High‐Dose, Short‐Course Levofloxacin for Community‐Acquired Pneumonia: A New Treatment Paradigm

Abstract

Levofloxacin demonstrates concentration-dependent bactericidal activity most closely related to the pharmacodynamic parameters of the ratio of area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) and the ratio of peak plasma concentration (C(max)) to MIC. Increasing the dose of levofloxacin to 750 mg exploits these parameters by increasing peak drug concentrations, allowing for a shorter course of treatment without diminishing therapeutic benefit. This was demonstrated in a multicenter, randomized, double-blind investigation that compared levofloxacin dosages of 750 mg per day for 5 days with 500 mg per day for 10 days for the treatment of mild to severe community-acquired pneumonia (CAP). In the clinically evaluable population, the clinical success rates were 92.4% (183 of 198 persons) for the 750-mg group and 91.1% (175 of 192 persons) for the 500-mg group (95% confidence interval, -7.0 to 4.4). Microbiologic eradication rates were 93.2% and 92.4% in the 750-mg and 500-mg groups, respectively. These data demonstrate that 750 mg of levofloxacin per day for 5 days is at least as effective as 500 mg per day for 10 days for treatment of mild-to-severe CAP.

Patient stratification in the management of acute bacterial exacerbation of chronic bronchitis: the role of levofloxacin 750 mg

“…Additionally, patients treated with levofloxacin 750 mg were more likely to experience an improvement in TDI score and earlier resolution of respiratory symptoms, such as increased sputum production, sputum purulence and cough, than their amoxicillin/clavulanate-treated counterparts in the complicated group. Similar findings were noted in a recent study of levofloxacin 750 mg for 5 days for communityacquired pneumonia [21].…”

General Principles of Antimicrobial Therapy

“…In view of the deleterious effects of prolonged courses of antimicrobial agents, including the potential for adverse reactions, problems with adherence, selection of antibiotic-resistant organisms, and high cost, a number of studies have tried to define the optimal duration of therapy, with an emphasis on shorter courses of therapy. For example, evidence supports limiting treatment of uncomplicated UTI in women to 3 days, 25 community-acquired pneumonia to 5 days, 26 and ventilator-associated pneumonia to 8 days. 27 However, when administering abbreviated treatment courses, it is important for clinicians to ensure that their patients fit For personal use.…”

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

“…Therapeutic drug monitoring of aminoglycosides in this context is primarily meant to ensure that trough concentrations are sufficiently low to minimize the potential for renal toxicity. For fluoroquinolones, an approach that optimizes the dose within a nontoxic range (e.g., ciprofloxacin, 600 mg every 12 h, or levofloxacin, 750 mg every 24 h, assuming preserved renal function) should provide the highest probability of a favorable microbiologic and clinical response [127,143,144].…”