scholarly journals Evolution of antibiotic cross‐resistance and collateral sensitivity in Staphylococcus epidermidis using the mutant prevention concentration and the mutant selection window

2020 ◽  
Vol 13 (4) ◽  
pp. 808-823 ◽  
Author(s):  
Natalie Ann Lozano‐Huntelman ◽  
Nina Singh ◽  
Alondra Valencia ◽  
Portia Mira ◽  
Maral Sakayan ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Cross Resistance ◽  
Mutant Selection ◽  
Collateral Sensitivity ◽  
Selection Window ◽  
Mutant Prevention Concentration

scholarly journals Determination of MIC, MPC, and MSW of Ilex paraguariensis Against Non-Typhoidal Salmonella with Identification of the Mechanisms of Resistance and Pathogenicity Factors

2020 ◽  
Author(s):  
Khaled El Khatib ◽  
Ribal Aby Hadeer ◽  
Anis Saad ◽  
Aline Kalaydjian ◽  
Elie Fayad ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Inhibitory Concentration ◽  
Ilex Paraguariensis ◽  
Salmonella Spp ◽  
Mutant Selection ◽  
Selection Window ◽  
Mutant Prevention Concentration ◽  
Resistance Patterns ◽  
Different Strains

Abstract Objective: This study investigated the antibacterial activity of Ilex paraguariensis extracts against 32 different strains of non-typhoidal Salmonella (NTS) through the determination of the Minimum Inhibitory Concentration (MIC), Mutant Prevention Concentration (MPC), Mutant Selection Window (MSW), and the detection of virulence genes by multiplex PCR assays. Results: The MIC values of Ilex paraguariensis against Salmonella spp. strains varied between 0.78 mg/ml and 6.25 mg/ml with a MIC 90 of 3.12 mg/ml. The highest MPC in this study was 48 mg/ml yielding a Mutant Selection Window of 41.75 mg/ml. The MSW values of the remaining strains varied between 1.56 and 8.87 mg/ml. Genes of pathogenicity detected in Salmonella spp. isolates were most commonly the stn, sdiA, invA, sopB, invH, and sopE genes. The antibacterial activity of Yerba Mate extracts was not affected by the antimicrobial resistance patterns or pathogenicity genes expressed. More work is needed to identify the active antibacterial compound(s) responsible for the antibacterial activity.

scholarly journals Synergistic Combination of Linezolid and Fosfomycin Closing Each Other’s Mutant Selection Window to Prevent Enterococcal Resistance

2021 ◽  
Vol 11 ◽  
Author(s):  
Lifang Jiang ◽  
Na Xie ◽  
Mingtao Chen ◽  
Yanyan Liu ◽  
Shuaishuai Wang ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Bacterial Resistance ◽  
Selection Index ◽  
Resistance Mechanism ◽  
Mutant Selection ◽  
Selection Window ◽  
Mutant Prevention Concentration ◽  
Resistant Mutants ◽  
Synergistic Combination ◽  
Selection Of

Enterococci, the main pathogens associated with nosocomial infections, are resistant to many common antibacterial drugs including β-lactams, aminoglycosides, etc. Combination therapy is considered an effective way to prevent bacterial resistance. Preliminary studies in our group have shown that linezolid combined with fosfomycin has synergistic or additive antibacterial activity against enterococci, while the ability of the combination to prevent resistance remains unknown. In this study, we determined mutant prevention concentration (MPC) and mutant selection window (MSW) of linezolid, fosfomycin alone and in combination including different proportions for five clinical isolates of Enterococcus and characterized the resistance mechanism for resistant mutants. The results indicated that different proportions of linezolid combined with fosfomycin had presented different MPCs and MSWs. Compared with linezolid or fosfomycin alone, the combination can restrict the enrichment of resistant mutants at a lower concentration. A rough positive correlation between the selection index (SI) of the two agents in combination and the fractional inhibitory concentration index (FICI) of the combination displayed that the smaller FICI of linezolid and fosfomycin, the more probable their MSWs were to close each other. Mutations in ribosomal proteins (L3 and L4) were the mechanisms for linezolid resistant mutants. Among the fosfomycin-resistant mutants, only two strains have detected the MurA gene mutation related to fosfomycin resistance. In conclusion, the synergistic combination of linezolid and fosfomycin closing each other’s MSW could effectively suppress the selection of enterococcus resistant mutants, suggesting that the combination may be an alternative for preventing enterococcal resistance. In this study, the resistance mechanism of fosfomycin remains to be further studied.

scholarly journals Mutant Selection Window and Characterization of Allelic Diversity for Ciprofloxacin-Resistant Mutants of Rhodococcus equi

2010 ◽  
Vol 54 (8) ◽  
pp. 3520-3523 ◽  
Author(s):  
Hidekazu Niwa ◽  
Brent A. Lasker
Keyword(s):  
Amino Acid ◽  
Allelic Diversity ◽  
Dna Gyrase ◽  
Rhodococcus Equi ◽  
Mutant Selection ◽  
Single Nucleotide ◽  
Selection Window ◽  
Mutant Prevention Concentration ◽  
Resistant Mutants

ABSTRACT The mutant prevention concentration (MPC) for ciprofloxacin was determined for two Rhodococcus equi strains. The MPC for both strains was 32 μg/ml, which is above the peak serum concentration of ciprofloxacin obtainable by oral administration in humans. Nine single nucleotide changes corresponding to eight amino acid substitutions in the quinolone resistance-determining regions of DNA gyrase subunits A and B were characterized. Only mutants with amino acid changes in Ser-83 of GyrA were highly resistant (≥64 μg/ml). Our results suggest that ciprofloxacin monotherapy against R. equi infection may result in the emergence of ciprofloxacin-resistant mutants.

scholarly journals Searching for the Optimal Predictor of Ciprofloxacin Resistance in Klebsiella pneumoniae by UsingIn VitroDynamic Models

2015 ◽  
Vol 60 (3) ◽  
pp. 1208-1215 ◽  
Author(s):  
Elena N. Strukova ◽  
Yury A. Portnoy ◽  
Andrey V. Romanov ◽  
Mikhail V. Edelstein ◽  
Stephen H. Zinner ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Area Under The Curve ◽  
Mutant Selection ◽  
Content Type ◽  
Selection Window ◽  
Mutant Prevention Concentration ◽  
Ciprofloxacin Resistance ◽  
Resistant Mutants ◽  
Time Courses ◽  
Selection Of

There is growing evidence of applicability of the hypothesis of the mutant selection window (MSW), i.e., the range between the MIC and the mutant prevention concentration (MPC), within which the enrichment of resistant mutants is most probable. However, it is not clear if MPC-based pharmacokinetic variables are preferable to the respective MIC-based variables as interstrain predictors of resistance. To examine the predictive power of the ratios of the area under the curve (AUC24) to the MPC and to the MIC, the selection of ciprofloxacin-resistant mutants of threeKlebsiella pneumoniaestrains with different MPC/MIC ratios was studied. Each organism was exposed to twice-daily ciprofloxacin for 3 days at AUC24/MIC ratios that provide peak antibiotic concentrations close to the MIC, between the MIC and the MPC, and above the MPC. ResistantK. pneumoniaemutants were intensively enriched at an AUC24/MIC ratio of 60 to 360 h (AUC24/MPC ratio from 2.5 to 15 h) but not at the lower or higher AUC24/MIC and AUC24/MPC ratios, in accordance with the MSW hypothesis. AUC24/MPC and AUC24/MIC relationships with areas under the time courses of ciprofloxacin-resistantK. pneumoniae(AUBCM) were bell shaped. These relationships predict highly variable “antimutant” AUC24/MPC ratios (20 to 290 h) compared to AUC24/MIC ratios (1,310 to 2,610 h). These findings suggest that the potential of the AUC24/MPC ratio as an interstrain predictor ofK. pneumoniaeresistance is lower than that of the AUC24/MIC ratio.

Susceptibility and PK/PD relationships of Staphylococcus aureus strains isolated from the milk of sheep and goats with clinical mastitis to five veterinary fluoroquinolones

2017 ◽  
Vol 180 (15) ◽  
pp. 376-376 ◽  
Author(s):  
J. M. Serrano-Rodríguez ◽  
C. Cárceles-García ◽  
C. M. Cárceles-Rodríguez ◽  
M. L. Gabarda ◽  
J. M. Serrano-Caballero ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Clinical Mastitis ◽  
The Other ◽  
Mutant Selection ◽  
Sheep And Goats ◽  
Selection Window ◽  
Mutant Prevention Concentration ◽  
Higher Doses ◽  
Selection Of

Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of veterinary fluoroquinolones as enrofloxacin, its metabolite ciprofloxacin, danofloxacin, difloxacin and marbofloxacin against Staphylococcus aureus strains (n=24) isolated from milk of sheep and goats affected by clinical mastitis were evaluated. The authors have used the MIC and MPC, as well as the pharmacokinetic-pharmacodynamic relationships in plasma and milk. MIC values were significantly different between drugs, unlike MPC values. Lower MIC values were obtained for danofloxacin and difloxacin, middle and higher values for enrofloxacin, ciprofloxacin and marbofloxacin. However, differences in MPC values were not found between drugs. At conventional doses, the AUC24/MIC and AUC24/MPC ratios were close to 30–80 hours and 5–30 hours, with exception of danofloxacin, in plasma and milk. The time inside the mutant selection window (TMSW) was close to 3–6 hours for enrofloxacin, ciprofloxacin and marbofloxacin, near to 8 hours for danofloxacin and 12–22 hours for difloxacin. From these data, the mutant selection window could be higher for danofloxacin and difloxacin compared with the other fluoroquinolones tested. The authors concluded that enrofloxacin and marbofloxacin, at conventional doses, could prevent the selection of bacterial subpopulations of S aureus, unlike danofloxacin and difloxacin, where higher doses could be used.

scholarly journals Pharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nayara Helisandra Fedrigo ◽  
Danielle Rosani Shinohara ◽  
Josmar Mazucheli ◽  
Sheila Alexandra Belini Nishiyama ◽  
Floristher Elaine Carrara-Marroni ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Combination Therapy ◽  
Polymyxin B ◽  
Dosage Interval ◽  
Combination Regimen ◽  
Mutant Selection ◽  
Selection Window ◽  
Mutant Prevention Concentration ◽  
Free Plasma

AbstractThe emergence of polymyxin resistance in Gram-negative bacteria infections has motivated the use of combination therapy. This study determined the mutant selection window (MSW) of polymyxin B alone and in combination with meropenem and fosfomycin against A. baumannii strains belonging to clonal lineages I and III. To evaluate the inhibition of in vitro drug resistance, we investigate the MSW-derived pharmacodynamic indices associated with resistance to polymyxin B administrated regimens as monotherapy and combination therapy, such as the percentage of each dosage interval that free plasma concentration was within the MSW (%TMSW) and the percentage of each dosage interval that free plasma concentration exceeded the mutant prevention concentration (%T>MPC). The MSW of polymyxin B varied between 1 and 16 µg/mL for polymyxin B-susceptible strains. The triple combination of polymyxin B with meropenem and fosfomycin inhibited the polymyxin B-resistant subpopulation in meropenem-resistant isolates and polymyxin B plus meropenem as a double combination sufficiently inhibited meropenem-intermediate, and susceptible strains. T>MPC 90% was reached for polymyxin B in these combinations, while %TMSW was 0 against all strains. TMSW for meropenem and fosfomycin were also reduced. Effective antimicrobial combinations significantly reduced MSW. The MSW-derived pharmacodynamic indices can be used for the selection of effective combination regimen to combat the polymyxin B-resistant strain.

scholarly journals Analysis of the Mutant Selection Window and Killing of Mycoplasma hyopneumoniae for Doxycycline, Tylosin, Danofloxacin, Tiamulin, and Valnemulin

2019 ◽  
Author(s):  
Zilong Huang ◽  
Chunxiao Mao ◽  
Yanzhe Wei ◽  
Xiaoyan Gu ◽  
Qinren Cai ◽  
...  
Keyword(s):  
Mycoplasma Hyopneumoniae ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Mutant Selection ◽  
Selection Window ◽  
Mutant Prevention Concentration ◽  
Agar Dilution ◽  
Minimal Concentration ◽  
Conventional Antibiotics ◽  
Microdilution Broth

AbstractMycoplasma hyopneumoniae is the major pathogenic microorganism causing enzootic pneumonia in pigs. With increasing resistance of M. hyopneumoniae to conventional antibiotics, treatment is becoming complicated. Herein, we investigated the mutant selection window (MSW) of doxycycline, tylosin, danofloxacin, tiamulin, and valnemulin for treating M. hyopneumoniae strain (ATCC 25934) to determine the likelihood of promoting resistance with continued use of these antibiotics. Minimum inhibitory concentration (MIC) values against M. hyopneumoniae were determined for each antimicrobial agent and ranged from 105 colony-forming units (CFU)/mL to 109 CFU/mL based on microdilution broth and agar dilution methods. The minimal concentration inhibiting colony formation by 99% (MIC99) and the mutant prevention concentration (MPC) were determined by the agar dilution method with three inoculum sizes. Antimicrobial killing was determined based on MIC99 and MPC values for all five agents. MIC values ranged from 0.001 to 0.25 μg/mL based on the microdilution broth method, and from 0.008 to 1.0 μg/mL based on the agar dilution method. MPC values ranged from 0.0016 to 10.24 μg/mL. MPC/MIC99 values were ordered tylosin >doxycycline >danofloxacin >tiamulin >valnemulin. MPC achieved better bactericidal action than MIC99. Based on pharmacodynamic analyses, danofloxacin, tylosin, and doxycycline are more likely to select resistant mutants than tiamulin and valnemulin.

scholarly journals CTX-M-33 Is a CTX-M-15 Derivative Conferring Reduced Susceptibility to Carbapenems

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
Laurent Poirel ◽  
José-Manuel Ortiz de la Rosa ◽  
Anaïs Richard ◽  
Marta Aires-de-Sousa ◽  
Patrice Nordmann
Keyword(s):  
Membrane Protein ◽  
Klebsiella Pneumoniae ◽  
Hydrolytic Activity ◽  
Sequence Type ◽  
High Rate ◽  
Mutant Selection ◽  
Content Type ◽  
Selection Window ◽  
Mutant Prevention Concentration ◽  
Lactamase Inhibitor

ABSTRACT CTX-M-type extended-spectrum β-lactamases (ESBLs) are widespread among Enterobacterales strains worldwide. The most common variant is CTX-M-15, which hydrolyzes ceftazidime at a high rate but spares carbapenems. Here, we identified CTX-M-33, a point mutation derivative of CTX-M-15 (Asp to Ser substitution at Ambler position 109) that exhibited low carbapenemase activity. β-Lactamase CTX-M-33 was identified in a Klebsiella pneumoniae isolate, belonging to sequence type 405 and lacking the outer membrane protein OmpK36, that was resistant to broad-spectrum cephalosporins and β-lactam/β-lactamase inhibitor combinations and displayed decreased susceptibility to carbapenems. Comparative hydrolytic activity assays showed that CTX-M-33 hydrolyzed ceftazidime at a lower level than CTX-M-15 but significantly hydrolyzed meropenem. In addition, CTX-M-33 showed higher mutant prevention concentration values and a wider mutant selection window in the presence of meropenem, in accordance with its observed hydrolytic properties. Here, we identified the very first CTX-M enzyme possessing weak carbapenemase activity, which may correspond to an emerging phenomenon, considering its possible evolution from the widespread ESBL CTX-M-15.

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