isepamicin and Fever

The pharmacokinetics (PK) of isepamicin were studied in 8 febrile neutropenic patients with hematologic malignancy and in 20 young women with acute pelvic inflammatory disease (PID). Isepamicin was given as a slow intravenous infusion over 30 min at a dose of 15 mg/kg once daily (OD). Serum levels of isepamicin were determined by fluorescence polarization immunoassay, and PK analyses were obtained based on a one-compartment open model after 24 hours (steady state) and after 7 days. On day 1, the volume of distribution (Vd) of isepamicin, for both populations, appeared about 30% higher than classically reported in healthy individuals: 0.31 and 0.36 L/kg for neutropenic and PID patients respectively. However on day 7, Vd displayed significant reduction (0.28 and 0.27 L/kg, respectively for neutropenic and PID patients). A reduction of isepamicin clearance was also observed between day 1 and day 7 (137 vs 120 mL/min and 130 vs 101 mL/min for neutropenic and PID populations, respectively). Such changes are consistent with a significant increase in the Cmax concentrations (45 vs 50 mg/L, and 38 vs 49 mg/L) and in the AUC (136 vs 158 and 137 vs 162 mg/L.h) observed after a week of treatment in neutropenic and PID patients, respectively. In conclusion, taking into account the importance of reaching early active concentrations, we recommend the use of higher loading dose of isepamicin (>15 mg/kg) in neutropenic cancer patients and in women with PID, particularly in case of a combination with a possibly ineffective antibacterial agent, in case of infection with bacteria at upper limit of susceptibility, in the presence of high infectious inoculum or in the presence of sequestered sites of infection.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Area Under Curve; Female; Fever; Gentamicins; Hematologic Neoplasms; Humans; Infusions, Intravenous; Middle Aged; Neutropenia; Pelvic Inflammatory Disease

The efficacy and safety of isepamicin at 7.5 mg/kg i.v. q 12 h was prospectively compared with that of amikacin at the same dose for the treatment of febrile neutropenic children with malignancies. Thirty-nine patients were enrolled in the study; 25 received isepamicin and 14 amikacin. Clinical and bacteriological response rates were 100% for both groups. No adverse events occurred. Median peak serum levels were 19.7 mg/l for isepamicin and 19.20 mg/l for amikacin. Median trough serum levels were 0.72 mg/l for isepamicin and 0.68 mg/l for amikacin. It was concluded that isepamicin was as effective and safe as amikacin for the treatment of febrile neutropenic children with malignancies, and might be used in areas where resistance to other aminoglycosides is a problem.

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Fever; Gentamicins; Humans; Male; Neoplasms; Neutropenia; Random Allocation

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