Fosfomycin (FOM) is an antibiotic which has varying application indications across the globe. European, Japanese, South African and Brazilian usage practices are much broader, involving multiple formulations of FOM than the currently limited application of FOM in the United States, where uncomplicated urinary tract infection represents the only indication for FOM-tromethamine. Based on early difficulty in determining FOMs genuine in vitro activity, there was initial skepticism about its efficacy and application range. However, in the mid 1970s, correctly executed experiments coupled with an improved understanding of microbiological concepts opened the door for broader use of FOM. During the following 40 years FOM was evaluated in pre-clinical and clinical trials in a wide range of applications and in a multitude of settings. The gathering of pharmacokinetic and pharmacodynamic data was incorporated into large scale studies in which FOM efficacy was further explored and proven. Among European nations, intravenous FOM-disodium for patients presenting with soft tissue infections, sepsis or deep seated infectious processes has become well accepted over the last two decades. The recent emergence of bacterial strains, which impede and encumber pharmacotherapy, namely, MRSA, ESBL and MSSA, lends itself to the idea of reviving long-standing, sensibly used antimicrobial agents like FOM. This review provides a comprehensive conspectus on FOM's history, mode of action, tissue penetration characteristics, resistance, antibacterial activity, combination partners and clinical uses among other facets of interest.
On the basis of relevant pharmacokinetic-pharmacodynamic indices, it seems that fosfomycin is an effective antibiotic for the treatment of deep-seated diabetic foot infections with osseous matrix involvement.
With the reservation that pharmacokinetic-pharmacodynamic targets for daptomycin in tissues are currently not established, we conclude that daptomycin given at intravenous doses of 6 mg/kg body weight once daily may be considered an effective treatment regimen in diabetic patients suffering from bacterial foot infection and osteomyelitis.
The present study aimed at assessing unbound extracellular concentrations of linezolid in inflamed soft tissue and bone of diabetic patients suffering from severe bacterial foot infections. Linezolid was administered intravenously twice daily at a dosage of 600 mg. At steady-state conditions, the microdialysis technique was utilised to sample serially interstitial space fluid from inflamed subcutaneous adipose tissue and metatarsal bone from 0-8h post dose in three representative patients. Mean peak concentrations of free linezolid in plasma, healthy subcutis, inflamed subcutis and cancellous bone were 16.6+/-3.0, 15.5+/-2.5, 15.8+/-2.8 and 15.1+/-4.1mg/L, respectively. The degree of tissue penetration as expressed by the ratio of the area under the concentration-time curve of free linezolid from 0-12h (fAUC(0-12)) in tissue to the fAUC(0-12) in plasma was 1.32+/-0.09, 1.12+/-0.22 and 1.09+/-0.11 for healthy subcutis, inflamed subcutis and bone, respectively. Based on currently available pharmacokinetic/pharmacodynamic targets, we conclude that linezolid administered at 600 mg twice daily may be considered an effective treatment in diabetic patients suffering from bacterial foot infection complicated by osteomyelitis.
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