isepamicin and Respiratory-Tract-Infections

Isepamicin is a new aminoglycoside antibiotic which has a superior stability to aminoglycoside-inactivating enzymes compared with other available aminoglycosides. In this multicentre, randomised, open study, the safety and efficacy of isepamicin plus ceftazidime was compared with that of amikacin plus ceftazidime in adults with acute lower respiratory tract infection. Patients with severe infections received intravenous administration of isepamicin 15 mg/kg once daily + ceftazidime 2g twice daily (n = 121) or amikacin 7.5 mg/kg twice daily + ceftazidime 2g twice daily (n = 61). Those with less severe infection received intramuscular or intravenous administration of isepamicin 8 mg/kg once daily + ceftazidime 1g twice daily (n = 56) or amikacin 7.5 mg/kg twice daily + ceftazidime 1g twice daily (n = 28). In the efficacy populations, the proportion of patients clinically cured in the isepamicin group (87/100; 87%) was similar to that in the amikacin group (36/47; 77%). Significantly more patients in the isepamicin group were cured or improved compared with the amikacin group (97% vs 89%; p = 0.042). The difference between treatment groups was also significant in patients with pneumonia (p = 0.05). The most commonly isolated target organisms were Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. The proportion of patients in the efficacy population whose pretreatment valid target organisms were eliminated was similar in each treatment group (90% isepamicin vs 89% amikacin). A retrospective analysis showed there were slightly fewer clinical successes and a higher death rate in patients with nosocomial rather than community acquired pneumonia. Both treatments were well tolerated . Fourteen per cent of isepamicin and 11% of amikacin patients experienced adverse events. The incidence of ototoxicity and nephrotoxicity was low.

Topics: Acute Disease; Amikacin; Anti-Bacterial Agents; Bronchitis; Ceftazidime; Cross Infection; Drug Administration Schedule; Drug Therapy, Combination; Female; Gentamicins; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Pneumonia, Bacterial; Respiratory Tract Infections; Retrospective Studies

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

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

Topics: Bacterial Infections; Cystitis; Gentamicins; Humans; Microbial Sensitivity Tests; Respiratory Tract Infections

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

Topics: Adult; Aged; Aged, 80 and over; Amikacin; Gentamicins; Humans; Middle Aged; Respiratory Tract Infections