Susceptibility profiles of Nocardia spp. to antimicrobial and antituberculotic agents detected by a microplate Alamar Blue assay

Pan Zhao,Zhenjun Li,Pengcheng Du,Xiujuan Zhang,Guilian Li,Luxi Li

doi:10.1038/srep43660

Abstract

Nocardia species are ubiquitous in natural environments and can cause nocardiosis. Trimethoprim-sulfamethoxazole has long been the monotherapy treatment of choice, but resistance to this treatment has recently emerged. In this study, we used microplate Alamar Blue assays to determine the antimicrobial susceptibility patterns of 65 standard Nocardia isolates, including 28 type strains and 20 clinical Nocardia isolates, to 32 antimicrobial agents, including 13 little studied drugs. Susceptibility to the most commonly used drug, trimethoprim-sulfamethoxazole, was observed in 98% of the isolates. Linezolid, meropenem, and amikacin were also highly effective, with 98%, 95%, and 90% susceptibility, respectively, among the isolates. The isolates showed a high percentage of resistance or nonsusceptibility to isoniazid, rifampicin, and ethambutol. For the remaining antimicrobials, resistance was species-specific among isolates and was observed in traditional drug pattern types. In addition, the antimicrobial susceptibility profiles of a variety of rarely encountered standard Nocardia species are reported, as are the results for rarely reported clinical antibiotics. We also provide a timely update of antimicrobial susceptibility patterns that includes three new drug pattern types. The data from this study provide information on antimicrobial activity against specific Nocardia species and yield important clues for the optimization of species-specific Nocardia therapies.

Highlights

Species that are isolated less frequently in the clinical laboratory have not been systematically tested, and only a few reports provide data on newer antimicrobials[1,4]
98% of isolates were susceptible to amikacin, whereas N. amikacinitolerans, N. wallacei, and N. blacklockiae isolates were highly resistant to amikacin (MIC ≥ 64 mg/L) (Tables S2 and S3)
Because the symptoms of Nocardia infection are similar to those of tuberculosis[10], which might result in misdiagnoses and erroneous treatment with antituberculotic antibiotics, we examined seven classic antituberculotic antibiotics, including rifampicin, isoniazid, streptomycin, ethambutol, gentamicin, clofazimine, and kanamycin, in this study

Summary

Introduction

Species that are isolated less frequently in the clinical laboratory have not been systematically tested, and only a few reports provide data on newer antimicrobials[1,4]. Routine antimicrobial susceptibility testing (AST) for Nocardia isolates includes the Etest and broth microdilution (BMD); in 20035, the National Committee for Clinical Laboratory Standards (NCCLS) recommended BMD as the reference method. In this study we report the use of a broth-based method, the microplate Alamar Blue assay, for MIC determination of Nocardia spp. This assay was previously used for MIC determination for Mycobacterium tuberculosis and nontuberculous mycobacterial complex isolates with favourable results[8,9]. This method is faster, more stable, and more accurate than the traditional BMD or Etest methods[9]

Methods

Results

Conclusion