isepamicin and Klebsiella-Infections

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

The efficacy and safety of isepamicin 7.5 mg/kg of body weight twice daily or amikacin the same dosage regimen for the treatment of various infections in neutropenic and non-neutropenic paediatric patients were compared in a prospective randomised trial. In total, 306 patients were enrolled and received at least one dose of randomised treatment (204 isepamicin, 102 amikacin: intent-to-treat population); 181 patients satisfied all criteria for evaluability (120 isepamicin, 61 amikacin: efficacy population). Clinical cure or improvement rates in the isepamicin and amikacin groups were: intent-to-treat population, 188/204 (92%) and 94/102 (92%), respectively; efficacy population, 117/120 (98%) and 58/61 (95%), respectively. The bacteriological elimination rate (efficacy population) in the isepamicin and amikacin treatment groups was 75/76 (99%) vs 35/38 (92%). Nephrotoxicity, defined as an increase in serum creatinine of 0.5 mg/dL or > or = 44.2 mumol/L from baseline, occurred in 4/187 (2%) and 1/191 (1%) children treated with isepamicin and amikacin, respectively. Definite ototoxicity at the > or = 20 dB threshold occurred in 3 (1 isepamicin and 2 amikacin) out of 56 children evaluated with at least two audiograms. Thus isepamicin was as effective and as well tolerated as amikacin in the treatment of various infections in paediatric patients.

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Drug Administration Schedule; Enterococcus faecalis; Escherichia coli Infections; Female; Gentamicins; Humans; Infant; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Male; Staphylococcal Infections; Staphylococcus epidermidis; Streptococcal Infections

We recently experienced the case of an intramuscular chloroma with infection in a 7-year-old boy diagnosed with acute myeloid leukemia. Conventional magnetic resonance imaging (MRI) showed that the lesion mimicked an abscess, but diffusion-weighted imaging showed no diffusion restriction. These results suggested that the interior cystic portion was serous. On histopathological findings, a chloroma was diagnosed on the wall of a mass. Culture of the interior fluid revealed that Klebsiella pneumoniae was present. MRI differentiation is difficult even with diffusion-weighted images.

Topics: Anti-Bacterial Agents; Antimetabolites, Antineoplastic; Child; Contrast Media; Cytarabine; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Gentamicins; Humans; Image Enhancement; Klebsiella Infections; Klebsiella pneumoniae; Leg; Leukemia, Myeloid, Acute; Magnetic Resonance Imaging; Male; Meropenem; Muscle Neoplasms; Necrosis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sarcoma, Myeloid; Teicoplanin; Thienamycins; Treatment Outcome

The effect of production of the aminoglycoside 6'-N-acetyltransferase [AAC(6')-IB] in Klebsiella pneumoniae on the outcome of amikacin and isepamicin treatment of rabbits with experimental endocarditis was assessed. Isogenic high-level (Hi) and low-level (Lo) AAC(6')-Ib-producing transconjugants (T) were constructed from clinical isolates with plasmid-borne resistance determinants. The MICs of amikacin and isepamicin, their bactericidal effects, and AAC(6')-Ib production appeared to be well correlated among the clinical isolates and the transconjugants. The susceptibility data determined in vitro, with MICs (in micrograms per milliliter) of amikacin and isepamicin for LoT and HiT of 4 and 0.5 and 32 and 8, respectively, were, however, not predictive of the in vivo efficacies of the drugs. While amikacin and isepamicin caused reductions in bacterial densities (log10 CFU per gram of cardiac vegetation) of 5.1 and 4.8 of the fully susceptible recipient strain (MICs of amikacin and isepamicin, 0.5 and 0.25, respectively), the reductions in density of both LoT and HiT caused by the two drugs (2.7 and 2.4 and 2.9 and 2.2, respectively) were only marginally significant, if at all. There was no significant difference (P > 0.05) when the reductions in density of LoT and HiT by either drug were compared or when the efficacies of the two drugs in reducing the density of any strain [non-AAC(6')-producing, LoT, or HiT] were compared (P > 0.5). It is concluded that AAC(6')-Ib in K.pneumoniae, even when produced at a low level and not conferring resistance to amikacin and isepamicin in vitro, compromises the efficacies of both drugs in vivo and possibly does so beyond the experimental model studied here.

Topics: Acetyltransferases; Amikacin; Animals; Anti-Bacterial Agents; Colony Count, Microbial; Drug Resistance, Microbial; Endocarditis; Female; Genes, Bacterial; Gentamicins; Klebsiella Infections; Klebsiella pneumoniae; Male; Mice; Rabbits