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En este trabajo se evaluó el efecto de las bacterias persistentes presentes en un inóculo de alta densidad de una cepa autóctona de Escherichia coli sobre la eficacia de enrofloxacina y ciprofloxacina mediante ensayos in vitro de curvas de muerte bacteriana y de determinación de la concentración preventiva de mutantes. En las curvas de muerte realizadas sobre inóculos de alta densidad, ningún antibiótico presentó actividad bactericida y solo permitieron la sobrevida de bacterias persistentes. En el ensayo para determinar la concentración preventiva de mutantes, sobre la superficie del agar de las placas con elevadas concentraciones de enrofloxacina y ciprofloxacina, las bacterias persistentes permanecieron viables sin desarrollar colonias y adoptando morfología filamentosa como una forma de adaptación y supervivencia. Se discute la utilidad clínica de las concentraciones preventivas de mutantes de enrofloxacina y ciprofloxacina sobre E. coli ya que, estas elevadas concentraciones permitirían la sobrevida de una sub-población de bacterias persistentes originando un reservorio biológico que podría dar origen a infecciones crónicas y a favorecer la emergencia de mutantes resistentes.
This work evaluated the effect of persister cells present in a high inocula size of a wild strain of Escherichia coli on the efficacy of enrofloxacin and ciprofloxacin by in vitro time-kill curve assays and mutant prevention concentration testing. In time-kill curves performed with high inocula size, no antibiotics showed bactericidal activity, but only allowed the survival of persister cells. In the assay to determine the mutant prevention concentration, on the surface of agar plates containing high enrofloxacin and ciprofloxacin concentrations, persister cells remained viable and without bacterial colonies development and adopting filamentous morphology as a form of adaptation and survival. The clinical usefulness of mutant prevention concentrations of enrofloxacin and ciproflocxacin against Escherichia coli is discussed, as these high concentrations would allow the survival of a sub-population of persister cells originating a biological reservoir that could give rise to chronic infections and favor the emergence of resistant mutants.
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Objective To investigate the potential tigecycline resistance of Klebsiella pneumoniae during treatment.Methods The minimum inhibitory concentrations (MICs) and the mutant prevention concentrations (MPCs) of tigecycline were determined for K.pneumoniae isolates with four different resistant profiles.Corr.elations between MICs and MPCs were analyzed.We combined with the pharmacokinetic parameters of tigecycline to estimate the potential of emerging resistance to tigecycline monotherapy in K.pneumoniae.Results The MPCs of tigecycline for the carbapenem-and fluoroquinolone-resistant isolates were found to be 8-fold higher than those for carbapenem-and quinolones-susceptible isolates.Our data showed that the MPCs range and MPC90 values of tigecycline were 4-512 mg/L and 64 mg/L,respectively,which were much higher than the therapeutic concentrations of tigecycline in serum and tissues.Conclusions Long-term tigecycline monotherapy may predispose the emergence of resistance in K.pneumoniae,which is not recommended.It is desirable to carry out ongoing monitoring of K.pneumoniae susceptibility and tigecycline treatment effect.
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BACKGROUND: Infection caused by multi-drug resistant (MDR) Gram-negative organisms such as Pseudomonas and Acinetobacter species is one of emerging important problems in modern hospitals. To treat multi-drug resistant non-fermenting Gram-negatives, polymyxins which were used in 1960s, but abandoned because of grave toxicities such as renal toxicity are reused. The objective of this study was to estimate the probability of resistance development of the clinical isolates of Pseudomonas aeruginosa to polymyxins. METHODS AND MATERIALS: Twenty-nine multidrug-resistant P. aeruginosa isolates were collected from Dankook University Hospital and Seoul National University Hospital in 2000 and tested for antimicrobial susceptibility test, minimal inhibitory concentration (MIC), mutant prevention concentration (MPC) and mutant frequency to ciprofloxacin and polymyxin B. RESULTS: The MIC50 and MIC90 of polymyxin B for the isolates were 2 and 2 microgram/mL, and those of ciprofloxacin were 0.5 and 4 microgram/mL, respectively. Thirteen of 29 isolates developed polymyxin B-resistant mutants but all 29 isolates, ciprofloxacin-resistant mutants. The MPC50 and MPC90 of polymyxin B were 32 and 64 microgram/mL, and those values of ciprofloxacin were 4 and 64 microgram/mL. Mutation frequencies of polymyxin B ranged from 2 x 10(-9) to 2 x 10(-7), and those of ciprofloxacin from 4 x 10(-10) to 5 x 10(-7). CONCLUSIONS: Mutation frequencies of polymyxin B were similar to those of ciprofloxacin, suggesting appreciable development of resistant mutants with wide usage of polymyxins.
Subject(s)
Acinetobacter , Ciprofloxacin , Mutation Rate , Polymyxin B , Polymyxins , Pseudomonas aeruginosa , Pseudomonas , SeoulABSTRACT
BACKGROUND: Infection caused by multi-drug resistant (MDR) Gram-negative organisms such as Pseudomonas and Acinetobacter species is one of emerging important problems in modern hospitals. To treat multi-drug resistant non-fermenting Gram-negatives, polymyxins which were used in 1960s, but abandoned because of grave toxicities such as renal toxicity are reused. The objective of this study was to estimate the probability of resistance development of the clinical isolates of Pseudomonas aeruginosa to polymyxins. METHODS AND MATERIALS: Twenty-nine multidrug-resistant P. aeruginosa isolates were collected from Dankook University Hospital and Seoul National University Hospital in 2000 and tested for antimicrobial susceptibility test, minimal inhibitory concentration (MIC), mutant prevention concentration (MPC) and mutant frequency to ciprofloxacin and polymyxin B. RESULTS: The MIC50 and MIC90 of polymyxin B for the isolates were 2 and 2 microgram/mL, and those of ciprofloxacin were 0.5 and 4 microgram/mL, respectively. Thirteen of 29 isolates developed polymyxin B-resistant mutants but all 29 isolates, ciprofloxacin-resistant mutants. The MPC50 and MPC90 of polymyxin B were 32 and 64 microgram/mL, and those values of ciprofloxacin were 4 and 64 microgram/mL. Mutation frequencies of polymyxin B ranged from 2 x 10(-9) to 2 x 10(-7), and those of ciprofloxacin from 4 x 10(-10) to 5 x 10(-7). CONCLUSIONS: Mutation frequencies of polymyxin B were similar to those of ciprofloxacin, suggesting appreciable development of resistant mutants with wide usage of polymyxins.
Subject(s)
Acinetobacter , Ciprofloxacin , Mutation Rate , Polymyxin B , Polymyxins , Pseudomonas aeruginosa , Pseudomonas , SeoulABSTRACT
OBJECTIVE To determine the mutant prevention concentration(MPC) of 3 cephalosporins against clinical isolates of Staphylococcus aureus and Streptococcus pneumoniae.METHODS Agar dilution was used to determine the minimum inhibitory concentration(MICs) and MPCs of cefaclor,cefprozil and cefuroxime against S.aureus and the MICs to Str.pneumoniae.The MPCs against Str.pneumoniae were determined by mixing-bacterium.RESULTS The MPCs and the ratio of MPC90/MIC90 of cefaclor,cefprozil and cefuroxime against S.aureus were 32,16;16,16;2,8;and the MPCs and the ratio of MPC90/MIC90 against Str.pneumoniae were 8,16;4,32;2,8,respectively.CONCLUSIONS The ability of cefuroxime for restricting the selection of resistant mutant of Str.aureus and S.pneumoniae is stronger than cefaclor and cefprozil.
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Objective To detect the mutant prevention concentration (MPC) of macrolide resistant Streptococcus pneumoniae, to amplify the resistance gene of Streptococcus pneumoniae mutants selected in the mutant selection window (MSW), and to investigate the mechanism in the resistance of Streptococcus pneumoniae to macrolides. Methods The Streptococcus pneumoniae strain ATCC49619 was enriched in broth, and the bacterial concentrations were adjusted to 1010 colony forming units per milliliter. The minimal inhibitory concentration (MIC), MIC for 99 % of input cells (MIC99), provisional MPC (MPCpr), and MPC of roxithromycin and azithromycin for Streptococcus pneumoniae were determined by agar plate dilution method. The ermB and mefA of Streptococcus pneumoniae mutants selected in the MSW were obtained by PCR method and sequencing. Results The MPCs of roxithromycin and azithromycin for ATCC49619 were 0.80 ?g/ml and 0.51 ?g/ml, and the MPC/MIC99 were 5.0 and 3.9. The ermB gene was detected in Streptococcus pneumoniae mutants selected in the MSW. Conclusion Adjustment of the drug dose may limit the enrichment of macrolide-resistant Streptococcus pneumoniae mutant. The mechanism in the resistance of Streptococcus pneumonia to macrolides may be associated with ermB genes carried.
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MIC,according to which,the antibiotics frequently used for treating respiratory infections were divided into three groups:Time-dependent(with minimal or no PAE),Concentration-dependent(with PAE),Time-dependent and Concentration-enhanced(with PAE),In addition,the most appropriate antibiotic administration methods are also explored respectively in the article.Finally,several measures of preventing emergence of resistance are proposed based on the theory of MPC.
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AIM:To compare the mutant prevention concentration(MPC)of linezolid and vancomycin against methicillin resistant staphylococcus aureus(MRSA)and study the correlation between minimal inhibitory concentration(MIC)and MPC.METHODS:MICs and MPCs of two drugs against 35 MRSA clinical stains were determined by agar plates dilution method.The correlations between MIC and MPC were determined by linear regression.The ability to restrict the resistance was evaluated according the pharmacokinetics of two drugs.RESULTS:The MPCs of two drugs against MRSA were 16 and 8 ?g/mL and the MPC/MIC was 8.MPCs and MICs correlated poorly(R2 were 0.32 and 0.008,respectively).According to pharmacokinetics of two drugs,the concentration of linezolid was inside the MSW(mutant selective window)for the entire dosage interval,while the concentration of vancomycin exceeded the MPC for the most dosage interval.CONCLUSION:The capacity of vancomycin for restricting the selection of MRSA resistant mutants is stronger than that of linezolid.There is low correlation between MPC and MIC.