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Drug Criteria & Outcomes
Fluoroquinolones: Predator or prey for infections?
By James Davis, PharmD candidate, Auburn (AL) University Harrison School of Pharmacy
Fluoroquinolones, a broad class of antibacterial agents, were historically used in the treatment of gram negative infections; however, with the development of later generation quinolones, use for coverage of gram positive infections such as with Streptococcus pneumoniae has become commonplace.
Quinolones with this increased spectrum of activity are classified as "third" and "fourth" generation, or "respiratory" quinolones, and consist of Levaquin® (levofloxacin), Avelox® (moxifloxacin), and Tequin® (gatifloxacin). These later generation fluoroquinolones have increased in therapeutic importance since their initial development, particularly in treatment of penicillin and macrolide resistant pneumococcal infections.1, 2 Maintaining effective treatments for S. pneumoniae infections is of utmost importance since it is a common pathogen in a variety of bacterial illnesses including meningitis, bacteremia, pneumonia, and otitis media.3 The formulary quinolone for Huntsville (AL) Hospital, Levaquin®, has maintained good coverage for S. pneumoniae infections throughout eleven years of use (percentage susceptibility of 99% to 100%, 2002 to 2005).4
The microbiological monitoring program, Tracking Resistance in the United States Today, or TRUST, reported results through 2002 suggesting that the occurrence of levofloxacin-resistant S. pneumoniae was 0.9% nationally, and regional data from Alabama, Kentucky, and Tennessee obtained through 2000 showed a 0.1% resistance rate.2, 5 Resistance rates for levofloxacin in the US appear to be increasing at a very gradual rate of approximately 0.1% per year.2, 6
Current research is unclear regarding the exact mechanism of fluoroquinolone resistance with S. pneumoniae, but has shown trends regarding the quinolone resistance-determining region (QRDR) of its DNA. Specific mutations in this region include parC, which is highly associated with ciprofloxacin resistance. Mutations that occur in both parC and gyrA are frequently indicative of levofloxacin resistance; however, these mutations are not absolute and may not imply resistance to all respiratory quinolones.7
Resistance appears to be most common for respiratory quinolones in patients > 65 years at 1.4% and is believed to be due to extensive use of these agents in this patient population.8 Resistant rates for quinolones used in treatment of pneumococcal infections are relatively low despite findings in a 2002 study that suggest overall quinolone prescribing in adults had increased over a seven year period.9
Experience has shown that a judicial approach to antibacterial usage and prevention of bacterial illness are crucial in maintaining an effective arsenal in treatment of any bacterial disease. One approach to maintain judicious antibiotic usage is the adult pneumonia protocol, which is currently being refined at Huntsville Hospital. This protocol uses a guideline based approach, and will improve antibiotic selection and use.10
Another example that shows promise in limiting quinolone usage is the utilization of available pneumococcal vaccinations in children and elderly populations. These vaccinations can help in preventing the occurrence of different types of pneumococcal infections and reduce selection pressure imposed by various antibacterial treatments for these infections.
A recent study from Tennessee showed decreases in penicillin-resistant pneumococcus in children from 1999 to 2002 of 59.8% to 30.4% respectively after introduction of the conjugate pneumococcal vaccine (PCV 7).11 There is, however, no exact correlation between penicillin and quinolone resistance observed with this study, but this does demonstrate that administration of pneumococcal vaccinations in children helps to maintain efficacy of primary antibacterial agents used in treatment of these infections.
In conclusion, it is clear that current rates of quinolone-resistant S. pneumoniae are relatively low. Fluoroquinolones maintain important utility in treatment of these infections, particularly in light of increasing penicillin and macrolide resistance with these bacteria. Quinolone efficacy has been preserved for S. pneumoniae despite slow increases in resistance per year and high rates of overall usage. Improvements in judicious utilization of respiratory quinolones by guideline based protocols and prevention of pneumococcal illness via vaccination shows the most promise in maintaining quinolones as a "predator" in pneumococcus infections.