fosfomycin and Respiratory-Tract-Infections

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

Topics: Anti-Bacterial Agents; Cefmetazole; Cephamycins; Drug Therapy, Combination; Fosfomycin; Humans; Methicillin; Minocycline; Ofloxacin; Oxazines; Penicillin Resistance; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus epidermidis; Tetracyclines

We conducted a multicenter trial to determine the clinical usefulness of the combined therapy with flomoxef (FMOX) and fosfomycin (FOM) (FF therapy) as an empirical therapy in the treatment of intractable respiratory tract infections, because FF therapy has clinically been proved to be very useful for the treatment of severe infections including MRSA infections. The overall efficacy rate of FF therapy was 69.2%. The efficacy rate for "pneumonia/lung abscess," which occupy the largest portions of respiratory tract infections, was 70.0%, showing a statistically significant difference from the efficacy rate for FMOX alone (56.7%) found in a previous study (P = 0.09 by chi-squared test). Although MRSA was eradicated in only 3 cases (37.5%) including superinfection cases, of 8 patients, from whom MRSA had been isolated as causative organisms, none of our patients were superinfected with MRSA. Thus it has been concluded that FF therapy is clinically very useful when used as an empirical therapy in the treatment of respiratory tract infections.

Topics: Aged; Aged, 80 and over; Bacterial Infections; Cephalosporins; Drug Therapy, Combination; Female; Fosfomycin; Humans; Incidence; Japan; Male; Methicillin Resistance; Middle Aged; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus aureus

Subjects in a cefotaxime (CTX) single administration group and in a CTX + fosfomycin (FOM) administration group were randomly selected for a comparative study on the utility of each product against respiratory tract infections. Overall improvement rates were 81.3% in 32 cases of the CTX single administration group, and 75.6% in 41 cases of the CTX + FOM concomitant administration group. No statistical difference was observed. As for adverse reactions and abnormal laboratory test results, pyrexia, thrombocytopenia, increases in GOT and GPT, and increase in GPT were observed in 4 cases of the CTX single administration group, while angialgia, increases in GOT and GPT (3 cases), and increases in BUN, (totalling 5), were observed in the CTX + FOM group. However, all the symptoms were transient, and none was serious in nature.

Topics: Adult; Aged; Aged, 80 and over; Cefotaxime; Clinical Trials as Topic; Drug Synergism; Drug Therapy, Combination; Female; Fosfomycin; Humans; Male; Middle Aged; Multicenter Studies as Topic; Respiratory Tract Infections

Topics: Ampicillin; Anti-Bacterial Agents; Clinical Trials as Topic; Fosfomycin; Humans; Kanamycin; Respiratory Tract Infections; Surgical Wound Infection; Urinary Tract Infections

In cystic fibrosis, chronic airways infection caused by Pseudomonas aeruginosa can be treated with inhaled antibiotics such as inhaled tobramycin, aztreonam or colistin. However, biofilm formation induced by this bacterium can reduce the effectiveness of such therapies and can contribute to antibiotic resistance. Inhaled antibiotic combination might represent an optimal antibiofilm strategy in this setting. This review discusses the rationale for combining the antibiotics as well as some emerging or existing combinations. Most of the combinations except for fosfomycin/tobramycin are at an early stage of development. The latter combination was found to be effective in Phase II clinical studies and is planned to be tested in Phase III trials. The clinical data on long-term efficacy are currently missing, but the existing evidence as well as the unmet therapeutic need can prompt the further evaluation of such compounds.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Clinical Trials as Topic; Cystic Fibrosis; Drug Combinations; Fosfomycin; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Tobramycin; Treatment Outcome

The amikacin-fosfomycin inhalation system (AFIS) is a combination of 2 antibiotics and an in-line nebulizer delivery system that is being developed for adjunctive treatment of pneumonia caused by Gram-negative organisms in patients on mechanical ventilation. AFIS consists of a combination of amikacin and fosfomycin solutions at a 5:2 ratio (amikacin, 3 ml at 100 mg/ml; fosfomycin, 3 ml at 40 mg/ml) and the PARI Investigational eFlow Inline System. In this antibiotic potentiation study, the antimicrobial activities of amikacin and fosfomycin, alone and in a 5:2 combination, were assessed against 62 Gram-negative pathogens from a worldwide antimicrobial surveillance collection (SENTRY). The amikacin MICs for 62 isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were ≥32 μg/ml (intermediate or resistant according to the Clinical and Laboratory Standards Institute [CLSI]; resistant according to the European Committee on Antimicrobial Susceptibility Testing [EUCAST]). Each isolate was tested against amikacin (0.25 to 1,024 μg/ml), fosfomycin (0.1 to 409.6 μg/ml), and amikacin-fosfomycin (at a 5:2 ratio) using CLSI reference agar dilution methods. The median MIC values for amikacin and fosfomycin against the 62 isolates each decreased 2-fold with the amikacin-fosfomycin (5:2) combination from that with either antibiotic alone. Interactions between amikacin and fosfomycin differed by isolate and ranged from no detectable interaction to high potentiation. The amikacin-fosfomycin (5:2) combination reduced the amikacin concentration required to inhibit all 62 isolates from >1,024 to ≤ 256 μg/ml and reduced the required fosfomycin concentration from 204.8 to 102.4 μg/ml. These results support continued development of the amikacin-fosfomycin combination for aerosolized administration, where high drug levels can be achieved.

Topics: Acinetobacter baumannii; Amikacin; Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Synergism; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Respiratory Tract Infections

Topics: Adult; Aged; Drug Therapy, Combination; Female; Fosfomycin; Humans; Male; Middle Aged; Norfloxacin; Respiratory Tract Infections

Topics: Abscess; Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Child; Drug Evaluation; Enteritis; Female; Fosfomycin; Humans; Male; Meningitis; Middle Aged; Respiratory Tract Infections; Urinary Tract Infections

Topics: Adolescent; Anti-Bacterial Agents; Bronchitis; Child; Child, Preschool; Fosfomycin; Humans; Laryngitis; Respiratory Tract Infections; Tracheitis

The Japan Research Committee of Fosfomycin was organized in the fall of 1972 to promote the basic and clinical studies on fosfomycin. First of all, a subcommittee of fosfomycin consisting of a limited number of members was organized to establish the methods of determination on its antibacterial activity and its concentration in the biological fluid, and the most applicable methods were devised. The clinical trials on its oral form in a small scale were commenced from spring in 1973, and then gradually expanded to almost all of Japan. The clinical trials on its parenteral intravenous form were also undertaken from the latter half of 1973. The basic and clinical results obtained from hospitals and institutes almost all over Japan, to which members of the above Committee belong, were presented by speakers under a hot discussion in two symposia which were held by the Japan Society of Chemotherapy; one on its oral form in June 1974, and another on its parenteral form in December 1974. I served as chairman in both of the symposia. The clinical results of fosfomycin in Japan which were mainly collected in both symposia are described below. Its antibacterial activity, and absorption and exretion will be presented elsewhere in this volume. Clinical results of its oral form: Dosage forms of fosfomycin-Ca salt, capsule and granules, were prepared for its clinical trials. It resulted effective in about 76% of 1,200 patients with infection due to gram-positive or gram-negative (Pseudomonas, Salmonella, Escherichia coli, etc.) bacteria in several fields. As far as rates of efficacy were concerned, it was more effective in surgical, urological, ophthalmic and some other fields than in internal and pediatric ones. Fosfomycin was given in a dose of 2-3 g/day for adults or 100-130 mg/kg for infants and children in most cases. Furthermore, it can be favorably mentioned that fosfomycin was proved to be effective in salmonellosis and resistant shigellosis by a certain research group specialized in the therapy of infectious enteritis. Clinical results of its parenteral form: Sterlized bulk material of fosfomycin-Na salt was prepared in a vial for clinical use. Similarly as in the case of oral form, it was applied to about 500 patients with several infections. It resulted effective in about 68% of them. This percentage was not as high because of the higher frequency of application to severe patients or patients with underlying disease. Fosfomycin was intravenously administered

Topics: Administration, Oral; Anti-Bacterial Agents; Bacterial Infections; Drug Evaluation; Enteritis; Female; Fosfomycin; Humans; Injections, Intravenous; Respiratory Tract Infections; Urinary Tract Infections

Since fosfomycin has behaved in vitro as a broad-spectrum antibiotic, an attempt has been made to evaluate this behaviour in controlled clinical study carried out at different Spanish hospitals. A total of 959 patients were treated for some of the following infectious clinical processes: gonococcal urethritis, typhoid fever, enterocolitis, acute and chronic urinary tract infections, osteomyelitis, chronic otorrhoea, septicaemia, meningitis, peritonitis, surgical and suppurative infections, bronchitis, pneumonia, pharyngoamygdalitis, burns, endometritis, ocular infection, whooping cough and nasal carriers of S. aureus. The results obtained as a function of the microorganism isolated in these clinical processes in percentage of clinical and bacteriological success have been 96% of the S. aureus infections, 95% of the Streptococcus sp. including S. pneumoniae, 90% of the N. gonorrhoeae infections, 94% of the E. coli infections including enteropathogenic E. coli, 90% of the S. marcescens infections, 76% of the Proteus sp. infections, 72% of the Klebsiella-Enterobacter infections, 66% of P. aeruginosa infections and 78% of the S. typhi infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Evaluation; Enteritis; Enterobacteriaceae Infections; Fosfomycin; Humans; Respiratory Tract Infections; Staphylococcal Infections; Streptococcal Infections; Urinary Tract Infections

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

A study was made of 40 patients suffering from clinically and bacteriologically demonstrated bacterial respiratory infections which were all treated with fosfomycin as the only antibiotic. Studies were made of the sensitivity of the isolated organisms and control of the eradicated and selected organisms. Analytical controls were performed on all patients before, during and after treatment. The average dose employed was 60 mg/kg/day, divided into four doses and administered parenterally. The duration of the treatment fluctuated between 6 and 11 days in 87% of the cases. A clinical and bacteriological evaluation was made of the results. The clinical response was satisfactory in 75% of the cases, partial in 7.5% and poor in 17.5%. The bacteriological evolution was satisfactory in 62.5%, partial in 12.5% and poor in 20%. It was not possible to control the evolution in 15% of the patients. The concentrations of the antibiotic were determined in the sputum of 6 patients and fluctuated between 0.6 and 12.9 mug/ml. In no case could any significant disorders be attributed to the antibiotic.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Child; Drug Evaluation; Female; Fosfomycin; Humans; Injections; Male; Middle Aged; Respiratory Tract Infections; Sputum; Time Factors

Results are presented for a series of 29 patients, 14 males and 15 females, with serious respiratory infections, in which fosfomycin proved effective. In all cases the study was completed by bacteriological, clinical, radiological and analytical controls. The average dose was 6 g/day (3 g orally and 3 g intramuscularly) for 1 or 2 weeks. The four isolated were P. aeruginosa, E. coli, Klebsiella-Enterobacter and D. pneumoniae. Overall sensitivity percentages were best for fosfomycin, gentamicin and colistin. Of the 29 germs isolated, only one strain of P. aeruginosa became resistant: this represents 3% resistance development. No side effects of intolerance or signs of hepatorenal insufficiency were observed during the treatment. Of the 29 patients treated, 22 were clinically cured, denoting 76% success.

Topics: Anti-Bacterial Agents; Child; Drug Evaluation; Female; Fosfomycin; Humans; Male; Respiratory Tract Infections; Sputum

Evaluation was made of the clinical-bacteriological results of treatment with fosfomycin on a group of 27 patients with infectious respiratory pathology. The group is made up of patients with respiratory infections diagnosed as pneumonias, bronchopneumonias, acute bronchitis and chronic bronchopneumopathies. The doses of fosfomycin used varied between 4 and 12 g/day, administered during a period of 1 or 2 weeks. The results of the treatment expressed in clinical and bacteriological parameters have been successful in 15 and 21 cases for their bacteriological response and their clinical response respectively.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Child; Drug Evaluation; Drug Resistance, Microbial; Female; Fosfomycin; Humans; Male; Middle Aged; Respiratory Tract Infections; Time Factors

30 patients with different infections were treated with fosfomycin: 13 had urinary infections, 14 had pneumonial infections, 2 had staphylococcus osteomyelitis and 1 had staphylococcus septicemia. The antibiotic was administered in doses ranging from 100 to 230 mg/kg/day, with periods of treatment that lasted from 5 to 58 days. The doses were administered every 6 h by the oral or intramuscular route. A total of 35 organisms were isolated: 7 E. coli, 7beta-hemolitic Streptococcus, 6 Proteus sp., 6 S. aureus, 6 S. viridans, 2 Klebsiella sp. and 1 negative coagulase S. aureus. All were sensitive to fosfomycin in vitro, as was revealed by the diffusion in discs method. The therapeutic results were good in 29 of the 30 cases (96.7%). There were no important side effects. A patient complained of a local pain in the area of the injection. The transaminases increased temporarily in 2 patients. One patient had a moderate eosinophilia while under treatment.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Fosfomycin; Humans; Injections, Intramuscular; Middle Aged; Respiratory Tract Infections; Time Factors; Urinary Tract Infections

Topics: Ampicillin; Anti-Bacterial Agents; Carbenicillin; Cephalosporins; Chloramphenicol; Cloxacillin; Fosfomycin; Gentamicins; Haemophilus Infections; Humans; Methicillin; Penicillin G; Polymyxins; Pseudomonas Infections; Respiratory Tract Infections; Sepsis; Staphylococcal Infections; Streptococcal Infections