Fluoroquinolones clinical effectiveness

The clinical effectiveness of aminoglycosides and fluoroquinolones is influenced both by the height of the peak plasma concentration relative to the minimum inhibitory concentration (Cmax MIC ratio) and the area under the plasma concentration-time curve that is above the MIC during the dosage interval (AUIC = AUC/MIC). The former is relatively more important for fluoroquinolones maximum activity is achieved when Cmax is in the range 5-10 times the MIC. 

Some clinicians believe that oral fluoroquinolones should be preferred treatments for osteomyelitis, whereas others believe that there have been inadequate studies to date to determine their comparative clinical effectiveness. 

The scientific literature is replete with proposals for numerical values of these indices, for example, Cmax MIC90 > 10 1 for aminoglycosides, AUC MIC9o ratio > 125 h for fluoroquinolones, and T >MIC9o > 50% for P-lactams. In fact, these values provide no more than a guide to clinically effective dosage for several reasons ... 

Rifaximin appears to be an ideal agent for the treatment of infectious watery diarrhea. It has shown excellent efficacy in numerous clinical trials of bacterial diarrhea. Its excellent side effect profile and lack of systemic absorption predict that it should be useful in treating hosts for whom the currently favored fluoroquinolones are contraindicated. Uses limited to enteric indications and its inherently low propensity to induce sustainable resistance among Gram-negative flora favor the sustained usefulness of rifaximin in the treatment of enteric syndromes. 

The data on the adverse reactions of the fluoroquinolones which have received the most extensive clinical evaluation (ciprofloxacin, ofloxacin, pefloxacin, norfloxacin and enoxacin), involving about 30,000 patients, have been the subject of a review [54a], An important point noted in this review involves the difficulty in detecting an important severe adverse reaction if it is of relatively low frequency, until there has been a very large patient exposure (some examples are provided in which at least 150,000-300,000 exposures would be required to observe the importance of side-effects, resulting in an alert, which have been discovered with specific drugs). However, the majority of side-effects observed thus far with the fluoroquinolones have been minor,... 

COPD exacerbations. Therefore, in exacerbation treatment with antibiotics is justified when the patient has at least two of three features of increased dyspnea, increased sputum volume, and sputum pu-rulence. Antibiotic choice will depend on local experience derived from local bacteriological sensitivity data. Older, less costly compounds such as tetracycline, doxycycline, amoxicillin, erythromycin, cefaclor etc. are often as effective as newer, more expensive ones. If resistant organisms are suspected or when the severity of the patients clinical condition puts them at high-risk of treatment failure, a second or third generation cephalosporin, fluoroquinolone, newer macrolide or broad-spectrum penicillin may be preferred. In cases of recurrent infection prolonged courses of antibiotics continuous or intermittent, may be useful. 

The effect of fluoroquinolone-resistance in Campylobacter on the clinical outcome of treatment with a fluoroquinolone is not yet clear. There are conflicting data on whether resistant Campylobacter can cause more severe disease. Although there has been little documented impact of this resistance on human health, current concern about the potential human health consequences if resistance were to increase and spread, is high. Tims, further research and data-gathering are essential to quantify this potential. In addition to quinolone resistance, coresistance... 

Fluoroquinolones are used in the treatment of purulent bronchitis and pneumonia and are hence likely to be administered concomitantly with theophylline. Drugs such as enoxacin and ciprofloxacin have been shown to reduce theophylline clearance by inhibiting metabolism. Lomefloxacin on the other hand has been shown to have no clinically significant effect on theophylline metabolism (40, 41). 

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