0
Correspondence |

Methicillin-Resistant Staphylococcus aureus Pneumonia Treatment: Do Not Confuse Pharmacokinetics and Pharmacodynamics FREE TO VIEW

Pierre Moine, MD, PhD; Jean-Pierre Bédos, MD, PhD
Author and Funding Information

Affiliations: University of Colorado at Denver, Denver, CO,  Centre Hospitalier de Versailles, Le Chesnay, France

Correspondence to: Pierre Moine, MD, PhD, Department of Anesthesiology, University of Colorado at Denver, Health Sciences Center, 4200 East Ninth Ave, B-113, Denver, CO 80262; e-mail: pierre.moine@uchsc.ed



Chest. 2007;132(3):1101. doi:10.1378/chest.06-2730
Text Size: A A A
Published online

To the Editor:

We have read with great interest the article in a recent issue of CHEST (October 2006) by Jeffres et al,1 which suggested that aggressive dosing strategies for vancomycin (eg, trough concentrations > 15 mg/L) may not offer any advantage over traditional dosing targets (range, 5 to 15 mg/L) in patients with methicillin-resistant Staphylococcus aureus (MRSA) health-care-associated pneumonia. A lack of response to treatment with vancomycin in patients infected with MRSA, and in patients infected with vancomycin intermediate-resistant S aureus (VISA) and heterogeneous VISA (hVISA),,3 has been increasingly reported despite apparent in vitro susceptibility (minimum inhibitory concentration [MIC], 2 mg/L).,23 Moreover, MRSA isolates that show reduced susceptibility to vancomycin (MIC, 2 mg/L) are highly prevalent among strains that cause invasive infections.2

In the study by Jeffres et al,1 the tested staphylococci exhibited a mean vancomycin zone diameter > 14 mm and would therefore be considered fully susceptible. Nevertheless, disk diffusion is not an acceptable method for testing of the vancomycin susceptibility of S aureus, specifically for the detection of VISA or hVISA.,34 Thus, the authors may not have excluded the idea that a lack of response to treatment was not associated with a high vancomycin MIC for MRSA (2 mg/L) or VISA/hVISA.

Unbound trough serum concentrations of vancomycin that are four to five times the MIC or 24-h area under the curve/MIC ratio of 400 were shown to be the pharmacodynamic parameters that best correlated with a successful clinical outcome.5 Considering that vancomycin is 50% protein-bound in serum and that lung concentrations will not exceed 20 to 30% of the serum concentrations,5 a trough serum concentration level of 15 to 25 mg/L may be adequate for the treatment of MRSA with a MIC at the breakpoint for susceptibility (2 mg/L), with a concentration of 30 to 40 mg/L being required for the treatment of VISA/hVISA pneumonia. Unfortunately, Jeffres et al1 did not consider the potential impact of variations in MRSA MICs on differences in outcome. Thus, it still seems appropriate to continue monitoring vancomycin serum levels in order to ensure effective therapeutic concentrations until the results of well-designed prospective clinical studies, including vancomycin MIC determinations, become available.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Jeffres, MN, Isakow, W, Doherty, JA, et al (2006) Predictors of mortality for methicillin-resistantStaphylococcus aureushealth-care-associated pneumonia: specific evaluation for vancomycin pharmacokinetic indexes.Chest130,947-955. [PubMed] [CrossRef]
 
Hidayat, LK, Hsu, DI, Quist, R, et al High dose vancomycin therapy for methicillin-resistantStaphylococcus aureusinfections: efficacy and toxicity.Arch Intern Med2006;166,2138-2144. [PubMed]
 
Appelbaum, PC The emergence of vancomycin-intermediate and vancomycin-resistantStaphylococcus aureus.Clin Microbiol Infect2006;12(suppl),16-23
 
Brown, DFJ, Edwards, DI, Hawkey, PM, et al Guidelines for the laboratory diagnosis and susceptibility testing of methicillin-resistantStaphylococcus aureus.J Antimicrob Chemother2005;56,1000-1018. [PubMed]
 
Rybak, MJ The pharmacokinetic and pharmacodynamic properties of vancomycin.Clin Infect Dis2006;42(suppl),S35-S39
 

Figures

Tables

References

Jeffres, MN, Isakow, W, Doherty, JA, et al (2006) Predictors of mortality for methicillin-resistantStaphylococcus aureushealth-care-associated pneumonia: specific evaluation for vancomycin pharmacokinetic indexes.Chest130,947-955. [PubMed] [CrossRef]
 
Hidayat, LK, Hsu, DI, Quist, R, et al High dose vancomycin therapy for methicillin-resistantStaphylococcus aureusinfections: efficacy and toxicity.Arch Intern Med2006;166,2138-2144. [PubMed]
 
Appelbaum, PC The emergence of vancomycin-intermediate and vancomycin-resistantStaphylococcus aureus.Clin Microbiol Infect2006;12(suppl),16-23
 
Brown, DFJ, Edwards, DI, Hawkey, PM, et al Guidelines for the laboratory diagnosis and susceptibility testing of methicillin-resistantStaphylococcus aureus.J Antimicrob Chemother2005;56,1000-1018. [PubMed]
 
Rybak, MJ The pharmacokinetic and pharmacodynamic properties of vancomycin.Clin Infect Dis2006;42(suppl),S35-S39
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543