isepamicin and Urinary-Tract-Infections

Isepamicin is a new aminoglycoside, derived from gentamicin B, which is more stable than other aminoglycosides against inactivating enzymes, and is less nephrotoxic. We evaluated the efficacy and safety of a once daily isepamicin in the treatment of complicated urinary tract infections (UTIs), as compared with amikacin. During the period May, 1997, to January, 1998, a total of 52 patients with similar demographic and baseline characteristics were enrolled into a prospective, randomized, open-label, single-center trial at the Veterans General Hospital-Kaohsiung. Eleven patients were excluded for protocol violation. The remaining 41 patients were included in the efficacy analysis. Study subjects included 16 men and 25 women, with a mean age of 57.9 (range 18-95) years. Clinical improvement was noted in 100% of patients in both the isepamicin and amikacin group. No statistically significant difference was observed between the 2 groups in regard to the rapidity of defervescence, relief of dysuria and urinary frequency, and clearance of bacteriuria and pyuria. Bacteriological cure rates were 89.4% for the isepamicin group and 100% for the amikacin group. Fifteen of 25 subjects who received isepamicin and 16 of 27 subjects who received amikacin had an adverse effect, all of which were considered to be mild except for one in the amikacin group, who had an adverse event of moderate severity (vomiting). Seven (3 isepamicin and 4 amikacin) adverse events were considered probably or possibly related to the study drug, which included eosinophilia (2 isepamicin), liver function impairment (1 isepamicin, 2 amikacin), renal function impairment (1 amikacin) and flushed face (1 amikacin). However, none of the patients had a life-threatening or severe adverse event that required discontinuation of the drug. These results show that once daily administration of isepamicin is as effective and safe as amikacin in treatment of complicated UTIs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Drug Administration Schedule; Female; Gentamicins; Humans; Male; Middle Aged; Prospective Studies; Urinary Tract 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

A multicentre, non-comparative study evaluated the efficacy and safety of the new aminoglycoside isepamicin in hospitalised patients with various infections. Isepamicin was administered once daily with the daily dosage stratified according to the severity of infection: 15 mg/kg isepamicin for severe potentially systemic infections (53 patients) or 8 mg/kg isepamicin for less severe and localised infections (56 patients). The largest groups of patients had urinary tract infection (n = 54) or lower respiratory tract infection (n = 31); smaller numbers of patients were enrolled with skin and soft tissue infections (n = 9), intra-abdominal infections (n = 8) or obstetric and gynaecological infections (n = 7). In the patients receiving 15 mg/kg isepamicin, clinical cure or improvement occurred in 19/21 patients with lower respiratory tract infections, 8/13 patients with urinary tract infections, 6/6 patients with skin infections, 5/6 patients with intra-abdominal infections and 6/7 patients with obstetric gynaecological infections. In the patients receiving 8 mg/kg isepamicin, 40 out of 41 patients with urinary tract infections were considered cured or improved as were 8/10 patients with lower respiratory tract infections, 1/3 patients with skin infections and 1/2 patients with intra-abdominal infections. Nine per cent of patients reported at least on adverse event during the study. Two patients (one from each dosage group) discontinued treatment because of adverse events, respiratory disorder and erythematous rash, but neither event was considered to be severe of life threatening No patients had evidence of ototoxicity by pure-tone audiometry and no patients had potentially significant increases in serum creatinine which were considered to be treatment related. The results of this study indicate that treatment with isepamicin once daily is effective and well tolerated in hospitalised adults with various infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Drug Administration Schedule; Female; Genital Diseases, Female; Gentamicins; Humans; Male; Middle Aged; Respiratory Tract Infections; Skin Diseases, Bacterial; Urinary Tract Infections

The efficacy of once-daily administration of isepamicin in hospitalized adult patients has been assessed in a multinational clinical trails programme. Following a small phase II programme, the phase III programmed assessed four main indications: lower respiratory tract infections (including nosocomial pneumonia), urinary tract, intra-abdominal and skin and soft tissue infections. The phase III trials were open, prospective, multicentre studies in which 1443 patients were randomised to receive either isepamicin (n = 1005) or amikacin (n = 438). The daily dose of isepamicin was dependent on the severity of infection (8 or 15 mg/kg once daily) while all patients received amikacin 7.5 mg/kg twice daily. A study of patients with nosocomial pneumonia had an additional treatment arm of isepamicin 7.5 mg/kg twice daily. The aminoglycosides were combined with other antimicrobial agents in accordance with current clinical practice depending on the site and severity of the infection and the type of organism isolated. Overall, clinical cure or improvement response rates of the isepamicin and amikacin regimens were comparable, ranging from 76-95% in the intent-to-treat population. Lower clinical response rates (62-63%) was observed in severely ill patients with nosocomial pneumonia in both the isepamicin and amikacin treatment groups. In the efficacy population, organism elimination rates of 90% were achieved with isepamicin and amikacin. Therefore, in adult patients with a wide range of infections requiring aminoglycoside therapy, once-daily dosing with isepamicin is as effective as twice- daily dosing with amikacin.

Topics: Abdomen; Adult; Aged; Amikacin; Anti-Bacterial Agents; Bacteremia; Drug Administration Schedule; Female; Gentamicins; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Prospective Studies; Respiratory Tract Infections; Skin Diseases, Bacterial; Urinary Tract Infections

In order to reduce the dosage of aminoglycoside in the treatment of patients with complicated urinary tract infections (UTI) in outpatient clinics and to improve cost benefits, we tried both ofloxacin (OFX) treatment and a combination treatment with OFX and a single dose of aminoglycoside (isepamicin). Both groups showed the same cure rate on day 5, but the bacteriuria elimination rate on day 1 was slightly higher in the isepamicin-OFX group. The recurrence rate on days 7-14 did not differ between the groups. This aminoglycoside-OFX treatment did not show significantly higher effectiveness against complicated UTI but resulted in earlier elimination of bacteriuria. These results suggest that this combination therapy may be cost effective in treating complicated UTI, because of the shorter treatment period required.

Topics: Administration, Oral; Adolescent; Aged; Bacteriuria; Drug Therapy, Combination; Gentamicins; Humans; Injections, Intramuscular; Male; Middle Aged; Ofloxacin; Recurrence; Remission Induction; Urinary Tract Infections

HAPA-B was administered intramuscularly to 20 patients with complicated urinary tract infections to evaluate its clinical effects and safety in conformity with the estimations of efficacy of antimicrobial agents standardized by the UTI Committee. The overall clinical efficacy was excellent in 5 patients, moderate in 8 patients and poor in 7 patients. The effectiveness rate was 65.0%. Overall clinical efficacy as classified by type of infection was 66.7% in 12 patients with a single infection, and 62.5% in 8 patients with mixed infection. Bacteriological studies showed that 29 of the 34 strains isolated from the urine of the 20 patients were completely eradicated, and that the bacteriological response was 85.3%. The following side effects were detected in both blood chemistry checks and clinical symptoms. Peripheral blood examinations showed an increase in eosinophil level in one patient. Kidney function tests revealed a slight elevation of s-creatinine in this patient, too. In another patient, eruptions developed on his body on the 2nd day, but it was not necessary to discontinue the administration of HAPA-B.

Topics: Adult; Aged; Aged, 80 and over; Clinical Trials as Topic; Drug Resistance, Microbial; Enterococcus faecalis; Escherichia coli; Female; Gentamicins; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Serratia marcescens; Urinary Tract Infections

To assess the usefulness of single dose treatment with isepamicin (ISP) against chronic complicated urinary tract infection (CC-UTI), laboratory and clinical studies were carried out. The results are summarised as follows. 1. Serum concentrations. Serum concentrations of the drug were assayed for patients after the administration of ISP at a dose of 400 mg by intravenous drip infusion for 30 or 60 minutes. Patients tested consisted of 3 groups with different degrees of renal functions (Ccr: ml/min); 1) normal, 130.8, 2) slightly impaired, 70.8, 3) moderately impaired, 45.9. When the peak/trough concentrations in the 3 groups were compared on 1st-2nd day/5th-6th day of the administration, no significantly different values were recognized among the 3 groups in the peak/trough concentrations. 2. Clinical efficacy Twenty three patients including 18 (78%) patients over 61 years of age were treated at a dose of 400 mg once a day for 4-10 days. Of 21 evaluable cases, 15 (71%) were evaluated as excellent or moderate according to the Japanese UTI criteria. Against the clinical isolates, 21 (68%) out of 31 strains were eradicated after the treatment. 3. Safety Neither subjective side reactions nor clinical abnormal values were encountered throughout the treatment. 4. Conclusions The clinical effectiveness of daily single dose treatment with ISP (400 mg once a day, i.v.d.) was considered to be almost comparable to the treatment with 200 mg twice a day. Furthermore, since no problems on safety were noted even in treating aged patients with slight to moderate renal impairments, the drug appears to be evaluated as highly useful.

Topics: Adult; Aged; Aged, 80 and over; Chronic Disease; Drug Administration Schedule; Drug Evaluation; Female; Gentamicins; Humans; Infusions, Intravenous; Male; Middle Aged; Urinary Bladder Neoplasms; Urinary Tract Infections