In vitro susceptibility testing of imipenem-relebactam and tedizolid against 102 Mycobacterium abscessus isolates.

OBJECTIVES: Mycobacterium abscessus is an emerging infection in people living with lung diseases, including cystic fibrosis (CF) and bronchiectasis, and it has limited treatment options and low cure rates. The off-label use of novel antibiotics developed for other bacterial pathogens offers potential new therapeutic options. We aimed to describe the in vitro activity of imipenem, imipenem-relebactam and tedizolid against comparator antibiotics in M. abscessus isolates from Australian patients with and without CF. METHODS: We performed susceptibility testing for imipenem-relebactam, tedizolid and comparator antibiotics by Clinical and Laboratory Standards Institute (CLSI) criteria against 102 clinical M. abscessus isolates, including 46 from people with CF. RESULTS: In this study, the minimum inhibitory concentration (MICs) of imipenem-relebactam was one-fold dilution less than of imipenem alone. The MIC50 and MIC90 of imipenem-relebactam were 8 and 16 mg/L, respectively, whereas for imipenem they were 16 and 32 mg/L. Tedizolid had an MIC50 and MIC90 of 2 and 4 mg/L, respectively. Forty non-CF isolates had linezolid susceptibility performed, with MIC50 and MIC90 values of 16 and 32 mg/L, respectively, measured. CONCLUSIONS: This study shows lower MICs for imipenem-relebactam and tedizolid compared to other more commonly used antibiotics and supports their consideration in clinical trials for M. abscessus treatment.

Characterization of pncA mutations in multi-drug and pyrazinamide resistant Mycobacterium tuberculosis isolates cultured from Queensland migrants and Papua New Guinea residents.

Outbreak of drug resistant tuberculosis in the Western province, Papua New Guinea is a concern to Queensland, Australia due to migration. We performed pncA mutation analysis and genotyping of multi-drug/pyrazinamide (MDR/PZA) resistant isolates from 18 Queensland (Qld) migrants and 81 Papua New Guinea (PNG) residents, to compare with phenotypic evidence of PZA resistance and to evaluate the genotypes obtained from the two countries. Seven different mutations were seen from Qld isolates of which 2 have not been described previously. A cluster of mutations were found between amino acids L35 and S65. Amongst the PNG isolates, 10 mutations were identified, of which 6 were unique and have not been described previously. Majority of the mutations formed 2 clusters, between amino acids Q10 to A20 and W68 to W119. Mutations identified at nucleotide (nt) position 202 and 307 were found to be the most common types, occurring in 25% and 51% of the PNG isolates respectively. The majority of the mutations were seen in MDR/PZA resistant isolates. These mutations could be utilized for direct screening of PZA resistance from PNG patient samples. Genotypic analysis of the isolates showed strong clustering amongst the PNG isolates as opposed to Qld isolates. A diversity of mutations and genotypes were seen amongst the Qld migrant isolates. Majority of PNG isolates had one genotype with two distinct pncA mutation patterns (T202C and T307G) which highlight on-going transmission. pncA mutation analysis provided a satisfactory alternative to PZA culture DST with high positive predictive value and an improved result turnaround time.

Evaluation of the GeneXpert MTB/RIF assay on extrapulmonary and respiratory samples other than sputum: a low burden country experience.

The aim of this study was to assess the performance of the GeneXpert MTB/RIF assay on extrapulmonary (EP) and respiratory (non-sputum) clinical samples of patients suspected of having tuberculosis (TB) from Queensland, Australia. A total of 269 EP and respiratory (non-sputum) clinical samples collected from Qld patients who were suspected of having TB were subjected to the GeneXpert MTB/RIF analysis, Ziehl-Neelsen (ZN) staining, Mycobacterium tuberculosis (MTB) culture and drug susceptibility testing. Phenotypic and genotypic data were compared. The overall performance analysis of the GeneXpert MTB/RIF assay for detection of MTB complex demonstrated sensitivity of 89%, specificity of 95%, PPV of 89% and NPV of 95% using culture as a reference standard. The GeneXpert MTB/RIF analysis of acid-fast bacilli (AFB) smear positive samples and AFB smear negative samples showed sensitivities of 100% and 77%, respectively. Looking at individual EP and respiratory (non-sputum) sample types, the sensitivity ranged from 60% to 100% although the specificity ranged from 33% to 100% with the specificity of lymph node tissue biopsy being the lowest. The GeneXpert MTB/RIF assay detected 11% more TB cases than culture and 27% more cases than ZN microscopy. Due to insufficient numbers of presenting rifampicin resistance cases, performance analysis of the GeneXpert MTB/RIF assay on rifampicin resistance could not be carried out. The GeneXpert MTB/RIF assay is potentially valuable for TB diagnosis in the majority of the EP and respiratory (other than sputum) samples in our setting. Although the GeneXpert MTB/RIF assay provides rapid diagnostic results, the overall sensitivity to rule out the disease is suboptimal for some specimen types. Performance varied according to specimen type and AFB smear status. The sensitivity and specificity of lymph node tissue was 63% and 33%. Care must be taken when using the GeneXpert MTB/RIF assay for detection of MTB in lymph node tissue samples. All samples should be cultured regardless of the GeneXpert MTB/RIF assay result.