Doxycycline for Community‐Acquired Pneumonia

Sir—I read with interest the article by Johnson [1] suggesting a more prominent role for doxycycline in empiric therapy for community-acquired pneumonia (CAP). A response by Lederman et al. [2] described an in vitro susceptibility survey that compared tetracycline with doxycy-cline against bacterial pathogens causing CAP. The survey emphasized the relative lack of susceptibility of Streptococcus pneumoniae to doxycycline, potentially limiting its usefulness for empiric treatment of CAP. Some key points about doxycycline were not included in either article. Led-erman et al. [2] argue the doxycycline is not much better than tetracycline in terms of pneumococcal resistance. Although the susceptibility breakpoint against S. pneu-moniae is the same for tetracycline and doxycycline (i.e., у2 mg/mL), the pharma-cokinetics/pharmacodynamics of doxy-cycline are very different from those of tetracycline. Interpretation of susceptibility breakpoints should be based on achievable serum concentrations. Serum concentrations of у2 mg/mL are difficult to achieve with tetracycline (the peak serum concentration after a 500-mg dose is ∼1.5 mg/mL) but are easily achieved with doxy-cycline (the peak serum concentration after a 100-mg intravenous or oral dose is ∼4 mg/mL, and it is ∼8 mg/mL after a 200-mg intravenous or oral dose). It is not appreciated by many clinicians that doxycycline is 5 times more lipid-soluble than tetracycline and has a much longer half-life (8 h vs. 18–22 h). Accordingly , when doxycycline is used for treatment of CAP, dosing should be initiated using a loading regimen, either intravenously or orally, depending upon the severity of the pneumonia. Doxycycline, 200 mg iv or po q12h, rapidly achieves therapeutic concentrations in serum/lung, with a peak serum concentration of ∼8 mg/mL. Without a loading regimen, optimal concentrations of doxycycline are achieved after 4–5 half-lives (i.e., ∼5 days into therapy). This has led some physicians to conclude that doxycycline has failed early in the course of treatment, not appreciating that administration of the usual 100-mg intravenous or oral dose, without a loading regimen, results in su-boptimal concentrations during the first 5 days of treatment. If a patient with CAP is ill enough to be hospitalized and doxy-cycline is selected, a loading regimen should be used [3, 4]. It is also not widely appreciated that the high dose of doxycycline (i.e., 200 mg iv or po q12h) demonstrates concentration-dependent killing kinetics. Doxycycline demonstrates concentration-dependent killing kinetics with the loading regimen, whereas, with 100 mg given intravenously or orally twice daily and without a loading regimen, doxycycline …