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Fosfomycin was discovered over four decades ago, yet has drawn renewed interest as an agent active against a range of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens. Its unique mechanism of action and broad spectrum of activity makes it a promising candidate in the treatment of various MDR/XDR infections. There has been a surge of in vitro data on its activity against MDR/XDR organisms, both when used as a single agent and in combination with other agents. In the United States, fosfomycin is only approved in an oral formulation for the treatment of acute uncomplicated urinary tract infections (UTIs), whereas in some countries both oral and intravenous formulations are available for various indications. Fosfomycin has minimal interactions with other medications and has a relatively favorable safety profile, with diarrhea being the most common adverse reaction. Fosfomycin has low protein binding and is excreted primarily unchanged in the urine. The clinical outcomes of patients treated with fosfomycin are favorable for uncomplicated UTIs, but data are limited for use in other conditions. Fosfomycin maintains activity against most Enterobacteriaceae including Escherichia coli , but plasmid-mediated resistance due to inactivation have appeared in recent years, which has the potential to compromise its use in the future. In this review, we summarize the current knowledge of this resurgent agent and its role in our antimicrobial armamentarium. [ABSTRACT FROM AUTHOR]

Summary: Objective: To determine resistance trends including the emergence of extensive drug resistance (XDR) in Mycobacterium tuberculosis (MTB) isolates from Pakistan. Methods: This was a retrospective analysis of MTB isolates (January 1990–June 2007) collected from the four provinces of Pakistan. Standard methods were used to isolate MTB. Susceptibility against rifampin, isoniazid, streptomycin, ethambutol, ethionamide, capreomycin, cycloserine, and ciprofloxacin was tested using the agar proportion method, while susceptibility to pyrazinamide was determined using BACTEC. Resistance over the study period was assessed using Chi-square for trend analysis. Results: Resistance in 15343 MTB isolates showed a steady increase over the study period; a significant trend of increasing resistance was noted in three of the four provinces included in the study. XDR-tuberculosis was first seen in 1998; to date 22 XDR cases have been documented. MTB resistance was significantly lower (p <0.001) in patients under 5 and over 60 years of age, and significantly higher in males than females (p <0.001). MTB resistance was also higher in pulmonary than extrapulmonary isolates (p <0.001). Conclusion: This study documenting a steady increase in resistance among MTB isolates and the emergence of XDR strains is concerning. The data highlight the need to ensure adequate treatment of cases in order to prevent a further increase in multidrug resistance within the country. The importance of developing systems for monitoring drug resistance through nationwide surveillance is emphasized. [Copyright &y& Elsevier]