fosfomycin and Cholecystitis

Consecutive adult patients requiring emergency abdominal surgery were randomly allocated to preoperative treatment with metronidazole-gentamicin (M-G) or metronidazole-fosfomycin (M-F). Postoperative continuation of antibiotics depended on the estimated risk of septic complications. Peroperatively the cases were stratified as group A, acute inflamed appendicitis, or absence of septic disorder--no postoperative antibiotics, group B, gangrenous appendicitis or cholecystitis or intestinal obstruction without resection, or operations with contamination regarded as minor (gastrotomy or enterotomy)--three further doses of antibiotics, or group C, perforated appendicitis, perforation of the alimentary tract, generalized peritonitis or gross contamination--antibiotics continued for 5 days. Assessment for septic complications was made in 381 patients (191 M-G, 190 M-F). The total incidence was 4.8% (M-G 7.8%, M-F 1.6%, p less than 0.01). The difference was mainly due to higher infection rate in patients stratified to group C and randomized to M-G. Stratification thus permitted restricted duration of antibiotic treatment with a low septic complication rate, significantly less with M-F than with M-G regimen.

Topics: Abdomen, Acute; Adolescent; Adult; Aged; Appendicitis; Cholecystitis; Clinical Trials as Topic; Drug Therapy, Combination; Female; Fosfomycin; Gentamicins; Humans; Male; Metronidazole; Middle Aged; Peritonitis; Postoperative Complications; Random Allocation; Sepsis

Fosfomycin (FOM) is a synthetic antibiotic having a unique structural formula and bactericidal mechanism and a broad spectrum of antimicrobial activity against various bacterial species. It has higher activity in vivo than in vitro. As therapy, FOM-Na in a daily dose of 4 g (2 g X 2) was given by intravenous drip infusion for 5 to 10 days to 6 cases with infectious diseases (2 cases of acute cholecystitis, 3 cases of acute localized peritonitis due to phlegmonous appendicitis and 1 case of acute diffuse peritonitis due to perforative appendicitis). The clinical response was rated as "excellent" in 1 case, "good" in 4 cases, "fair" in 1 case and "poor" in none. No adverse effects were observed in any of the patients. Six clinical isolates were obtained, and these consisted of 4 strains of Escherichia coli and 1 strain each of Klebsiella pneumoniae, and Bacteroides fragilis. The MICs of FOM were from 6.25 to 12.5 micrograms/ml for E. coli, 50 micrograms/ml for K. pneumoniae, and 100 micrograms/ml for B. fragilis. FOM-Na was administered to the 6 cases intravenously in a dose of 2 g before surgery, and tissue specimens and body fluid samples were taken during the operation. The FOM concentration was determined by bioassay with a Proteus sp. (MB 838) as the test organism. The mean FOM concentration in bile from the common bile duct was 61.85 +/- 17.13 micrograms/ml (n = 5) at 95 to 108 minutes after FOM-Na intravenous bolus injection. The mean FOM concentration in the gall bladder bile was 80.06 +/- 92.36 micrograms/ml, while that in the gall bladder wall was 146.65 +/- 39.10 micrograms/g. The mean FOM concentration in purulent ascites was 58.20 +/- 13.29 micrograms/ml, 36.22 +/- 14.63 micrograms/g in the appendix wall and 12.64 +/- 11.34 micrograms/ml in pus in the appendix. The FOM concentrations in the infected tissues and body fluids thus exceeded the MICs of FOM for the pathogenic bacteria. Therefore, FOM-Na appears to be a very useful drug when used for chemotherapy of infections encountered in the surgical field.

Topics: Acute Disease; Adolescent; Adult; Aged; Appendix; Ascitic Fluid; Bile; Child; Cholecystitis; Drug Resistance, Microbial; Female; Fosfomycin; Gallbladder; Humans; Infusions, Parenteral; Kinetics; Male; Middle Aged; Peritonitis

Serum and bile levels of fosfomycin sodium (FOM-Na) were evaluated and the pharmacokinetic parameters were estimated in 10 patients with various forms of biliary drainage (PTCD or T-tube). Clinical trials of FOM-Na were also performed in another 11 patients with bile duct infections and the clinical efficacy was estimated. Mean serum level of FOM-Na after drip infusion of 2 g fosfomycin sodium was 145.43 micrograms/ml at 1 hour, meanwhile bile level was 31.49 micrograms/ml at 2 hours. Serum level of FOM-Na was interpreted by the pharmacokinetic analysis after the damping GAUSS-NEWTON method using the one-compartment open model and bile level of FOM-Na by the damping GAUSS-NEWTON method and deconvolution method. Mean Vd was 12.16 L/body and half-time of serum level was 1.75 hours. Lag-time of bile level was 0.9 hour, Tmax 2.01 hours. The clinical efficacy of FOM-Na was determined excellent without any adverse effect. FOM-Na was remarkably effective in 91% of the patients. Hence, the first choice of FOM-Na against bile duct infections could be recommended.

Topics: Aged; Anti-Bacterial Agents; Bile; Bile Duct Neoplasms; Cholangitis; Cholecystitis; Female; Fosfomycin; Humans; Kinetics; Male; Middle Aged