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

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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No Decrease in Susceptibility to NVC-422 in Multiple-Passage Studies with Methicillin-Resistant Staphylococcus aureus, S. aureus, Pseudomonas aeruginosa, and Escherichia coli

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05985-11 ◽

2012 ◽

Vol 56 (5) ◽

pp. 2753-2755 ◽

Cited By ~ 13

Author(s):

Louisa D'Lima ◽

Lisa Friedman ◽

Lu Wang ◽

Ping Xu ◽

Mark Anderson ◽

...

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Fusidic Acid ◽

Methicillin Resistant Staphylococcus Aureus ◽

Cross Resistance ◽

Methicillin Resistant ◽

Content Type ◽

E Coli ◽

Resistant Strains

ABSTRACTTwenty-five serial passages ofEscherichia coli,Pseudomonas aeruginosa, andStaphylococcus aureusand 50 passages of methicillin-resistantStaphylococcus aureusresulted in no significant increase in NVC-422 MICs, while ciprofloxacin MICs increased 256-fold forE. coliand 32-fold forP. aeruginosaandS. aureus. Mupirocin, fusidic acid, and retapamulin MICs for MRSA increased 64-, 256-, and 16-fold, respectively. No cross-resistance to NVC-422 was observed with mupirocin-, fusidic acid-, and retapamulin-resistant strains.

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Fusidic Acid Resistance Determinants in Staphylococcus aureus Clinical Isolates

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00523-10 ◽

2010 ◽

Vol 54 (12) ◽

pp. 4985-4991 ◽

Cited By ~ 45

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.

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Emergence of a mupirocin-resistant, methicillin-susceptible Staphylococcus aureus clone associated with skin and soft tissue infections in Greece

BMC Microbiology ◽

10.1186/s12866-021-02272-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Nikolaos Giormezis ◽

Anastassios Doudoulakakis ◽

Katerina Tsilipounidaki ◽

Maria Militsopoulou ◽

George Kalogeras ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Soft Tissue ◽

Fusidic Acid ◽

Tertiary Care ◽

Pfge Type ◽

Soft Tissue Infections ◽

Pfge Typing ◽

Genes Encoding ◽

Clonal Distribution ◽

High Level

Abstract Background Staphylococcus aureus causes various infections, including skin and soft tissue infections (SSTIs). In this study, methicillin-susceptible S. aureus (MSSA) from SSTIs among patients in three tertiary-care hospitals in Greece were studied in terms of antimicrobial resistance, clonal distribution, toxin and adhesin genes carriage. Results During a five-year period (2014–2018), 6145 S. aureus were recovered from 13,244 patients with SSTIs and tested for antimicrobial susceptibility. MSSA were 4806 (78.21 %) including 1484 isolates with mupirocin minimum inhibitory concentration (MIC) > 64 mg/L (30.88 %). Two hundred and sixty representative mupirocin-resistant MSSA were analyzed for genes encoding Panton-Valentine leukocidin (PVL, lukS/lukF-PV), exfoliative toxins (eta, etb), adhesin FnbA (fnbA) and resistance genes mupA (high-level resistance to mupirocin), fusB (fusidic acid), aminoglycosides’ modifying enzymes, ermA, ermC and msrA (macrolides/lincosamides) by PCRs. Strains were classified into clones by PFGE and MLST. All mupirocin-resistant MSSA were penicillin-resistant; 92.7 % expressed resistance to fusidic acid and 88.9 % to tobramycin. All 260 molecularly analyzed isolates were mupA-positive; all fusidic acid-resistant (241/260) carried fusB whereas, the tobramycin-resistant ones (230), ant(4′)-Ia. The majority carried eta (93.85 %), etb (98.08 %) and fnbA (88.85 %). PFGE typing revealed a mostly unvarying population; 260 MSSA were grouped into three types. One major eta/etb-positive clone comprising of 258/260 strains (99.2 %), PFGE type 1, was classified as ST121, including nine strains co-carrying PVL. Another PVL-positive strain was identified as ST1, and one toxins-negative as ST21. Conclusions A mupirocin-resistant MSSA clone, ST121, carrying resistance, exfoliative toxins and adhesin genes, was spread and predominated in SSTIs from patients in Greece during the five-year studied period.

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Characterisation of methicillin-resistant Staphylococcus aureus from Kuwait hospitals with high-level fusidic acid resistance

Journal of Medical Microbiology ◽

10.1099/0022-1317-49-5-419 ◽

2000 ◽

Vol 49 (5) ◽

pp. 419-426 ◽

Cited By ~ 6

Author(s):

E.E. UDO ◽

L.E. JACOB

Keyword(s):

Staphylococcus Aureus ◽

Fusidic Acid ◽

Methicillin Resistant Staphylococcus Aureus ◽

Acid Resistance ◽

Methicillin Resistant ◽

High Level

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PBP 4 Mediates High-Level Resistance to New-Generation Cephalosporins in Staphylococcus aureus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00358-16 ◽

2016 ◽

Vol 60 (7) ◽

pp. 3934-3941 ◽

Cited By ~ 20

Author(s):

Liana C. Chan ◽

Aubre Gilbert ◽

Li Basuino ◽

Thaina M. da Costa ◽

Stephanie M. Hamilton ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Core Genome ◽

Binding Protein ◽

Penicillin Binding Protein ◽

Methicillin Resistant ◽

Content Type ◽

Resistant Strains ◽

High Level ◽

New Generation ◽

Level Resistance

ABSTRACTStaphylococcus aureusis an important cause of both hospital- and community-associated methicillin-resistantS. aureus(MRSA) infections worldwide. β-Lactam antibiotics are the drugs of choice to treatS. aureusinfections, but resistance to these and other antibiotics make treatment problematic. High-level β-lactam resistance ofS. aureushas always been attributed to the horizontally acquired penicillin binding protein 2a (PBP 2a) encoded by themecAgene. Here, we show thatS. aureuscan also express high-level resistance to β-lactams, including new-generation broad-spectrum cephalosporins that are active against methicillin-resistant strains, through an uncanonical core genome-encoded penicillin binding protein, PBP 4, a nonessential enzyme previously considered not to be important for staphylococcal β-lactam resistance. Our results show that PBP 4 can mediate high-level resistance to β-lactams.

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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)

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkab098 ◽

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.

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CD4 T Cell Antigens from Staphylococcus aureus Newman Strain Identified following Immunization with Heat-Killed Bacteria

Clinical and Vaccine Immunology ◽

10.1128/cvi.05642-11 ◽

2012 ◽

Vol 19 (4) ◽

pp. 477-489 ◽

Cited By ~ 9

Author(s):

Paulraj K. Lawrence ◽

Bachra Rokbi ◽

Nadège Arnaud-Barbe ◽

Eric L. Sutten ◽

Junzo Norimine ◽

...

Keyword(s):

Staphylococcus Aureus ◽

T Cell ◽

Reverse Genetics ◽

Vaccine Development ◽

Protein A ◽

Cd4 T Cell ◽

Content Type ◽

Intramammary Infections ◽

T Cell Antigens ◽

Ifn Γ

ABSTRACTStaphylococcus aureusis a commensal bacterium associated with the skin and mucosal surfaces of humans and animals that can also cause chronic infection. The emergence of antibiotic-resistant strains such as methicillin-resistantS. aureus(MRSA) and strains causing chronic intramammary infections (IMI) in cows results in severe human and livestock infections. Conventional approaches to vaccine development have yielded only a few noneffective vaccines against MRSA or IMI strains, so there is a need for improved vaccine development. CD4 T lymphocytes are required for promoting gamma interferon (IFN-γ) mediated immunoglobulin isotype switching in B lymphocytes to produce high-affinity IgG antibodies and IFN-γ-mediated phagocyte activation for an effective resolution of bacterial infection. However, the lack of known CD4 T cell antigens fromS. aureushas made it difficult to design effective vaccines. The goal of this study was to identifyS. aureusproteins recognized by immune CD4 T cells. Using a reverse genetics approach, 43 antigens were selected from theS. aureusNewman strain. These included lipoproteins, proteases, transcription regulators, an alkaline shock protein, conserved-domain proteins, hemolysins, fibrinogen-binding protein, staphylokinase, exotoxin, enterotoxin, sortase, and protein A. Screening of expressed proteins for recall T cell responses in outbred, immune calves identified 13 proteins that share over 80% sequence identity among MRSA or IMI strains. These may be useful for inclusion in a broadly protective multiantigen vaccine against MRSA or IMI.

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In VitroEfficacies and Resistance Profiles of Rifampin-Based Combination Regimens for Biofilm-Embedded Methicillin-Resistant Staphylococcus aureus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01236-13 ◽

2013 ◽

Vol 57 (11) ◽

pp. 5717-5720 ◽

Cited By ~ 31

Author(s):

Hung-Jen Tang ◽

Chi-Chung Chen ◽

Kuo-Chen Cheng ◽

Kuan-Ying Wu ◽

Yi-Chung Lin ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Fusidic Acid ◽

Antibacterial Activities ◽

Methicillin Resistant ◽

Content Type ◽

Biofilm Model ◽

Rifampin Resistance ◽

Combination Regimens ◽

Resistant Mutation

ABSTRACTTo compare thein vitroantibacterial efficacies and resistance profiles of rifampin-based combinations against methicillin-resistantStaphylococcus aureus(MRSA) in a biofilm model, the antibacterial activities of vancomycin, teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, and tigecycline alone or in combination with rifampin against biofilm-embedded MRSA were measured. The rifampin-resistant mutation frequencies were evaluated. Of the rifampin-based combinations, rifampin enhances the antibacterial activities of and even synergizes with fusidic acid, tigecycline, and, to a lesser extent, linezolid, fosfomycin, and minocycline against biofilm-embedded MRSA. Such combinations with weaker rifampin resistance induction activities may provide a therapeutic advantage in MRSA biofilm-related infections.

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Ceftaroline Activity against Bacterial Pathogens Frequently Isolated in U.S. Medical Centers: Results from Five Years of the AWARE Surveillance Program

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04614-14 ◽

2015 ◽

Vol 59 (4) ◽

pp. 2458-2461 ◽

Cited By ~ 22

Author(s):

Helio S. Sader ◽

Robert K. Flamm ◽

Jennifer M. Streit ◽

David J. Farrell ◽

Ronald N. Jones

Keyword(s):

Staphylococcus Aureus ◽

Streptococcus Pneumoniae ◽

Bacterial Pathogens ◽

Surveillance Program ◽

Broth Microdilution ◽

Methicillin Resistant ◽

Content Type ◽

Medical Centers ◽

Resistant Strains

ABSTRACTA total of 84,704 isolates were collected from 191 medical centers in 2009 to 2013 and tested for susceptibility to ceftaroline and comparator agents by broth microdilution methods. Ceftaroline inhibited allStaphylococcus aureusisolates at ≤2 μg/ml and was very active against methicillin-resistant strains (MIC at which 90% of the isolates tested are inhibited [MIC90], 1 μg/ml; 97.6% susceptible). AmongStreptococcus pneumoniaeisolates, the highest ceftaroline MIC was 0.5 μg/ml, and ceftaroline activity against the most commonEnterobacteriaceaespecies (MIC50, 0.12 μg/ml; 78.9% susceptible) was similar to that of ceftriaxone (MIC50, ≤0.25 μg/ml; 86.8% susceptible).

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