fosfomycin and Pneumonia

The aim of the study was to evaluate clinical and microbiological efficacy and safety of intravenous fosfomycin for the treatment of carbapenem-resistant

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pneumonia; Urinary Tract Infections

Unfortunately, the options for treating multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections are extremely limited. Recently, fosfomycin and minocycline were newly introduced as a treatment option for MDR A. baumannii infection. Therefore, we investigated the efficacy of the combination of colistin with fosfomycin and minocycline, respectively, as therapeutic options in MDR A. baumannii pneumonia. We examined a carbapenem-resistant A. baumannii isolated from clinical specimens at Severance Hospital, Seoul, Korea. The effect of colistin with fosfomycin, and colistin with minocycline on the bacterial counts in lung tissue was investigated in a mouse model of pneumonia caused by MDR A. baumannii. In vivo, colistin with fosfomycin or minocycline significantly (p < 0.05) reduced the bacterial load in the lungs compared with the controls at 24 and 48 h. In the combination groups, the bacterial loads differed significantly (p < 0.05) from that with the more active antimicrobial alone. Moreover, the combination regimens of colistin with fosfomycin and colistin with minocycline showed bactericidal and synergistic effects compared with the more active antimicrobial alone at 24 and 48 h. This study demonstrated the synergistic effects of combination regimens of colistin with fosfomycin and minocycline, respectively, as therapeutic options in pneumonia caused by MDR A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Fosfomycin; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Minocycline; Pneumonia; Tigecycline

Latest trials failed to confirm merits of nebulized amikacin for critically ill patients with nosocomial pneumonia. We studied various nebulized and IV antibiotic regimens in a porcine model of severe Pseudomonas aeruginosa pneumonia, resistant to amikacin, fosfomycin, and susceptible to meropenem.. Prospective randomized animal study.. Animal Research, University of Barcelona, Spain.. Thirty female pigs.. The animals were randomized to receive nebulized saline solution (CONTROL); nebulized amikacin every 6 hours; nebulized fosfomycin every 6 hours; IV meropenem alone every 8 hours; nebulized amikacin and fosfomycin every 6 hours; amikacin and fosfomycin every 6 hours, with IV meropenem every 8 hours. Nebulization was performed through a vibrating mesh nebulizer. The primary outcome was lung tissue bacterial concentration. Secondary outcomes were tracheal secretions P. aeruginosa concentration, clinical variables, lung histology, and development of meropenem resistance.. We included five animals into each group. Lung P. aeruginosa burden varied among groups (p < 0.001). In particular, IV meropenem and amikacin and fosfomycin + IV meropenem groups presented lower P. aeruginosa concentrations versus amikacin and fosfomycin, amikacin, CONTROL, and fosfomycin groups (p < 0.05), without significant difference between these two groups undergoing IV meropenem treatment. The sole use of nebulized antibiotics resulted in dense P. aeruginosa accumulation at the edges of the interlobular septa. Amikacin, amikacin and fosfomycin, and amikacin and fosfomycin + IV meropenem effectively reduced P. aeruginosa in tracheal secretions (p < 0.001). Pathognomonic clinical variables of respiratory infection did not differ among groups. Resistance to meropenem increased in IV meropenem group versus amikacin and fosfomycin + meropenem (p = 0.004).. Our findings corroborate that amikacin and fosfomycin alone efficiently reduced P. aeruginosa in tracheal secretions, with negligible effects in pulmonary tissue. Combination of amikacin and fosfomycin with IV meropenem does not increase antipseudomonal pulmonary tissue activity, but it does reduce development of meropenem-resistant P. aeruginosa, in comparison with the sole use of IV meropenem. Our findings imply potential merits for preemptive use of nebulized antibiotics in order to reduce resistance to IV meropenem.

Topics: Administration, Inhalation; Administration, Intravenous; Amikacin; Animals; Anti-Bacterial Agents; Bacterial Load; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Fosfomycin; Lung; Meropenem; Nebulizers and Vaporizers; Pneumonia; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Random Allocation; Swine; Trachea

Reference is made to the results obtained in 24 children, from 11 months to 12 years, affected with acute pneumopathies and treated with fosfomycin with a dosage of 200 mg/kg/day. In all cases a clinical, radiological, biological and bacteriological study was carried out. At the same time, levels of fosfomycin in plasma and sputum were checked every 5 days during the course of treatment. In the 4 cases of pleurisy the level of antibiotic in the pleural liquid was also checked. The concentration of fosfomycin in the sputum gives very variable results with average values oscillating between 16.5 and 23.4% of the plasmatic level respectively at the beginning and end of treatment, a cumulative effect of the antibiotic being observed. Concentration in pleural liquid oscillates between 39 and 50%. The clinical, radiological and biological evolution has been favourable iin 21 cases, unfavourable in two cases and in one case treatment had to be suspended because of the apparition of a cutaneous necrosis. Apart from this case no notable toxic effects were observed. Children do not support intramuscular injections very well and intravenous injections often cause phlebitis.

Topics: Anti-Bacterial Agents; Bronchitis; Child; Child, Preschool; Drug Evaluation; Fosfomycin; Humans; Infant; Pleura; Pleurisy; Pneumonia; Respiratory Tract Infections; Sputum; Tracheitis