isepamicin and Pseudomonas-Infections

In a series of three prospective, randomised, multicentre trials, isepamicin (15 mg/kg or 8 mg/kg once daily depending on severity of infection) was compared with amikacin (7.5 mg/kg twice daily) in a total 252 adult hospitalised patients (mean age 51-54 years) with urinary tract infection. Pretreatment pathogens included Escherichia coli, which was isolated from approximately 50% of patients, and Pseudomonas aeruginosa, which was isolated from approximately 10% of patients with severe infections. The most commonly occurring primary diagnoses were complicated pyelonephritis, uncomplicated pyelonephritis and complicated lower urinary tract infection. For the patients included in the efficacy population, elimination of the pathogens occurred for all infections combined, in 92/101 (91%) patients in the isepamicin group and 51/55 (93%) patients in the amikacin group. Adverse events occurred in 15% of isepamicin patients and 6% of amikacin patients. Ototoxicity at the > or = dB threshold was noted in one isepamicin and two amikacin patients, but none of these patients had associated clinical signs of auditory or vestibular toxicity. Four isepamicin and four amikacin patients had potentially significant increases in serum creatinine indicative of possible nephrotoxicity.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Escherichia coli Infections; Female; Follow-Up Studies; Gentamicins; Humans; Male; Middle Aged; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Urinary Tract Infections

In a prospective multicentre open trial, hospitalised adult patients with acute lower respiratory tract infections, mainly pneumonia or bronchitis, were randomised to receive either isepamicin 8 or 15 mg/kg once daily depending on the severity of the infection or amikacin 7.5 mg/kg twice daily. Patients with infections known to be caused by Pseudomonas aeruginosa were to be given concomitant treatment with ceftazidime. In the intent-to-treat population, i.e. patients who received at least one dose randomised treatment, a clinical cure or improvement at the end of treatment was seen in 112/125 (90%) isepamicin patients and 55/60 (92%) amikacin patients. The corresponding rates for patients with a primary diagnosis of pneumonia were 45/52 (87%) and 25/28 (89%). Cure/improvement rates for patients with P. aeruginosa as the causative pathogen (34 of whom also received ceftazidime) were 28/30 (93%) and 16/18 (89%), respectively. In the efficacy population (patients who had a valid pretreatment culture and who met other evaluability criteria), total elimination (documented or presumed if infection had resolved) of target pathogens occurred in 54/63 (86%) of isepamicin patients and 25/30 (83%) of amikacin patients. P. aeruginosa, Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus were commonly isolated pathogens. Treatment-related adverse were mainly mild or moderate in severity and occurred in 10% of isepamicin patients and 13% of amikacin patients. Four patients (3 isepamicin and 1 amikacin) discontinued treatment because of severe adverse events and a further isepamicin patient withdrew because of a mild adverse event. Nephrotoxicity and ototoxicity occurred infrequently.

Topics: Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Bronchitis; Drug Administration Schedule; Drug Therapy, Combination; Female; Gentamicins; Gram-Negative Bacterial Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Pneumonia, Bacterial; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections

Two hundred and three patients with skin and skin structure infections were treated with isepamicin once daily or amikacin twice daily in an open, randomised, comparative multicentre trial. Patients were randomised to treatment with isepamicin or amikacin in a 2:1 ratio. Severe infections (63 patients) were treated with isepamicin 15 mg/kg once daily (n = 15) or amikacin 7.5 mg/kg twice daily (n - 18), less severe infections (140 patients) with isepamicin 8 mg/kg once daily (n = 93) or amikacin 7.5 mg/kg twice daily (n = 47). The overall clinical response rate at the end of treatment was excellent in all treatment groups (94-96% cured or improved) with no significant differences between isepamicin and amikacin in patients with either server or less severe infections. The most commonly isolated target pathogens were Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis and Staphylococcus aureus. Overall, in patients who had a valid target pathogen isolated prior to treatment and who met other evaluability criteria, bacteriological eradication was achieved in over 90% of patients; amikacin patients with severe infections had a somewhat lower eradication rate (82%). Over all infections, 4/110 (4%) patients in the isepamicin group and 5/54 (9%) patients in the amikacin had organisms which persisted. Adverse events were reported in 12% of patients in the isepamicin group and 6% in the amikacin group. The most frequently reported adverse event in the isepamicin group as headache. Two patients (one in each treatment group), both of whom experienced skin rashes, were withdrawn. Potentially clinically significant changes in serum creatinine occurred in two patients, who received isepamicin and one who received amikacin (who was withdrawn from the study). Ototoxicity was rare, occurring in one patient treated with isepamicin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Drug Administration Schedule; Escherichia coli Infections; Female; Gentamicins; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Proteus Infections; Proteus mirabilis; Pseudomonas aeruginosa; Pseudomonas Infections; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Staphylococcus aureus

Synergistic activities of isepamicin (ISP) and a beta-lactam antibiotic such as piperacillin (PIPC) or cefotaxime (CTX) against Pseudomonas aeruginosa were demonstrated in vitro and in vivo. In vitro synergistic activity was observed when ISP was used together PIPC or CTX. The synergy observed in vitro was reproduced in vivo against experimental mouse infections, and a ISP-PIPC or a ISP-CTX combination showed significantly greater protective effects than individual antibiotics by themselves.

Topics: Animals; Anti-Bacterial Agents; Cefotaxime; Drug Synergism; Drug Therapy, Combination; Gentamicins; Male; Mice; Mice, Inbred ICR; Peritonitis; Piperacillin; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections