Significant Difference in Drug Susceptibility Distribution between Mycobacterium avium and Mycobacterium intracellulare

Abstract

c M ycobacterium avium and M. intracellulare are referred as the M. avium complex (MAC) (1) and are known as causative agents of opportunistic infections in humans (1-3). The first-line recommended treatment consists of a combination of either clarithromycin or azithromycin with rifampin and ethambutol, the two latter drugs being considered companion drugs to prevent the emergence of macrolide resistance (4, 5). Amikacin is an alternative to macrolides for the treatment of MAC lung cavitary disease or in case of macrolide resistance (6). To date, the treatment guidelines have referred to MAC as a complex (4), but there are no clear data regarding the antibiotic susceptibility of each species separately. Therefore, we sought to delineate the clarithromycin and amikacin susceptibility profiles of both species (4, 5).All of the clinically relevant MAC isolates sent to the French National Reference Center for Mycobacteria between 2009 and 2011 were routinely identified by using GenoType Mycobacterium CM/AS line probe assays (Hain, Lifescience) as recommended by the manufacturer, leading to the identification of M. avium or M. intracellulare (7). After the exclusion of duplicates, only isolates from patients with no history of previous antibiotic treatment were selected to be representative of a wild population. MICs were determined by the broth microdilution method with Sensititre SLOMYCO (Biocentric) (8). The Kruskal-Wallis test was used for statistical comparisons. Epidemiological cutoff (ECOFF) values were determined as values larger than the modal MIC plus one 2-fold dilution (variability of the test) and including at least 95% of the isolates tested.One hundred eighty-six M. avium and 154 M. intracellulare isolates were studied. The distributions of clarithromycin and amikacin MICs were unimodal for both species (Fig. 1). Clarithromycin MICs were lower for M. intracellulare than for M. avium isolates (MIC 50 , 2 versus 8 mg/liter, respectively; P Ͻ 0.001) ( Table 1). The same observation was made for amikacin MICs, although the difference was not as drastic (MIC 50 , 8 versus 16 mg/liter, respectively; P Ͻ 0.001). Consequently, the tentative ECOFFs were slightly lower for M. intracellulare than for M. avium (Table 1).Many studies report MAC as a single entity. Our results demonstrate that M. avium and M. intracellulare have different patterns of clarithromycin and amikacin susceptibility. Such a difference has been previously reported (9, 10), but recent data considering both clarithromycin and standardized methods (recommended by CLSI [8]) were lacking at the time of those publi- (7,12). In fine, our results need to be further confirmed by a definitive species identification method, such as sequencing. LETTER TO THE EDITORIn conclusion, there are differences in antibiotic susceptibility between MAC species in terms of MIC 50 s and ECOFFs. Whether these differences are clinically relevant remains to be determined; indeed, there are not a wide variety of drugs and dosage options for the treatment of MAC infect...

Rational Choice of Antibiotics and Media for Mycobacterium avium Complex Drug Susceptibility Testing

“…Regarding MIC profiles among MAC members, our data confirm previous studies showing that MICs for M. avium are rather equivalent to or higher than those for other members of the MAC (Renvoisé et al, 2014;Litvinov et al, 2018). Also, rifampin MICs for M. chimaera isolates were lower than for M. avium, in line with a recent study (Maurer et al, 2018).…”

Differential drug susceptibility patterns of Mycobacterium chimaera and other members of the Mycobacterium avium-intracellulare complex

“…However, as the overall number of M. intracellulare isolates with clarithromycin MICs >64 mg/L was small (n ¼ 7, all from individual patients) this finding may be locally confounded. In addition, clarithromycin MICs were lower for M. intracellulare than for M. avium isolates in another monocentric study by Renvois e et al [5]. Taken together, these findings exemplify the need for collecting data from multiple laboratories for ECOFF determination to rule out overinterpretation of observations, which may be due to local phenomena.…”

A Clofazimine-Containing Regimen Confers Improved Treatment Outcomes in Macrophages and in a Murine Model of Chronic Progressive Pulmonary Infection Caused by the Mycobacterium avium Complex

“…In our study, a total of seven MAC strains had MIC values from 1 to 4 mg/L, consistent with the range reported for CFZ in previous studies ( Huang et al, 2018 ; Kwak et al, 2020 ). Since drug options have been limited for MAC-PD treatment, the general choice of drug regimen has been empirically selected based on MIC determination ( Renvoise et al, 2014 ). However, unexpectedly, RIF showed the weakest correlation between its in vitro MIC and intracellular anti-MAC activity.…”