The global prevalence of fusidic acid resistance in clinical isolates of Staphylococcus aureus: a systematic review and meta-analysis.
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ABSTRACT: Background and aim
Staphylococcus aureus (S. aureus) is one of the most common pathogens causing nosocomial and community-acquired infections with high morbidity and mortality rates. Fusidic acid has been increasingly used for the treatment of infections due to methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). The present study aimed to determine the precise prevalence of fusidic acid resistant MRSA (FRMRSA), fusidic acid resistant MSSA (FRMSSA), and total fusidic acid resistant S. aureus (FRSA) on a global scale.Methods
Several international databases including Medline, Embase, and the Web of Sciences were searched (2000-2020) to discern studies addressing the prevalence of FRSA, FRMRSA, and FRMSSA. STATA (version14) software was used to interpret the data.Results
Of the 1446 records identified from the databases, 215 studies fulfilled the eligibility criteria for the detection of FRSA (208 studies), FRMRSA (143 studies), and FRMSSA (71 studies). The analyses manifested that the global prevalence of FRSA, FRMRSA, and FRMSSA was 0.5%, 2.6% and 6.7%, respectively.Conclusion
This meta-analysis describes an increasing incidence of FRSA, FRMSSA, and FRMRSA. These results indicate the need for prudent prescription of fusidic acid to stop or diminish the incidence of fusidic acid resistance as well as the development of strategies for monitoring the efficacy of fusidic acid use.
SUBMITTER: Hajikhani B
PROVIDER: S-EPMC8088720 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Genome-wide transcriptional profiling studies of the growth of bacteria with antimicrobial agents often reveals aspects of the drug-specific protective bacterial response. Fusidic acid is a steroid antimicrobial that inhibits protein synthesis by interfering with the release of elongation factor G (EF-G) after it has functioned in the translocation step. Two hundred and seventy two genes were both up- and down-regulated in a fusidic acid-susceptible strain of Staphylococcus aureus following challenge with 2 mg/L-1 fusidic acid for 15 min. Many genes altered by fusidic acid challenge are associated with protein synthesis such as fusA, which encodes EF-G which was up-regulated following exposure to the drug. The Staphylococcus microarray meta-database which curates and compares S. aureus transcriptome data revealed that the fusidic acid stimulon has the greatest overlap with the S. aureus cold shock- and stringent-responses. Six out of 9 autolysin genes making up the two component YycFG regulon (ssaA1-ssaA4, isaA and sceD) were also upregulated by fusidic acid; as were a carboxylesterase (est) and two putative Emr-Qac-like multidrug efflux pumps (emr-qac1 and emr-qac2). Genes down-regulated by fusidic acid induction encode a putative secreted acid phosphatase (sapS) and a number of protease genes (yjbG1, yjbG2, htrA1 and htrA2). Transcriptional analysis in conjunction with mutant fusidic acid susceptibility experiments revealed that th45 e virulence gene regulatory agr operon, a YycFG controlled peptidoglycan hydrolase gene isaA and the proteases htrA1 and htrA2 are required for the expression of wild-type levels of fusidic acid susceptibility.
2008-08-25 | GSE12210 | GEO
Project description:BackgroundThe 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. This study aimed to examine these three antibiotics resistance in 1206 MRSA clinical isolates from Eastern China. Phenotypic MUP, FA and RET resistance was determined by minimum inhibitory concentrations (MICs), and genotypic by PCR and DNA sequencing of the mupA/B, fusB-D, cfr, vgaA/Av/ALC/B/C/E, lsaA-C/E and salA and mutations in ileS, fusA/E, rplC, and 23S RNA V domain. The genetic characteristics of resistance isolates were conducted by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST).ResultsOverall MRSA MUP, FA and RET resistance was low (5.1, 1.0 and 0.3%, respectively). MupA was the mechanism of high-level MUP resistance. All low-level MUP resistance isolates possessed an equivocal mutation N213D in IleS; of these, 2 reported an additional V588F mutation with an impact on the Rossman fold. FusA mutations, such as L461K, H457Q, H457Y and V90I were the primary FA mechanisms among high-level resistance isolates, most of which also contained fusC; however, all low-level resistance strains carried fusB. Except lsaE gene detected in one isolate, no other resistance mechanisms tested were found among RET-resistant isolates. Additionally, sixteen PFGE types (A-P) were observed, among which type B was the most common (49/76, 64.5%), followed by types E and G (4/76, 5.3% each) and types C and M (3/76, 3.9% each). All resistant strains were divided into 15 ST types by MLST. ST764 (24/76, 31.6%), ST630 (11/76, 14.5%), ST239 (9/76, 11.8%) and ST5 (7/76, 9.2%) were the major types. PFGE type B isolates with the aforementioned STs were mainly found in mupirocin resistant isolates.ConclusionsMUP, FA and RET exhibited highly activity against the MRSA isolates. Acquired genes and chromosome-borne genes mutations were responsible for MUP and FA resistance; however, the mechanism for some RET-resistant isolates remains to be further elucidated. Also, the surveillance to MUP in MRSA should be strengthened to prevent elevated resistance due to the expansion of clones.
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