This Puscast reviews infectious disease literature from the last two weeks of August 2018, focusing on epidemiology, clinical trials, and microbiology. Key topics include the expected trade-off of increased STDs accompanying effective HIV PrEP, differing hantavirus epidemiology in China, and a critique of weak statistical associations between CMV and neurocognitive decline in HIV patients (likely P-hacking). The discussion heavily scrutinizes recent clinical papers, particularly an Endocarditis oral therapy trial criticized for aggressive exclusions, and a Cellulitis trial that compared a new, expensive antibiotic (Delafloxacin) against an egregiously inappropriate standard of care (Vancomycin + Aztreonam), a comparison the speaker dismisses as damaging to antibiotic stewardship. New Borrelia species definitions and the infection risk associated with the cancer drug Ibrutinib are also covered.
Puscast: Infectious Disease Literature Review (August 2018)
0:34 PrEP Consequences (STDs): Pre-exposure prophylaxis (PrEP) is highly effective against HIV, but its use among men who have sex with men (MSM) correlates directly with a decline in condom use. This decline resulted in an increase in rectal chlamydia and other sexually transmitted diseases. As far as I can tell, this is an expected outcome.
1:22 Hantavirus Epidemiology: A 48-year review of hemorrhagic fever with renal syndrome (HFRS) in China showed that initial urbanization led to increased HFRS infections due to rats and poor living conditions. Infections subsequently decreased as urban living conditions improved, contrasting with the predominantly rural US Hantavirus pattern.
2:49 CMV and HIV Neurocognition: A study associated higher anti-CMV IgG levels with worse neurocognitive performance in HIV patients on HAART. The P-value was $0.059$, which is statistically weak. I remain convinced that findings are likely not significant unless the P-value is far lower (e.g., $P < 0.005$). Given the large number of parameters tested, this looks suspiciously like P-hacking and is likely "sound and fury signifying nothing."
4:32 Pox Virus Risk: The cessation of smallpox vaccination is leading to waning human immunity. A new orthopox virus reported in Italy (rodents $\to$ cat death) raises concerns about increased zoonotic pox transmission in a non-immune human population over the next decades.
6:00 Candidatus Borrelia: Discusses newly described tick-borne Borrelia species. Clarifies that the taxonomic designation Candidatus means the prokaryote cannot be maintained in a microbial culture collection (interim status).
7:18 Lyme Disease Spread:Borrelia burgdorferi (Lyme agent) is increasingly found in ticks within the Tennessee Valley, suggesting geographic expansion, probably because "the rents are lower."
7:45Elizabeth Kingi Irony: Outbreaks of Elizabeth Kingi are waterborne. A recent Singapore outbreak was ironically spread through hand hygiene, where staff washed hands in contaminated tap water before spreading the organism.
11:13 Endocarditis Risk (Non-Dental): A US study suggests routine outpatient procedures (e.g., gastroscopy, colonoscopy, coronary angio, transfusion) may increase the risk of endocarditis, though current guidelines do not recommend prophylaxis for these.
12:45 Oral Endocarditis Therapy (NEJM): A trial found oral therapy was non-inferior to IV therapy for treating endocarditis after 17 days of initial IV treatment. The speaker dismisses this as reflecting only "what you can get away with," noting the study excluded $78%$ (1,554 of 2,000) of potential patients, retaining only highly stable, immunologically robust individuals.
16:04 C. diff Probiotics and Treatment: Probiotics show moderate evidence for reducing C. diff risk, but their safety profile is inadequately documented. The Lancet suggests metronidazole should never be used for C. diff. Fidaxomicin is superior to vancomycin but cost-prohibitive for most.
17:26 Alcohol and Pneumonia: Alcohol intake is linked to an increased risk of community-acquired pneumonia (approx. $8%$ increase per 10-20g/day). I don't care, quality of life matters.
18:59 Cellulitis Trial Critique (Steer Manure): A trial compared Delafloxacin (IV/Oral) to Vancomycin + Aztreonam for cellulitis. The speaker vehemently rejects the comparator arm, arguing that typical cellulitis requires simple, cheap therapy (like Cefazolin, $4 for a course) and that the $1500$ comparator (Vanc + Aztreonam) is inappropriate and wasteful. This study is "steer manure" and will negatively influence community antibiotic prescribing; journals (like Clinical Infectious Diseases) must exercise better antibiotic stewardship starting with publication standards.
23:20 TB Treatment Deficiencies: Low INH/Rifampin blood concentrations in HIV co-infected patients delayed culture conversion (extended infectivity) but did not affect cure. Higher MICs (even in the sensitive range) correlated with increased relapse risk. TB therapy needs to adopt standards from treating other bacterial processes, including consistent MIC determination and drug level monitoring.
24:56 Ibrutinib Risk: The cancer drug Ibrutinib (Bruton tyrosine kinase inhibitor) increases the risk for secondary bacterial and invasive fungal infections, even in non-neutropenic/non-lymphopenic patients.