Iclaprim is a novel bacterial dihydrofolate reductase inhibitor in Phase 3 clinical development for the treatment of acute bacterial skin and skin structure infections and hospital acquired bacterial pneumonia caused by Gram-positve bacteria. Daptomycin, linezolid and vancomycin are commonly used antibiotic for these indications. With increase selective pressure to these generic antibiotics, outbreaks of bacterial resistance to these antibiotics have been reported. This in vitro study evaluated the activity of iclaprim against methicillin-resistant Staphylococcus aureus (MRSA) isolates, which were also not susceptible to daptomycin, linezolid or vancomycin. Iclaprim had an MIC ≤1 µg/ml to the majority of MRSA isolates that were nonsusceptible to daptomycin (5 of 7 71.4%), linezolid (26 of 26 100%), or vancomycin (19 of 28 66.7%). In time-kill curves analyses, iclaprim demonstrated ≥3 log10 reduction in CFU/mL at 4-8 hours for tested strains and isolates nonsusceptible to linezolid or vancomycin. Together these data support the use of iclaprim in serious infections caused by MRSA nonsusceptible to daptomycin, linezolid or vancomycin. Show less

Co-infection of HIV with Mycobacterium tuberculosis is a common event, particularly in developing countries. The emergence and spread of multidrug resistant tuberculosis (MDR-TB) is an increasing public problem in India. The drug-resistant M. tuberculosis strains are posing a significant challenge to TB control. This study used PCR to characterize mutations inside the rifampicin resistance-determining region (RRDR) of the rpoB gene in the rifampicin-resistant M. tuberculosis co-infected with HIV. All the rifampicin-resistant strains had missense mutations. Sequence analysis detected a single or multiple hotspot mutations in the RRDR region of the rpoB gene at codons 516, 512 and 531, in most strains. Furthermore, mutations also occur at codons 512, 514, 517 and 526. The results suggest that hotspot mutations in the rpoB gene are not the sole contributors to MDR-TB co-infected with HIV. Show less