isepamicin and Bacteremia

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

Aminoglycosides possess in vitro activity against aerobic and facultative Gram-negative bacilli. However, nationwide surveillance on susceptibility data of Acinetobacter baumannii complex and Pseudomonas aeruginosa to aminoglycosides was limited, and aminoglycoside resistance has emerged in the past decade. We study the in vitro susceptibility of A. baumannii complex and other nonfermentative Gram-negative bacilli (NFGNB) to aminoglycosides.. A total of 378 NFGNB blood isolates causing healthcare-associated bloodstream infections during 2008 and 2013 at four medical centers in Taiwan were tested for their susceptibilities to four aminoglycosides using the agar dilution method (gentamicin, amikacin, tobramycin, and isepamicin) and disc diffusion method (isepamicin).. A. baumannii was highly resistant to all four aminoglycosides (range of susceptibility, 0-4%), whereas >80% of Acinetobacter nosocomialis and Acinetobacter pittii blood isolates were susceptible to amikacin (susceptibility: 96% and 91%, respectively), tobramycin (susceptibility: 92% and 80%, respectively), and isepamicin (susceptibility: 96% and 80%, respectively). All aminoglycosides except gentamicin possessed good in vitro activity (>94%) against P. aeruginosa. Amikacin has the best in vitro activity against P. aeruginosa (susceptibility, 98%), followed by A. nosocomialis (96%), and A. pittii (91%), whereas tobramycin and isepamicin were less potent against A. pittii (both 80%). Aminoglycoside resistances were prevalent in Stenotrophomonas maltophilia and Burkholderia cepacia complex blood isolates in Taiwan.. Genospecies among the A. baumannii complex had heterogeneous susceptibility profiles to aminoglycosides. Aminoglycosides, except gentamicin, remained good in vitro antimicrobial activity against P. aeruginosa. Further in vivo clinical data and continuous resistance monitoring are warranted for clinical practice guidance.

Topics: Acinetobacter baumannii; Amikacin; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Burkholderia cepacia; Cross Infection; Drug Resistance, Bacterial; Gentamicins; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Stenotrophomonas maltophilia; Tobramycin

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