Abstract
Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality worldwide and places a large burden on medical and economic resources, particularly if hospitalization is required. Indeed, it has been estimated that annual costs of inpatient treatment of patients with CAP currently exceed $US6 billion in the US; a large proportion of this cost is directly related to the duration of hospital stay. Initial antibacterial therapy for CAP is usually empirical, as culture and antibacterial sensitivity test results are rarely available at initial diagnosis. Importantly, treatment must be initiated promptly to achieve the best patient outcome thereby potentially reducing healthcare costs, largely as a result of a decrease in hospitalisation. Any agent selected for empirical therapy should have good activity against pathogens associated with CAP, a favorable tolerability profile and be administered in a simple dosage regimen for good compliance.
Streptococcus pneumoniae remains the most common causative pathogen in nonsevere and severe CAP, although the incidence of this organism varies widely. S. pneumoniae strains with decreased susceptibility to penicillin have become increasingly prevalent over the past 30 years and are now a serious problem worldwide. In addition, an increase in the prevalence of pneumococci resistant to macrolides has been observed in Europe over recent years. Mycoplasma pneumoniae and Chlamydia pneumoniae are among the most common atypical pathogens isolated from patients with CAP. Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis are less commonly identified as causative organisms.
Because the spectrum of antibacterial activity of levofloxacin includes the pathogens associated with CAP, including penicillin-resistant S. pneumoniae, it is included in US guidelines as an option for the empirical therapy of patients with mild or more severe disease. Levofloxacin is recommended for the initial treatment of outpatients and inpatients with suspected penicillin-resistant S. pneumoniae infection and is particularly useful in geographical areas where there is a high incidence of drug-resistant pneumococci. Nevertheless, β-lactam antibacterial agents, in particular penicillin, remain agents of first choice for the treatment of CAP (caused by penicillin-susceptible pathogens) in many European countries.
Levofloxacin monotherapy shows good efficacy in the treatment of patients with CAP and is generally well tolerated. Phototoxicity has been infrequently reported with levofloxacin (incidence 0.03% in 1 study) and occurs less commonly than with sparfloxacin (reported incidence 8%). In addition, the drug has a pharmacokinetic profile that allows a simple administration schedule and offers the potential for intravenous to oral sequential therapy. In randomized comparative trials, intravenous or oral levofloxacin was more effective than intravenous ceftriaxone and/or oral cefuroxime axetil, at least as effective as azithromycin plus ceftriaxone and similar in efficacy to both amoxicillin/clavulanic acid and gatifloxacin. Data comparing the efficacy of levofloxacin with other newer fluoroquinolones, such as moxifloxacin, are as yet unavailable.
Levofloxacin was also a beneficial treatment for CAP from a pharmacoeconomic perspective. A critical pathway that used levofloxacin for the treatment of patients with CAP led to a decrease in healthcare resource costs compared with conventional management in a randomized controlled trial conducted in Canada. As a treatment for CAP, levofloxacin was less costly than intravenous ceftriaxone and was more cost effective than cefuroxime plus erythromycin, or ceftriaxone or ciprofloxacin.
Conclusions
Levofloxacin monotherapy is efficacious and shows pharmacoeconomic benefits when used as empirical treatment for adult patients with CAP. The drug has a broad spectrum of antibacterial activity, is administered in a simple dosage regimen and offers the potential for intravenous to oral sequential therapy; it is also well tolerated and is an option for patients allergic to penicillin or macrolides. Levofloxacin has a particularly useful role in the empirical treatment of patients with infections caused by S. pneumoniae in geographical areas where penicillin-resistant strains of pneumococci are prevalent.
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Various sections of the manuscript reviewed by: J.M. Blondeau, Department of Clinical Microbiology, Saskatoon and District Health and St. Paul’s Hospital, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; B. Feagan, London Clinical Trials Research Group, London, Ontario, Canada; T.M. File, Jr., Northeastern Ohio Universities College of Medicine, Rootstown, Ohio, USA; S.R. Norrby, Department of Infectious Diseases and Medical Microbiology, Division of Infectious Diseases, Lund University, Lund, Sweden; C.S. Palmer, MEDTAP International Inc., Bethesda, Maryland, USA.
Data Selection
Sources: Medical literature published in any language since 1966 on Levofloxacin, identified using Medline, supplemented by AdisBase (a proprietary database of Adis International, Auckland, New Zealand). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.
Search strategy: AdisBase search terms were ‘Community-Acquired Pneumonia’ and (‘guideline’ or ‘guideline-utilization’ or ‘practice-guideline’ or ‘disease-management-programs’ or ‘treatment-algorithms’ or ‘reviews-on-treatment’ or ‘drug-evaluations’ or ‘epidemiology’ or ‘cost-of-illness’ or ‘pathogenesis’), or ‘Levofloxacin’ and (‘review’ or ‘clinical-study’). Medline search terms were ‘Community Acquired Pneumonia and (‘guidelines’ or ‘decision-making’ or ‘health-policy’ or ‘managed-care-programs’ or ‘epidemiology’ or ‘outcome-assessment-health-care’ or ‘clinical-protocols’ or ‘guideline in pt’ or ‘practice-guideline in pt’), or ‘Levofloxacin’ and ‘review in pt’. Searches were last updated 12 Dec 2000.
Selection: Studies in patients with community-acquired pneumonia who received levofloxacin. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic, pharmacokinetic, pharmacoeconomic and epidemiological data are also included.
Index terms: Levofloxacin, community-acquired pneumonia, therapeutic use, pharmacodynamics, pharmacokinetics, disease management, review on treatment.
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Perry, C.M., Goa, K.L. Community-Acquired Pneumonia and its Management. Dis-Manage-Health-Outcomes 9, 43–64 (2001). https://doi.org/10.2165/00115677-200109010-00005
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DOI: https://doi.org/10.2165/00115677-200109010-00005