fosfomycin and Otitis-Media

Fosfomycin (FOM) otic solution was administered to 587 patients with suppurative otitis media infections including 190 patients in the dose-establishment test, 126 patients in the open clinical trial and 271 patients in the double blind test. Various bacteria were detected in the 549 cases in which bacteriological investigation was possible. Main bacteria detected from the above cases were S. aureus (261 strains, 47.5%), P. aeruginosa (93 strains, 16.9%), coagulase negative Staphylococci (CNS) (89 strains, 16.2%), Providencia spp. (35 strains, 6.4%) and Proteus spp. (28 strains, 5.1%). Twenty-seven strains of anaerobic bacteria (4.9%) were also detected. The MIC of FOM, and the reference drug, chloramphenicol (CP), fradiomycin (FRM), cefmenoxime (CMX) and cephalexin (CEX), were determined up to a concentration of 800 micrograms/ml with inoculum sizes of 10(6) and 10(8) CFU/ml. About 30% of S. aureus was multi-drug resistant, including methicillin and cephems, but FOM showed excellent antibacterial activity against it. The FOM had superior antibacterial activity against P. aeruginosa to CP, FRM and CMX, and was also active against other bacteria. The antibacterial activity of FOM was inferior to other drugs against CNS, Enterobacter spp., P. putida and P. cepacia. The detection rate of these bacteria, however, was low and since their role as causative organisms is not well defined, the inferior activity of FOM has no effect on the bacteriological evaluation of FOM. Since the concentration in the tympanic cavity about 1 hour after the administration of 3% FOM solution was estimated to be 2,000 to 3,000 micrograms/ml, it could be presumed that bacteria inhibited by 800 micrograms/ml of FOM at an inoculum size of 10(8) CFU/ml would be eradicable. The low ototoxicity of FOM is likely due to its characteristic as an inhibitor of bacterial cell wall synthesis. From these results, 3% FOM otic solution may be considered as a remarkably useful topical preparation for the treatment of suppurative otitis media.

Topics: Administration, Topical; Clinical Trials as Topic; Double-Blind Method; Drug Resistance, Microbial; Enterobacteriaceae; Fosfomycin; Humans; Otitis Media; Otitis Media, Suppurative; Pseudomonas aeruginosa; Staphylococcus aureus

Studies on a combination therapy of fosfomycin (FOM) and norfloxacin (NFLX) against chronic otitis media were performed, and the following results were obtained. 1. The fractional inhibitory concentration index (FIC index) < or = 0.5 between FOM and NFLX showed 66.7% (4/6) against S. aureus isolated from chronic otitis media and 80.5% (4/5) against P. aeruginosa. 2. Clinical effects was excellent in 2 cases (18.2%), good in 6 cases (54.5%) and poor in 3 cases (27.3%). 3. Bacteriologically 9 strains out of 11 patients were eradicated after the combination treatment; 5/6 in S. aureus and 4/5 in P. aeruginosa. 4. No adverse effect and abnormal laboratory findings were observed in this study. It is suggested that the combination of FOM otic solution and NFLX is useful for the treatment of chronic otitis media.

Topics: Administration, Oral; Administration, Topical; Anti-Bacterial Agents; Anti-Infective Agents; Chronic Disease; Drug Therapy, Combination; Fosfomycin; Humans; Norfloxacin; Otitis Media; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus

Clinical isolates from patients with otitis media and/or otitis externa were collected at otorhinology clinics nationwide and sent to us during 1989, 1991 and 1993. Minimum inhibitory concentrations (MICs) of fosfomycin (FOM) and of reference drugs against these strains were determined to investigate year-to-year antibacterial activity of FOM. A comparative analysis of the results revealed trends described below. 1. The MIC90 of FOM against Staphylococcus aureus subsp. aureus increased 4 times by 1993 as compared to those measured for strains isolated in 1984 and 1985, when FOM for otic use was under development. This was thought to be due to the recent increase in the detection frequency of methicillin-resistant S. aureus (MRSA) which is also resistant to FOM. 2. No annual changes were seen for MIC distribution of FOM against Proteus group and Pseudomonas aeruginosa. 3. Since there was no large annual change in the antibacterial activity of FOM against recent clinical isolates obtained from patients with otitis media and/or otitis externa, FOM may be considered as one of the useful drugs even now, in the mid-1990's.

Topics: Drug Resistance, Microbial; Fosfomycin; Humans; Methicillin Resistance; Otitis Externa; Otitis Media; Proteus; Pseudomonas aeruginosa; Staphylococcus aureus

The efficacy of a combination of cefaclor and fosfomycin otic solution was investigated in 81 children with acute otitis media, who needed myringotomy for severe erythema and swelling of the tympanic membrane. The patients were followed up for one year to investigate correlations between test findings of early treatment and both clinical course and prognosis. These drugs were used for 10 days, and the effects of combined use were evaluated from findings in the tympanic membrane after the 10-day period. Three stages were assessed; cured, recovered and unchanged. In cured and recovered cases, the administration was evaluated to be effective. Within 2 weeks after the start of treatment, views of the ears, nose and epipharynx were roentgenographically examined for shadows of mastoid pneumatization and the paranasal sinuses, and the presence or absence of adenoid vegetation. After the antibiotic administration, the patients were instructed to visit us at least once every 3 months to rule out recurrence of acute otitis media and otitis media with effusion (possibly occurring one year after treatment). The following results were obtained. 1. The two drug combination was effective in 99% of patients, produced no side effects, and was deemed extremely useful. 2. The course of acute otitis media tended to be significantly prolonged in patients with mastoid pneumatization and paranasal sinus shadows as revealed by roentgenography.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adolescent; Cefaclor; Child; Child, Preschool; Drug Evaluation; Drug Therapy, Combination; Female; Fosfomycin; Humans; Male; Otitis Media; Prognosis; Recurrence

Fosfomycin is a relatively new antibiotic drug, deriving from streptomyces species. Its special chemical structure and small molecular size provide a very good diffusion into tissues like bone, fascia and wound exudates as well. In a clinical study Fosfomycin was given to 26 patients with infections mainly of the middle ear and mastoid as well as other ENT-infections. Clinical success, laboratory investigations and bacteriology are described in detail. The drug proved to be of special value in the treatment of chronic purulent otitis, purulent or chronic secreting tympanoplasties or other postoperative middle-ear affections when caused by penicillin-resistant staphylococci, proteus-species and pseudomonas aeruginosa. In the other cases treatment results were good corresponding to the bactericidal spectrum of Fosfomycin. There was one treatment failure in our series, but no reverse reaction at all.

Topics: Adolescent; Anti-Bacterial Agents; Child; Fosfomycin; Humans; Male; Mastoiditis; Microbial Sensitivity Tests; Otitis Media; Proteus Infections; Staphylococcal Infections

The pharmacokinetics of fosfomycin in the ear and eye fluids and in serum are studied after intramuscular administration of 300 and 600 mg per kg respectively to 11 groups of 7 guniea pigs each. Maximal fosfomycin concentrations in the perilymph and aqueous humour are about 12% of the serum peak concentrations and the aqueous humour concentrations are similar to those of the aminoglycoside antibiotics, whereas the fosfomycin concentrations in the perilymph are twice as high as those in the aminoglycoside antibiotics. A retention of fosfomycin in the perilymph, similar to that of the aminoglycoside antibiotics, can be observed. The fosfomycin half-lives in serum, aqueous humour and perilymph are 1.1, 3,7 and 4.9 hours, respectively. The discussion mainly concerns the validity, after suitable adaptation, of the experimental results and their clinical importance for therapy and prophylaxis of the infectious inner ear complications due to the usual germs of chronic otitis media as well as for the treatment of certain eye infections.

Topics: Animals; Anti-Bacterial Agents; Aqueous Humor; Fosfomycin; Guinea Pigs; Injections, Intramuscular; Otitis Media; Perilymph

A group of 24 patients with suppurated chronic processes of the medial ear have been treated with fosfomycin. All the cases were studied bacteriologically, isolating in the pus or exudates pathogenic bacterial flora, in which P. aeruginosa (40%) of the isolations) and S. aureus (23%) predominated. The sensitiveness of the strains isolated to fosfomycin was 94%. The results obtained were 21 clinical cures accompanied by the sterility of the exudates and 3 failures, which represents 87.5% success and 12.5% failures. These results are considered very satisfactory in view of the complexity and chronicity of the processes treated. It is also pointed out that fosfomycin totally lacks ototoxicity, being, therefore, a suitable antibiotic for treating chronic infectious processes of the ear.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Child; Chronic Disease; Drug Evaluation; Female; Fosfomycin; Humans; Male; Middle Aged; Otitis Media; Time Factors