This podcast, covering infectious disease literature from early August 2012, reviews findings related to antibiotic efficacy, toxicity, diagnostic utility, and genetic predispositions to infection. Notable points include the discovery that serious infection risk from TNF inhibitors in Rheumatoid Arthritis patients is heavily concentrated in the first year of therapy, and that the fluoroquinolone moxifloxacin carries a significantly doubled risk of fatal hepatotoxicity compared to other agents. The speaker critiques the clinical inferiority of vancomycin for surgical prophylaxis, citing studies showing increased MSSA infections when used alone. Diagnostic utility is questioned by a JAMA review demonstrating that isolated fever or leukocytosis poorly predicts bacteremia, and by data showing VAP Gram stains are useful only if negative. Finally, the review highlights escalating global resistance in N. gonorrhoeae (necessitating IM Ceftriaxone combinations) and reinforces the utility of screening for colorectal neoplasia following Streptococcus gallolyticus bacteremia.
Infectious Disease Literature Review (August 1β15, 2012)
1:20 Risk of Infection with TNF Inhibitors: Studies show that the risk of serious infection doubles in RA patients after starting TNF inhibitors, but this risk fades after the first year. Furthermore, methotrexate doses exceeding 8 mg/week independently increase infection risk. (I find the rapid fading of risk slightly surprising, suggesting strong selection bias or adherence issues.)
2:51 Fluoroquinolone Liver Toxicity: A large epidemiological study found that patients on moxifloxacin were twice as likely to be admitted to the hospital with liver toxicity compared to clarithromycin. Levofloxacin showed a similar, less pronounced effect. Although rare (6 admissions per 100,000 exposures), two-thirds of these patients died. Ciprofloxacin did not share this risk, as far as I can tell.
4:39 Vancomycin (Vanco) Failure in Prophylaxis: Vanco is criticized as a "crappy antibiotic" with high failure rates against Staph compared to beta-lactams. A study comparing Vanco to beta-lactams for surgical prophylaxis found Vanco resulted in a higher overall infection rate (5.3% vs 3.2%), specifically increasing MSSA infections. Key Takeaway: If Vanco must be used due to MRSA concern, it should be combined with a beta-lactam for effective surgical prophylaxis.
6:47 Utility of Blood Cultures: A JAMA review noted blood cultures have a low overall yield (e.g., 2% in cellulitis). Isolated elevated temperature or leukocytosis does not predict bacteremia. The best predictors are severe chills (rigors) and the presence of SIRS. (Clinical practice often ignores this data due to a perceived unwillingness to miss a positive culture, which I find inefficient but predictable.)
9:39 H1N1 Neurologic Involvement: A review of severe/fatal H1N1 cases in California (2,000 total) showed that a significant 20% had neurologic manifestations (seizures, encephalitis). This occurred predominantly in pediatric cases and Asian Pacific Islanders.
10:42 Genetic Risk for Influenza Severity: A Chinese study demonstrated that a polymorphism in the CD55 protein is associated with a higher likelihood of severe influenza, providing molecular backing for previous epidemiological suggestions of genetic susceptibility.
12:23 Genetic Risk for Bactrim Hypersensitivity: The severe reaction to TMP/SMX (specifically sulfamethoxazole) is genetically programmed in some patients, linked to polymorphisms in the glutamate cysteine ligase catalytic subunit.
13:41 HIV and Tuberculosis: Placing HIV patients on Highly Active Antiretroviral Therapy (ART) markedly decreases the spread of tuberculosis.
14:01 HIV and Cardiovascular Risk: Cardiovascular disease is a major cause of death in HIV patients. Risk factors for myocardial infarction include plasma HIV levels >50, low nadir CD4 count, and high CD4:CD8 ratio. Aspirin decreases platelet hyperactivity, supporting the thesis that chronic inflammation drives prothrombotic vascular events in these patients.
15:05 Gonorrhea Resistance Crisis: Resistance to oral cephalosporins is escalating rapidly (e.g., 0% to 6.5% in Portland). Key Takeaway: The CDC mandates combination therapy: IM Ceftriaxone (250 mg) plus oral Azithromycin (1g) or Doxycycline (7 days) for uncomplicated cases. Any alternative therapy requires a test of cure a week later. (At the current rate, therapy for gonorrhea will likely disappear soon, as far as I can estimate.)
16:47S. gallolyticus and Cancer Screening:Streptococcus gallolyticus subspecies gallolyticus (formerly S. bovis Type 1) bacteremia is a highly effective screening tool for colorectal neoplasia. A study showed 69/98 scoped patients had adenomas or carcinomas.
18:01 Gram Stain Utility in VAP: A negative Gram stain (no organisms seen) from respiratory samples is highly associated with the absence of Ventilator-Associated Pneumonia (VAP). However, a positive Gram stain poorly predicts the cultured causative organism and should not be used to definitively guide specific therapy.
19:56 Macrolides and Pseudomonas: Contrary to the belief that macrolides only act via immunomodulation in Pseudomonas infections, testing the organism in eukaryotic growth media revealed direct susceptibility, suggesting antimicrobial effects may contribute to clinical efficacy.
21:10 Ancient TB Zoonosis: Gas chromatography identified evidence of tuberculosis in a 17,000-year-old skeleton of an extinct bison, predating the oldest confirmed human TB evidence (9,000 years). This strongly suggests tuberculosis originated as a zoonosis.
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