cilastatin--imipenem-drug-combination and Leukemia

Using the envelope method, we allocated 125 patients with infections accompanied by hematopoietic disorders into two groups treated with imipenem/cilastatin sodium (IPM/CS) at a daily dose of 1 g/1 g b.i.d. (group BID) or 0.5 g/0.5 g q.i.d. (group QID), and obtained the following results. 1. In group BID, ANLL was observed in 25 patients; ALL in 6; and NHL in 12. In group QID, ANLL was observed in 27 patients; ALL in 7; and NHL in 13. 2. In group BID, efficacy rates were 54.5% (6/11) in sepsis, 63.0% (17/27) in fever of undetermined origin and 50.0% (4/8) in pneumonia, thus the overall efficacy was 61.8% (34/55). In group QID, efficacy rates were 66.7% (4/6) in sepsis, 76.0% (19/25) in fever of undetermined origin and 35.7% (5/14) in pneumonia, thus the over all was 61.1% (33/54). No significant difference in response rates were observed between the two groups. 3. Bacteriologically, 22 bacterial strains were isolated in group BID and 21 21 strains, in group QID. The eradication rates after treatment with IPM/CS was 100% in group BID and 66.7% in group QID. 4. Side effects were observed in 8 patients in group BID and 3 in group QID. Laboratory examination revealed abnormal values in 9 patients in group BID and 6 in group QID. However, all of the side effects disappeared after the suspension or discontinuation of IPM/CS. The efficacies of IPM/CS therapy for severe infections in patients with hematopoietic disease were similar between 1 g/1 g b.i.d. and 0.5 g/0.5 g q.i.d. groups.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Japan; Leukemia; Lymphoma; Male; Middle Aged

One hundred and thirty-nine consecutive episodes of fever were evaluated in 55 patients with hematological disorders during persistent neutropenia. In 121 instances, patients were given trimethoprim-sulfamethoxazole + amikacin (TMP/SMZ + AMI) as an initial antibiotic regimen with clinical success in 51% (i.e. antibiotic treatment was not changed within the first 7 days). Imipenem/cilastatin (I/C) therapy was instituted in: (a) 22 episodes with clinical failure and fever of unknown origin during TMP/SMZ + AMI therapy and (b) 18 episodes with a second fever episode during initially successful TMP/SMZ + AMI therapy. The response rate for all 40 I/C treated episodes was 80%. One neutropenic patient in the whole series died from infectious complications within four weeks from institution of therapy. TMP/SMZ+AMI seems to be a safe and inexpensive "standard" antibiotic regimen in neutropenic patients. I/C appears to have good efficacy when used as secondary therapy after failure with TMP/SMZ+AMI.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Bacterial Infections; Bone Marrow Transplantation; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Fever; Hematologic Diseases; Humans; Imipenem; Leukemia; Lymphoma; Male; Middle Aged; Neutropenia; Pneumocystis Infections; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination

Imipenem/cilastatin sodium (IPM/CS) was administered to a total of 67 patients with severe infections complicating hematological disorders and solid tumors. Fifty patients are included in the present analysis of efficacy and 64 in that of safety. 1. Out of 31 patients with hematological disorders, responses were excellent in 10 patients, good in 10 patients, and the efficacy rate was 64.5%. Out of 19 patients with solid tumors, responses were excellent in 8 patients, good in 8 patients and the efficacy rate was 84.2%. 2. For patients whose responses to other antibiotics had been poor, the efficacy rate was 59.3% in the group with hematological disorders and 62.5% in the group with solid tumors. 3. The relationship between the neutrophil count and efficacy was studied in the patients with hematological disorders. The efficacy rate for 8 patients whose neutrophil counts were 500/mm3 or less was 75.0%. 4. For the patients with hematological disorders, the efficacy rate for patients from whom causative organisms were isolated was 70.0% and that for patients for whom they were unknown was 61.9%. 5. Adverse reactions were observed in 3 patients and abnormal laboratory test results in 2 patients. However, they were mild and disappeared after discontinuation of this drug. From these results, IPM/CS is considered to be a useful antibiotic for the treatment of severe infections complicating hematological disorders and solid tumors.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Evaluation; Female; Humans; Imipenem; Leukemia; Lymphoma; Male; Middle Aged; Myeloproliferative Disorders; Neoplasms

To study the clinical features and the incidence of early infectious complications following children hematopoietic stem cells transplantation (HSCT).. The clinical data of 29 cases with early infectious complications following HSCT was retrospectively analyzed.. The incidence of early infectious complications following HSCT in 31 children (including 22 cord blood transplantation and 9 peripheral blood stem cells transplantation) was 94% (29/31). The first occurrence of the early infectious complications was at a median of 6 (0 - 22) days, the peak time of incidence was at a median of 4 - 7 days post transplantation. The duration of the first early infectious complications was at a median of 9 (3 - 20) days. The occurrence of the second early infectious complications was at a median of 19 (13 - 27) days. For all of the 29 children, when they developed early infectious complications their absolute neutrophil counts (ANC) were all > 0.5 x 10(9)/L. The most common infectious sites were the digestive tract (oral and gastro-intestinal mucositis) and then the respiratory tract. Gram negative blood infections were quite frequent and Pseudomonas aeruginosa was common in the oral-pharynx discharge cultures. Two children had Mycoplasma pneumonia infections and there were 4 incidences with fever but no definite infectious foci. The incidence and duration of early infectious complications following hematopoietic stem cells transplantation were associated with the duration of neutropenia. The source and the MNCs dose of the graft, the difference of conditioning regimen and GVHD prophylaxis method did not have a significant impact on the incidence and duration of early infectious complications. Antibiotic prophylaxis (including Tienam) could delay the occurrence of the early infections significantly.. The incidence and duration of early infectious complications following hematopoietic stem cells transplantation were directly associated with the duration of neutropenia. Tienam regimen could postpone the early infections incidence and had effect of preventing the early infectious complications.

Topics: Adolescent; Antibiotic Prophylaxis; Child; Child, Preschool; China; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Hematopoietic Stem Cell Transplantation; Humans; Imipenem; Incidence; Infections; Leukemia; Male; Retrospective Studies; Time Factors

Antibiotic monotherapy is increasingly an option for the initial empiric treatment of febrile neutropenic cancer patients. We noted in a previous study that response to empiric therapy was related more to disease classification (solid tumors vs. leukemia) than to the regimen chosen. In the present study we based empiric monotherapy on the underlying disease in treating 240 episodes of fever and neutropenia in 145 children. Patients with leukemia or Stage III/IV non-Hodgkin's lymphoma (higher risk group) were treated with imipenem-cilastatin, whereas those with solid tumors or Stage I/II non-Hodgkin's lymphoma (lower risk group) received ceftriaxone. The regimens were modified in 15% of lower risk and 45% of higher risk episodes. Overall successful outcomes were obtained in 93.2% of the higher risk (n = 119) and 97.5% of the lower risk (n = 121) episodes. The two groups differed significantly in duration of neutropenia, frequency of positive blood cultures and superinfection and the need for modification of the monotherapy (P < 0.05). Empiric monotherapy based on primary disease appears to be safe and effective for febrile neutropenic children with cancer at our Brazilian institution. Further studies will be needed before these findings can be generalized to patient populations in other settings.

Topics: Adolescent; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Fever; Humans; Imipenem; Infant; Leukemia; Lymphoma, Non-Hodgkin; Male; Neoplasms; Neutropenia

The pharmacokinetics of imipenem/cilastatin were studied in febrile neutropenic patients with haematological malignancies. The peak plasma concentrations (36.4 +/- 4.96 mg/l), plasma half-life (60 min), volume of distribution (0.28 +/- 0.02 l/kg) and plasma clearance (3.23 +/- 0.38 ml/min/kg) were comparable with those in normal healthy volunteers suggesting that the drug handling is not appreciably altered in this group of patients. The administration of 12.5 mg/kg (max 1 g), 6-hourly achieved levels that were up to 3.5 times MICs of most relevant bacteria. The drug therefore has a potential use as empirical monotherapy in febrile neutropenic patients.

Topics: Acute Disease; Adult; Agranulocytosis; Blood Preservation; Chromatography, High Pressure Liquid; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Half-Life; Humans; Imipenem; Leukemia; Lymphoma, Non-Hodgkin; Male; Metabolic Clearance Rate; Middle Aged; Neutropenia

We report here four patients with acute leukemia, who developed seizure or tremor following treatment with imipenem, a new broad-spectrum antibiotic. All four patients had no renal dysfunction and recovered after discontinuation of the drug. Two patients who developed seizure had a past history of cerebral hemorrhage with symptoms of meningitis in one and the other had received frequent intrathecal injections of methotrexate. Seizure also occurred in another patient who was given multiple intrathecal injections of methotrexate. The remaining old patient developed tremor after the first administration of imipenem which did not progress to convulsion. Cerebral hemorrhage or meningitis is known to predispose patients for convulsion following imipenem treatment. In addition, the present study suggests that central nervous system damage related with intrathecal injections of methotrexate may be a predisposing factor. Thus, imipenem should be given with caution to acute leukemia patients who often have risk factors for developing imipenem-related complications.

Topics: Acute Disease; Adult; Aged; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Leukemia; Middle Aged; Seizures; Tremor