Fluoroquinolones response

Discuss ways to promote an optimal response to therapy, how to manage adverse reactions, and important points to keep in mind when educating patients about the use of a fluoroquinolone or aminoglycoside. 

It has been reported that common serotypes of Salmonella were found responsible for human bacteremia in 0.5-2.5% of culture-confirmed salmonellosis cases in the United Kingdom and in fewer than 6% in the United States. Untreated or ineffectively treated Salmonella bacteremia in humans can be fatal. There has been only one published case of a nonfatal infection by a Salmonella typhimurium DT204c resistant strain of animal origin that failed to respond to fluoroquinolone therapy (33). 

Campylobacter species are most commonly responsible for outbreaks of bacterial gastroenteritis in developed countries. The majority of die gastrointestinal Campylobacter infections do not require antibiotic treatment and are selflimiting. Where treatment is required, erythromycin is usually recommended. However, fluoroquinolones are often also used pending laboratory results, because they can cover additional bacterial pathogens and are better tolerated than erythromycin. 

The generic nature of the antiserum was shown by good relative cross-reactivities with penicillin type (3-lactam antibiotics such as amoxicillin (50%), ampicillin (47%), and penicillin V (145%), and a lower response to the isoxazolyl penicillins such as oxacillin, cloxacillin, and dicloxacillin. No cross-reactivity was obtained for cephalosporin type p-lactam antibiotics (cephapirin), cloramphenicol, or fluoroquinolones (enrofloxacin and ciprofloxacin). 

When the fluoroquinolones were first introduced, there was optimism that resistance would not develop. Although no plasmid-mediated resistance has been reported, resistance of MRSA, pseudomonas, coagulase-negative staphylococci and enterococci has unfortunately emerged due to chromosomal mutations. Crossresistance exists among the quinolones. The mechanisms responsible for this resistance include ... 

An increased expression of efflux pumps, which prevents accumulation of the quinolone in the bacterial cell. Thus, the efflux pump NorA is responsible for the reduced sensitivity of S. aureus to hydrophilic fluoroquinolones such as norfloxacin, ciprofloxacin and ofloxacin, whereas quinolones such as sparfloxacin, trovafloxacin and moxifloxacin are not as greatly affected thereby. 

Moxifloxacin has a broad spectrum of activity which includes Gram-positive cocci, atypical pathogens and anaerobic bacteria responsible, inter alia, for infections of the respiratory tract. Moreover, moxifloxacin is one of the most effective fluoroquinolones against pneumococci, including the penicillin- and macrolide-resistant strains. The development of resistance to moxifloxacin is slower than that of the other fluoroquinolones. 

Warfarin The exact warfarin-quinolone drug interaction is unknown. Reduction of intestinal flora responsible for vitamin K production by antibiotics is probable, as are deaeased metabolism and clearance of warfarin due to CYP450 inhibition by the quinolones. Multivalent cations such as aluminum, magnesium, calcium, iron, zinc, and multivitamins with minerals may chelate with fluoroquinolones and decease the oral absorption if administered concurrently. 

The infecting organisms causing pyelonephritis are typically similar to the infecting pathogens responsible for lower UTIs. In uncomplicated cases, antibiotics used for treatment of lower tract Infections also can be used for the treatment of upper tract infections. These agents typically include fluoroquinolones and TMP-SMX. In more serious cases, pyelonephritis may be accompanied by bacteremia, warranting hospitalization and parenteral therapy. 

Because fluoroquinolones have a wide therapeutic index and dose-dependent toxicity, routine drug monitoring is not indicated. Monitoring fluoroquinolone concentration is indicated in renal failure, which wfll cause fluoroquinolones to accumulate. Optimal response occurs when serum concentration exceeds 1.5 Llg/mL. Activity is maintained as long as the trough concentration is >0.2flg/mL. Coadministration with antacids, ferrous sulfate, food, or sucralfate reduces absorption by 30% to 60%. Co-administration with morphine reduces absorption by >50%. 

Therapy with antibiotics generally should be continued for at least 7 to 10 days. Studies evaluating shorter treatment courses (usually 5 days) with the fluoroquinolones, second- and third-generation cephalosporins, and macrolide antimicrobials have demonstrated comparable efficacy with the longer treatment regimens. If the patient deteriorates or does not improve as anticipated, hospitalization may be necessary, and more aggressive attempts should be made to identify potential pathogens responsible for the exacerbation. 

Regardless of which antibiotic is selected, careful attention to predetermined outcome measures should be monitored closely in each patient to determine the success or failure of the therapeutic intervention. Oral antibiotics with broader antibacterial spectra (e.g., cefixime, amoxicillin-clavulanate, fluoroquinolones, or aza-lides) that possess more potent in vitro activity against sputum isolates generally are not needed as initial therapy because chnical response often appears independent of the pathogen s in vitro susceptibility for many patients. ... 

Rash, in areas of the body exposed to UV light, may be indicative of drug phototoxicity. Among the antibacterial agents, the tetracyclines and the sulfonamides are notably phototoxic. More recently, the fluoroquinolones have been implicated in phototoxic responses, and because these antibiotics are widely used, the incidence of this type of adverse effect is increasing. 

The fluoroquinolones are bactericidal analogs of nalidixic add that interfere with bacterial DNA synthesis. They inhibit topoisomerase II (DNA gyrase), blocking the relaxation of super-coiled DNA, required for replication, and topoisomerase IV, responsible for separation of replicated DNA during cell division. 

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