Antimicrobial Susceptibility of Clinical and Environmental Mycobacterium chimaera Isolates

Abstract

Mycobacterium chimaera is a slow-growing nontuberculous Mycobacterium species belonging to the Mycobacterium avium complex (MAC). It has been identified globally as the cause of a large outbreak of cardiovascular infections following open heart surgery, but it can also cause respiratory infections in individuals with underlying structural pulmonary disease. Invasive M. chimaera infections are associated with poor clinical responses, and the optimal antibiotic treatment regimen for these infections is not known. In this study, the drug susceptibility profiles of clinical and environmental M. chimaera isolates for antimicrobial agents that are commonly considered for treatment of MAC infections were determined. All M. chimaera isolates were susceptible to clarithromycin, with a median MIC of 2 μg/ml, while 98% (85/87 isolates) were susceptible to amikacin. Twenty-five percent of isolates (22/87 isolates) had intermediate susceptibility and 52% (46/87 isolates) were resistant to moxifloxacin. Similarly, 39% of isolates (34/87 isolates) had intermediate susceptibility and 39% (34/87 isolates) were resistant to linezolid. MIC breakpoints derived from the literature were used to determine resistance to rifampin (16/87 isolates [18%]), ethambutol (10/87 isolates [11%]), rifabutin (2/87 isolates [2%]), and streptomycin (1/87 isolates [1%]). In conclusion, our results showed that clarithromycin, amikacin, rifabutin, and streptomycin had the best activity against M. chimaera isolates, while susceptibility rates were lower for rifampin and ethambutol. In contrast, there was a high prevalence of isolates that were not susceptible to moxifloxacin or linezolid. While factors in addition to antibiotic susceptibility may determine the outcomes of treatment of M. chimaera infections, our results should inform the selection of antimicrobials as part of the overall therapeutic strategy.

Different clinical features of patients with pulmonary disease caused by various Mycobacterium avium–intracellulare complex subspecies and antimicrobial susceptibility

“…In the current study, the susceptibility rates of all MAC species to clarithromycin and inhaled amikacin were 98.6% for both; however, the drug resistance rates were 32.6%, 85.5% and 91.5% for intravenous amikacin, moxifloxacin and linezolid, respectively. Consistent with the current findings, previous studies have indicated that clarithromycin demonstrates the best antimicrobial activity against common MAC species (Cho et al, 2018;Mok et al, 2019;Wei et al, 2015;Zhao et al, 2014). Reportedly, some studies have indicated low moxifloxacin and linezolid resistance rates in M. avium (Wei et al, 2015).…”

“…Reportedly, some studies have indicated low moxifloxacin and linezolid resistance rates in M. avium (Wei et al, 2015). However, most studies have reported higher moxifloxacin and linezolid resistance rates, which are similar to the current findings among the MAC isolates (Mok et al, 2019;Zhao et al, 2014). Compared with other species, it was observed that MAsH isolates demonstrated the lowest rate of resistance to moxifloxacin and, although 26.2% of MAC isolates were resistant to intravenous amikacin, most MAC isolates (98.6%) were still susceptible to inhaled amikacin.…”

International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass

“…It remains unclear whether the fact that post-CPB surgery infections have a common source of infection contributes to the particular AST pattern. Wild-type M. chimaera strains are susceptible to macrolides [7,15,95] and, to date, no isolate with clarithromycin resistance has been recovered [7,15,82]. One patient who received prolonged macrolide treatment and suffered infection relapse had an isolate that demonstrated intermediate resistance to clarithromycin (MIC of 16 to 32 mg/mL depending on pH) [52].…”

Therapeutic Drug Monitoring in Non-Tuberculosis Mycobacteria Infections

“…Because of the MIC distribution, doses up to 1800 mg/day were required to optimize the bactericidal effect, resulting in a high adverse event rate [95]. A recent publication testing antimicrobial susceptibilities of the newly recognized pathogen M. chimaera [96] [69], 15% and 18%, respectively, were resistant to linezolid.…”

“…Because of the MIC distribution, doses up to 1800 mg/day were required to optimize the bactericidal effect, resulting in a high adverse event rate [ 95 ]. A recent publication testing antimicrobial susceptibilities of the newly recognized pathogen M. chimaera [ 96 ] demonstrated 39% of isolates (34/87 isolates) had intermediate susceptibility and 39% (34/87 isolates) were resistant to linezolid. Of 37 M. abscessus and M. fortuitum isolates tested by Zhang et al [ 69 ], 15% and 18%, respectively, were resistant to linezolid.…”