scholarly journals In vitro activity and resistance rates of topical antimicrobials fusidic acid, mupirocin and ozenoxacin against skin and soft tissue infection pathogens obtained across Canada (CANWARD 2007–18)

2021 ◽  
Author(s):  
George G Zhanel ◽  
Heather J Adam ◽  
Melanie Baxter ◽  
Philippe R S Lagace-Wiens ◽  
James A Karlowsky
Keyword(s):  
Soft Tissue ◽  
Fusidic Acid ◽  
Acid Resistance ◽  
In Vitro Activity ◽  
Low Level ◽  
Topical Antimicrobials ◽  
High Level ◽  
Resistance Rates ◽  
Level Resistance

Abstract Background Current antimicrobial susceptibility/resistance data versus skin and soft tissue infection (SSTI) pathogens help to guide empirical treatment using topical antimicrobials. Objectives To assess the in vitro activity and resistance rates of fusidic acid, mupirocin, ozenoxacin and comparator agents against pathogens isolated from patients with SSTIs in Canada. Methods SSTI isolates of MSSA (n = 422), MRSA (n = 283) and Streptococcus pyogenes (n = 46) obtained from CANWARD 2007–18 were tested using CLSI broth microdilution. Fusidic acid low-level resistance was defined as an MIC of ≥2 mg/L and high-level resistance as an MIC ≥512 mg/L. Mupirocin high-level resistance was defined as an MIC ≥512 mg/L and low-level resistance was an MIC of 2–256 mg/L. Results Low-level and high-level fusidic acid resistance in MSSA was 10.9% and 1.7%, respectively. Low-level and high-level fusidic acid resistance in MRSA was 10.6% and 3.5%, respectively. High-level mupirocin resistance was identified in 1.4% of MSSA and 14.1% of MRSA, respectively. Versus MSSA, ozenoxacin demonstrated MIC50 and MIC90 of 0.004 and 0.25 mg/L, respectively. Against MRSA, ozenoxacin inhibited all isolates at an MIC of ≤0.5 mg/L, including isolates with ciprofloxacin MICs >2 mg/L, clarithromycin-resistant, clindamycin-resistant, high-level fusidic acid-resistant and high-level mupirocin-resistant isolates. Conclusions We conclude that fusidic acid low-level resistance exceeded 10% for both MSSA and MRSA while fusidic acid high-level resistance was ≤3.5%. Mupirocin high-level resistance exceeded 10% in MRSA. Ozenoxacin is active versus SSTI pathogens including MRSA resistant to fluoroquinolones, macrolides, clindamycin, fusidic acid and mupirocin.

scholarly journals Efficacy of vancomycin and teicoplanin alone and in combination with streptomycin in experimental, low-level vancomycin-resistant, VanB-type Enterococcus faecalis endocarditis.

1996 ◽  
Vol 40 (1) ◽  
pp. 55-60 ◽  
Author(s):  
D P Nicolau ◽  
M N Marangos ◽  
C H Nightingale ◽  
K B Patel ◽  
B W Cooper ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Resistant Strain ◽  
Low Level ◽  
Vancomycin Resistant ◽  
Low Levels ◽  
High Level ◽  
Isogenic Strains ◽  
Level Resistance

The efficacy of vancomycin (VM) and teicoplanin (TE), alone and in combination with streptomycin (SM), against enterococci that express low-level VanB-type VM resistance was investigated in experimental endocarditis using isogenic strains of Enterococcus faecalis susceptible to glycopeptides and aminoglycosides or inducibly resistant to low levels of VM (MIC = 16 micrograms/ml). VM was significantly less active against the resistant strain than against the susceptible strain, establishing that low-level VanB-type VM resistance can influence therapeutic efficacy. By contrast, TE had equally good activity against both strains. VM or TE combined with SM was synergistic and bactericidal against the resistant strain in vitro. While both combinations were efficient in reducing bacterial density in vivo, TE plus SM was significantly superior to VM plus SM if valve sterilization was considered. These data suggest that despite the presence of low-level VanB-type resistance, combination therapy with a glycopeptide and SM (and presumably other aminoglycosides to which there is not high-level resistance) will nevertheless provide effective bactericidal activity.

scholarly journals Prevalence and molecular characterization of methicillin-resistant Staphylococcus aureus with mupirocin, fusidic acid and/or retapamulin resistance

2020 ◽  
Author(s):  
Wenjing Chen ◽  
Chunyan He ◽  
Han Yang ◽  
Wen Shu ◽  
Zelin Cui ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Fusidic Acid ◽  
Resistance Mechanisms ◽  
Antibiotics Resistance ◽  
Genetic Characteristics ◽  
Methicillin Resistant ◽  
Low Level ◽  
High Level ◽  
Level Resistance

Abstract Data on the prevalence of resistance to mupirocin (MUP), fusidic acid (FA) and retapamulin (RET) in methicillin-resistant Staphylococcus aureus (MRSA) from China are still limited. In this study we examined these three antibiotics resistance pheno and geno-typically in 1206 MRSA clinical isolates. Phenotypic MUP, FA and RET resistance was determined by MICs, and genotypically by PCR and DNA sequencing examining genes mupA / B , fusB - D , cfr and vgaA / Av , and mutations in ileS , fusA / E , rplC , and 23S RNA V domain. The genetic characteristics of resistance isolates were conducted by PFGE and MLST. Overall MRSA MUP, FA and RET resistance was low (5.1%, 1.0% and 0.3%, respectively). The mupA was the mechanism of high-level MUP resistance. All low-level MUP resistance isolates possessed an equivocal mutation N213D in IleS, and 2 of them additionally had the reported V588F mutation impacting the Rossman fold. FusA mutations, such as L461K, H457Q, H457Y and V90I, were the primary FA resistance mechanisms among high-level resistance isolates, most of which contained fusC ; however, all low-level resistance strains carried fusB . No resistance mechanisms detected were found among RET resistance isolates. Genetic analysis demonstrated clone spread for MUP resistance isolates. In conclusion, MUP, FA and RET exhibited highly activity against MRSA isolates. Acquired genes and chromosome-borne genes mutations were responsible for MUP and FA resistance, and further investigation is needed to uncover the RET resistance mechanisms. Moreover, the surveillance to MUP in MRSA should be strengthened to prevent resistance increase due to the expansion of clones.

scholarly journals In VitroActivity of Simeprevir against Hepatitis C Virus Genotype 1 Clinical Isolates and Its Correlation with NS3 Sequence and Site-Directed Mutants

2015 ◽  
Vol 59 (12) ◽  
pp. 7548-7557 ◽  
Author(s):  
Thierry Verbinnen ◽  
Bart Fevery ◽  
Leen Vijgen ◽  
Tom Jacobs ◽  
Sandra De Meyer ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Genotype 1 ◽  
Low Level ◽  
Fold Reduction ◽  
Hcv Genotype 1 ◽  
High Level ◽  
Ns3 Protease ◽  
Level Resistance

ABSTRACTSimeprevir (TMC435) is a once-daily, single-pill, oral hepatitis C virus (HCV) NS3 protease inhibitor approved for the treatment of chronic HCV infection. Phenotypic characterization of baseline isolates and isolates from HCV genotype 1-infected patients failing with a simeprevir-based regimen was performed using chimeric replicons carrying patient-derived NS3 protease sequences. Cutoff values differentiating between full susceptibility to simeprevir (≤2.0-fold reduction in simeprevir activity) and low-level versus high-level resistance (≥50-fold reduction in simeprevir activity) were determined. The median simeprevir fold change in the 50% effective concentration (FC) of pretreatment genotype 1a isolates, with and without Q80K, and genotype 1b isolates was 11, 0.9, and 0.4, respectively. Naturally occurring NS3 polymorphisms that reduced simeprevir activity, other than Q80K, were uncommon in the simeprevir studies and generally conferred low-level resistancein vitro. Although the proportion of patients with failure differed by HCV geno/subtype and/or presence of baseline Q80K, the level of simeprevir resistance observed at failure was similarly high irrespective of type of failure, HCV genotype 1 subtype, and presence or absence of baseline Q80K. At the end of the study, simeprevir activity against isolates that lost the emerging amino acid substitution returned to pretreatment values. Activity of simeprevir against clinical isolates and site-directed mutant replicons harboring the corresponding single or double amino acid substitutions correlated well, showing that simeprevir resistance can be attributed to these substitutions. In conclusion, pretreatment NS3 isolates were generally fully susceptible (FC, ≤2.0) or conferred low-level resistance to simeprevirin vitro(FC, >2.0 and <50). Treatment failure with a simeprevir-based regimen was associated with emergence of high-level-resistance variants (FC, ≥50).

scholarly journals Low-Level Resistance to Rifampin in Streptococcus pneumoniae

2003 ◽  
Vol 47 (3) ◽  
pp. 863-868 ◽  
Author(s):  
Patricia Stutzmann Meier ◽  
Silvia Utz ◽  
Suzanne Aebi ◽  
Kathrin Mühlemann
Keyword(s):  
Streptococcus Pneumoniae ◽  
Point Mutations ◽  
Low Level ◽  
Development Of Resistance ◽  
Rifampin Resistance ◽  
High Level ◽  
Tissue Compartments ◽  
Level Resistance

ABSTRACT Rifampin is recommended for combination therapy of meningitis due to β-lactam-resistant Streptococcus pneumoniae. High-level rifampin resistance (MIC, ≥4 mg/liter) has been mapped to point mutations in clusters I and III of rpoB of the pneumococcus. The molecular basis of low-level resistance (MICs, ≥0.5 and <4 mg/liter) was analyzed. Spontaneous mutants of clinical pneumococcal isolates were selected on Columbia sheep blood agar plates containing rifampin at 0.5, 4, 10, or 50 mg/liter. Low-level resistance could be assigned to mutations in cluster II (I545N, I545L). Sensitive (MIC, <0.048 mg/liter) wild-type strains acquired low-level resistance at a rate approximately 10 times higher than that at which they acquired high-level resistance (average mutation frequencies, 2.4 × 10−7 for low-level resistance versus 2.9 × 10−8 for high-level resistance [P < 0.0001]). In second-step experiments, the frequencies of mutations from low- to high-level resistance were over 10 times higher than the frequencies of mutations from susceptibility to high-level resistance (average mutation frequencies, 7.2 × 10−7 versus 5.0 × 10−8 [P < 0.001]). Mutants with low-level resistance were stable upon passage. Sequencing of a clinical isolate with low-level resistance (MIC, 0.5 mg/liter) revealed a Q150R mutation upstream of cluster I. The frequencies of mutations to high-level resistance for this strain were even higher than the rates observed for the in vitro mutants. Therefore, a resistance-mediating mutation located outside clusters I, II, and III has been described for the first time in the pneumococcus. In vitro low-level rifampin resistance in S. pneumoniae could be mapped to cluster II of rpoB. Mutants of pneumococcus with low-level resistance may be selected in vivo during therapy in tissue compartments with low antibiotic concentrations and play a role in the development of resistance.

scholarly journals Fusidic Acid Resistance Determinants in Staphylococcus aureus Clinical Isolates

2010 ◽  
Vol 54 (12) ◽  
pp. 4985-4991 ◽  
Author(s):  
Hsiao-Jan Chen ◽  
Wei-Chun Hung ◽  
Sung-Pin Tseng ◽  
Jui-Chang Tsai ◽  
Po-Ren Hsueh ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Fusidic Acid ◽  
Acid Resistance ◽  
Nucleotide Sequencing ◽  
Methicillin Resistant ◽  
Resistance Determinants ◽  
High Level ◽  
Flanking Regions ◽  
First Time ◽  
Level Resistance

ABSTRACT A total of 71 fusidic acid-resistant Staphylococcus aureus (45 methicillin-resistant and 26 methicillin-susceptible) isolates were examined for the presence of resistance determinants. Among 45 fusidic acid-resistant methicillin-resistant S. aureus (MRSA), isolates, 38 (84%) had fusA mutations conferring high-level resistance to fusidic acid (the MIC was ≥128 μg/ml for 22/38), none had fusB, and 7 (16%) had fusC. For 26 fusidic acid-resistant methicillin-susceptible S. aureus (MSSA), only 3 possessed fusA mutations, but 15 (58%) had fusB and 8 (31%) had fusC. Low-level resistance to fusidic acid (MICs ≤ 32 μg/ml) was found in most fusB- or fusC-positive isolates. For 41 isolates (38 MRSA and 3 MSSA), with fusA mutations, a total of 21 amino acid substitutions in EF-G (fusA gene) were detected, of which R76C, E444K, E444V, C473S, P478S, and M651I were identified for the first time. The nucleotide sequencing of fusB and flanking regions in an MSSA isolate revealed the structure of partial IS257-aj1-LP-fusB-aj2-aj3-IS257-partial blaZ, which is identical to the corresponding region in pUB101, and the rest of fusB-carrying MSSA isolates also show similar structures. On the basis of spa and staphylococcal cassette chromosome mec element (SCCmec) typing, two major genotypes, spa type t037-SCCmec type III (t037-III; 28/45; 62%) and t002-II (13/45; 29%), were predominant among 45 MRSA isolates. By pulsed-field gel electrophoresis analysis, 45 MRSA isolates were divided into 12 clusters, while 26 MSSA isolates were divided into 15 clusters. Taken together, the distribution of fusidic acid resistance determinants (fusA mutations, fusB, and fusC) was quite different between MRSA and MSSA groups.

scholarly journals The Prevalence and Determinants of Fusidic Acid Resistance Among Methicillin-Resistant Staphylococcus aureus Clinical Isolates in China

2021 ◽  
Vol 8 ◽  
Author(s):  
Huilin Zhao ◽  
Xinyi Wang ◽  
Bingjie Wang ◽  
Yanlei Xu ◽  
Lulin Rao ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Fusidic Acid ◽  
Inner Mongolia ◽  
Methicillin Resistant ◽  
Autonomous Region ◽  
Low Level ◽  
Broth Microdilution Method ◽  
High Level ◽  
Inner Mongolia Autonomous Region ◽  
Level Resistance

The significant increase in resistance of methicillin-resistant Staphylococcus aureus (MRSA) to fusidic acid (FA) is a worrying public concern. However, the data on the prevalence of FA-resistant MRSA isolates in China is still limited. This study aims to investigate the prevalence of FA resistance and resistance determinants among MRSA isolates from six tertiary hospitals in different regions of China between 2016 and 2020. The antimicrobial susceptibility of MRSA isolates was performed by disk diffusion test and broth microdilution method. Whole-genome sequencing was conducted to evaluate the determinants of FA resistance and molecular characterization of FA-resistant MRSA isolates. In this study, a total of 74 (74/457, 16.2%) isolates were identified to be FA-resistant among 457 non-duplicate MRSA isolates. The prevalence of 74 FA-resistant isolates was as follows: Hubei (28/70, 40%), Shanghai (18/84, 21.4%), Jiangxi (7/58, 12.1%), Inner Mongolia Autonomous Region (6/38, 15.8%), Guangdong (12/112, 10.7%), and Sichuan (3/95, 3.2%). The mutations in fusA were present in 79.7% (59/74) of FA-resistant MRSA isolates, with 54 (54/74, 73%) having L461K mutation and conferring high-level resistance [Minimum Inhibitory Concentration (MIC)&gt;128 μg/ml]. Acquired gene, fusB, with low-level resistance (MIC &lt;16 μg/ml) was found in 20.3% (15/74) FA-resistant MRSA isolates. ST5-MRSA-II-t2460 was the most prevalence clone with high-level resistance, accounting for 51.4% (38/74), which was distributed in Hubei (24/28, 85.7%), Inner Mongolia Autonomous Region (4/6, 66.7%), Shanghai (7/18, 38.9%), and Guangdong (3/12, 25%). ST630-t4549 MRSA isolates with low-level resistance were the most common in Jiangxi (3/7, 42.9%) and Sichuan (2/3, 66.7%). In brief, the prevalence of FA resistance among MRSA isolates in China was relatively high with geographic differences. High-level FA resistance was associated mostly with fusA mutations, especially the L461K mutation, whereas fusB usually conferred the low-level resistance to FA. The spread of ST5-MRSA-II-t2460 clone with high-level resistance to FA contributed greatly to the increase of FA-resistant MRSA isolates in most regions, especially in Hubei.

scholarly journals High-level fluoroquinolone resistance in Streptococcus pneumoniae requires mutations in parC and gyrA.

1996 ◽  
Vol 40 (12) ◽  
pp. 2760-2764 ◽  
Author(s):  
C Janoir ◽  
V Zeller ◽  
M D Kitzis ◽  
N J Moreau ◽  
L Gutmann
Keyword(s):  
Streptococcus Pneumoniae ◽  
Quinolone Resistance ◽  
Fluoroquinolone Resistance ◽  
Clinical Samples ◽  
Low Frequencies ◽  
Low Level ◽  
Resistant Strains ◽  
High Level ◽  
Level Resistance

The mechanism of high-level fluoroquinolone resistance was studied in strains of Streptococcus pneumoniae, either selected in vitro or isolated from clinical samples. By using DNA from these high-level-resistant strains, low-level-resistant transformants (MIC of pefloxacin, > or = 32 micrograms/ml; MIC of ciprofloxacin, 4 micrograms/ml; MIC of sparfloxacin, 0.50 micrograms/ml) were obtained at high frequencies (ca.10(-2)), while high-level-resistant transformants (MIC of pefloxacin, > or = 64 micrograms/ml; MIC of ciprofloxacin, 16 to 64 micrograms/ml; MIC of sparfloxacin, > or = 8 micrograms/ml) were obtained only at low frequencies (ca.10(-4)). This suggested that mutations in at least two unlinked genes were necessary to obtain high-level resistance. Low-level resistance was associated with ParC mutations (change from Ser to Tyr at position 79 [Ser79Tyr], Ser79Phe, or Asp83Gly). ParC mutations were associated, in high-level-resistant strains and transformants, with alterations in the quinolone resistance-determining region of GyrA (Ser84Tyr, Ser84Phe, and/or Glu88Lys). Low-level resistance was shown to be necessary for expression of the gyrA mutations. No mutation in the region corresponding to the quinolone resistance-determining region of GyrB and no alteration of drug accumulation were found.

scholarly journals Characterization of Saccharomyces cerevisiae strains displaying high-level or low-level resistance to trichothecene antibiotics

1990 ◽  
Vol 267 (3) ◽  
pp. 709-713 ◽  
Author(s):  
M Fernandez-Lobato ◽  
M Cannon ◽  
J A Mitlin ◽  
R C Mount ◽  
A Jimenez
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Ribosome Biogenesis ◽  
Gene Encoding ◽  
Ribosomal Subunits ◽  
Low Level ◽  
Ribosomal Protein L3 ◽  
High Level ◽  
Level Resistance

Biochemical and genetic analyses have been carried out on Saccharomyces cerevisiae strains characterized in vivo as sensitive, low-level-resistant or high-level-resistant to trichothecene antibiotics. Levels of drug resistance in vitro were determined for each strain and for suitable diploids derived from them. Ribosome biogenesis was also studied in selected haploids. It is suggested that resistance in all cases results from a mutation in the gene encoding ribosomal protein L3. If this is indeed the situation, then different mutations in this same gene not only can cause low-level or high-level resistance to trichothecene antibiotics but also can affect the maturation of either 40 S or 60 S ribosomal subunits.

scholarly journals Emergence of a Staphylococcus aureus Clone Resistant to Mupirocin and Fusidic Acid Carrying Exotoxin Genes and Causing Mainly Skin Infections

2017 ◽  
Vol 55 (8) ◽  
pp. 2529-2537 ◽  
Author(s):  
Anastassios Doudoulakakis ◽  
Iris Spiliopoulou ◽  
Nikolaos Spyridis ◽  
Nikolaos Giormezis ◽  
John Kopsidas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Fusidic Acid ◽  
Protein A ◽  
Acid Resistance ◽  
Content Type ◽  
Staphylococcal Infections ◽  
Genes Encoding ◽  
Topical Antimicrobials ◽  
Resistant Strains ◽  
High Level

ABSTRACTSkin and soft tissue infections (SSTIs) caused by mupirocin-resistantStaphylococcus aureusstrains have recently increased in number in our settings. We sought to evaluate the characteristics of these cases over a 43-month period. Data for all community-acquired staphylococcal infections caused by mupirocin-resistant strains were retrospectively reviewed. Genes encoding products producing high-level resistance (HLR) to mupirocin (mupA), fusidic acid resistance (fusB), resistance to macrolides and lincosamides (ermCandermA), Panton-Valentine leukocidin (PVL) (lukS/lukF-PV), exfoliative toxins (etaandetb), and fibronectin binding protein A (fnbA) were investigated by PCRs in 102 selected preserved strains. Genotyping was performed by SCCmecandagrtyping, whereas clonality was determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). A total of 437 cases among 2,137 staphylococcal infections were recorded in 2013 to 2016; they were all SSTIs with the exception of 1 case of primary bacteremia. Impetigo was the predominant clinical entity (371 cases [84.9%]), followed by staphylococcal scalded skin syndrome (21 cases [4.8%]), and there were no abscesses. The number of infections detected annually increased during the study years. All except 3 isolates were methicillin susceptible. The rates of HLR to mupirocin and constitutive resistance to clindamycin were 99% and 20.1%, respectively. Among the 102 tested strains, 100 (98%) weremupApositive and 97 (95%) werefusBpositive, 26/27 clindamycin-resistant strains (96.3%) wereermApositive, 83 strains (81.4%) werelukS/lukFpositive, 95 (93%) carried bothetaandetbgenes, and 99 (97%) werefnbApositive. Genotyping of methicillin-sensitiveS. aureus(MSSA) strains revealed that 96/99 (96.7%) belonged to one main pulsotype, pulsotype 1, classified as sequence type 121 (ST121). The emergence of a single MSSA clone (ST121) causing impetigo was documented. Resistance to topical antimicrobials and a rich toxinogenic profile confer to this clone adaptability for spread in the community.

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