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 ◽  
...  

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)>128 μg/ml]. Acquired gene, fusB, with low-level resistance (MIC <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.

2020 ◽  
Author(s):  
Wenjing Chen ◽  
Chunyan He ◽  
Han Yang ◽  
Wen Shu ◽  
Zelin Cui ◽  
...  

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.


2010 ◽  
Vol 54 (12) ◽  
pp. 4985-4991 ◽  
Author(s):  
Hsiao-Jan Chen ◽  
Wei-Chun Hung ◽  
Sung-Pin Tseng ◽  
Jui-Chang Tsai ◽  
Po-Ren Hsueh ◽  
...  

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.


2015 ◽  
Vol 59 (5) ◽  
pp. 2960-2963 ◽  
Author(s):  
Liana C. Chan ◽  
Li Basuino ◽  
Binh Diep ◽  
Stephanie Hamilton ◽  
Som S. Chatterjee ◽  
...  

ABSTRACTThe role ofmecAmutations in conferring resistance to ceftobiprole and ceftaroline, cephalosporins with anti-methicillin-resistantStaphylococcus aureus(MRSA) activity, was determined with MRSA strains COL and SF8300. The SF8300 ceftaroline-passaged mutant carried a singlemecAmutation, E447K (E-to-K change at position 447), and expressed low-level resistance. This mutation in COL conferred high-level resistance to ceftobiprole but only low-level resistance to ceftaroline. The COL ceftaroline-passaged mutant, which expressed high-level resistance to ceftobiprole and ceftaroline, had mutations inpbp2,pbp4, andgdpPbut notmecA.


1999 ◽  
Vol 43 (11) ◽  
pp. 2813-2816 ◽  
Author(s):  
Thomas A. Wichelhaus ◽  
Volker Schäfer ◽  
Volker Brade ◽  
Boris Böddinghaus

ABSTRACT Mutations of the rpoB gene conferring resistance to rifampin were analyzed in 40 methicillin-resistant Staphylococcus aureus isolates obtained from six countries. Interestingly, the majority of clinical isolates showed multiple mutations withinrpoB. The amino acid substitution 481His→Asn was the most prevalent one, capable of conferring low-level resistance on its own. Cross-resistance to rifampin, rifabutin, and rifapentine was demonstrated for all mutants identified. The level of resistance to rifamycins correlated with both the mutation position and type of amino acid substitution.


2017 ◽  
Vol 9 (04) ◽  
pp. 239-242 ◽  
Author(s):  
Jutang Babat Ain Tiewsoh ◽  
Meena Dias

Abstract BACKGROUND: Staphylococcus is the most common pathogen causing infection in hospitals. They also colonize the healthcare workers who serve as reservoir of infection. Emergence of methicillin-resistant Staphylococcus aureus (MRSA) is a burning issue throughout the world contributing to significant morbidity and mortality. Use of mupirocin to eradicate the carrier state is the need of the hour. OBJECTIVES: To screen healthcare workers (HCWs) and medical students for MRSA and to know the susceptibility of mupirocin in this group. MATERIALS AND METHODS: A total of 432 students, nursing staff, doctors and house-keeping staff were screened for MRSA for 4 months. The MRSA and methicillin-resistant coagulase-negative Staphylococcus (MRCoNS) isolates were then tested for mupirocin resistance. RESULTS: Out of 432 samples, 24 (5.55%) were MRSA and 104 (24.07%) were MRCoNS. Only 4.16% (n = 1) showed high-level resistance to mupirocin among the MRSA isolates, while resistance among MRCoNS was higher at 6.7% (n = 7) for low-level resistance and 17.30% (n = 18) for high-level resistance. CONCLUSION: MRSA colonization of HCWs may serve as a source of infection and mupirocin resistance should be screened for all whether working in Intensive Care Units or not and if detected, alternative treatment should be used which will result in appropriate use of this antibiotic for decolonization.


2015 ◽  
Vol 59 (5) ◽  
pp. 2799-2806 ◽  
Author(s):  
Andrew D. Berti ◽  
Sarah L. Baines ◽  
Benjamin P. Howden ◽  
George Sakoulas ◽  
Victor Nizet ◽  
...  

ABSTRACTDaptomycin is increasingly used in combination with other antibiotics to enhance antimicrobial efficacy and/or to mitigate the emergence of daptomycin nonsusceptibility (DNS). This study used a clinical methicillin-resistantStaphylococcus aureus(MRSA) strain in which DNS emerged upon therapy to examine the influence of antibiotic combinations on the development of mutations in specific genes (mprF,rpoBC,dltA,cls2, andyycFG) previously associated with DNS. Whole genomes of bacteria obtained following 28 days ofin vitroexposure to daptomycin with or without adjunctive clarithromycin, linezolid, oxacillin, or trimethoprim-sulfamethoxazole were sequenced, and the sequences were compared to that of the progenitor isolate. The addition of oxacillin to medium containing daptomycin prevented the emergence ofmprFmutation but did not preventrpoBCmutation (P< 0.01). These isolates maintained susceptibility to daptomycin during the combined exposure (median MIC, 1 mg/liter). Daptomycin plus clarithromycin or linezolid resulted in low-level (1.5 to 8 mg/liter) and high-level (12 to 96 mg/liter) DNS, respectively, and did not preventmprFmutation. However, these same combinations preventedrpoBCmutation. Daptomycin alone or combined with linezolid or trimethoprim-sulfamethoxazole resulted in high-level DNS and mutations inmprFplusrpoBC,cls2, andyycFG. Combining daptomycin with different antimicrobials alters the mutational space available for DNS development, thereby favoring the development of predictable collateral susceptibilities.


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