fosfomycin and Bronchiectasis

We sought to evaluate published evidence regarding clinical or microbiological outcomes related to the use of inhaled antibiotics other than aminoglycosides, polymyxins and aztreonam. A systematic search of PubMed and Scopus databases as well as bibliographies of eligible articles was performed. In total, 34 eligible studies were identified. Among several inhaled β-lactams, ceftazidime was used with varying success in the prevention and treatment of ventilator-associated pneumonia (VAP) and improved clinical outcomes in chronic Pseudomonas aeruginosa lower respiratory tract infections (LRTIs) in patients with cystic fibrosis (CF) or bronchiectasis. Inhaled vancomycin, as an adjunctive therapy, was effective in treating Gram-positive VAP, whilst inhaled levofloxacin, ciprofloxacin and an inhaled combination of fosfomycin and tobramycin were associated with improved microbiological or clinical outcomes in chronic LRTI in patients with CF or bronchiectasis. In conclusion, published evidence is heterogeneous with regard to antibiotics used, studied indications, patient populations and study designs. Therefore, although the currently available data are encouraging, no safe conclusion regarding the effectiveness and safety of the drugs in question can be reached.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Bronchiectasis; Cystic Fibrosis; Fosfomycin; Humans; Pneumonia, Ventilator-Associated; Quinolones; Respiratory Tract Infections; Treatment Outcome

To compare the in vitro and in vivo activities of a 4:1 (w/w) fosfomycin/tobramycin combination (FTI) with those of fosfomycin and tobramycin alone against cystic fibrosis (CF) and non-CF bronchiectasis pathogens.. Clinical isolates of CF Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Stenotrophomonas maltophilia, Burkholderia cepacia complex, Escherichia coli and Klebsiellia spp. were evaluated by MIC, MBC, post-antibiotic effect (PAE), synergy, time-kill, a rat pneumonia model and spontaneous mutation frequency (SMF).. FTI showed high activity against E. coli, H. influenzae, S. aureus and Klebsiella spp. For the S. aureus strains, 75% of which were methicillin resistant (MRSA), FTI had a lower MIC(90) than tobramycin. For P. aeruginosa, FTI had a lower MIC(90) than fosfomycin, but tobramycin was more active than either. Synergy studies showed no antagonism between fosfomycin and tobramycin, and 93% of the isolates demonstrated no interaction. FTI was rapidly bactericidal and exhibited concentration-dependent killing in time-kill studies. In the rat pneumonia model, FTI and tobramycin demonstrated bactericidal killing of P. aeruginosa; both were more active than fosfomycin alone. The SMF for S. aureus resistance to FTI was 2-4 log(10) lower than that for tobramycin and 2-7 log(10) lower than that for fosfomycin. For P. aeruginosa, the FTI SMF was 2-3 log(10) lower than that for fosfomycin and 1-2 log(10) lower than that for tobramycin.. FTI is a broad-spectrum antibiotic combination with high activity in vitro and in vivo. These data suggest FTI could be a potential treatment for respiratory infections caused by gram-positive and gram-negative aerobic bacteria.

Topics: Administration, Inhalation; Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bronchiectasis; Colony Count, Microbial; Drug Combinations; Drug Interactions; Fosfomycin; Humans; Lung; Male; Microbial Sensitivity Tests; Microbial Viability; Pneumonia, Bacterial; Rats; Tobramycin; Treatment Outcome