Monday, February 4, 2013

Double coverage: FQ and AG

The empiric use of two antimicrobial agents with similar spectrum of coverage (aka double coverage) is often fancied for a few reasons:
  • Synergy, either clinical or pharmacokinetic, between two antimicrobial agents.
  • Differing resistance patters to increase likelihood of adequate coverage of the suspected organism.
  • Prevention of the development of resistance. 

Often, the second agent to be considered is either a fluoroquinolone (cipro/levo/moxi) or an aminoglycoside (amikacin/gentamicin/tobramycin). There is little, if any, data to steer towards one class or another. Often, the answer as to which one to pick comes down to local resistance patterns by consulting your hospital’s antibiogram (Although there are several limitations to the use of antibiograms - see a previous post).

It is important to understand that empiric double coverage is generally not appropriate for a typical community acquired infection. Mostly because there are obvious downsides to doubling up; higher drug cost, potential of increased toxicities (ie nephrotoxicity), risk of superinfection or c.diff.

Somewhat conflicting however, is the data investigating the clinical outcomes associated with empiric double coverage. These outcomes associated with empiric double coverage do not overwhelmingly support this strategy in all patients.  One would assume that by providing double coverage up front would be beneficial. But in seriously or critically ill patients, double coverage with a beta-lactam and either aminoglycosides or fluroquinolones has not demonstrated a reduction in mortality at 28 days.  In the studies that have shown benefit with double coverage, the source of infection is usually urine. Although, this is less likely a benefit of double coverage or and more likely providing an agent that has better penetration to the source of infection. 

While the data may be lacking, certain patient populations would, at least theoretically benefit from empiric double coverage. For example, patients who are neutropenic, in shock (septic) or have suspected Pseudomonas (MDR pathogen) infection may benefit. In these cases, by double covering, our chance of providing adequate coverage of the affecting organism(s) increases. In fact, there has been a plethora of recent data associating “inappropriate” initial antimicrobial therapy and worse outcomes. Getting right, right away counts.

Lee CC, et al. Impact of inappropriate empirical antibiotic therapy on outcome of bacteremic adults visiting the ED. American Journal of Emergency Medicine (2012) 30, 1447–1456
Lee CC. Different impact of the appropriateness of empirical antibiotics for bacteremia among younger adults and the elderly in the ED. Am J Emerg Med. 2012 Sep 20.
Kang CI, et al. Clinical impact of inappropriate initial antimicrobial therapy on outcome in bacteremic biliary tract infections. Scand J Infect Dis. 2012 Oct 31. [Epub ahead of print]

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