Fluoroquinolone activity

Agents Chemother., 1998, 42, 703-704. Biedenbach DJ, et al. BAY 12-8039, a novel fluoroquinolone. Activity against important respiratory tract pathogens. Diagn. Microbiol. Infect. Dis., 1998, 32, 45-50. 

A fluorine atom in position 6 of the basic structure of quinolones enhances the antimicrobial activity considerably. All widely used quinolones are fluorinated in position 6 and the term fluoroquinolones is often used to describe these drugs. However, some new quinolones with similar antimicrobial activity are not fluorinated in position 6 (e.g. garenoxacin, PGE9262932) and therefore the term quinolones is more appropriate to describe this group of antimicrobial agents. 

Discuss preadministration and ongoing assessment activities the nurse should perform on the patient taking the fluoroquinolones and aminoglycosides. 

Over 10000 quinolone antibacterial agents have now been synthesized. Nalidixic acid is regarded as the progenitor of the new quinolones. It has been used for several years as a clinically important drug in the treatment of urinary tract infections. Since its clinical introduction, other 4-quinolone antibacterials have been synthesized, some of which show considerably greater antibacterial potency. Furthermore, this means that many types of bacteria not susceptible to nahdixic acid therapy m be sensihve to the newer derivahves. The most important development was the introduction of a fluorine substituent at C-6, which led to a considerable increase in potency and spectrum of activity compared with nalidixic add. These second-generation quinolones are known as fluoroquinolones, examples of which are ciprofloxacin and norfloxacin (Fig. 5.19). 

Wetzstein H-G, N Schmeer, W Karl (1997) Degradation of the fluoroquinolone enrofloxacin by the brown-rot fungus Gleophyllum striatum identification of metabolites. Appl Environ Microbiol 63 4272-4281. Wondrack LM, C-A Hsu, MT Abbott (1978) Thymine-7-hydroxylase and pyrimidine deoxyribonucleoside 2 -hydroxylase activities in Rhodotorula glutinis. J Biol Chem 253 6511-6515. 

Complicated exacerbation FEV, less than 50% predicted Comorbid cardiac disease Greater than or equal to 3 exacerbations per year Antibiotic therapy in the previous 3 months Above organisms plus drug-resistant pneumococci, P-lactamase-producing H. influenzae and M. catarrhalis, Escherichia coli, Proteus spp., Enterobacter spp., Klebsiella pneumoniae Oral P-Lactam/P-Iactamase inhibitor (amoxicil 1 i n-clavulanate) Fluoroquinolone with enhanced pneumococcal activity (levofloxacin, gemifloxacin, moxifloxacin) Intravenous P-Iactam/P-Iactamase inhibitor (ampicillin-sulbactam) Second- or third-generation cephalosporin (cefuroxime, ceftriaxone) Fluoroquinolone with enhanced pneumococcal activity (levofloxacin, moxifloxacin)... 

Association to allopurinol, amiodarone, fluoroquinolones, carbamazepine, pheno-barbital, rifampicin, and others Inhibition of CYP activity by the drugs... 

Approximately 30% to 40% of H. influenzae are ampicillin resistant. For this reason, many clinicians use a third-generation cephalosporin (cefotaxime or ceftriaxone) for initial antimicrobial therapy. Once bacterial susceptibilities are available, ampicillin may be used if the isolate proves ampicillin sensitive. Cefepime and fluoroquinolones are suitable alternatives regardless of /1-lactamase activity. 

M. pneumoniae, if suspected by history or positive cold agglutinins (titers greater than or equal to 1 32) or if confirmed by culture or serology, may be treated with azithromycin. Also, a fluoroquinolone with activity against these pathogens (levofloxacin) may be used in adults. 

In complicated exacerbations where drug-resistant pneumococci, /J-lacta-mase-producing H. influenzae and M. catarrhalis, and some enteric gramnegative organisms maybe present, recommended therapy includes amox-icillin/clavulanate or a fluoroquinolone with enhanced pneumococcal activity (levofloxacin, gemifloxacin, moxifloxacin). 

In complicated exacerbations with risk of Pseudomonas aeruginosa, recommended therapy includes a fluoroquinolone with enhanced pneumococcal and P. aeruginosa activity (levofloxacin). If IV therapy is required, a /f lactamase resistant penicillin with antipseudomonal activity or a third- or fourth-generation cephalosporin with antipseudomonal activity should be used. 

The first members of the new fluoroquinolone class (such as norfloxacin (2a), enoxacin (5), pefloxacin (6), ciprofloxacin (2b) and ofloxacin (7)), are generally somewhat less active versus Gram-positive species than Gram-negative... 

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