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

Brian Wispelwey; Katherine R Schafer

Disclosures

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

In This Article

Role of Fluoroquinolones in the Treatment of CAP

The use of prescription fluoroquinolones increased more than threefold in both the outpatient setting and the emergency department in the USA and Canada between 1995 and 2002.[39,40] The fluoroquinolones indicated for the management of CAP include moxifloxacin and levofloxacin for the treatment of mild, moderate or severe CAP caused by S. pneumoniae (including DRSP and MDRSP), H. influenzae, M. pneumoniae, C. pneumoniae, Haemophilus parainfluenzae, M. catarrhalis, Klebsiella pneumoniae and methicillin-susceptible S. aureus.[41,42] Gemifloxacin has also been approved by the FDA since 2003 for the treatment of CAP of mild-to-moderate severity caused by the above pathogens, with the exception of H. influenzae and S. aureus.[43] According to the IDSA/ATS guidelines, fluoroquinolones are not the drugs of choice for uncomplicated CAP in the outpatient setting. The antipneumococcal fluoroquinolones (moxifloxacin, gemifloxacin or levofloxacin [750 mg]) are recommended for outpatients who have a penicillin allergy or who have complicated CAP associated with malignancy, asplenia, alcoholism, immunosuppressing conditions or use of immunosuppressants, or comorbidities such as diabetes mellitus or chronic heart, lung, liver or renal disease.[1,2,44] The fluoroquinolones are also recommended for outpatients who have used antimicrobials within the previous 3 months, or who have other risks for DRSP infection (see Table 3 ).[44]

The respiratory fluoroquinolones (levofloxacin, moxifloxacin and gemifloxacin) have broad-spectrum activity that covers Gram-positive, Gram-negative and atypical pathogens.[2,45] All fluoroquinolones exhibit high antimicrobial activity against S. pneumoniae, including DRSP and MDRSP.[2,41–43,45] For example, in an in vitro pharmacokinetic model, moxifloxacin exhibited rapid bactericidal effect against ten S. pneumoniae strains, including DRSP, with a 99.9% kill of eight strains occurring within 1–3 h after dosing. Levofloxacin was also found to be bactericidal against all ten strains, but required an additional 4–5 h to achieve similar effects.[46]

As shown in Table 4 & Table 5 , all three respiratory fluoroquinolones have good pharmacokinetic and pharmacodynamic profiles against S. pneumoniae infection.[45,47,48] The ratio of AUC/MIC is an important parameter for predicting clinical and/or bacteriological success. In all three agents, AUC/MIC is greater than 30, and it is greater than 100 in moxifloxacin and gemifloxacin.[45,47] An AUC/MIC ratio of 30–40 is considered the minimum necessary to achieve success against S. pneumoniae; however, a ratio approaching 100 has recently been recommended for fluoroquinolones to optimize rapidity of bacterial killing and decrease emergence of resistance in patients with CAP.[47]

A comparison of antimicrobial activities, MIC90, and the ratio of the AUC to the MIC, as seen in Table 4 , suggests that the microbiologic potency against S. pneumoniae is higher with moxifloxacin than with levofloxacin.[45,47] An in vitro pharmacodynamic study of moxifloxacin and levofloxacin against various CAP pathogens demonstrates that moxifloxacin yields higher AUC/MIC and Cmax/MIC against Gram-positive bacteria than levofloxacin 500 or 750 mg once daily.[49]

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