba encephalitis associated with tap water use in nasal irrigation/CPAP devices, alongside a recommendation for a recent NEJM malaria review. Finally, the FDA's authorization of the first over-the-counter, entirely at-home test for chlamydia, gonorrhea, and trichomoniasis is covered.
Puscast Episode 78: Reviewing Recent ID Literature
0:00:03 Introduction: Drs. Daniel Griffin and Sarah Dong introduce Puscast Episode 78, recorded April 9, 2025, reviewing recent infectious disease literature.
0:02:09 Demise of the Milwaukee Protocol: Discussion of a CID article arguing for abandoning the Milwaukee Protocol for rabies treatment. Despite initial hope from a single survivor case in 2004, the protocol (involving induced coma, ketamine, ribavirin, amantadine) has shown no subsequent evidence of efficacy over two decades, with at least 64 documented failures and questionable survivor claims. Key Takeaway: The Milwaukee Protocol for rabies is considered ineffective and should be abandoned to pursue new therapeutic approaches.
0:06:41 Herpes Zoster Vaccination and Dementia: A study in Nature examined the effect of the original live attenuated zoster vaccine (Zostavax) on dementia rates in Wales, using a natural experiment based on birthdate eligibility. Key Takeaway: Vaccination was associated with a significant reduction (approx. 20% relative reduction or 3.5 percentage points absolute reduction over 7 years) in new dementia diagnoses, suggesting a potential protective effect.
0:09:33 Updated CMV Management Guidelines: Review of the 10th European Conference recommendations (Lancet ID) for CMV management in allergenic HCT and T-cell therapy patients. Letermovir is now the standard recommendation for primary prophylaxis in adult CMV-seropositive recipients. Maribavir is highlighted for resistant/refractory cases. Key Takeaway: Guidelines emphasize letermovir for prophylaxis and provide updated strategies for resistant/refractory CMV, including the role of maribavir and CMV-specific T-cells.
0:13:30 EBV Exposure and Crohn's Disease: A study in Gastroenterology using data from the military PREDICTS cohort suggests a link between Epstein-Barr Virus (EBV) infection and subsequent Crohn's disease development. Key Takeaway: Increased exposure to EBV (sero-conversion) was observed 5-7 years before Crohn's diagnosis, suggesting EBV may be a preceding factor, similar to its link with MS.
0:16:50 New UTI Antibiotic Approved (Jepotidacin/Blue Jepida): The FDA approved GSK's jepotidacin (marketed as Blue Jepida), a first-in-class oral antibiotic for uncomplicated UTIs in females (12+ years). It inhibits bacterial DNA replication via topoisomerase II and DNA gyrase. Key Takeaway: Blue Jepida offers a new oral option for UTIs, effective against common pathogens and potentially resistant strains, based on non-inferiority/superiority to nitrofurantoin in Phase 3 trials.
0:19:01 Pediatric Febrile UTI Treatment Duration (Induti Trial): A Lancet ID paper reports on the Danish Induti trial comparing individualized (stopping 3 days after improvement, min 4 days) vs. standard 10-day antibiotic treatment for febrile UTIs in children (3 months-12 years). Key Takeaway: Individualized treatment led to significantly fewer antibiotic days (median 5.3 vs 10) but an increased risk of recurrent UTI within 28 days (11% vs 6%). Non-inferiority was not met for the 28-day outcome, raising questions about balancing recurrence risk and antibiotic exposure.
0:25:04 Antibiotics and Myasthenia Gravis Exacerbations: A retrospective review (Muscle & Nerve) examined exacerbation rates in Myasthenia Gravis patients after receiving ciprofloxacin, levofloxacin, or azithromycin. Key Takeaway: Exacerbation rates were low (1.5-2.4%) and similar to the background rate seen with amoxicillin (1.3%), questioning the traditionally emphasized high risk of these antibiotics in MG patients.
0:27:39 Cost of Blood Cultures in LMICs: A comment in Lancet Microbe highlights the high cost of blood cultures (often >$5-15 USD) as a significant barrier to diagnosis in low- and middle-income countries, impacting both patients and healthcare facilities. Key Takeaway: Affordability remains a major challenge for accessing essential diagnostic tools like blood cultures in many resource-limited settings.
0:31:01 Anaplasmosis Trends and Features: A CID retrospective study from Mayo Clinic reviews anaplasmosis cases over a decade. Most cases were outpatient. Hospitalized patients were older and more often immunocompromised. The classic triad (leukopenia, thrombocytopenia, transaminitis) was present in only ~25% but associated with hospitalization risk. Key Takeaway: Provides updated epidemiology and clinical features of anaplasmosis, noting the relative infrequency of the classic triad.
0:33:44 Fungal Disease Coverage in Textbooks: An OFID paper critiques the coverage of mycology in major ID and Internal Medicine textbooks (e.g., Harrison's, Mandel's), finding deficiencies, outdated information, and gaps, particularly in prevention and treatment details. Key Takeaway: Standard medical textbooks may not provide adequate or up-to-date information on fungal diseases, emphasizing the need to rely on current guidelines and peer-reviewed literature.
0:37:58Kazakhstania Fungemia Case Report: An OFID article reports the first documented human case of fungemia caused by Kazakhstania, an emerging opportunistic yeast (formerly Candida species), in a malnourished patient with complex gastrointestinal issues. Key Takeaway: Highlights the emergence of previously unrecognized fungal pathogens like Kazakhstania.
0:39:19 Plasma Cell-Free DNA for Invasive Fungal Disease: A CID case-control study evaluated plasma microbial cell-free DNA sequencing (cfDNA, e.g., Karius test) for diagnosing invasive fungal diseases in immunocompromised patients. Key Takeaway: cfDNA testing showed high specificity (100%) but moderate sensitivity (~50%, higher for proven vs. probable, and notably high for mucormycosis), suggesting potential as a non-invasive diagnostic tool, especially for ruling in infection.
0:43:53 Fatal Naegleria fowleri from Splash Pad: An MMWR report details a fatal case of primary amoebic meningoencephalitis (PAM) caused by Naegleria fowleri in an infant after exposure to a public splash pad in Arkansas. Key Takeaway: Reinforces the risk of Naegleria fowleri infection from inadequately treated recreational water sources like splash pads.
0:45:55 Fatal Acanthamoeba Encephalitis from Tap Water: Another MMWR report describes fatal Acanthamoeba encephalitis in a patient who regularly used untreated tap water in an electronic nasal irrigation device and a CPAP machine. Key Takeaway: Emphasizes the danger of using non-sterile water (tap water) for nasal irrigation or CPAP humidification, as it can lead to rare but fatal amoebic infections.
0:47:22 NEJM Malaria Review: Recommendation to read a comprehensive review article on malaria published in the New England Journal of Medicine, noting its inclusion of modern topics like vaccines and monoclonal antibodies.
0:48:18 First At-Home STI Test Authorized: The FDA granted marketing authorization for the Visby Medical Women's Sexual Health Test, the first test for chlamydia, gonorrhea, and trichomoniasis that can be bought over-the-counter and performed entirely at home, delivering results via an app in ~30 minutes. Key Takeaway: This authorization marks a significant step in increasing accessibility for STI testing.