Fluoroquinolones in the Management of Community-acquired Pneumonia in Primary Care

Brian Wispelwey; Katherine R Schafer


Expert Rev Anti Infect Ther. 2010;8(11):1259-1271. 

In This Article

Abstract and Introduction


A literature search was conducted to evaluate the pharmacokinetic and pharmacodynamic profile of the respiratory fluoroquinolones (gemifloxacin, levofloxacin and moxifloxacin) and their efficacy and safety in the management of community-acquired pneumonia (CAP). Data show that CAP is a common presentation in primary care practice, and is associated with high rates of morbidity and mortality, particularly in the elderly. Although the causative pathogens differ depending on treatment setting and patient factors, Streptococcus pneumoniae is the primary pathogen in all treatment settings. As a class, the respiratory fluoroquinolones have a very favorable pharmacokinetic and pharmacodynamic profile. Pharmacodynamic criteria suggest that moxifloxacin and gemifloxacin are more potent against S. pneumoniae, which may have the added benefit of reducing resistance selection and enhancing bacterial eradication. The respiratory fluoroquinolones are also generally well tolerated, and are first-line options for outpatient treatment of CAP in patients with comorbidities or previous antibiotic use.


Community-acquired pneumonia (CAP) continues to be an important cause of morbidity and mortality. In 2005, pneumonia and influenza combined were the eighth leading cause of death in the USA,[1,101] and pneumonia remains the number one cause of death among infectious diseases.[2,3] Each year, an estimated 5.6 million cases of CAP are reported, with the majority – approximately 80% – being managed in the primary care setting. However, more than 1.3 million patients with CAP require hospitalization,[4,5] and up to 10% of those are placed in the intensive care unit (ICU).[2] The average length of hospital stay for patients with pneumonia is 5.1 days, while those placed in a skilled nursing facility after receiving a primary diagnosis of pneumonia have an average length of stay of 124 days.[102]

Although the mortality rate is relatively low in the CAP population treated on an outpatient basis (<1–5%), it is considerably higher in those admitted to the hospital (12%), and ranges from 40–50% in those with severe CAP who require the ICU.[2,6] CAP is also associated with a significant economic burden. The annual cost of antimicrobial therapy alone is nearly US$100 million,[7] and total costs are estimated to range between US$10 and US$12.2 billion, much of which can be attributed to costs associated with hospitalization.[7–9] The causative pathogens in CAP differ, depending upon the treatment setting (e.g., outpatient, hospital and ICU).[1,2] Yet, Streptococcus pneumoniae is the major pathogen in all CAP populations, and drug-resistant S. pneumoniae (DRSP) is an increasing threat.[1,2]

Until the year 2000, pneumococcal resistance rose rapidly, but the intervening years have seen a leveling off, or even a decrease in resistance to penicillin and the cephalosporins that may be related to use of the conjugated pneumococcal vaccine.[1,10,11] Compared with prior years, use of the vaccine was associated with a 69% decrease in the incidence of invasive pneumococcal disease in children, and an 8–32% decrease among adults, depending on age.[11] Additionally, 35% fewer infections due to penicillin-nonsusceptible strains occurred in 2001 than in 1999.[11] However, replacement strains that are not covered by the vaccine have emerged, and some have demonstrated multidrug resistance.[12]

When analyzing the implications of pneumococcal resistance, it is important to discuss the meaning of treatment 'failure'. As with any pathology, it is essential to consider the context in which disease occurs. Infections exist within the milieu of the patient, choice of antibiotic, epidemiology and resistance profiles.[13] It is therefore inappropriate to label a poor outcome as treatment failure due to inherent antibiotic resistance when it could be attributed to natural disease course in the context of other factors.

Furthermore, the discrepancy between in vitro and in vivo resistance cannot be overstated. For example, bacteria classified as resistant in vitro may actually be susceptible in vivo when using an antibiotic at higher doses.[13] This inconsistency contributes to misclassification errors in outcome analysis which has complicated the interpretation of resistance data. In vitro resistance does not necessarily correlate with clinical failure, making treatment failure a concept with limited utility in this context.[14]

Consequently, the clinical implications of resistance are not clear, as current levels of resistance to the β-lactams do not appear to be associated with treatment failure in CAP, when appropriate agents and doses are administered. However, failures have occurred due to resistance to the macrolide class, levofloxacin and ciprofloxacin, when used in the treatment of pneumococcal pneumonia.[1] The level of resistance is an important consideration, particularly for some sites of infection (e.g., meningitis is a more problematic infection than pneumonia).[2]


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