How long should I treat my patient with urinary tract infection and E. Coli bacteremia?

Although traditionally 7 to 14 days of antibiotic therapy has been recommended for Gram-negative bacteremia, more recent studies suggest that shorter antibiotic treatment courses are as effective as longer treatments for a variety of infections, particuarly those due to Enterobacteriaceae (eg, E. Coli, Klebsiella sp) in patients with low severity illness (1).

 
A 2019 randomized-controlled study involving primarily patients with bacteremia caused by E. Coli or Klebsiella sp. (~75%) with most cases associated with UTI (~70%) found that 7 days was as effective as 14 days of treatment in hemodynamically stable patients who are afebrile for at least 48 hours without an ongoing focus of infection (1). More specifically, there was no significant difference between the 2 groups in the rates of relapse of bacteremia or mortality at 14 or 28 days.

 
An accompanying editorial concluded that “7 days of treatment may be sufficient for hospitalized, non-critically ill patients with Gram-negative bacteremia and with signs of early response to treatment” (2).  Again, the accent should be on hemodynamically stable patients who respond rapidly to treatment. 

 
These articles reflect a recent overall trend in antibiotic therapy that favors shorter courses of therapy for many common infections, as nicely summarized by a 2016 article (3).
• Community-acquired pneumonia                               3-5 days (vs 7-10 days)
• Nosocomial pneumonia                                                 8 days or less (vs 10-15 days)
• Pyelonephritis                                                                  5-7 days (vs 10-14 days)
• Intraabdominal infection                                             4 days (vs 10 days)
• COPD acute exacerbation                                             5 days or less (vs >6 days)
• Acute bacterial sinusitis                                               5 days (vs 10 days)
• Cellulitis                                                                            5-6 days (vs 10 days)

 

 

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References
1. Yahav D, Franceschini E, Koppel F, et al. Seven versus 14 days of antibiotic therapy for uncomplicated Gram-negative bacteremia: A noninferiority randomized controlled trial. Clin Infect Dis 2019; 69:1091-8. https://academic.oup.com/cid/article/69/7/1091/5237874
2. Daneman D, Fowler RA. Shortening antibiotic treatment durations for bacteremia. Clin Infect Dis 2019;69:1099-1100. https://academic.oup.com/cid/article-abstract/69/7/1099/5237877?redirectedFrom=fulltext
3. Spellberg B. The new antibiotic mantra: “ Shorter is better”. JAMA Intern Med 2016;176:1254-55. https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2536180

How long should I treat my patient with urinary tract infection and E. Coli bacteremia?

Why is latent tuberculosis usually treated with one antibiotic while active tuberculosis is treated with 2 or more drugs?

Conventional wisdom has been that in active tuberculosis (TB) patients harbor large numbers of replicating Mycobacterium tuberculosis (Mtb), requiring multiple antibiotics to prevent the emergence of resistant mutants. In contrast, Mtb under latent or “inactive” conditions is presumed to have little capacity for mutation due to reduced bacterial replication, thus generally requiring only one antibiotic for preventive therapy.1

However, the assumption that Mtb has a low capacity for mutation in latent TB due to slow bacterial replication has been challenged in recent years. An experimental study in macaque monkeys with latent Mtb infection using whole genome sequencing demonstrated that despite reduced replication, Mtb acquires a similar number of chromosomal mutations during latency as it does during active infection.1

This finding supports the more current and evolving concept of latent TB which assumes diverse mycobacterial growth states, ranging from complete absence of organisms to actively replicating bacterial populations.2 It also explains why, although effective, isoniazid monotherapy may be a risk factor for the emergence of INH resistance in latent TB. 1,3

 Bonus Pearl: Did you know that INH treatment of latent TB in adults is 60-80% protective when given for 6 months, and 90% protective when given for 9 months? 4

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References

  1. Ford CB, Lin PL, Chase M, et al . Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection. Nat Genet. 2011;43:482-86. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101871/
  2. Gideon HP, Flynn JL. Latent tuberculosis: what the host “sees”? Immunol Res 2011;50:202-12. https://www.ncbi.nlm.nih.gov/pubmed/21717066
  3. Balcells ME, Thomas SL, Faussett PG, et al. Isoniazid preventive therapy and risk for resistant tuberculosis. Emerg Infect Dis 2006;12:744-51. https://www.ncbi.nlm.nih.gov/pubmed/16704830
  4. Piccini P, Chiappini E, Tortoli E, et al. Clinical peculiarities of tuberculosis. BMC Infect Dis 2014; 14 (Suppl 1):S4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015485/

 

Why is latent tuberculosis usually treated with one antibiotic while active tuberculosis is treated with 2 or more drugs?