The Continuing Threat of Methicillin-Resistant Staphylococcus aureus
Abstract
1. Introduction
2. MRSA Colonization and Screening
3. Genetics of MRSA, Typing Methods
4. Treatment Considerations, Emerging Concepts
5. Concluding Remarks
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
Abbreviations | Full |
AST | antimicrobial susceptibility testing |
CA | community-acquired; CAMERA |
CAMERA | combination antibiotic therapy for methicillin-resistant Staphylococcus aureus infection (clinical trial) |
CAP | community-acquired pneumonia |
CC | clonal complex |
CDC | US Centers for Disease Control and Prevention |
cgMLST | core genome multi-locus sequence typing |
CLSI | Clinical and Laboratory Standards Institute |
CoNS | coagulase-negative Staphylococcus |
CO-MRSA | community-onset MRSA |
CRISPR/Cas9 | lustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 |
CYP | cytochrome P450 |
DHFR | dihydrofolate-reductase |
ESBL | extended-spectrum β-lactamase |
ESCMID | European Society of Clinical Microbiology and Infectious Diseases |
EU | European Union |
EUCAST | European Committee on Antimicrobial Susceptibility Testing |
FDA | US Food and Drug Administration |
HA | hospital-associated |
HAP | hospital-acquired pneumonia |
hVISA | heterogeneous vancomycin-intermediate S. aureus |
HLA | human leukocyte antigen |
IAI | intra-abdominal infection |
LA | livestock-associated |
MALDI-TOF MS | matrix-assisted laser desorption/ionization time-of-flight mass spectrometry |
MAO-A | monoamine-oxidase-A |
MFS | major facilitator superfamily |
MDR | multidrug-resistant |
MIC | minimal inhibitory concentration |
MLST | multi-locus sequence typing |
MRSA | methicillin/oxacillin-resistant S. aureus |
NGS | next-generation sequencing |
NP | nanoparticle |
OPAT | outpatient parenteral antibiotic therapy |
PFGE | pulse-field gel electrophoresis |
PBP | penicillin-binding protein |
QS | quorum sensing |
UTI | urinary tract infection |
PDI | prosthetic device infection |
PCR | polymerase chain reaction |
PVL | Panton–Valentine leucocidin |
QRDR | quinolone resistance-determining region |
QTc | corrected QT-interval |
RNA | ribonucleic acid |
RNAi | RNA-interference |
SCV | small-colony variant |
SMX/TMP | co-trimoxazole |
SSTI | skin and soft tissue infection |
ST | sequence type |
ssDNA | single-strand DNA |
ssRNA | single-strand RNA |
TDM | therapeutic drug monitoring |
TAT | turnaround time |
TLR | toll-like receptor |
TSS | toxic shock syndrome |
TSST | toxic shock syndrome toxin |
UTI | urinary tract infection |
VAP | ventilator-associated pneumonia |
VISA | vancomycin-intermediate S. aureus |
VNTR | variable number tandem repeat |
VRE | vancomycin-resistant enterococci |
VRSA | vancomycin-resistant S. aureus |
WGS | whole-genome sequencing |
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Antibiotic Class (with Examples) | Advantages Indications (in Italics) | Disadvantages |
---|---|---|
SMX/TMP | Available for oral and parenteral use Good tolerability Price of therapy Wide range of indications | Resistance levels iv. infusion has to be administered in a large volume of fluid |
Tetracyclines/Glycylcyclines (doxycycline, tygecycline) | Broad spectrum activity Wide range of indications (tigecycline: SSTIs, cIAI, CAP) | Doxycycline: resistance levels Tygecycline: black box warning, iv. only Severe nausea and vomiting (dose-limiting side effect) |
Novel tetracycline-derivatives (eravacycline, omadacycline) | Broad spectrum activity CAP, SSTIs | Severe nausea and vomiting (dose-limiting side effect) Parenteral only Resistance expression/horizontally transmitted resistance genes |
Glycopeptides (vancomycin, teicoplainin) | Gold standard of MRSA-therapy for a long time Extensive clinical data available regarding its usePrice of therapy Wide range of indications | MIC creep Parenteral only (with exceptions) TDM required (due to nephrotoxicity and ototoxicity) Resistance expression (hVISA, VISA, VRSA) |
Lipoglycopeptides (telavancin, dalbavancin, oritavancin) | Long half-life (single-dose therapy) Useful in OPAT There is no need for TDM SSTIs, bone and joint infections HAP, VAP (telavancin) | Parenteral only Price of therapy Cannot be removed by dialysis Increased mortality in renal insufficiency Resistance expression/horizontally transmitted resistance genes |
Oxazolidinones (linezolid, tedizolid) | Available for oral and parenteral use SSTIs, bone and joint infections | Drug-drug interactions MAO-inhibition (Serotonin-syndrome) Price of therapy Resistance expression/horizontally transmitted resistance genes |
Lipopeptides (daptomycin) | Bloodstream infections, infective endocarditis, SSTIs | Not useful in pneumonia Parenteral only Resistance expression/horizontally transmitted resistance genes |
5th generation cephalosporins (ceftaroline, ceftobiprole) | Good tolerability SSTIs, CAP, HAP, MRSA bacteremia | Price of therapy Hydrolized by ESBLs (mixed infections) Resistance expression/horizontally transmitted resistance genes |
Older fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) | Available for oral and parenteral use Extensive clinical data available regarding their use Good tolerability Accumulation in the intracellular space Price of therapy Broad-spectrum activity Wide range of indications | Side effect profile (especially in light of recent developments) Resistance levels and rapid resistance development |
Next-generation fluoroquinolones (delafloxacin; avarofloxacin, finafloxacin, zaborfloxacin, nemonoxacin) | Available for oral and parenteral use Broad-spectrum activity Accumulation in the intracellular space Presently studied in a wide range of indications (e.g., cSSTI, CAP, HAP, cUTI MDR gonorrhea) | Black box warining Side effect profile Price of therapy |
Mupirocin | Price of therapy Dose-dependent bactericidal activity Topical agent for MRSA nasal decolonization Additonal indications are being studied | Resistance development Risk of toxicity when used orally/parenterally |
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Gajdács, M. The Continuing Threat of Methicillin-Resistant Staphylococcus aureus. Antibiotics 2019, 8, 52. https://doi.org/10.3390/antibiotics8020052
Gajdács M. The Continuing Threat of Methicillin-Resistant Staphylococcus aureus. Antibiotics. 2019; 8(2):52. https://doi.org/10.3390/antibiotics8020052
Chicago/Turabian StyleGajdács, Márió. 2019. "The Continuing Threat of Methicillin-Resistant Staphylococcus aureus" Antibiotics 8, no. 2: 52. https://doi.org/10.3390/antibiotics8020052
APA StyleGajdács, M. (2019). The Continuing Threat of Methicillin-Resistant Staphylococcus aureus. Antibiotics, 8(2), 52. https://doi.org/10.3390/antibiotics8020052