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Correspondence |

Antibiotics Selection for Bacteremic PneumoniaResponse FREE TO VIEW

George Dimopoulos, MD, PhD, FCCP
Author and Funding Information

Affiliations: University Hospital “ATTIKON”, Athens, Greece,  Division of Pulmonary and Critical Care, University of Connecticut School of Medicine, Farmington, CT

Correspondence to: George Dimopoulos MD, PhD, FCCP, Department of Intensive Care, University Hospital “ATTIKON,” 1 Rimini av. 12462, Haidari, Athens, Greece; e-mail: dimop@panafonet.gr



Chest. 2007;132(1):360-361. doi:10.1378/chest.07-0706
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Published online

I read with interest the article by Metersky and coworkers1 (February 2007) regarding antibiotics for bacteremic pneumonia. The authors1 showed improved outcomes with macrolides but not with fluoroquinolones. The authors1 reviewed the charts of 2,209 patients admitted to the hospital with bacteremic pneumonia between 1998 and 2001 and concluded that the initial antibiotic coverage with a β-lactam along with a macrolide was associated with an improved outcome. In contrast, treatment with fluoroquinolones was related to worse outcome. According to blood culture results, bacteremic pneumonia was due to Streptococcus pneumoniae (38%) followed by Staphylococcus aureus (14%) and Streptococcus spp. (other; 14%) [Table 1]. The most common antibiotics used as monotherapy or as combination therapy within 24 h of hospital admission are shown in Table 2.,1

When reading this article, the main message is that early administration of a macrolide plus a β-lactam lead to a better outcome of bacteremic pneumonia, confirming the results of previous studies.23 However, there are two main points that need to be addressed: (1) the authors do not mention the used dose of levofloxacin (500 mg qid, 500 mg bid, or 750 mg/d); and (2) as the authors used in the title the term fluoroquinolones (probably they mean respiratory quinolones), what would be the potential therapeutic benefit of moxifloxacin in these patients (especially in elderly patients)?4

Regarding levofloxacin, it is well known that at a dose of 500 mg bid maintains an area under the curve/minimum inhibitory concentration ratio of 95 (with a ratio of area under the curve over 24 h/minimum inhibitory concentration > 30 to 40 h an optimal antimicrobial activity against Gram-positive microorganisms is achieved). In addition, monotherapy with moxifloxacin has been found to be superior in the treatment of community acquired pneumonia compared to a standard combination regimen including a β-lactam and a β-lactamase inhibitor with or without a macrolide.56

The author has no conflict of interest to disclose.

Dr. Metersky has served on an advisory board/speaker’s bureau for the following pharmaceutical companies: Aventis, Bayer, Ortho, Pfizer, Schering.

Metersky, MI, Ma, A, Houck, PM, et al (2007) Antibiotics for bacteremic pneumonia: improved outcomes with macrolides but not fluoroquinolones.Chest131,466-473. [PubMed] [CrossRef]
 
Garcia, VE, Mensa, J, Martinez, JA, et al Lower mortality among patients with community-acquired pneumonia treated with a macrolide plus a β-lactam agent versus a β-lactam alone.Eur J Clin Microbiol Infect Dis2005;24,190-195. [PubMed]
 
Lujan, M, Gallego, M, Fontanals, D, et al Prospective observational study of bacteremic pneumococcal pneumonia: effect of discordant therapy on mortality.Crit Care Med2004;32,625-631. [PubMed]
 
Anzueto, A, Niederman, MS, Pearle, J, et al Community-Acquired Pneumonia Recovery in the Elderly study group: Community-Acquired Pneumonia Recovery in the Elderly (CAPRIE); efficacy and safety of moxifloxacin therapy versus that of levofloxacin therapy.Clin Infect Dis2006;42,73-81. [PubMed]
 
Drusano, GL, Preston, SL, Fowler, C, et al Relationship between fluoroquinolone area under the curve: minimum inhibitory concentration ratio and the probability of eradication of the infecting pathogen, in patients with nosocomial pneumonia.J Infect Dis2004;189,1590-1597. [PubMed]
 
Finch, R, Schürman, D, Collins, O, et al Randomized controlled trial of sequential intravenous (iv) and oral moxifloxacin compared with sequential iv and oral co-amoxicclav with or without clarithromycin in patients with community-acquired pneumonia requiring initial parenteral treatment.Antimicrob Agents Chemother2002;46,1746-1754. [PubMed]
 
To the Editor:

We wish to thank Dr. Dimopoulos for his interest in our study.1 Dr. Dimopoulus raises three issues. First, he asks if only respiratory fluoroquinolones were included in the fluoroquinolone group. We suspect that Dr. Dimopoulus is concerned that the poor activity of ciprofloxacin against Gram-positive organisms such as Streptococcus pneumonaie could explain why patients receiving fluoroquinolones had poorer adjusted outcomes than patients receiving macrolides. While we included patients receiving ciprofloxacin in the fluoroquinolone group, only 12 received fluoroquinolone monotherapy (1.3% of the fluoroquinolone patients), and only 1 of these patients died (8.3%); thus, it is unlikely that poorer outcomes in this small group explained our results. Dr. Dimopoulus correctly notes that various dosing regimens for levofloxacin are used around the world, and suggests that dosages > 500 mg/d have theoretical benefit based on pharmacokinetic and pharmacodynamic parameters. Although we did not abstract antibiotic dosages, we suspect that most patients received 500 mg/d of levofloxacin because other dosing regimens were not commonly used for community-acquired pneumonia prior to 2001 in the United States. However, we are not aware of any convincing data to suggest that higher doses of levofloxacin result in improved outcomes in patients with community-acquired pneumonia. Finally, Dr. Dimopoulus notes that in contrast to our results, randomized, controlled trials have demonstrated equivalent or superior outcomes with fluoroquinolones when compared to regimens including macrolides. As mentioned in our article,,1others have noted disparate results of randomized trials (almost all antibiotic registration studies) vs retrospective studies23 of patients with community-acquired pneumonia. This may be because patients enrolled in antibiotic registration trials are not representative of most pneumonia patients,2 or because retrospective studies are subject to bias from potentially important patient-related factors not being included in the multivariable analyses. Only a large randomized trial can answer this important question.

References
Metersky, MI, Ma, A, Houck, PM, et al Antibiotics for bacteremic pneumonia: improved outcomes with macrolides but not fluoroquinolones.Chest2007;131,466-473. [PubMed] [CrossRef]
 
Shefet, D, Robenshtok, E, Paul, M, et al Empirical atypical coverage for inpatients with community-acquired pneumonia.Arch Intern Med2005;165,1992-2000. [PubMed]
 
Mills, GD, Oehley, MR, Arrol, B Effectiveness of β-lactam antibiotics compared with antibiotics active against atypical pathogens in non-severe community acquired pneumonia: meta-analysis.BMJ2005;330,456-462. [PubMed]
 

Figures

Tables

References

Metersky, MI, Ma, A, Houck, PM, et al (2007) Antibiotics for bacteremic pneumonia: improved outcomes with macrolides but not fluoroquinolones.Chest131,466-473. [PubMed] [CrossRef]
 
Garcia, VE, Mensa, J, Martinez, JA, et al Lower mortality among patients with community-acquired pneumonia treated with a macrolide plus a β-lactam agent versus a β-lactam alone.Eur J Clin Microbiol Infect Dis2005;24,190-195. [PubMed]
 
Lujan, M, Gallego, M, Fontanals, D, et al Prospective observational study of bacteremic pneumococcal pneumonia: effect of discordant therapy on mortality.Crit Care Med2004;32,625-631. [PubMed]
 
Anzueto, A, Niederman, MS, Pearle, J, et al Community-Acquired Pneumonia Recovery in the Elderly study group: Community-Acquired Pneumonia Recovery in the Elderly (CAPRIE); efficacy and safety of moxifloxacin therapy versus that of levofloxacin therapy.Clin Infect Dis2006;42,73-81. [PubMed]
 
Drusano, GL, Preston, SL, Fowler, C, et al Relationship between fluoroquinolone area under the curve: minimum inhibitory concentration ratio and the probability of eradication of the infecting pathogen, in patients with nosocomial pneumonia.J Infect Dis2004;189,1590-1597. [PubMed]
 
Finch, R, Schürman, D, Collins, O, et al Randomized controlled trial of sequential intravenous (iv) and oral moxifloxacin compared with sequential iv and oral co-amoxicclav with or without clarithromycin in patients with community-acquired pneumonia requiring initial parenteral treatment.Antimicrob Agents Chemother2002;46,1746-1754. [PubMed]
 
Metersky, MI, Ma, A, Houck, PM, et al Antibiotics for bacteremic pneumonia: improved outcomes with macrolides but not fluoroquinolones.Chest2007;131,466-473. [PubMed] [CrossRef]
 
Shefet, D, Robenshtok, E, Paul, M, et al Empirical atypical coverage for inpatients with community-acquired pneumonia.Arch Intern Med2005;165,1992-2000. [PubMed]
 
Mills, GD, Oehley, MR, Arrol, B Effectiveness of β-lactam antibiotics compared with antibiotics active against atypical pathogens in non-severe community acquired pneumonia: meta-analysis.BMJ2005;330,456-462. [PubMed]
 
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