Drug susceptibility profiles of Mycobacterium abscessus isolated in the state of São Paulo, 2008-2024

Abstract

Introduction. Infections caused by Mycobacterium abscessus, an environmentally prevalent, rapidly growing mycobacteria, are increasingly frequent in developed countries.Objective. To analyse the drug susceptibility profiles of M. abscessus isolated in the state of São Paulo from 2008 to 2024.Methods. Of the 2,402 M. abscessus isolates identified during those 17 years, 558 (23.2%) met the American Thoracic Society's microbiologic and clinical criteria for drug susceptibility testing (DST), which was performed for five agents - clarithromycin, amikacin, cefoxitin, ciprofloxacin, and doxycycline.Results. Clarithromycin showed a dramatic increase in resistance phenotype from ≤10% in the early period to 73-90% over the last 8 years. Over half those isolates demonstrated inducible resistance. Resistance to amikacin was found in fewer than 5% of isolates from 2016 to 2021. In 2022, that result increased to 13%, but for 2023 and 2024, it had fallen back to 2%. Over the past decade, cefoxitin DST has reported the majority of isolates as intermediate, a problematic result in M. abscessus group (MAG) infections, which typically require long-term treatment for successful outcomes. Since 2018, the annual susceptibility rate has been ≤18%, and in five of the 7 years, ≤7%. Ciprofloxacin was typically assessed as susceptible from 2009 to 2011, then decreased sharply to ≤20% over the next several years, and since 2018, the rate has been less than 5%. Through the entire study, doxycycline resistance has remained consistently high; in the years since 2018, ≤6% of isolates have been susceptible.Conclusion. This study demonstrates wide variation among MAG clinical isolates in the frequency of susceptibility, both across different agents and within individual agents over time. These results emphasize the importance of performing high-quality DST on MAG clinical isolates and suggest the need to consider revising the standard panel of drugs tested.

Keywords: minimal inhibitory concentration; non-tuberculous mycobacteria; resistance.

Fig. 1.. Total number of isolates identified as MAG and the number for which DST was performed from 2008 to 2024. The increase in DST after 2015 reflects the initiation of selecting isolates for testing based on bacteriological criteria as recommended by CLSI (see text for details). Adolfo Lutz Institute, São Paulo, Brazil.

Fig. 2.. Susceptibility profiles for five drugs in MAG isolates from 2008 to 2024. The graphs show the profiles of clarithromycin (a), amikacin (b), cefoxitin (c), ciprofloxacin (d) and doxycycline (e). DST result labels: I, intermediate; I.R, induced resistance; R, resistant; S, susceptible. Note: For clarithromycin, beginning in 2016, resistance (r) is based on readings taken on Day 3 of incubation; IR is based on readings from Days 4 through 14 of incubation. Institute Adolfo Lutz, São Paulo, Brazil.