netilmicin and Neoplasms

The authors had for aim to assess the effectiveness and toxicity of a piperacillin-tazobactam-netilmicin combination, and the possibility of avoiding using glycopeptide, in children with febrile neutropenic episodes induced by chemotherapy.. A retrospective study was made, including children treated for a febrile neutropenic episode (absolute neutrophile count < 0.5 x 10(9)/l) by a piperacillin-tazobactam-netilmicin combination. If fever persisted 48 hours after the beginning of antibiotic therapy, a glycopeptide could be added. The responses to the treatment were defined as follows: 1) total success (no fever or documented infection) at 48 hours and at 72 hours following the beginning of treatment; 2) partial success (apyrexia beyond 72 hours without any therapeutic change); 3) failure (persistent infectious signs 48 hours after the introduction of glycopeptide).. Sixty-nine episodes were assessable, corresponding to 41 patients, treated for a solid tumour (29), an acute leukaemia in remission (11), or a metabolic disease (1). The febrile episodes were divided into fever of unknown origin (71%), microbiologically documented fever (12%), and clinically documented fever (17%). No death occurred, no toxicity was reported. With this antibiotic therapy, total success at 72 hours was observed in 72% in case of fever of unknown origin and 45% in case of documented infections. The success rate reached 84% when a glycopeptide was added (30% of the cases).. The piperacillin-tazobactam-netilmicin combination is very effective and well tolerated in probabilistic treatment of febrile neutropenia induced by chemotherapy, but does not allow to decreasing the frequency of glycopeptide administration.

Topics: Adolescent; Anti-Bacterial Agents; Antineoplastic Agents; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Drug Combinations; Drug Evaluation; Escherichia coli Infections; Female; Fever; Fever of Unknown Origin; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Male; Neoplasms; Netilmicin; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Postoperative Complications; Retrospective Studies; Treatment Outcome; Urinary Tract Infections

The aim of this study was to evaluate the efficacy and safety of meropenem plus amikacin compared with piperacillin-tazobactam plus netilmicin for initial empirical antibiotic treatment of high-risk febrile neutropenia in children with cancer. Patients with hematologic malignancy (leukemia or stage III/IV non-Hodgkin lymphoma) who presented with fever and neutropenia (ANC < 500/mm3) and patients with solid tumors who presented with fever and severe neutropenia (ANC < 100/mm3) were considered to be at high risk and eligible for this study. In this prospective study, 33 patients with 50 febrile neutropenic episodes received i.v. neropenem (20 mg/kg every 8 h) plus amikacin (15 mg/kg/d in 2 divided doses) (in 31 episodes) or piperacillin/tazobactam (100 mg/4 mg/kg every 8 h) plus netilmicin (7 mg/kg every 24 h) (in 19 episodes). Clinical response was determined at 72 h and at completion of the therapy. The groups were comparable in terms of age, sex, initial ANC, use of growth factors, and classification of the infections. An infection was documented microbiologically in 12 episodes (39%) in the meropenem plus amikacin group and in 8 episodes (42%) in the piperacillin/tazobactam plus netilmicin group. Of the 22 microbiological isolates, 37% were gram-positives, 45% were gram-negatives, and 18% were fungi. Most of the clinically documented infections were of lower respiratory tract, gastrointestinal mucosa, or urinary tract origin. The mean duration of neutropenia was 9 days in both groups. Fever persisted for 1-30 days (mean 3 vs. 5 days). The success rate with initial empiric therapy was 52% in the meropenem plus amikacin and 42% in the piperacillin/tazobactam plus netilmicin group, respectively (p = .5). Total success rate (with or without modification) was 97% vs. 90% in the episodes. Three patients died due to infection (1 vs. 2 patients). No major adverse effects were observed in each group. Empirical therapy with meropenem plus amikacin or piperacillin/tazobactam plus netilmicin for high-risk febrile neutropenia is equally effective and safe in pediatric cancer patients.

Topics: Amikacin; Anti-Bacterial Agents; Drug Therapy, Combination; Fever; Fungi; Gram-Negative Bacteria; Gram-Positive Bacteria; Hematologic Neoplasms; Humans; Infections; Meropenem; Neoplasms; Netilmicin; Neutropenia; Penicillanic Acid; Piperacillin; Tazobactam; Thienamycins

Infection remains the major cause of morbidity and mortality in immunocompromised children with malignancy. In addition, the economic impact of antibiotic treatment should always be evaluated, especially in developing countries. In our center between January 1998 and January 1999, 73 children with hematological malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML)]; 9 children with solid tumors (rhabdomyosarcoma, neuroblastoma) had 87 febrile neutropenic episodes (related to chemotherapy). These children were randomized prospectively into three treatment groups. The first group (n: 28) received cefepime plus netilmicin, while the second group (n: 29) was treated with ceftazidime plus amikacin and the third (n: 30) with meropenem as monotherapy. The aim of the study was to compare the success rates and cost of fourth generation cephalosporin plus aminoglycoside and monotherapy of meropenem with ceftazidime plus amikacin, which is the standard therapy for febrile neutropenia. Microbiologically documented infections were 29.9%, clinically documented infections were 9.2% and 60.9% of the febrile neutropenic episodes were considered to be FUO. Gram-positive microorganisms were the most commonly isolated agents from blood cultures [MRSA (Methicillin Resistant Staphylococcus aureus) in 6 patients and MSSA (Methicillin Sensitive Staphylococcus aureus) in 4 patients]. The success rates were 78.5%, 79.3% and 73.3 % for the 1st, 2nd and 3rd groups respectively. In 4 patients (4.5%) fever responded only to amphotericin-B therapy. There was no statistically significant difference between the three treatment regimens with respect to efficacy, safety and tolerance (chi2 test, p>0.05), but while the third and fourth generation cephalosporins + aminoglycosides were comparable for cost, the monotherapy regimen was the most expensive. The main determining factors for the choice of treatment of febrile neutropenic children, especially in a developing country, are cost, presence of indwelling catheter and the bacterial flora of the unit, as well as efficacy.

Topics: Adolescent; Adult; Amikacin; Cefepime; Cephalosporins; Child; Child, Preschool; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Fever; Humans; Infant; Male; Meropenem; Neoplasms; Netilmicin; Neutropenia; Prospective Studies; Thienamycins; Turkey

To study the pharmacokinetics of netilmicin in Chinese haematology-oncology patients and to determine the pharmacokinetic differences, if any, between this patient subpopulation of Chinese and Caucasians.. A prospective study was carried out in the adult oncology unit of a major hospital in Hong Kong. During a 6 week period in 1997, all patients commencing on netilmicin therapy were monitored; the patients' demographics, clinical status, netilmicin dose and regimen, and drug administration/blood sampling time were collected. Pharmacokinetic parameters were generated using the USC*PACK package based on specifics of the patients themselves and Caucasians matched for the same patients' parameters using the Bayesian alogrithms.. A total of 22 patients were enrolled into the study. Twenty-nine sets of levels were drawn, but only 25 sets from 18 patients (86%) were interpretable. The predicted peak (7.47+/-1.46 microg ml-1 ) and trough levels (1.39+/-0.96 microg ml-1 ) generated by USC*PACK were found to be significantly higher than the levels observed (6.01+/-1.14 microg ml-1 and 0.93+/-0.71 microg ml-1, respectively). Netilmicin clearance, volume of distribution and rate of elimination were all significantly higher in this Chinese subpopulation than those predicted for matched Caucasians. Conclusion Alterations in the netilmicin pharmacokinetics observed in our study population might be related to the disease state and/or ethics of the study patient population. Direct application of Caucasian based population pharmacokinetic parameters to this subgroup of Chinese patients may not be appropriate and may result in underdose.

Topics: Adolescent; Adult; Aged; Asian People; Female; Gentamicins; Hong Kong; Humans; Male; Middle Aged; Neoplasms; Netilmicin; Prospective Studies

A prospective, randomized study was conducted to determine if recombinant human granulocyte-macrophage colony-stimulating factor (rh-GMCSF) (Escherichia coli-derived) could improve response rates to antibiotic therapy and shorten the duration of neutropenia in cancer patients.. A total of 107 febrile neutropenic cancer patients were randomly assigned to empiric therapy with ticarcillin-clavulanate (4 g ticarcillin + 0.1 g clavulanate i.v. every 4 hours) plus netilmicin (2 mg/kg i.v. every 8 hours) with or without rh-GMCSF (3 micrograms/kg per day i.v.). Clinical improvement, duration of neutropenia, and toxicity were monitored.. Addition of rh-GMCSF to the antibiotics significantly improved the response rate (96% versus 82%, P = 0.03), but not the survival rate (93% versus 93%), in the evaluable patients. This difference in response rate was not significant when considering all patients in an intent-to-treat analysis. The number of patients who recovered from severe neutropenia ( < 100 cells/microliter) during the period of observation in the study was significantly greater among patients receiving the colony-stimulating factor, although the median duration of neutropenia was not affected. Superinfections and subsequent infections were not significantly different among the two treatment regimens. Side effects were more common among patients treated with the colony-stimulating factor.. Our data do not support the routine administration of rh-GMCSF with antibiotics for patients with fever and neutropenia. Further studies should be conducted to identify those patients most likely to benefit from rh-GMCSF therapy, such as patients with persistent profound neutropenia and refractory infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Clavulanic Acid; Clavulanic Acids; Drug Administration Schedule; Drug Combinations; Escherichia coli; Fever; Gentamicins; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Middle Aged; Neoplasms; Netilmicin; Neutropenia; Penicillins; Prospective Studies; Remission Induction; Superinfection; Survival Rate; Ticarcillin

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Drug Therapy, Combination; Female; Fever; Gentamicins; Humans; Male; Neoplasms; Netilmicin; Neutropenia; Pefloxacin; Teicoplanin

In a comparative randomized trial, teicoplanin 5 mg/kg plus either netilmicin 5 mg/kg or pefloxacine 10 mg/kg was administered in a once daily empiric therapy to 40 cancer patients with fever and neutropenia after cytotoxic chemotherapy. Both regimens were analyzed with respect to the localisation of the underlying disease, catheter presence and agents isolated from blood culture. The cure and improvement rate were 80% (teicoplanin plus netilmicin) and 85% (teicoplanin plus pefloxacin), with no statistically significant difference between the groups. Teicoplanin with either an aminoglycoside or a quinolone administered once daily seems to be a suitable approach in empiric therapy for fever in neutropenia and may prevent catheter insertion in cancer patients.

Topics: Adult; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Humans; Leukemia, Myeloid, Acute; Male; Neoplasms; Netilmicin; Neutropenia; Pefloxacin; Teicoplanin

In a prospective, randomized trial, netilmicin given once daily (OD) was compared in terms of efficacy and safety with the conventional 8-hourly dosing regimen (TD), both in combination with a broad spectrum beta-lactam, as initial empirical therapy for febrile neutropenic patients; the total daily dosage of netilmicin in each group was 6 mg/kg body weight. Twenty-nine of the 116 (25%) evaluable patients had microbiologically documented septicaemia, most of which were caused by Gram-positive bacteria, 41 (35%) had microbiologically documented infection without bacteraemia and 46 (40%) had possible infection. Highest peak serum concentrations of netilmicin in the OD group were significantly higher and trough serum concentrations significantly lower than in the TD group. A multivariate analysis revealed that neither the dosage regimen nor the peak serum concentration of netilmicin were determinants of a favourable outcome. The response rates of both groups to the initial treatment regimens were comparable and increased similarly following modification of the initial therapy. Response rates were particularly poor in patients with lower respiratory tract infection and in those who remained neutropenic throughout the course of treatment. The incidence of nephrotoxicity was low and did not differ significantly between groups. Once-daily dosing of netilmicin appears to be as effective and as safe as thrice-daily dosing, but is unlikely to further improve the response of febrile neutropenic patients to empirical therapy.

Topics: Anemia, Aplastic; Anti-Bacterial Agents; beta-Lactams; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Neoplasms; Netilmicin; Neutropenia; Prospective Studies

The pharmacologic parameters and toxicity of netilmicin (6 mg/kg/day) given once daily (qd) or thrice daily (tid) for the treatment of urinary tract infections were studied in a randomized prospective study of 60 cancer patients. The overall efficacy was 96%. Nephrotoxicity, assessed by the measure of urinary excretion of phospholipids, was lower for the patients receiving the qd regimen than for those receiving the tid regimen. Elevation of serum creatinine (20% over baseline) occurred in one patient receiving the qd regimen and in three receiving the tid regimen. Cochleotoxicity, assessed by pure-tone audiometry (250 to 18,000 Hz) occurred in one patient receiving the qd regimen and none receiving the tid regimen. Concentrations in sera were measured on days 1 and 5. No significant accumulation was observed in either group. Median serum bactericidal titers, expressed as reciprocal values (percentage of the sera with a titer greater than or equal to 8), were measured against 25 test organisms in samples collected 6 h after the administration of netilmicin and were, for the qd group, 16 (82%) against members of the family Enterobacteriaceae and less than 2 (8%) against Pseudomonas aeruginosa, and for the tid group, 4 (57%) against members of the Enterobacteriaceae and less than 2 (0%) against P. aeruginosa. The rate of killing in serum was rapid (2 to 3 log in 2 h against P. aeruginosa; 3 to 5 log in 2 h against members of the Enterobacteriaceae) and correlated with the sampling time and hence the concentration in serum of netilmicin. The duration of the postantibiotic effect in serum depended also on the strain and the sampling time of the serum.

Topics: Adult; Aged; Aged, 80 and over; Bacteria; Blood Bactericidal Activity; Cochlea; Female; Hearing Disorders; Humans; Kidney Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Netilmicin; Urinary Tract Infections

Efficacy of the cephalosporin, ceftriaxone, was compared with that of the combination of the aminoglycoside, netilmicin, and the penicillin, azlocillin, in the treatment of febrile episodes in immunocompromised neutropenic children undergoing chemotherapy for neoplastic disease. During 100 separate febrile episodes, 40 strains of bacteria were isolated from the blood of 34 patients and a further 55 strains from other sites. Nine strains (four of which were staphylococci) to both netilmicin and azlocillin. There was no difference in clinical response between the two therapeutic regimens as assessed 4 and 7 days after treatment began. Ceftriaxone had the considerable practical advantages of once daily dosage without a need for blood monitoring. Ceftriaxone would appear to be effective as initial monotherapy in the treatment of bacterial infections in severely neutropenic children.

Topics: Adolescent; Agranulocytosis; Azlocillin; Bacteria; Bacterial Infections; Ceftriaxone; Child; Child, Preschool; Fever; Humans; Infant; Neoplasms; Netilmicin; Neutropenia; Randomized Controlled Trials as Topic

We prospectively compared the efficacy and safety of netilmicin sulfate or tobramycin sulfate in conjunction with piperacillin sodium in 118 immunocompromised patients with presumed severe infections. The two treatment regimens were equally efficacious. Nephrotoxicity occurred in a similar proportion in patients treated with netilmicin and tobramycin (17% vs 11%). Ototoxicity occurred in four (9.5%) of 42 netilmicin and piperacillin and in 12 (22%) of 54 tobramycin and piperacillin-treated patients. Of those evaluated with posttherapy audiograms, three of four netilmicin and piperacillin-treated patients had auditory thresholds return to baseline compared with one of nine tobramycin and piperacillin-treated patients. The number of greater than or equal to 15-dB increases in auditory threshold as a proportion of total greater than or equal to 15-dB changes (increases and decreases) was significantly lower in netilmicin and piperacillin- vs tobramycin and piperacillin-treated patients (18 of 78 vs 67 of 115). We conclude that aminoglycoside-associated ototoxicity was less severe and more often reversible with netilmicin than with tobramycin.

Topics: Adult; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Drug Therapy, Combination; Hearing Loss; Humans; Immune Tolerance; Infections; Middle Aged; Neoplasms; Netilmicin; Piperacillin; Prospective Studies; Random Allocation; Tobramycin

For the treatment of febrile episodes in granulocytopenic cancer patients, a combination of bactericidal and intravenously administered broad spectrum agents is recommended. An aminoglycoside plus a beta-lactame (piperacillin, azlocillin or IIIrd generation cephalosporins) are the drugs of first choice in an empiric approach. Because of frequent parenteral interventions (e.g. catheters, cannulations) in thrombopenic patients with multifactorial immunosuppression, we consider the application of once daily drugs, such as ceftriaxone, netilmicin or amikacin. For single dose treatment (1st day two applications), we used ceftriaxone in combination with netilmicin or amikacin as the first approach and retrospectively evaluated 47 patients for efficacy and safety.

Topics: Adult; Agranulocytosis; Amikacin; Bacterial Infections; Ceftriaxone; Drug Therapy, Combination; Female; Fever; Humans; Male; Middle Aged; Neoplasms; Netilmicin; Retrospective Studies

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Agranulocytosis; Bacterial Infections; Drug Therapy, Combination; Humans; Middle Aged; Neoplasms; Netilmicin; Spiramycin

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; Female; Gentamicins; Humans; Male; Middle Aged; Neoplasms; Netilmicin

Topics: Amikacin; Aminoglycosides; Bacterial Infections; Carbenicillin; Gentamicins; Humans; Microbial Sensitivity Tests; Neoplasms; Netilmicin; Penicillin Resistance; Penicillins; Ticarcillin; Tobramycin

Ninety-two patients with cancer with 100 infectious episodes were treated with netilmicin sulfate, a new aminoglycoside. Netilmicin was administered intravenously, either intermittently or by continuous infusion. The overall cure rate was 60%. Gram-negative bacilli were the most common causative organisms and the response rate for these infections was 32/53 (60%). The most common pathogens were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Pneumonia, urinary tract infection, and septicemia were the most common types of infection treated and the response rates were 23/47 (49%), 19/21 (90%), and 9/17 (53%), respectively. Nephrotoxicity occurred in ten patients (6%) who had normal renal function initially. Netilmicin is an effective aminoglycoside with a spectrum of antibacterial activity similar to that of gentamicin sulfate and it appears to be less nephrotoxic.

Topics: Bacterial Infections; Escherichia coli Infections; Gentamicins; Humans; Injections, Intravenous; Klebsiella Infections; Neoplasms; Netilmicin; Pseudomonas Infections