isepamicin and Gram-Negative-Bacterial-Infections

We sought to review the potential role of isepamicin against infections with contemporary Gram-negative bacteria. We searched PubMed and Scopus databases to identify relevant microbiological and clinical studies published between 2000 and 2010, and we retrieved 11 and three studies, respectively. A total of 4901 isolates were examined in the in vitro studies. Isepamicin had higher in vitro activity compared with amikacin in four studies, was as active as amikacin in six studies and in the remaining study both were inactive. Regarding specifically the studies that included multidrug-resistant bacteria, isepamicin appeared superior to amikacin in two studies, as active as amikacin in one study and both did not exhibit activity in one study. In the clinical studies, isepamicin was as active as amikacin for the treatment of 55 children with urinary tract infections. In conclusion, isepamicin might be active in vitro against Gram-negative bacteria with resistance to amikacin and other aminoglycosides.

Topics: Adult; Amikacin; Anti-Bacterial Agents; Child; Child, Preschool; Databases, Bibliographic; Drug Administration Schedule; Drug Resistance, Bacterial; Gentamicins; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infant; Microbial Sensitivity Tests

Isepamicin is a new aminoglycoside with in-vitro activity superior to amikacin. It is a poor substrate for the 6'-aminoacetyltransferase-I enzyme which inactivates amikacin and therefore organisms possessing this enzyme are not resistant to isepamicin. The aim of this study was to compare the efficacy and safety of co-administration of isepamicin once daily plus ceftriaxone to amikacin twice daily plus ceftriaxone to amikacin twice daily plus ceftriaxone in febrile neutropenic cancer patients. Febrile episodes in 235 patients (156 in isepamicin group and 79 in amikacin group) were treated in this study. They occurred in 218 different patients. Fifteen patients were enrolled twice and one three times. Response rates to the two treatment regimens for microbiologically documented episodes, clinically documented episodes and further unexplained fever were similar. Tolerance of the treatment regimens, as measured by serum creatinine levels, hypoaccousia and cutaneous allergy was also similar in both treatment groups. In conclusion, isepamicin given once daily when combined with ceftriaxone in the treatment of febrile episodes in neutropenic cancer patients was as effective and no more toxic than amikacin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Bone Marrow Transplantation; Ceftriaxone; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Gentamicins; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Superinfection

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

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

Isepamicin is a new aminoglycoside antibiotic which possesses greater stability to aminoglycoside-inactivating enzymes compared with other available aminoglycosides. In this prospective, randomised, open trial, the safety and efficacy of intravenous administration of isepamicin was compared with that of intravenous amikacin in seriously ill adults with nosocomial pneumonia or septicaemia. Each study aminoglycoside was administered concurrently with ceftazidime or imipenem. Patients were randomised to receive isepamicin 15 mg/kg once daily, isepamicin 7.5 mg/kg twice daily or amikacin 7.5 mg/kg twice daily. For patients with nosocomial pneumonia, the proportions of patients in the intent-to-treat population (n = 130) who were clinically cured at the end of treatment were similar in each treatment group: 18/44 (41%) isepamicin once daily; 19/45 (42%) isepamicin twice daily; and 17/41 (42%) amikacin. Corresponding results for the efficacy population (n = 58) were: 12/20 (60%) isepamicin once daily; 14/21 (67%) isepamicin twice daily; 9/17 (53%) amikacin. In patients with septicaemia, clinical cure was achieved in 8/10 (80%) patients treated with isepamicin once daily, compared with 8/13 (62%) patients who received isepamicin twice daily, and 7/12 (58%) patients treated with amikacin. For both diagnoses, there were no statistically significant differences between the treatment groups in clinical cure rate. The most commonly isolated target pathogen was Pseudomonas aeruginosa. For both nosocomial pneumonia and septicaemia, the proportion of patients in the intent-to-treat population whose pretreatment valid target pathogens were eliminated was similar in each treatment group. In total, 51 patients (30%) died during study, mostly due to disease progression or complications, or concurrent illness. All three treatment regimens were well tolerated. The proportion of patients experiencing at least one adverse event was 11%, 25% and 9% for isepamicin once daily, isepamicin twice daily and amikacin, respectively. The incidence of ototoxicity and nephrotoxicity was relatively low in both treatment groups.

Topics: Amikacin; Anti-Bacterial Agents; Bacteremia; Cross Infection; Drug Therapy, Combination; Female; Gentamicins; Gram-Negative Bacterial Infections; Humans; Lactams; Male; Middle Aged; Pneumonia, Bacterial; Prospective Studies

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

The alarmingly increasing resistance rates among non-fermenting Gram-negative species, particularly Pseudomonas aeruginosa and Acinetobacter baumannii, intensified the interest in alternative antibiotic treatment options. Isepamicin, an old aminoglycoside, may play a role in the treatment of patients with infections caused by those multi-drug resistant pathogens. We evaluated the antimicrobial activity of isepamicin against non-fermenting Gram-negative isolates collected of the microbiological laboratory at the University Hospital of Heraklion, Crete, Greece from 2004 to the first trimester of 2011. We tested a total of 4,219 isolates (66.2 % Pseudomonas spp., 30 % Acinetobacter spp., 3.8 % other non-fermenters). The lower respiratory tract, pus, and urine were the most frequent sites of isolation (29.7 %, 19.9 %, and 12.9 %, respectively). Overall, 2768 (65.6 %) of the evaluated isolates were susceptible to isepamicin (including 79.9 % of Pseudomonas spp, 37.2 % of Acinetobacter spp, 43.1 % of other non-fermenters). Isepamicin exhibited higher antimicrobial activity compared to broad spectrum penicillins, cephalosporins, other aminoglycosides, carbapenems, and fluoroquinolones. Only colistin was more active than isepamicin. Additionally, 41.7 % of carbapenem-resistant and 53.2 % of colistin-resistant P. aeruginosa isolates were susceptible to isepamicin. The susceptibility rates for the respective types of A. baumannii isolates were 12 % and 6.2 %. Yet, isepamicin was active against 29.2 % of A. baumannii that were resistant to all other tested aminoglycosides. Isepamicin exhibits considerable antimicrobial activity against Gram-negative non-fermenters in a region with high antimicrobial resistance. Particularly, isepamicin may provide a therapeutic option for infections from carbapenem- and colistin-resistant P. aeruginosa and other aminoglycoside-resistant A. baumannii. Further modifications in the aminoglycoside molecule may provide formulations with enhanced antimicrobial activity.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Gentamicins; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Greece; Humans; Microbial Sensitivity Tests; Prevalence

Isepamicin is a newly introduced aminoglycoside in Taiwan. Since in vitro data for isepamicin against nosocomial Gram-negative bloodstream infection from Taiwan are limited, we compared the activity of isepamicin, amikacin, gentamicin and tobramycin against nosocomial Gram-negative blood isolates.. A total of 247 non-duplicate nosocomial blood isolates of Gram-negative bacteria collected between January 2003 and December 2003 in a major teaching hospital in Taiwan were tested for their in vitro susceptibilities to gentamicin, tobramycin, amikacin, and isepamicin using the agar dilution method. The isolates included Escherichia coli (31 isolates), Klebsiella pneumoniae (31), Enterobacter cloacae (30), Serratia marcescens (31), Morganella morganii (21), Citrobacter freundii (10), Pseudomonas aeruginosa (31), Acinetobacter baumannii (31), and Stenotrophomonas maltophilia (31).. Overall, isepamicin had high antibacterial activity against the tested Gram-negative bacteria. For the 154 Enterobacteriaceae isolates, isepamicin had the lowest minimum concentration inhibiting 90% of isolates (MIC90) among the tested drugs, while its resistance rate (3.9%) was equal to that of amikacin (3.9%) and lower than those of tobramycin (18.2%) and gentamicin (21.4%). For the 93 of non-fermentative Gram-negative bacilli isolates, isepamicin had the lowest MIC90, and a resistance rate (23.7%) lower than those of amikacin (27.9%), tobramycin (38.7%) and gentamicin (40.9%).. The in vitro activity of isepamicin against Gram-negative bacteria isolates was equal or similar to amikacin and superior to other tested aminoglycosides. In view of its potential for less nephrotoxicity and ototoxicity than other aminoglycosides, isepamicin is a drug of choice for the empirical treatment of nosocomial infections caused by Gram-negative bacteria.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Cross Infection; Gentamicins; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Taiwan

The study of the mechanisms of aminoglycoside resistance in gramnegative pathogens of nosocomial infections in 14 hospitals of Russia showed that the basic mechanism was production of aminoglycoside modifying enzymes, mainly adenylyl transferase ANT(2"), acetyl transferases AAC(3)-V and ACC(6)-I, and phosphotransferases APH(3')-I and APH(3')-VI. In all the hospitals enzymes modifying gentamicin and tobramycin were wide spread while the resistance phenotypes to aminoglycosides were different in separate hospitals. Isepamycin proved to be the most active aminoglycoside. Recommendations for the use of antibiotics in hospital formulas and empiric therapy should be developed on the basis of the local specific features of the resistance in nosocomial pathogens to aminoglycosides.

Topics: Acetyltransferases; Aminoglycosides; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Gentamicins; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infection Control; Nucleotidyltransferases; Phosphotransferases; Russia; Substrate Specificity

Topics: Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Cefepime; Cephalosporins; Ciprofloxacin; Colony Count, Microbial; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Gentamicins; Gram-Negative Bacterial Infections; Microbial Sensitivity Tests; Stenotrophomonas maltophilia; Time Factors