scholarly journals Two-Site Evaluation of the Colistin Broth Disk Elution Test To Determine Colistin In Vitro Activity against Gram-Negative Bacilli

2018 ◽  
Vol 57 (2) ◽  
Author(s):  
Patricia J. Simner ◽  
Yehudit Bergman ◽  
Marisol Trejo ◽  
Ava A. Roberts ◽  
Remy Marayan ◽  
...  
Keyword(s):  
Growth Control ◽  
Practical Method ◽  
Clinical Isolates ◽  
Gram Negative ◽  
Content Type ◽  
Mueller Hinton ◽  
Site Evaluation ◽  
Broth Macrodilution ◽  
Mueller Hinton Broth

ABSTRACT Limited methods for colistin MIC determination are available to clinical microbiology laboratories. The purpose of this study was to evaluate the accuracy of the colistin broth disk elution (CBDE) test compared to that of broth microdilution (BMD) for identifying colistin MICs. CBDE was compared to colistin BMD using a collection of Gram-negative bacilli tested at two U.S. microbiology laboratories. The isolates tested included 121 retrospective clinical isolates, 45 prospective clinical isolates, and 6 mcr-1-positive Escherichia coli isolates. CBDE was performed with four 10-ml cation-adjusted Mueller-Hinton broth tubes per isolate, to which 0, 1, 2, and 4 colistin 10-µg disks were added, generating final concentrations in the tubes of 0 (growth control), 1, 2, and 4 µg/ml, respectively. MICs were evaluated visually and interpreted using Clinical and Laboratory Standards Institute breakpoints. Site 2 also compared CBDE to the reference broth macrodilution (BMAD) method (n = 110 isolates). Overall, CBDE yielded a categorical agreement (CA) and essential agreement (EA) of 98% and 99%, respectively, compared to the results of colistin BMD. Very major errors occurred for mcr-1-producing strains, with MICs fluctuating from 2 to 4 µg/ml on repeat testing. The results for all other isolates were in CA with those of BMD. CBDE versus BMAD had an EA of 100% and a CA of 100%. Compared to currently used techniques, CBDE is an easy and practical method to perform colistin MIC testing. Some mcr-1-producing isolates yielded MICs of 2 µg/ml by CBDE and 4 µg/ml by BMD. As such, the results for isolates with colistin MICs of 2 µg/ml by CBDE should be confirmed by the reference BMD method, and isolates with MICs of ≥2 µg/ml should be evaluated for the presence of mcr genes.

scholarly journals In Vitro Activity of the Siderophore Cephalosporin, Cefiderocol, against a Recent Collection of Clinically Relevant Gram-Negative Bacilli from North America and Europe, Including Carbapenem-Nonsusceptible Isolates (SIDERO-WT-2014 Study)

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Meredith A. Hackel ◽  
Masakatsu Tsuji ◽  
Yoshinori Yamano ◽  
Roger Echols ◽  
James A. Karlowsky ◽  
...  
Keyword(s):  
North America ◽  
North American ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Content Type ◽  
Mueller Hinton ◽  
Recent Collection ◽  
Mueller Hinton Broth

ABSTRACT Cefiderocol (formerly S-649266) is an investigational siderophore cephalosporin. Iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB) was prepared according to the Clinical and Laboratory Standards Institute (CLSI) protocol and used to perform broth microdilution testing of cefiderocol against a 2014-2015 collection of clinical isolates of Gram-negative bacilli from North America (n = 4,239) and Europe (n = 4,966). The concentrations of cefiderocol inhibiting 90% of isolates tested (MIC90s) were 0.5 μg/ml (North America; n = 3,007) and 1 μg/ml (Europe; n = 3,080) for all isolates of Enterobacteriaceae; 1 μg/ml (North America; n = 30) and 4 μg/ml (Europe; n = 139) for meropenem-nonsusceptible (MIC ≥ 2 μg/ml) isolates of Enterobacteriaceae; 0.5 μg/ml for both North American (n = 765) and European (n = 765) isolates of Pseudomonas aeruginosa; 0.5 μg/ml (North America; n = 151) and 1 μg/ml (Europe; n = 202) for meropenem-nonsusceptible (MIC ≥ 4 μg/ml) isolates of P. aeruginosa; 1 μg/ml for both North American (n = 309) and European (n = 839) isolates of all Acinetobacter baumannii strains as well as for both North American (n = 173) and European (n = 595) isolates of meropenem-nonsusceptible A. baumannii; and 0.5μg/ml (North America; n = 152) and 0.25 μg/ml (Europe; n = 276) for isolates of Stenotrophomonas maltophilia. MICs of cefiderocol were ≤4 μg/ml for 99.9% (6,078/6,087) of all Enterobacteriaceae, 97.0% (164/169) of meropenem-nonsusceptible Enterobacteriaceae, 99.9% (1,529/1,530) of all P. aeruginosa isolates, 100% (353/353) of meropenem-nonsusceptible P. aeruginosa isolates, 97.6% (1,120/1,148) of all A. baumannii isolates, 96.9% (744/768) of meropenem-nonsusceptible A. baumannii isolates, 100% of isolates of S. maltophilia (428/428) and 93.8% of isolates of Burkholderia cepecia (11/12). We conclude that cefiderocol demonstrated potent in vitro activity against a recent collection of clinical isolates of commonly encountered Gram-negative bacilli, including carbapenem-nonsusceptible isolates.

scholarly journals In Vitro Activity of the Siderophore Cephalosporin, Cefiderocol, against Carbapenem-Nonsusceptible and Multidrug-Resistant Isolates of Gram-Negative Bacilli Collected Worldwide in 2014 to 2016

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Meredith A. Hackel ◽  
Masakatsu Tsuji ◽  
Yoshinori Yamano ◽  
Roger Echols ◽  
James A. Karlowsky ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Content Type ◽  
Microdilution Method ◽  
Mueller Hinton ◽  
Broth Microdilution Method ◽  
Mueller Hinton Broth

ABSTRACT The in vitro activity of the investigational siderophore cephalosporin, cefiderocol (formerly S-649266), was determined against a 2014–2016, 52-country, worldwide collection of clinical isolates of carbapenem-nonsusceptible Enterobacteriaceae (n = 1,022), multidrug-resistant (MDR) Acinetobacter baumannii (n = 368), MDR Pseudomonas aeruginosa (n = 262), Stenotrophomonas maltophilia (n = 217), and Burkholderia cepacia (n = 4) using the Clinical and Laboratory Standards Institute (CLSI) standard broth microdilution method. Iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB), prepared according to a recently approved (2017), but not yet published, CLSI protocol, was used to test cefiderocol; all other antimicrobial agents were tested using CAMHB. The concentration of cefiderocol inhibiting 90% (MIC90) of isolates of carbapenem-nonsusceptible Enterobacteriaceae was 4 μg/ml; cefiderocol MICs ranged from 0.004 to 32 μg/ml, and 97.0% (991/1,022) of isolates demonstrated cefiderocol MICs of ≤4 μg/ml. The MIC90s for cefiderocol for MDR A. baumannii, MDR P. aeruginosa, and S. maltophilia were 8, 1, and 0.25 μg/ml, respectively, with 89.7% (330/368), 99.2% (260/262), and 100% (217/217) of isolates demonstrating cefiderocol MICs of ≤4 μg/ml. Cefiderocol MICs for B. cepacia ranged from 0.004 to 8 μg/ml. We conclude that cefiderocol demonstrated potent in vitro activity against a 2014–2016, worldwide collection of clinical isolates of carbapenem-nonsusceptible Enterobacteriaceae, MDR A. baumannii, MDR P. aeruginosa, S. maltophilia, and B. cepacia isolates as 96.2% of all (1,801/1,873) isolates tested had cefiderocol MICs of ≤4 μg/ml.

scholarly journals In Vitro Activity of Cefiderocol, a Siderophore Cephalosporin, against Multidrug-Resistant Gram-Negative Bacteria

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Shazad Mushtaq ◽  
Zahra Sadouki ◽  
Anna Vickers ◽  
David M. Livermore ◽  
Neil Woodford
Keyword(s):  
Dipicolinic Acid ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Content Type ◽  
Mueller Hinton ◽  
Mueller Hinton Broth

ABSTRACT Cefiderocol is a parenteral siderophore cephalosporin with a catechol-containing 3′ substituent. We evaluated its MICs against Gram-negative bacteria, using iron-depleted Mueller-Hinton broth. The panel comprised 305 isolates of Enterobacterales, 111 of Pseudomonas aeruginosa, and 99 of Acinetobacter baumannii, all selected for carbapenem resistance and multidrug resistance to other agents. At 2 and 4 μg/ml, cefiderocol inhibited 78.7 and 92.1%, respectively, of all Enterobacterales isolates tested, with rates of 80 to 100% for isolates with all modes of carbapenem resistance except NDM enzymes (41.0% inhibited at 2 μg/ml and 72.1% at 4 μg/ml) or combinations of extended-spectrum β-lactamase (ESBL) and porin loss (61.5% inhibited at 2 μg/ml and 88.5% at 4 μg/ml). Cefiderocol also inhibited 81.1 and 86.5% of all P. aeruginosa isolates at 2 and 4 μg/ml, respectively, with rates of 80 to 100% for isolates with VIM, IMP, GES, or VEB β-lactamases and slightly lower rates for those with NDM (45.5% at 2 μg/ml and 72.7% at 4 μg/ml) and PER (66.7% at 2 μg/ml and 73.3% at 4 μg/ml) enzymes; 63.3% of P. aeruginosa isolates were inhibited at the FDA’s 1-μg/ml breakpoint. Lastly, cefiderocol at 2 and 4 μg/ml inhibited 80.8 and 88.9% of the A. baumannii isolates, respectively, with rates of >85% for isolates with OXA-51-like, -23, -24, or -58 enzymes and 50% at 2 μg/ml and 80% at 4 μg/ml for those with NDM carbapenemases. Dipicolinic acid and avibactam weakly potentiated cefiderocol against Enterobacterales isolates with metallo-β-lactamases (MBLs) and serine carbapenemase, respectively, indicating incomplete β-lactamase stability.

scholarly journals In Vitro Activities of Daptomycin against 2,789 Clinical Isolates from 11 North American Medical Centers

2001 ◽  
Vol 45 (6) ◽  
pp. 1919-1922 ◽  
Author(s):  
Arthur L. Barry ◽  
Peter C. Fuchs ◽  
Steven D. Brown
Keyword(s):  
Clinical Isolates ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Medical Centers ◽  
Mueller Hinton ◽  
Calcium Cations ◽  
Important Exception ◽  
Mueller Hinton Broth

ABSTRACT The in vitro activity of daptomycin is affected by the concentration of calcium cations in the test medium. Mueller-Hinton broth is currently adjusted to contain 10 to 12.5 mg of magnesium per liter and 20 to 25 mg of calcium per liter, but for testing of daptomycin, greater concentrations of calcium (50 mg/liter) are recommended to better resemble the normal concentration of ionized calcium in human serum. Two levels of calcium were used for broth microdilution tests of 2,789 recent clinical isolates of gram-positive bacterial pathogens. MICs of daptomycin were two- to fourfold lower when the broth contained additional calcium. For most species, however, the percentages of strains that were inhibited by 2.0 μg of daptomycin per ml were essentially identical with the two broth media. Enterococci were the important exception; i.e., 92% were inhibited when tested in calcium-supplemented broth but only 35% were inhibited by 2.0 μg/ml without the additional calcium. This type of information should be considered when selecting criteria for defining in vitro susceptibility to daptomycin.

scholarly journals Cefiderocol Antimicrobial Susceptibility Testing Considerations: the Achilles' Heel of the Trojan Horse?

2020 ◽  
Vol 59 (1) ◽  
pp. e00951-20 ◽  
Author(s):  
Patricia J. Simner ◽  
Robin Patel
Keyword(s):  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
Antimicrobial Susceptibility Testing ◽  
Disk Diffusion ◽  
Research Use ◽  
Gram Negative ◽  
Content Type ◽  
Mueller Hinton

ABSTRACTCefiderocol (formerly S-649266) is a novel siderophore-conjugated cephalosporin with activity against a broad array of multidrug-resistant (MDR), aerobic Gram-negative bacilli. The siderophore component binds iron and uses active iron transport for drug entry into the bacterial periplasmic space. The cephalosporin moiety is the active antimicrobial component, structurally resembling a hybrid between ceftazidime and cefepime. Like other β-lactam agents, the principal bactericidal activity of cefiderocol occurs via inhibition of bacterial cell wall synthesis by binding of penicillin-binding proteins (PBPs) and inhibiting peptidoglycan synthesis, leading to cell death. Iron concentrations need to be taken into consideration when in vitro antimicrobial susceptibility to cefiderocol is determined. Broth microdilution (BMD) and disk diffusion methods have been developed to determine in vitro activity of cefiderocol. For BMD, cation-adjusted Mueller-Hinton broth (CAMHB) requires iron depletion to provide MICs predictive of in vivo activity. A method to prepare iron-depleted CAMHB (ID-CAMHB) has been described by the Clinical and Laboratory Standards Institute (CLSI). For disk diffusion, standard Mueller-Hinton agar is recommended, presumably because iron is bound in the medium. Currently, clinical FDA and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints and investigational (research-use-only) CLSI breakpoints exist for interpreting cefiderocol susceptibility results for certain Gram-negative bacilli. Cefiderocol does not have clinically relevant activity against Gram-positive or anaerobic organisms. FDA or EUCAST breakpoints should be applied to interpret results for Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex for patient care until the investigational status has been removed from CLSI breakpoints. Further clinical outcome data are required to assess the effectiveness of cefiderocol for treatment of other Acinetobacter species (non-baumannii complex) and Stenotrophomonas maltophilia at this time, and, as such, antimicrobial susceptibility testing of these organisms should be limited to research use in the scenario of limited treatment options.

scholarly journals ARGONAUT-I: Activity of Cefiderocol (S-649266), a Siderophore Cephalosporin, against Gram-Negative Bacteria, Including Carbapenem-Resistant Nonfermenters and Enterobacteriaceae with Defined Extended-Spectrum β-Lactamases and Carbapenemases

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Michael R. Jacobs ◽  
Ayman M. Abdelhamed ◽  
Caryn E. Good ◽  
Daniel D. Rhoads ◽  
Kristine M. Hujer ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Stenotrophomonas Maltophilia ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Extended Spectrum ◽  
Mueller Hinton ◽  
Mueller Hinton Broth

ABSTRACT The activity of the siderophore cephalosporin cefiderocol is targeted against carbapenem-resistant Gram-negative bacteria. In this study, the activity of cefiderocol against characterized carbapenem-resistant Acinetobacter baumannii complex, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Enterobacteriaceae strains was determined by microdilution in iron-depleted Mueller-Hinton broth. The MIC90s against A. baumannii, S. maltophilia, and P. aeruginosa were 1, 0.25, and 0.5 mg/liter, respectively. Against Enterobacteriaceae, the MIC90 was 1 mg/liter for the group harboring OXA-48-like, 2 mg/liter for the group harboring KPC-3, and 8 mg/liter for the group harboring TEM/SHV ESBL, NDM, and KPC-2.

scholarly journals Simple Phenotypic Tests To Improve Accuracy in Screening Chromosomal and Plasmid-Mediated Colistin Resistance in Gram-Negative Bacilli

2020 ◽  
Vol 59 (1) ◽  
pp. e01701-20
Author(s):  
Fernando Pasteran ◽  
Diego Danze ◽  
Alejandra Menocal ◽  
Carla Cabrera ◽  
Ignacio Castillo ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Agar Plate ◽  
Systematic Screening ◽  
Gram Negative ◽  
Content Type ◽  
Mueller Hinton ◽  
Improve Accuracy ◽  
Mueller Hinton Agar ◽  
Phenotypic Tests ◽  
Mueller Hinton Broth

ABSTRACTCLSI and EUCAST recommend that only broth microdilution (BMD) should be used for routine colistin susceptibility testing; however, this technique can be difficult to perform in resource-poor settings. The purpose of this study was to evaluate the accuracy of a colistin agar spot test (COL-AS) and a colistin drop test (COL-DT) compared to BMD. COL-AS and COL-DT were assessed with a collection of 271 Gram-negative bacilli clinical isolates: 195 Enterobacterales (including 63 mcr-1 positive strains), 37 Acinetobacter spp., and 39 Pseudomonas aeruginosa. For COL-AS, 3.0 μg/ml (final concentration) of colistin was added to a Mueller-Hinton agar plate and subsequently swabbed with a 0.5 McFarland standard suspension of the tested strain within a 1 cm2 spot. For COL-DT, 10 μl of a 16 μg/ml colistin solution was dripped on the surface of a Mueller-Hinton agar plate, previously inoculated with a lawn of the tested strain (0.5 McFarland standard). Colistin solution was made either by dissolving powder or by disk elution in cation-adjusted Mueller-Hinton broth (CA-MHB). Overall, 141/271 (52%) isolates were categorized as colistin resistant by reference BMD. COL-AS yielded a categorical agreement (CA) of 95.5% compared to BMD, with 0.7% very major errors and 3.8% major errors. COL-DT yielded a CA of 96.2% compared to BMD, with 0.7% and 0% very major errors and 3.1% and 3.8% major errors, for colistin powder and disk elution solutions, respectively. Most major errors occurred for mcr-1 strains with MICs that fluctuated from 2 to 4 μg/ml according to the method used. In conclusion, we developed and validated methods suited to the systematic screening of resistance to colistin in Gram-negative bacilli.

scholarly journals In Vitro Activity of Cefepime-Zidebactam, Ceftazidime-Avibactam, and Other Comparators against Clinical Isolates of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii: Results from China Antimicrobial Surveillance Network (CHINET) in 2018

2020 ◽  
Vol 65 (1) ◽  
pp. e01726-20
Author(s):  
Yang Yang ◽  
Yan Guo ◽  
Dandan Yin ◽  
Yonggui Zheng ◽  
Shi Wu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Clinical Isolates ◽  
Surveillance Network ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active ◽  
Carbapenem Resistant ◽  
Almost All

ABSTRACTThis study evaluated the in vitro activity of cefepime-zidebactam in comparison with that of ceftazidime-avibactam and other comparators against clinically significant Gram-negative bacillus isolates. A total of 3,400 nonduplicate Gram-negative clinical isolates were collected from 45 medical centers across China in the CHINET Program in 2018, including Enterobacterales (n = 2,228), Pseudomonas aeruginosa (n = 657), and Acinetobacter baumannii (n = 515). The activities of cefepime-zidebactam and 20 comparators were determined by broth microdilution as recommended by the Clinical and Laboratory Standards Institute. Cefepime-zidebactam demonstrated potent activity against almost all Enterobacterales (MIC50/90, 0.125/1 mg/liter) and good activity against P. aeruginosa (MIC50/90, 2/8 mg/liter). Among the 373 carbapenem-resistant Enterobacteriaceae isolates, 57.3% (213/373) and 15.3% (57/373) were positive for blaKPC-2 and blaNDM, respectively. Cefepime-zidebactam showed a MIC of ≤2 mg/liter for 92.0% (196/213) of blaKPC-2 producers and 79.7% (47/59) of blaNDM producers. Ceftazidime-avibactam showed good in vitro activity against Enterobacterales (MIC50/90, 0.25/2 mg/liter; 94.0% susceptible) and P. aeruginosa (MIC50/90, 4/16 mg/liter; 86.9% susceptible). Ceftazidime-avibactam was active against 9.1% of carbapenem-resistant Escherichia coli isolates (63.6% were blaNDM producers) and 84.6% of Klebsiella pneumoniae isolates (74.3% were blaKPC producers). Most (90.1%) blaKPC-2 producers were susceptible to ceftazidime-avibactam. Cefepime-zidebactam demonstrated limited activity (MIC50/90, 16/32 mg/liter) against the 515 A. baumannii isolates (79.2% were carbapenem resistant), and ceftazidime-avibactam was less active (MIC50/90, 64/>64 mg/liter). Cefepime-zidebactam was highly active against clinical isolates of Enterobacterales and P. aeruginosa, including blaKPC-2-positive Enterobacterales and blaNDM-positive Enterobacterales and carbapenem-resistant P. aeruginosa. And ceftazidime-avibactam was highly active against blaKPC-2-positive Enterobacterales and carbapenem-resistant P. aeruginosa.

scholarly journals Pharmacodynamic Profiling of a Siderophore-Conjugated Monocarbam in Pseudomonas aeruginosa: Assessing the Risk for Resistance and Attenuated Efficacy

2015 ◽  
Vol 59 (12) ◽  
pp. 7743-7752 ◽  
Author(s):  
Aryun Kim ◽  
Amy Kutschke ◽  
David E. Ehmann ◽  
Sara A. Patey ◽  
Jared L. Crandon ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Body Weight ◽  
Iron Uptake ◽  
Threshold Concentration ◽  
Content Type ◽  
Adaptive Resistance ◽  
Mueller Hinton ◽  
Mueller Hinton Broth

ABSTRACTThe objective of this study was to investigate the risk of attenuated efficacy due to adaptive resistance for the siderophore-conjugated monocarbam SMC-3176 inPseudomonas aeruginosaby using a pharmacokinetic/pharmacodynamic (PK/PD) approach. MICs were determined in cation-adjusted Mueller-Hinton broth (MHB) and in Chelex-treated, dialyzed MHB (CDMHB). Spontaneous resistance was assessed at 2× to 16× the MIC and the resulting mutants sequenced. Efficacy was evaluated in a neutropenic mouse thigh model at 3.13 to 400 mg/kg of body weight every 3 h for 24 h and analyzed for association with free time above the MIC (fT>MIC). To closer emulate the conditions of thein vivomodel, we developed a novel assay testing activity mouse whole blood (WB). All mutations were found in genes related to iron uptake:piuA,piuC,pirR,fecI, andpvdS. Against fourP. aeruginosaisolates, SMC-3176 displayed predictable efficacy corresponding to thefT>MIC using the MIC in CDMHB (R2= 0.968 to 0.985), with stasis to 2-log kill achieved at 59.4 to 81.1%. Efficacy did not translate forP. aeruginosaisolate JJ 4-36, as thein vivoresponses were inconsistent withfT>MIC exposures and implied a threshold concentration that was greater than the MIC. The results of the mouse WB assay indicated that efficacy was not predictable using the MIC for JJ 4-36 and four additional isolates, against whichin vivofailures of another siderophore-conjugated β-lactam were previously reported. SMC-3176 carries a risk of attenuated efficacy inP. aeruginosadue to rapid adaptive resistance preventing entry via the siderophore-mediated iron uptake systems. Substantialin vivotesting is warranted for compounds using the siderophore approach to thoroughly screen for thisin vitro-in vivodisconnect inP. aeruginosa.

scholarly journals In VitroSusceptibility Testing of a Novel Benzimidazole, SPR719, against Nontuberculous Mycobacteria

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Barbara A. Brown-Elliott ◽  
Aileen Rubio ◽  
Richard J. Wallace
Keyword(s):  
Nontuberculous Mycobacteria ◽  
Treatment Options ◽  
Active Form ◽  
Mycobacterium Abscessus ◽  
Nontuberculous Mycobacterium ◽  
Content Type ◽  
Clinical Laboratories ◽  
Mueller Hinton ◽  
Mueller Hinton Broth

ABSTRACTNontuberculous mycobacterium (NTM) infections are increasing globally. TheMycobacterium aviumcomplex (MAC) andMycobacterium abscessusare the most frequently encountered NTM among clinical laboratories, and treatment options are extremely limited. In this study, thein vitropotency of a novel benzimidazole, SPR719, the microbiologically active form of the orally available prodrug SPR720, was tested against several species of NTM. MICs were determined for 161 isolates of NTM of 13 taxa (seven species, three subspecies, and three groups/complexes) in cation-adjusted Mueller-Hinton Broth, as described and recommended by the Clinical and Laboratory Standards Institute (CLSI M24-A2). Comparator antimicrobials included amikacin, cefoxitin, ciprofloxacin, clarithromycin, doxycycline, imipenem, linezolid, minocycline, moxifloxacin, tigecycline, and trimethoprim-sulfamethoxazole (TMP-SMX) for the rapidly growing mycobacteria (RGM), amikacin and clarithromycin for the MAC, and amikacin, ciprofloxacin, clarithromycin, doxycycline, linezolid, moxifloxacin, rifabutin, rifampin, and TMP-SMX for the other slowly growing NTM. SPR719 was found to be potent against multiple clinical strains of NTM with an MIC50range of 0.25 to 4 μg/ml for several species of NTM. These findings support the further advancement of SPR720 for the treatment of NTM disease.

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