isepamicin and Cross-Infection

The alarming epidemic of multidrug-resistant bacteria and the reluctance of the pharmaceutical industry to invest in the development of new antibiotics have forced clinicians to reintroduce forgotten antibiotics into their practice. This review highlights the effectiveness and safety of older antibiotics when used in the treatment of infections of critically ill patients.. Polymyxins emerged as useful antibiotics for the treatment of infections due to multidrug-resistant Gram-negative bacteria, in particular Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae. The nephrotoxicity and neurotoxicity associated with their use are less frequent and serious than previously reported. In addition, aerosolized polymyxins may be a useful weapon in the treatment of hospital-acquired pneumonia. Fosfomycin and chloramphenicol have a wide antimicrobial spectrum, are used extensively in Europe and Africa, respectively, and may have an expanded role in our antimicrobial arsenal. Fusidic acid remains active against various staphylococcal strains, while isepamicin (an aminoglycoside used in some European countries) is slightly more effective than amikacin against some Gram-negative bacteria.. The declining investment of the pharmaceutical industry in the development of new antibiotics and the increasing antimicrobial resistance create a fertile ground for the study and, probably, revival of older antibiotics for use, especially in critically ill patients.

Topics: Anti-Bacterial Agents; Chloramphenicol; Critical Illness; Cross Infection; Drug Resistance, Bacterial; Drug Utilization; Fosfomycin; Fusidic Acid; Gentamicins; Humans; Polymyxins

A population approach was used to determine isepamicin pharmacokinetics in 196 intensive care unit patients treated for nosocomial pneumonia with isepamicin and a broad-spectrum beta-lactam. Patients were randomized in four groups with respect to the following isepamicin dosing regimens: (i) 15 mg/kg od for 5 days or (ii) 10 days, (iii) 25 mg/kg on the first day followed by 15 mg/kg od for 4 days or (iv) 9 days. A total of 1489 serum isepamicin concentrations were measured (median, eight per patient; range, 1-18). Mean +/- S.D. 1 h-peak levels at day 1 were 76 +/- 32 mg/L after the 25 mg/kg dose (n = 85) and 43 +/- 15 mg/L after the 15 mg/kg dose (n = 99). A bicompartmental model was fitted to the data by a mixed-effect modelling approach. Isepamicin clearance was related to age, bodyweight and serum creatinine level. Central volume of distribution was related to bodyweight. Pharmacokinetic parameters were independent of the dosage in the range 15-25 mg/kg and were not different in the patients treated for 5 or 10 days. Bayesian estimates of individual pharmacokinetic parameters were used to calculate various surrogate markers of isepamicin exposure to be tentatively correlated with clinical outcome and nephrotoxicity. No correlation was found between peak, AUC or their ratio with MIC and clinical efficacy. A weak correlation was found between the increase of serum creatinine level (day 1 versus day 5) and isepamicin 24 h trough level at day 1 (R2 = 0.10). These data do not favour a systematic therapeutic monitoring of isepamicin in intensive care unit patients, at least with the doses and antibiotic combinations used in this study.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bayes Theorem; Creatinine; Cross Infection; Dose-Response Relationship, Drug; Female; Gentamicins; Humans; Intensive Care Units; Kidney; Male; Middle Aged; Models, Biological; Pneumonia, Bacterial; Treatment Outcome

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

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

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

Seven bla(IMP-1)-harboring Acinetobacter sp. isolates and one Pseudomonas putida clinical isolate were recovered from hospitalized patients. All isolates possessed a class 1 integron, named In86, carrying the same cassette array [bla(IMP1), aac(6')-31, and aadA1], which was plasmid located in five of the isolates. This report describes the ability of nonfermentative nosocomial pathogens to acquire and disseminate antimicrobial resistance determinants.

Topics: Acinetobacter; Amino Acid Sequence; Aminoglycosides; Anti-Bacterial Agents; Base Sequence; Brazil; Codon, Terminator; Cross Infection; Drug Resistance, Multiple, Bacterial; Gene Transfer, Horizontal; Genes, Bacterial; Hospitals; Humans; Integrons; Microbial Sensitivity Tests; Molecular Sequence Data; Open Reading Frames; Plasmids; Pseudomonas putida; Transcription, Genetic

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

isepamicin is a new aminoglycoside with a spectrum of activity similar to amikacin with an advantage of possessing a high level of stability against different aminoglycoside modifying enzymes. the in vitro susceptibility of nosocomial isolates obtained from patients admitted to the All India Institute of Medical Sciences, New Delhi during October-December, 1999 was tested against isepamicin and compared with other aminoglycosides.. a total of 251 clinical isolates were studied which included Escherichia coli 87, Klebsiella pneumoniae 54, Pseudonomas aeruginosa 38, Staphylococcus aureus 27 (methicillin resistant S. aureus 15, methicillin sensitive S. aureus 12), Acinetobacter species 26, Enterobacter aerogenes 9, Proteus mirabilis 5, Proteus vulgaris 2, and Citrobacter species 3. The minimum inhibitory concentration (MIC) against isepamicin and other aminoglycosides including amikacin, gentamicin, netilmicin and tobramycin was done using NCCLS guidelines. The cut-off values of isepamicin were used as that of amikacin.. we found that overall 153 nosocomial isolates were sensitive to isepamicin as compared to 95 for amikacin in this hospital. Isepamicin showed a superior in vitro activity compared to the other aminoglycosides tested.. isepamicin can be a good alternative in multidrug resistant nosocomial isolates in hospitals where amikacin resistance is emerging.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cross Infection; Drug Resistance, Bacterial; Gentamicins; Humans; In Vitro Techniques; India; Microbial Sensitivity Tests

To evaluate the respective interest of amikacin and isepamicin in P. aeruginosa infection, the resistance level was ascertained using the disk method. Susceptibility was also tested for gentamicin, tobramycin and netilmicin. Isolates came from three surgical units and from two intensive care units. Serotyping was proceeded, and isolates coming from the same patient, with the same susceptibility pattern and the same serotype was included once only: 197 strains were thus obtained. Resistance level was 22.3% for amikacin, and 28.4% for isepamicin. Discrepancies were found in 14.7% of cases (major: 8.1%; minor: 6.6%). Discordant strains were more susceptible to amikacin than to isepamicin in 30/37 cases, and more susceptible to isepamicin in 7/37 cases. This difference was highly significant (paired Chi-2 test: p < 10(-4). The best susceptibility to amikacin was found in all serotypes and units.

Topics: Amikacin; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Microbial; Gentamicins; Humans; Intensive Care Units; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Surgery Department, Hospital

A total of 1896 isolates of Pseudomonas aeruginosa resistant to aminoglycosides and isolated during the period 1983-1989 in two Belgian general hospitals were included in this study. The most frequently encountered O serotypes were O4, O11, O12 and non-typable isolates. The majority of the isolates showed resistance to extended spectrum beta-lactam antibiotics (cefotaxime, ceftriaxone and cefepime). However, a low degree of resistance was found for ceftazidime. By contrast, amikacin and isepamicin, remained active on a significant number of aminoglycoside resistant isolates. In both hospitals, impermeability and AAC(3)II enzyme production were the most prevalent aminoglycoside resistance mechanisms. There were marked differences between the two hospitals with regard to the distribution of the O-serotypes and resistance profiles.

Topics: Amikacin; Anti-Bacterial Agents; Belgium; beta-Lactams; Cross Infection; Drug Resistance, Microbial; Gentamicins; Hospitals; Humans; Pseudomonas aeruginosa; Serotyping