ABSTRACT
BACKGROUND: Amikacin is a first-line drug that must be evaluated when performing an antimycobacterial susceptibility test (AST) for Mycobacterium avium complex (MAC). However, the presence of sporadic trailing growth in MAC makes determining the precise point for reading its minimal inhibitory concentration (MIC) challenging. METHODS: Susceptibility was re-tested for 134 MAC clinical isolates using the Sensititre SLOMYCOI panel, the rrs gene was sequenced, and amikacin exposure history was investigated. The MIC50, MIC90, and the epidemiological cut-off value (ECOFF) were calculated using the EUCAST method. RESULTS: After re-testing and ignoring trailing growth, of the 22 M. intracellulare isolates originally classified as resistant to amikacin according to the CLSI guideline, 10 strains were reclassified as intermediate and four as susceptible. Similarly, from the seven resistant M. avium strains, one was reclassified as intermediate and four as susceptible. No rrs gene mutations were detected in any isolates, including resistant strains. When ignoring trailing growth, the calculated MIC50, MIC90, and ECOFF values closely aligned with the EUCAST MIC distribution. CONCLUSION: To maintain the current CLSI breakpoint, trailing growth should be ignored when reading the amikacin MIC of MAC. To read the MIC at complete bacterial inhibition, the CLSI breakpoint needs to be raised.
Subject(s)
Mycobacterium avium-intracellulare Infection , Mycobacterium tuberculosis , Humans , Mycobacterium avium Complex/genetics , Amikacin/pharmacology , Mycobacterium avium-intracellulare Infection/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Microbial Sensitivity TestsSubject(s)
Antineoplastic Agents , Clonal Evolution , Leukemia, Myeloid, Acute , fms-Like Tyrosine Kinase 3 , Humans , Antineoplastic Agents/therapeutic use , Clonal Evolution/genetics , Drug Resistance, Neoplasm , fms-Like Tyrosine Kinase 3/antagonists & inhibitors , Fusion Proteins, bcr-abl/genetics , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Protein Kinase Inhibitors/therapeutic useABSTRACT
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the expansion of myeloid lineage cells. Chronic myeloid leukemia (CML) is characterized by a BCR-ABL1 fusion gene that causes constitutive tyrosine kinase activity. Polycythemia vera, essential thrombocythemia, and primary myelofibrosis (PMF) are frequently associated with driver mutations in genes such as JAK2, CALR, and MPL and are mutually exclusive of BCR-ABL1. Herein, we report the first case study of a patient diagnosed with accelerated-phase CML while undergoing treatment for initial JAK2 V617F-positive, BCR-ABL1-negative PMF. This finding emphasizes the importance of BCR-ABL1 testing in patients with an atypical BCR-ABL1-negative MPN disease course.
