rifampin and Leukemia--Myeloid--Acute

Chryseobacterium meningosepticum is a ubiquitous Gram-negative bacillus historically associated with meningitis in premature neonates. We report 15 positive cultures and 6 cases of infection among immunocompromised adults at our institution over a 10-year period and review the English-language literature on C. meningosepticum. Excluding the present series, there are 308 reports of positive cultures in the literature, of which 59% were determined to represent true infections. Sixty-five percent of those infected were younger than 3 months of age. Meningitis was the most common infectious syndrome among neonates, seen in 84% of cases and associated with a 57% mortality rate. Less commonly reported infections among infants included sepsis (13%) and pneumonia (3%). Pneumonia was the most frequent infection among the postneonatal group, accounting for 40% of cases, followed by sepsis (24%), meningitis (18%), endocarditis (3%), cellulitis (3%), abdominal infections (3%), eye infections (3%), and single case reports of sinusitis, bronchitis, and epididymitis. The 6 cases in our series were all adults, with a mean age of 58.7 years. Sites of C. meningosepticum infection were limited to the lungs, bloodstream, and biliary tree. Infection in our series was associated with prolonged hospitalization, prior exposure to multiple antibiotics, and host immunocompromise, particularly neutropenia. C. meningosepticum is resistant to multiple antibiotics, and disk dilution is notoriously unreliable for antibiotic sensitivity testing. Sensitivity testing on the 15 isolates from our institution revealed the most efficacious antibiotics to be minocycline (100% sensitive), rifampin (93%), trimethoprim-sulfamethoxazole (67%), and ciprofloxacin (53%). In contrast to reports in the literature, the isolates in our series displayed widespread resistance to vancomycin (100% resistant or intermediately sensitive), erythromycin (100%), and clindamycin (86%). These findings have important implications for the clinician when choosing empiric antibiotic regimens for patients with risk factors for C. meningosepticum infection.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotics, Antitubercular; Breast Neoplasms; Ciprofloxacin; Drug Resistance, Microbial; Female; Flavobacterium; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Infant; Infant, Newborn; Leukemia, Myeloid, Acute; Liver Transplantation; Male; Meningitis, Bacterial; Middle Aged; Minocycline; Pneumonia, Bacterial; Rifampin; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination

The remission duration (RD) of 22 adult acute myelogenous leukaemia patients who received maintenance rifampicin treatment during 24 episodes was significantly longer than RD in 29 complete remission patients who received conventional maintenance chemotherapy (25 versus 9 months, p less than 0.003). Although this study was not randomized, the observed RD in the rifampicin group suggests a suppressive activity upon regrowth of residual disease in acute myelogenous leukaemia during apparent complete remission.

Topics: Clinical Trials as Topic; Follow-Up Studies; Humans; Leukemia, Myeloid, Acute; Prognosis; Random Allocation; Rifampin

Develop a physiologically based pharmacokinetic (PBPK) model of ivosidenib using in vitro and clinical PK data from healthy participants (HPs), refine it with clinical data on ivosidenib co-administered with itraconazole, and develop a model for patients with acute myeloid leukemia (AML) and apply it to predict ivosidenib drug-drug interactions (DDI).. An HP PBPK model was developed in Simcyp Population-Based Simulator (version 15.1), with the CYP3A4 component refined based on a clinical DDI study. A separate model accounting for the reduced apparent oral clearance in patients with AML was used to assess the DDI potential of ivosidenib as the victim of CYP3A perpetrators.. For a single 250 mg ivosidenib dose, the HP model predicted geometric mean ratios of 2.14 (plasma area under concentration-time curve, to infinity [AUC. Potentially clinically relevant DDI effects with CYP3A4 inducers and moderate and strong inhibitors co-administered with ivosidenib were predicted. Considering the challenges of conducting clinical DDI studies in patients, this PBPK approach is valuable in ivosidenib DDI risk assessment and management.

Topics: Administration, Oral; Antineoplastic Agents; Area Under Curve; Computer Simulation; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Female; Fluconazole; Glycine; Healthy Volunteers; Humans; Itraconazole; Ketoconazole; Leukemia, Myeloid, Acute; Male; Microsomes, Liver; Models, Biological; Pyridines; Rifampin

The multidrug resistance protein (MRP) is a drug efflux membrane pump conferring multidrug resistance to tumor cells. Clinical trials have been undertaken to improve the effectiveness of chemotherapy by adding an MRP inhibitor to the treatment regimen. This study attempted not only to determine novel resistance mechanisms in MRP-overexpressing AML cells (AML-2/DX100) by chronic exposure to doxorubicin in the presence of an MRP inhibitor probenecid but also to find out whether probenecid could increase MRP levels. AML-2/DXPBA cultured in the presence of probenecid (600 microM) and doxorubicin (100 ng/ml) showed a higher level of the multidrug resistance (MDR) phenotype when compared to AML-2/DX100. AML-2/DXPBA showed increased levels of MRP compared to those of AML-2/DX100. Probenecid increased the MRP levels without an increase in MRP mRNA in AML-2/WT in both a time- and dose-dependent manner. Of the MRP inhibitors including probenecid, ofloxacin, erythromycin, and rifampicin used in this study, only probenecid showed a marked chemosensitizing effect in AML-2/DX100 but not in HL-60/Adr, suggesting that the chemosensitizing effects of the MRP inhibitors vary according to the type of resistant cells. The maximum noncytotoxic concentrations of these MRP inhibitors increased the MRP levels to various degrees in both AML-2/WT and HL-60/WT. However, the chemosensitizing effects of the MRP inhibitors were not correlated with their MRP-increasing effects. Altogether, MRP inhibitors such as probenecid have been shown to function as a double-edged sword, indicating that they are not only an effective chemosensitizer of MRP-associated MDR tumor cells but also an MRP activator. Therefore caution should be taken whenever using MRP inhibitors to reverse MRP-mediated multidrug resistance in clinical cancer chemotherapy as well as when used to inhibit MRP expression in vitro.

Topics: Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP-Binding Cassette Transporters; Blotting, Western; Cell Division; Cell Survival; Dose-Response Relationship, Drug; Doxorubicin; Drug Resistance, Neoplasm; Enzyme Inhibitors; Erythromycin; HL-60 Cells; Humans; Leukemia, Myeloid, Acute; Multidrug Resistance-Associated Proteins; Ofloxacin; Probenecid; Protein Synthesis Inhibitors; Reverse Transcriptase Polymerase Chain Reaction; Rifampin; RNA, Messenger; Tumor Cells, Cultured; Uricosuric Agents; Vincristine

We evaluate the efficacy of rifampin combined with low dose harringtonine in acute leukemia (Group A, acute lymphocytic leukemia (ALL) 6 cases and acute non-lymphocytic leukemia (ANLL) 8 cases) in comparison with the patients treated with low dose harringtonine only (Group B, 8 ALL, and 5 ANLL). The complete remission (CR) rate in Groups A and B was 64.3% and 23.1%, while the median CR duration, 17 months and 8 months respectively, Group A was more effective than Group B. We also consider that rifampin and low dose harringtonine are more applicable for treatment of ANLL patients without peripheral leukocytosis and those complicated with infection.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Harringtonines; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rifampin

A thrush-like oral infection with subsequent alveolar abscess formation and a positive blood culture due to Trichosporon capitatum developed in a patient with acute myelogenous leukaemia. Later T. capitatum was identified by indirect immunofluorescence in multiple splenic abscesses. The infection was controlled by immediate aggressive treatment with amphotericin B, flucytosine and rifampicin and by splenectomy. This case of systemic T. capitatum infection resembles somewhat the invasive mycosis due to candida.

Topics: Abscess; Adult; Amphotericin B; Blood; Female; Flucytosine; Humans; Leukemia, Myeloid, Acute; Mitosporic Fungi; Mycoses; Rifampin; Splenic Diseases

Topics: Anemia; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Aspirin; Bone Marrow Diseases; Hematologic Diseases; Humans; Leukemia, Myeloid, Acute; Neutropenia; Rifampin; Thrombocytopenia

Pulmonary aspergillosis developed in a 62-year-old man with acute myelogenous leukemia. Therapy with amphotericin B and 5-fluorocytosine was begun. Synergy between amphotericin B and rifampin was demonstrated in vitro, and therapy with firampin replaced 5-fluorocytosine. Progressive clearing of the pulmonary lesion ensued, suggesting in vivo efficacy as well. Further studies of patients utilizing this regimen are warranted.

Topics: Amphotericin B; Aspergillosis; Aspergillus fumigatus; Drug Synergism; Flucytosine; Humans; In Vitro Techniques; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Middle Aged; Radiography; Rifampin

Topics: Adult; Hepatitis A; Hepatitis B Antigens; Hepatitis B virus; Humans; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Male; Microscopy, Electron; Rifampin

Topics: Base Sequence; Carbon Isotopes; Chromatin; DNA, Neoplasm; Escherichia coli; Humans; Kinetics; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocytes; Nucleic Acid Denaturation; Nucleic Acid Hybridization; Peptide Chain Initiation, Translational; Potassium Chloride; Rifampin; RNA Nucleotidyltransferases; RNA, Neoplasm; Templates, Genetic; Thymidine; Transcription, Genetic; Tritium

Topics: Adolescent; Adult; Aged; Bronchitis; Bronchopneumonia; Enterobacteriaceae; Feeding and Eating Disorders; Female; Haemophilus influenzae; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Nausea; Neoplasm Metastasis; Pleural Neoplasms; Pleurisy; Pleuropneumonia; Pneumonia, Pneumococcal; Pulmonary Emphysema; Rifampin; Sputum; Staphylococcus