This installment of the Puscast reviews infectious disease literature from early August 2012, focusing primarily on antibiotic efficacy, drug toxicities, genetic predispositions to infection outcomes, and diagnostic utility. Key findings include the double risk of serious infection within the first year of starting TNF inhibitors for rheumatoid arthritis, the elevated (though low absolute) risk of fatal liver toxicity associated with moxifloxacin, and further evidence detailing the poor performance of vancomycin as a surgical prophylactic agent against MSSA. The host expresses typical professional frustration with clinical practices regarding blood cultures and the misuse of antibiotic terminology. Novel insights into Neisseria gonorrhoeae resistance trends, the high rate of neurological involvement in severe H1N1, and the likely zoonotic origin of tuberculosis (based on ancient bison data) are also discussed.
Infectious Disease Literature Review (August 1–15, 2012)
1:20 Infection Risk with TNF Inhibitors: Risk of serious infection doubles in the first year after starting Tumor Necrosis Factor (TNF) inhibitors in RA patients; this risk curiously fades afterward. Patients on >8 mg/week of methotrexate were also at higher risk of significant infection.
2:40 Fluoroquinolone Liver Toxicity: A large epidemiological study found that moxifloxacin and levofloxacin double the risk of hospitalization due to liver toxicity compared to clarithromycin. The absolute risk is low (6 admissions per 100,000 exposures), but approximately two-thirds of admitted patients died. I don't care much for fluoroquinolones, as far as I can tell.
4:05 Critique of Vancomycin Prophylaxis: Vancomycin is labeled a "crappy" antibiotic. A study comparing Vanco vs. beta-lactams for surgical prophylaxis found that Vanco increased MSSA infections, resulting in a 5.3% infection rate (vs. 3.2% for beta-lactams).
Takeaway (6:17): If vancomycin must be used for MRSA concern, it should be combined with a beta-lactam (like cefazolin) to ensure good surgical prophylaxis against MSSA.
6:47 Utility of Blood Cultures (BCx): A JAMA review suggests BCx yield is low (e.g., cellulitis 2%). Neither isolated fever (>101°F) nor isolated leukocytosis reliably predicts bacteremia.
Takeaway (7:47): The strongest predictors for positive BCx are severe chills (rigors) and the presence of SIRS. I estimate studies like this will have minimal clinical impact because clinicians are unwilling to risk missing bacteremia.
9:10 H1N1 Neurologic Manifestations: A California series of severe/fatal H1N1 cases (2,000 total) found a 20% rate of neurologic manifestations (most commonly seizures, 30 cases of encephalitis). This disproportionately affected pediatric and Asian Pacific Islander populations.
10:42 Genetic Predisposition to Severe Flu: A Chinese study linked a polymorphism in the CD55 protein to severe influenza, backing up prior epidemiological suggestions of a genetic component to mortality risk.
12:23 Bactrim Hypersensitivity: Hypersensitivity reactions, common in HIV patients, are genetically predisposed via polymorphisms in the glutamate cysteine ligase catalytic subunit, which affects the metabolism of sulfamethoxazole into reactive, toxic agents.
13:41 HIV & HAART Benefits: HAART (antiretroviral therapy) significantly decreases the chance of tuberculosis spread.
14:01 HIV & Cardiovascular Disease: Cardiovascular disease (MI) is a major cause of death in HIV patients. Risk factors include plasma HIV levels >50, low CD4 nadir, and a high CD4/CD8 ratio. Aspirin is beneficial in decreasing prothrombotic, inflammatory platelet hyperactivity.
14:55 Gonorrhea Resistance: Resistance to oral cephalosporins is escalating rapidly (e.g., Portland 0% to 6.5%).
CDC Recommendation (15:46): Treatment must now use IM Ceftriaxone (250 mg) plus either Azithromycin (1g PO) or Doxycycline (100mg BID x 7d). Alternatives require a mandatory test of cure one week later.
16:39Streptococcus gallolyticus (formerly S. bovis): Bacteremia with this organism is a strong marker for colorectal neoplasia. 69 out of 98 scoped patients had adenomas or invasive carcinomas—a strikingly high correlation.
17:50 Gram Stains in VAP: For Ventilator-Associated Pneumonia (VAP) diagnosis, a negative Gram stain (no organism seen) is highly associated with no VAP. However, a positive Gram stain correlates poorly with the final culture results and cannot be used to guide therapy.
19:35 Macrolides and Pseudomonas: The long-held belief that macrolide efficacy against Pseudomonas (e.g., in CF) is purely immunomodulatory is challenged. Pseudomonas is susceptible to macrolides when tested in eukaryotic growth media, suggesting a direct antimicrobial effect may also be relevant. I hate being wrong, but this is interesting data quality critique.
21:05 Ancient TB Zoonosis: Tuberculosis evidence was found in a 17,000-year-old extinct bison skeleton, significantly predating the oldest confirmed human evidence (9,000 years). This strongly suggests a zoonotic origin for TB.