title: Drug susceptibility testing and pharmacokinetics question current treatment regimens in Mycobacterium simiae complex disease.
abstract: The Mycobacterium simiae complex bacteria can cause opportunistic infections in humans. In the case of definite disease, there are no evidence-based treatment regimens and outcomes are very disappointing. To increase the evidence base underpinning treatment regimens for M. simiae complex disease, drug susceptibility patterns and rifampicin/ethambutol synergy were assessed retrospectively in 69 clinical M. simiae complex isolates from 60 patients (22 patients with M. simiae, 24 with Mycobacterium lentiflavum, 8 with Mycobacterium triplex, 5 with Mycobacterium parascrofulaceum and 1 with Mycobacterium stomatepiae) submitted to the mycobacteriology laboratory at National Jewish Health (Denver, CO). Quantitative drug susceptibility testing (DST) was performed using the radiometric BacTec 460 macrodilution method. Results were related to pharmacokinetic (PK) measurements, where available. All M. simiae complex species proved susceptible to clarithromycin and, to a lesser extent, rifabutin, clofazimine, streptomycin and moxifloxacin. Synergy or additive action between rifampicin and ethambutol was observed for all species except M. simiae. Mycobacterium simiae is poorly susceptible in vitro to rifampicin and ethambutol alone as well as in combination; PK measurements support the limited efficacy of these drugs against M. simiae. The triple-drug regimen of a rifamycin, ethambutol and a macrolide may be advised to treat disease caused by M. lentiflavum, M. triplex, M. parascrofulaceum and M. stomatepiae; for M. simiae, this regimen appears less active. These findings may partly explain the limited treatment results in M. simiae disease. A treatment regimen including a macrolide, moxifloxacin and one or two additional drugs based on DST results may be advisable; clofazimine and amikacin or streptomycin are potential candidates.
authors.affiliation: Division of Mycobacterial and Respiratory Infections, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA. j.vaningen@mmb.umcn.nl
authors.forename: Jakko
authors.initials: J
authors.lastname: van Ingen
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Totten
authors.forename: Leonid B
authors.initials: LB
authors.lastname: Heifets
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Boeree
authors.forename: Charles L
authors.initials: CL
authors.lastname: Daley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009161:Mycobacterium / Q000187:drug effects* / Q000302:isolation & purification; D009164:Mycobacterium Infections / Q000188:drug therapy / Q000382:microbiology*; D009894:Opportunistic Infections / Q000188:drug therapy / Q000382:microbiology*; D017211:Treatment Failure; D014481:United States; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents