scholarly journals Susceptibility trends of zoliflodacin against multidrug-resistant Neisseria gonorrhoeae clinical isolates in Nanjing, China (2014-2018)

2020 ◽  
Author(s):  
Wenjing Le ◽  
Xiaohong Su ◽  
Xiangdi Lou ◽  
Xuechun Li ◽  
Xiangdong Gong ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Dna Sequencing ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Extended Spectrum ◽  
High Level ◽  
Level Resistance

ABSTRACTPreviously, we reported potent activity of a novel spiropyrimidinetrione, zoliflodacin, against N. gonorrhoeae isolates from symptomatic men in Nanjing, China, collected in 2013. Here, we investigated trends of susceptibilities of zoliflodacin in 986 gonococcal isolates collected from men between 2014 and 2018. N. gonorrhoeae isolates were tested for susceptibility to zoliflodacin and seven other antibiotics. Mutations in gyrA, gyrB, parC and parE genes were determined by PCR and DNA sequencing. The MIC of zoliflodacin for N. gonorrhoeae ranged from ≤0.002 to 0.25 mg/L; the overall MIC50s and MIC90s were 0.06 mg/L and 0.125mg/L in 2018, increasing two-fold from 2014. However, the percent of isolates with lower zoliflodacin MICs declined in each year sequentially while the percent with higher MICs increased yearly (P≤0.00001). All isolates were susceptible to spectinomycin but resistant to ciprofloxacin (MIC ≥1 μg/ml); 21.2% (209/986) were resistant to azithromycin (≥1 μg/ml), 43.4% (428/986) were penicillinase-producing (PPNG), 26.9% (265/986) tetracycline-resistant (TRNG) and 19.4% (191/986) were multi-drug resistant (MDR) isolates. Among 143 isolates with higher zoliflodacin MICs (0.125-0.25 mg/L), all had quinolone resistance associated double or triple mutations in gyrA; 139/143 (97.2%) also had mutations in parC. There were no D429N/A and/or K450T mutations in GyrB identified in the 143 isolates with higher zoliflodacin MICs; a S467N mutation in GyrB was identified in one isolate. We report that zoliflodacin has excellent in vitro activity against clinical gonococcal isolates, including those with high-level resistance to ciprofloxacin, azithromycin and extended spectrum cephalosporins.

scholarly journals Susceptibility trends of zoliflodacin against multidrug-resistant Neisseria gonorrhoeae clinical isolates in Nanjing, China (2014-2018)

2020 ◽  
pp. AAC.00863-20
Author(s):  
Wenjing Le ◽  
Xiaohong Su ◽  
Xiangdi Lou ◽  
Xuechun Li ◽  
Xiangdong Gong ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Extended Spectrum ◽  
High Level ◽  
Level Resistance

Previously, we reported potent activity of a novel spiropyrimidinetrione, zoliflodacin, against N. gonorrhoeae isolates from symptomatic men in Nanjing, China, collected in 2013. Here, we investigated trends of susceptibilities of zoliflodacin in 986 isolates collected from men between 2014 and 2018. N. gonorrhoeae isolates were tested for susceptibility to zoliflodacin and seven other antibiotics. Mutations in gyrA, gyrB, parC, parE and mtrR genes were determined by PCR and sequencing. The MICs of zoliflodacin ranged from ≤0.002 to 0.25 mg/L; the overall MIC50s and MIC90s were 0.06 mg/L and 0.125mg/L in 2018, increasing two-fold from 2014. However, the percent of isolates with lower zoliflodacin MICs declined in each year sequentially while the percent with higher MICs increased yearly (P≤0.00001). All isolates were susceptible to spectinomycin but resistant to ciprofloxacin (MIC ≥1 mg/L); 21.2% (209/986) were resistant to azithromycin (≥1 mg/L), 43.4% (428/986) were penicillinase-producing (PPNG), 26.9% (265/986) tetracycline-resistant (TRNG) and 19.4% (191/986) were multi-drug resistant (MDR) isolates. Among 202 isolates tested, all were quinolone resistant with double or triple mutations in gyrA; One hundred ninety three (193/202; 95.5%) also had mutations in parC. There were no D429N/A and/or K450T mutations in GyrB identified in the 143 isolates with higher zoliflodacin MICs; a S467N mutation in GyrB was identified in one isolate. We report that zoliflodacin continues to have excellent in vitro activity against clinical gonococcal isolates, including those with high-level resistance to ciprofloxacin, azithromycin and extended spectrum cephalosporins.

scholarly journals Sequence of quinolone resistance-determining region of gyrA gene for clinical isolates and for an in vitro-selected quinolone-resistant strain of Coxiella burnetii.

1996 ◽  
Vol 40 (4) ◽  
pp. 870-873 ◽  
Author(s):  
D Musso ◽  
M Drancourt ◽  
S Osscini ◽  
D Raoult
Keyword(s):  
Amino Acid ◽  
Coxiella Burnetii ◽  
Resistant Strain ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Low Level ◽  
Nucleotide Mutation ◽  
High Level ◽  
Level Resistance

We report the sequence of the quinolone resistance-determining region of the gyrA genes of either susceptible or low-level-resistant clinical isolates of Coxiella burnetii. The sequences of low-level (MICs, 4 micrograms/ml) and high-level (MICs, 8 and 16 micrograms/ml) resistant strains stepwise selected in vitro were also determined. The gene sequences of all of the clinical isolates and that of the in vitro-selected low-level-resistant strain were identical. Sequence analysis of the in vitro-selected high-level-resistant strain revealed a nucleotide mutation leading to an amino acid substitution of Gly in place of Glu at position 87 of the GyrA amino acid sequence. These results indicate that high-level resistance to ciprofloxacin is associated with a nucleotide mutation in gyrA, whereas low-level resistance to quinolones is not.

Rapid Emergence of High-Level Resistance to Quinolones in Campylobacter jejuni Associated with Mutational Changes in gyrA and parC

1998 ◽  
Vol 42 (12) ◽  
pp. 3276-3278 ◽  
Author(s):  
Amera Gibreel ◽  
Eva Sjögren ◽  
Bertil Kaijser ◽  
Bengt Wretlind ◽  
Ola Sköld
Keyword(s):  
Campylobacter Jejuni ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
High Level ◽  
Chromosomal Mutations ◽  
Rapid Emergence ◽  
Level Resistance

ABSTRACT Quinolone resistance in clinical isolates of Campylobacter jejuni in Sweden increased more than 20-fold at the beginning of the 1990s. Resistance to 125 μg of ciprofloxacin per ml in clinical isolates was associated with chromosomal mutations in C. jejuni leading to a Thr-86-Ile substitution in thegyrA product and a Arg-139-Gln substitution in theparC product.

scholarly journals Genetic Basis of Multidrug Resistance in Acinetobacter baumannii Clinical Isolates at a Tertiary Medical Center in Pennsylvania

2008 ◽  
Vol 52 (11) ◽  
pp. 3837-3843 ◽  
Author(s):  
Jennifer M. Adams-Haduch ◽  
David L. Paterson ◽  
Hanna E. Sidjabat ◽  
Anthony W. Pasculle ◽  
Brian A. Potoski ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Genetic Basis ◽  
Medical Center ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Clinical Microbiology Laboratory ◽  
Carbapenemase Gene ◽  
Methylase Gene ◽  
High Level

ABSTRACT A total of 49 unique clinical isolates of multidrug-resistant (MDR) Acinetobacter baumannii identified at a tertiary medical center in Pittsburgh, Pennsylvania, between August 2006 and September 2007 were studied for the genetic basis of their MDR phenotype. Approximately half of all A. baumannii clinical isolates identified during this period qualified as MDR, defined by nonsusceptibility to three or more of the antimicrobials routinely tested in the clinical microbiology laboratory. Among the MDR isolates, 18.4% were resistant to imipenem. The frequencies of resistance to amikacin and ciprofloxacin were high at 36.7% and 95.9%, respectively. None of the isolates was resistant to colistin or tigecycline. The presence of the carbapenemase gene bla OXA-23 and the 16S rRNA methylase gene armA predicted high-level resistance to imipenem and amikacin, respectively. bla OXA-23 was preceded by insertion sequence ISAba1, which likely provided a potent promoter activity for the expression of the carbapenemase gene. The structure of the transposon defined by ISAba1 differed from those reported in Europe, suggesting that ISAba1-mediated acquisition of bla OXA-23 may occur as an independent event. Typical substitutions in the quinolone resistance-determining regions of the gyrA and parC genes were observed in the ciprofloxacin-resistant isolates. Plasmid-mediated quinolone resistance genes, including the qnr genes, were not identified. Fifty-nine percent of the MDR isolates belonged to a single clonal group over the course of the study period, as demonstrated by pulsed-field gel electrophoresis.

scholarly journals In Vitro Activity and MIC of Sitafloxacin against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis Isolated in Thailand

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Manoon Leechawengwongs ◽  
Therdsak Prammananan ◽  
Sarinya Jaitrong ◽  
Pamaree Billamas ◽  
Nampueng Makhao ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Critical Concentration ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

ABSTRACT New fluoroquinolones (FQs) have been shown to be more active against drug-resistant Mycobacterium tuberculosis strains than early FQs, such as ofloxacin. Sitafloxacin (STFX) is a new fluoroquinolone with in vitro activity against a broad range of bacteria, including M. tuberculosis. This study aimed to determine the in vitro activity of STFX against all groups of drug-resistant strains, including multidrug-resistant M. tuberculosis (MDR M. tuberculosis), MDR M. tuberculosis with quinolone resistance (pre-XDR), and extensively drug-resistant (XDR) strains. A total of 374 drug-resistant M. tuberculosis strains were tested for drug susceptibility by the conventional proportion method, and 95 strains were randomly submitted for MIC determination using the microplate alamarBlue assay (MABA). The results revealed that all the drug-resistant strains were susceptible to STFX at a critical concentration of 2 μg/ml. Determination of the MIC90s of the strains showed different MIC levels; MDR M. tuberculosis strains had a MIC90 of 0.0625 μg/ml, whereas pre-XDR and XDR M. tuberculosis strains had identical MIC90s of 0.5 μg/ml. Common mutations within the quinolone resistance-determining region (QRDR) of gyrA and/or gyrB did not confer resistance to STFX, except that double mutations of GyrA at Ala90Val and Asp94Ala were found in strains with a MIC of 1.0 μg/ml. The results indicated that STFX had potent in vitro activity against all the groups of drug-resistant M. tuberculosis strains and should be considered a new repurposed drug for treatment of multidrug-resistant and extensively drug-resistant TB.

scholarly journals Diverse Cytomegalovirus UL27 Mutations Adapt to Loss of Viral UL97 Kinase Activity under Maribavir

2008 ◽  
Vol 53 (1) ◽  
pp. 81-85 ◽  
Author(s):  
Sunwen Chou
Keyword(s):  
Kinase Activity ◽  
Kinase Inhibitor ◽  
Genetic Defect ◽  
Laboratory Strain ◽  
Clinical Isolates ◽  
Drug Selection ◽  
Normal Expression ◽  
High Level ◽  
Level Resistance

ABSTRACT In vitro resistance to maribavir (MBV), a cytomegalovirus UL97 kinase inhibitor currently in clinical trials, is known to result from viral UL97 mutations that confer moderate to high-level resistance and UL27 mutations that confer low-level resistance. To add to the four reported UL27 mutations, cytomegalovirus isolates or strains were propagated under MBV. Four clinical isolates evolved UL27 mutations, which were first detected after 8 to 30 passages under drug selection. In three separate experiments, laboratory strain T2294, which contained an exonuclease mutation, developed UL27 mutations at 10 to 12 passages under MBV. Most of these isolates and strains also developed a UL97 mutation, commonly T409M, before or after the appearance of the UL27 mutation. The passage of two laboratory strains genetically defective in UL97, in the absence of MBV, likewise resulted in UL27 mutations. The nine UL27 mutations observed included multiple instances of point, stop, and frameshift mutations, which were individually transferred to a reference CMV strain and which were shown to confer two- to threefold increases in MBV inhibitory concentrations. In contrast, seven common UL27 amino acid changes found in baseline clinical isolates conferred no MBV resistance. The mutants with UL27 mutations had slightly attenuated growth. The frequent mutation of UL27 suggests that its normal expression is mildly disadvantageous to the virus in the absence of UL97 kinase activity, whether the latter results from MBV inhibition or a genetic defect. Although the function of UL27 is unknown, it does not appear to be a direct antiviral target for MBV.

scholarly journals Resistance Levels and rpoB Gene Mutations among In Vitro-Selected Rifampin-Resistant Mycobacterium tuberculosis Mutants

2006 ◽  
Vol 50 (8) ◽  
pp. 2860-2862 ◽  
Author(s):  
Emma Huitric ◽  
Jim Werngren ◽  
Pontus Juréen ◽  
Sven Hoffner
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Point Mutations ◽  
Gene Mutations ◽  
Rpob Gene ◽  
Clinical Isolates ◽  
Large Deletions ◽  
High Level ◽  
Level Resistance

ABSTRACT The distribution and resistance levels of 189 in vitro-selected rifampin-resistant Mycobacterium tuberculosis mutants of Beijing and other genotypes were determined. Apart from a higher amount of codon 522 point mutations and large deletions, a spread of mutations similar to that reported for clinical isolates was seen. Most mutations were correlated with high-level resistance; a lower level, or a MIC of <16 mg/liter, was associated with codon 522 mutations. Multiple mutations were detected in two Beijing mutants.

scholarly journals Genetic Analyses of Mutations Contributing to Fluoroquinolone Resistance in Clinical Isolates ofStreptococcus pneumoniae

2001 ◽  
Vol 45 (12) ◽  
pp. 3517-3523 ◽  
Author(s):  
L. M. Weigel ◽  
G. J. Anderson ◽  
R. R. Facklam ◽  
F. C. Tenover
Keyword(s):  
Amino Acid ◽  
Antimicrobial Agents ◽  
Clinical Isolates ◽  
Fluoroquinolone Resistance ◽  
Cross Resistance ◽  
Genetic Analyses ◽  
High Level ◽  
Susceptibility Profiles ◽  
Level Resistance

ABSTRACT Twenty-one clinical isolates of Streptococcus pneumoniae showing reduced susceptibility or resistance to fluoroquinolones were characterized by serotype, antimicrobial susceptibility, and genetic analyses of the quinolone resistance-determining regions (QRDRs) of gyrA,gyrB, parC, and parE. Five strains were resistant to three or more classes of antimicrobial agents. In susceptibility profiles for gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, ofloxacin, sparfloxacin, and trovafloxacin, 14 isolates had intermediate- or high-level resistance to all fluoroquinolones tested except gemifloxacin (no breakpoints assigned). Fluoroquinolone resistance was not associated with serotype or with resistance to other antimicrobial agents. Mutations in the QRDRs of these isolates were more heterogeneous than those previously reported for mutants selected in vitro. Eight isolates had amino acid changes at sites other than ParC/S79 and GyrA/S81; several strains contained mutations in gyrB, parE, or both loci. Contributions to fluoroquinolone resistance by individual amino acid changes, including GyrB/E474K, ParE/E474K, and ParC/A63T, were confirmed by genetic transformation of S. pneumoniae R6. Mutations in gyrB were important for resistance to gatifloxacin but not moxifloxacin, and mutation of gyrAwas associated with resistance to moxifloxacin but not gatifloxacin, suggesting differences in the drug-target interactions of the two 8-methoxyquinolones. The positions of amino acid changes within the four genes affected resistance more than did the total number of QRDR mutations. However, the effect of a specific mutation varied significantly depending on the agent tested. These data suggest that the heterogeneity of mutations will likely increase as pneumococci are exposed to novel fluoroquinolone structures, complicating the prediction of cross-resistance within this class of antimicrobial agents.

scholarly journals In Vitro Selection and Characterization of Bacillus anthracis Mutants with High-Level Resistance to Ciprofloxacin

2003 ◽  
Vol 47 (7) ◽  
pp. 2362-2365 ◽  
Author(s):  
Lance B. Price ◽  
Amy Vogler ◽  
Talima Pearson ◽  
Joseph D. Busch ◽  
James M. Schupp ◽  
...  
Keyword(s):  
Bacillus Anthracis ◽  
In Vitro Selection ◽  
Quinolone Resistance ◽  
Second Step ◽  
Ciprofloxacin Resistance ◽  
High Level ◽  
Level Resistance

ABSTRACT Mutants of attenuated Bacillus anthracis with high-level ciprofloxacin resistance were isolated using a three-step in vitro selection. Ciprofloxacin MICs were 0.5 μg/ml for first-step mutants, which had one of two gyrA quinolone resistance-determining region (QRDR) mutations. Ciprofloxacin MICs were 8 and 16 μg/ml for second-step mutants, which had one of three parC QRDR mutations. Ciprofloxacin MICs for third-step mutants were 32 and 64 μg/ml. Mutants for which MICs were 64 μg/ml had one of two additional mutations within the gyrA QRDR or one of two mutations within the gyrB QRDR. Mutants for which MICs were 32 μg/ml had no additional target modifications but showed evidence of enhanced ciprofloxacin efflux.

Sign in / Sign up

Export Citation Format

Share Document