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Fosfomycin suppresses chemokine induction in airway epithelial cells infected with respiratory syncytial virus

Okabayashi T, Yokota S, Yoto Y, Tsutsumi H, Fujii N. Clin Vaccine Immunol. 2009 Jun;16(6):859-65.

Respiratory syncytial virus (RSV) infects airway epithelial cells, causing bronchiolitis and pneumonia. Inflammation is mediated by various cytokines secreted from RSV-infected airway epithelial cells, and it promotes the pathogenesis of RSV-related diseases. Fosfomycin (FOF) is approved as a treatment for various bacterial infectious diseases, including respiratory infectious diseases, in Japan. FOF is suggested to exhibit immunomodulatory effects on lipopolysaccharide-stimulated monocytes and T lymphocytes, in addition to its antimicrobial activity. We investigated the effect of FOF on the cytokine production of an airway epithelial cell line, A549, infected with RSV. RSV-induced cytokines, such as regulated on activation, normal T-cell expressed and secreted (RANTES), interleukin-8 (IL-8), and IL-6, in infected A549 cells. We found that FOF decreased the levels of RSV-induced RANTES and IL-8 but not the level of RSV-induced IL-6. The RANTES promoter was activated by RSV infection. Site-directed mutagenesis analysis of the RANTES promoter showed that NF-kappaB-binding motifs had a critical role in RSV-induced RANTES promoter activity. A luciferase reporter gene assay and a DNA-binding assay indicated that FOF suppressed the NF-kappaB activity induced by RSV infection. These results demonstrate that FOF treatment suppresses the RSV-induced transcription of the chemokines RANTES and IL-8 in airway epithelial cells.

In vitro activity of fosfomycin against ESBL-producing enterobacteria of urinary origin.In vitro activity of fosfomycin against ESBL-producing enterobacteria of urinary origin.

Hernandez M, Garcia J, and Munoz J. Rev Esp Quimioter 2009;22(1):25-29. Hernandez M, Garcia J, and Munoz J. Rev Esp Quimioter 2009;22(1):25-29.

In vitro activity of fosfomycin, compared with other antibiotics used for urinary tract infections (UTI), against extended spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae clinical isolates obtained from UTIs, was determined. The activity of fosfomycin, co-trimoxazole, ciprofloxacin, nitrofurantoin, amoxicillin/ clavulanic acid and gentamicin against 71 ESBL-producing E. coli clinical isolates and 13 ESBLproducing K. pneumoniae clinical isolates obtained from UTI was studied by the agar-dilution method or E-test. E. coli isolates produced mainly CTX-M type ESBL (76.1%), especially CTX-M 14 (56.3 %). K. pneumoniae isolates produced most predominantly SHV-type ESBL (92.3%), mainly SHV-2 (76.9 %). Gentamicin (4.4 %), fosfomycin (5.6 %) and nitrofurantoin (5.6 %) showed the lowest resistance proportions against E. coli. Co-trimoxazole and ciprofloxacin (7.7 %) showed the lowest resistance proportions against K. pneumoniae. Key words: Escherichia coli. Klebsiella pneumoniae. Extended spectrum beta-lactamase (ESBL)

Fosfomycin for the treatment of infections caused by Gram-positive cocci with advanced antimicrobial drug resistance: a review of microbiological, animal and clinical studies.

Falagas M.; Roussos N.; Gkegkes I.; et al. Expert Opinion on Investigational Drugs, 2009; 18 (7): 921-944.Falagas M.; Roussos N.; Gkegkes I.; et al. Expert Opinion on Investigational Drugs, 2009; 18 (7): 921-944.

Background: The advancing antimicrobial drug resistance in Gram-positive cocci complicates the selection of appropriate therapy. The re-evaluation of older antibiotics may prove useful in expanding relevant therapeutic options. Objective: We sought to evaluate fosfomycin for the treatment of infections caused by methicillin-resistant staphylococci, vancomycin-resistant enterococci, and penicillin-non-susceptible pneumococci. Methods: We searched in PubMed, Scopus, and the Cochrane Library for studies evaluating the antimicrobial activity of fosfomycin against the above-mentioned pathogens, or the in vivo or clinical effectiveness of fosfomycin for the treatment of infections caused by these pathogens. Results/conclusions: As reported in the identified studies, the susceptibility rate of methicillin-resistant Staphylococcus aureus to fosfomycin was ? 90% in 12/22, and 50 - 90% in 7/22 studies; the cumulative susceptibility rate was 87.9% (4240/4892 isolates). The cumulative susceptibility rate of vancomycin-resistant enterococci to fosfomycin was 30.3% (183/604 isolates), and that of penicillin-non-susceptible pneumococci was 87.2% (191/219 isolates). Clinical data show that fosfomycin, primarily in combination regimens, has been associated with clinical success in 28/29 (96.6%) cases of infection (mainly pneumonia, bacteremia, and meningitis) by fosfomycin-susceptible isolates of methicillin-resistant S. aureus. The above data support further research on the role of fosfomycin against infections caused by Gram-positive cocci with advanced antimicrobial drug resistance.

Fosfomycin for the treatment of infections caused by multidrug-resistant non-fermenting Gram-negative bacilli: a systematic review of microbiological, animal and clinical studies.Fosfomycin for the treatment of infections caused by multidrug-resistant non-fermenting Gram-negative bacilli: a systematic review of microbiological, animal and clinical studies.

Falagas ME, Kastoris AC, Karageorgopoulos DE, Rafailidis PI. Int J Antimicrob Agents. 2009 Aug;34(2):111-20.Falagas ME, Kastoris AC, Karageorgopoulos DE, Rafailidis PI. Int J Antimicrob Agents. 2009 Aug;34(2):111-20.

The treatment of multidrug-resistant (MDR), extensively drug-resistant or pandrug-resistant non-fermenting Gram-negative bacterial infections constitutes a challenge in an era of few new antibiotic choices. This mandates the re-evaluation of already existing antibiotics such as fosfomycin. We systematically reviewed the literature to assess the clinical and microbiological effectiveness of fosfomycin in the treatment of these infections by searching PubMed, Scopus and the Cochrane Library databases. In 23 microbiological studies identified, 1859 MDR non-fermenting Gram-negative bacterial isolates were examined. The susceptibility rate to fosfomycin of MDR Pseudomonas aeruginosa isolates was >or=90% and 50-90% in 7/19 and 4/19 relevant studies, respectively. Cumulatively, 511/1693 (30.2%) MDR P. aeruginosa isolates were susceptible to fosfomycin. Serotype O12 isolates exhibited greater susceptibility. Only 3/85 (3.5%) MDR Acinetobacter baumannii and 0/31 MDR Burkholderia spp. isolates were susceptible to fosfomycin. Variable criteria of susceptibility were used in the included studies. Fosfomycin was synergistic in combination with a beta-lactam, aminoglycoside or ciprofloxacin in 46/86 (53.5%) MDR P. aeruginosa isolates. One animal study found a good therapeutic effect of the combination fosfomycin/gentamicin against MDR P. aeruginosa endocarditis. In six clinical studies, 33 patients with MDR P. aeruginosa infections (mainly pulmonary exacerbations of cystic fibrosis) received fosfomycin (25/33 in combination with other antibiotics); 91% of the patients clinically improved. In conclusion, fosfomycin could have a role as a therapeutic option against MDR P. aeruginosa infections. Further research is needed to clarify the potential utility of this agent.