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 |
References
- Murray, P.R.; Baron, E.J.; Jorgensen, J.H.; Landry, M.L.; Pfaller, M.A. Manual of Clinical Microbiology, 9th ed.; American Society for Microbiology: Washington, DC, USA, 2007; ISBN 978-1-55581-371-0. [Google Scholar]
- Pulverer, G. Taxonomy of Staphylococcus aureus. Zentralbl. Bakteriol. Mikrobiol. Hyg. A. 1986, 262, 425–437. [Google Scholar] [CrossRef]
- Shaw, C.; Stitt, J.M.; Cowan, S.T. Staphylococci and their Classification. J. Gen. Microbiol. 1951, 5, 1010–1023. [Google Scholar] [CrossRef]
- Melter, O.; Radojevič, B. Small colony variants of Staphylococcus aureus--review. Folia Microbiol. (Praha) 2010, 55, 548–558. [Google Scholar] [CrossRef]
- Tong, S.Y.C.; Davis, J.S.; Eichenberger, E.; Holland, T.L.; Fowler, V.G. Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management. Clin. Microbiol. Rev. 2015, 28, 603–661. [Google Scholar] [CrossRef]
- Becker, K.; Heilmann, C.; Peters, G. Coagulase-Negative Staphylococci. Clin. Microbiol. Rev. 2014, 27, 870–926. [Google Scholar] [CrossRef]
- Gould, D.; Chamberlaine, A. Staphylococcus aureus: A review of the literature. J. Clin. Nurs. 1995, 4, 5–12. [Google Scholar] [CrossRef]
- Garcia, L.G.; Lemaire, S.; Kahl, B.C.; Becker, K.; Proctor, R.A.; Denis, O.; Tulkens, P.M.; Van Bambeke, F. Antibiotic activity against small-colony variants of Staphylococcus aureus: Review of in vitro, animal and clinical data. J. Antimicrob. Chemother. 2013, 68, 1455–1464. [Google Scholar] [CrossRef]
- Kahl, B.C.; Becker, K.; Löffler, B. Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections. Clin. Microbiol. Rev. 2016, 29, 401–427. [Google Scholar] [CrossRef]
- Proctor, R.A.; Kriegeskorte, A.; Kahl, B.C.; Becker, K.; Löffler, B.; Peters, G. Staphylococcus aureus Small Colony Variants (SCVs): A road map for the metabolic pathways involved in persistent infections. Front. Cell. Infect. Microbiol. 2014, 4. [Google Scholar] [CrossRef]
- Menetrey, A.; Janin, A.; Pullman, J.; Overcash, J.S.; Haouala, A.; Leylavergne, F.; Turbe, L.; Wittke, F.; Nicolas-Métral, V. Bone and Joint Tissue Penetration of the Staphylococcus-Selective Antibiotic Afabicin in Patients Undergoing Elective Hip Replacement Surgery. Antimicrob. Agents Chemother. 2019, 63. [Google Scholar] [CrossRef]
- Kang, C.-I.; Song, J.-H.; Ko, K.S.; Chung, D.R.; Peck, K.R. Clinical features and outcome of Staphylococcus aureus infection in elderly versus younger adult patients. Int. J. Infect. Dis. 2011, 15, e58–e62. [Google Scholar] [CrossRef]
- Kobayashi, S.D.; Malachowa, N.; DeLeo, F.R. Pathogenesis of Staphylococcus aureus Abscesses. Am. J. Pathol. 2015, 185, 1518–1527. [Google Scholar] [CrossRef]
- Gijón, M.; Bellusci, M.; Petraitiene, B.; Noguera-Julian, A.; Zilinskaite, V.; Sanchez Moreno, P.; Saavedra-Lozano, J.; Glikman, D.; Daskalaki, M.; Kaiser-Labusch, P.; et al. Factors associated with severity in invasive community-acquired Staphylococcus aureus infections in children: A prospective European multicentre study. Clin. Microbiol. Infect. 2016, 22, 643.e1–643.e6. [Google Scholar] [CrossRef]
- Ericson, J.E.; Popoola, V.O.; Smith, P.B.; Benjamin, D.K.; Fowler, V.G.; Benjamin, D.K.; Clark, R.H.; Milstone, A.M. Burden of Invasive Staphylococcus aureus Infections in Hospitalized Infants. JAMA Pediatr. 2015, 169, 1105–1111. [Google Scholar] [CrossRef]
- Wang, L.J.; Dong, F.; Qian, S.Y.; Yao, K.H.; Song, W.Q. Clinical and Molecular Epidemiology of Invasive Staphylococcus aureus Infections in Chinese Children: A Single-center Experience. Chin. Med. J. (Engl.) 2017, 130, 2889–2890. [Google Scholar] [CrossRef]
- Powers, M.E.; Wardenburg, J.B. Igniting the Fire: Staphylococcus aureus Virulence Factors in the Pathogenesis of Sepsis. PLoS Pathog. 2014, 10, e1003871. [Google Scholar] [CrossRef]
- Oogai, Y.; Matsuo, M.; Hashimoto, M.; Kato, F.; Sugai, M.; Komatsuzawa, H. Expression of Virulence Factors by Staphylococcus aureus Grown in Serum. Appl. Environ. Microbiol. 2011, 77, 8097–8105. [Google Scholar] [CrossRef]
- Silversides, J.A.; Lappin, E.; Ferguson, A.J. Staphylococcal toxic shock syndrome: Mechanisms and management. Curr. Infect. Dis. Rep. 2010, 12, 392–400. [Google Scholar] [CrossRef]
- Kumar, A.; Tassopoulos, A.M.; Li, Q.; Yu, F.-S.X. Staphylococcus aureus protein A induced inflammatory response in human corneal epithelial cells. Biochem. Biophys. Res. Commun. 2007, 354, 955–961. [Google Scholar] [CrossRef]
- Lacey, K.A.; Geoghegan, J.A.; McLoughlin, R.M. The Role of Staphylococcus aureus Virulence Factors in Skin Infection and Their Potential as Vaccine Antigens. Pathogens 2016, 5. [Google Scholar] [CrossRef]
- Gomes-Fernandes, M.; Laabei, M.; Pagan, N.; Hidalgo, J.; Molinos, S.; Villar Hernandez, R.; Domínguez-Villanueva, D.; Jenkins, A.T.A.; Lacoma, A.; Prat, C. Accessory gene regulator (Agr) functionality in Staphylococcus aureus derived from lower respiratory tract infections. PLoS ONE 2017, 12, e0175552. [Google Scholar] [CrossRef]
- Haque, S.; Ahmad, F.; Dar, S.A.; Jawed, A.; Mandal, R.K.; Wahid, M.; Lohani, M.; Khan, S.; Singh, V.; Akhter, N. Developments in strategies for Quorum Sensing virulence factor inhibition to combat bacterial drug resistance. Microb. Pathog. 2018, 121, 293–302. [Google Scholar] [CrossRef]
- Seidl, K.; Stucki, M.; Ruegg, M.; Goerke, C.; Wolz, C.; Harris, L.; Berger-Bächi, B.; Bischoff, M. Staphylococcus aureus CcpA affects virulence determinant production and antibiotic resistance. Antimicrob. Agents Chemother. 2006, 50, 1183–1194. [Google Scholar] [CrossRef]
- Erdem, H.; Tetik, A.; Arun, O.; Besirbellioglu, B.A.; Coskun, O.; Eyigun, C.P. War and infection in the pre-antibiotic era: The Third Ottoman Army in 1915. Scand. J. Infect. Dis. 2011, 43, 690–695. [Google Scholar] [CrossRef]
- Gaynes, R. The Discovery of Penicillin—New Insights After More Than 75 Years of Clinical Use. Emerg. Infect. Dis. 2017, 23, 849–853. [Google Scholar] [CrossRef]
- Davies, J.; Davies, D. Origins and Evolution of Antibiotic Resistance. Microbiol. Mol. Biol. Rev. 2010, 74, 417–433. [Google Scholar] [CrossRef]
- Papanicolas, L.E.; Bell, J.M.; Bastian, I. Performance of phenotypic tests for detection of penicillinase in Staphylococcus aureus isolates from Australia. J. Clin. Microbiol. 2014, 52, 1136–1138. [Google Scholar] [CrossRef]
- Holten, K.B.; Onusko, E.M. Appropriate Prescribing of Oral Beta-Lactam Antibiotics. AFP 2000, 62, 611–620. [Google Scholar]
- Lobanovska, M.; Pilla, G. Penicillin’s Discovery and Antibiotic Resistance: Lessons for the Future? Yale J. Biol. Med. 2017, 90, 135–145. [Google Scholar]
- Eady, E.A.; Cove, J.H. Staphylococcal resistance revisited: Community-acquired methicillin resistant Staphylococcus aureus—An emerging problem for the management of skin and soft tissue infections. Curr. Opin. Infect. Dis. 2003, 16, 103–124. [Google Scholar] [CrossRef]
- Sabath, L.D.; Finland, M. Inactivation of methicillin, oxacillin and ancillin by Staphylococcus aureus. Proc. Soc. Exp. Biol. Med. 1962, 111, 547–550. [Google Scholar] [CrossRef]
- Turner, N.A.; Sharma-Kuinkel, B.K.; Maskarinec, S.A.; Eichenberger, E.M.; Shah, P.P.; Carugati, M.; Holland, T.L.; Fowler, V.G. Methicillin-resistant Staphylococcus aureus: An overview of basic and clinical research. Nat. Rev. Microbiol. 2019, 17, 203. [Google Scholar] [CrossRef]
- Mylonas, I. Antibiotic chemotherapy during pregnancy and lactation period: Aspects for consideration. Arch. Gynecol. Obstet. 2011, 283, 7–18. [Google Scholar] [CrossRef]
- Boucher, H.W.; Talbot, G.H.; Bradley, J.S.; Edwards, J.E.; Gilbert, D.; Rice, L.B.; Scheld, M.; Spellberg, B.; Bartlett, J. Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America. Clin. Infect. Dis. 2009, 48, 1–12. [Google Scholar] [CrossRef]
- van Duin, D.; Paterson, D. Multidrug Resistant Bacteria in the Community: Trends and Lessons Learned. Infect. Dis. Clin. N. Am. 2016, 30, 377–390. [Google Scholar] [CrossRef]
- Kaur, D.C.; Chate, S.S. Study of Antibiotic Resistance Pattern in Methicillin Resistant Staphylococcus Aureus with Special Reference to Newer Antibiotic. J. Glob. Infect. Dis. 2015, 7, 78–84. [Google Scholar] [CrossRef]
- Gajdács, M.; Paulik, E.; Szabó, A. [The opinions of community pharmacists related to antibiotic use and resistance] (article in Hungarian). Acta Pharm. Hung. 2018, 88, 249–252. [Google Scholar]
- Gajdács, M.; Paulik, E.; Szabó, A. [The attitude of community pharmacists towards their widening roles in the prevention and treatment of infectious diseases in the southeast region of Hungary] (article in Hungarian). Gyógyszerészet 2019, 63, 26–30. [Google Scholar]
- Santajit, S.; Indrawattana, N. Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens. Biomed. Res. Int. 2016, 2016. [Google Scholar] [CrossRef]
- Dyar, O.J.; Huttner, B.; Schouten, J.; Pulcini, C. What is antimicrobial stewardship? Clin. Microbiol. Infect. 2017, 23, 793–798. [Google Scholar] [CrossRef]
- Ha, D.R.; Haste, N.M.; Gluckstein, D.P. The Role of Antibiotic Stewardship in Promoting Appropriate Antibiotic Use. Am. J. Lifestyle Med. 2017. [Google Scholar] [CrossRef]
- Bergeron, J. Prudent use of antibiotics. Can. Vet. J. 2014, 55, 714. [Google Scholar]
- Phillips, I. Prudent Use of Antibiotics: Are Our Expectations Justified? Clin. Infect. Dis. 2001, 33, S130–S132. [Google Scholar] [CrossRef]
- Lee, B.Y.; Singh, A.; David, M.Z.; Bartsch, S.M.; Slayton, R.B.; Huang, S.S.; Zimmer, S.M.; Potter, M.A.; Macal, C.M.; Lauderdale, D.S.; et al. The economic burden of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Clin. Microbiol. Infect. 2013, 19, 528–536. [Google Scholar] [CrossRef]
- Gajdács, M. Extra deaths due to pandrug resistant bacteria: A survey of the literature. Egészségfejlesztés 2019, 60, 31–36. [Google Scholar]
- Cosgrove, S.E.; Sakoulas, G.; Perencevich, E.N.; Schwaber, M.J.; Karchmer, A.W.; Carmeli, Y. Comparison of Mortality Associated with Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Meta-analysis. Clin. Infect. Dis. 2003, 36, 53–59. [Google Scholar] [CrossRef] [PubMed]
- van Hal, S.J.; Jensen, S.O.; Vaska, V.L.; Espedido, B.A.; Paterson, D.L.; Gosbell, I.B. Predictors of Mortality in Staphylococcus aureus Bacteremia. Clin. Microbiol. Rev. 2012, 25, 362–386. [Google Scholar] [CrossRef] [PubMed]
- Perez, F.; Salata, R.A.; Bonomo, R.A. Current and novel antibiotics against resistant Gram-positive bacteria. Infect. Drug Resist. 2008, 1, 27–44. [Google Scholar] [CrossRef] [PubMed]
- Hassoun, A.; Linden, P.K.; Friedman, B. Incidence, prevalence, and management of MRSA bacteremia across patient populations—A review of recent developments in MRSA management and treatment. Crit. Care 2017, 21. [Google Scholar] [CrossRef] [PubMed]
- Graffunder, E.M.; Venezia, R.A. Risk factors associated with nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection including previous use of antimicrobials. J. Antimicrob. Chemother. 2002, 49, 999–1005. [Google Scholar] [CrossRef] [PubMed]
- Rosendal, K.; Jessen, O. Epidemic spread of Staphylococcus aureus PHAGE-TYPE 83A. Acta Pathol. Microbiol. Scand. 1964, 60, 571–576. [Google Scholar] [CrossRef] [PubMed]
- Enright, M.C.; Robinson, D.A.; Randle, G.; Feil, E.J.; Grundmann, H.; Spratt, B.G. The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proc. Natl. Acad. Sci. USA 2002, 99, 7687–7692. [Google Scholar] [CrossRef] [PubMed]
- Morell, E.A.; Balkin, D.M. Methicillin-Resistant Staphylococcus Aureus: A Pervasive Pathogen Highlights the Need for New Antimicrobial Development. Yale J. Biol. Med. 2010, 83, 223–233. [Google Scholar]
- David, M.Z.; Daum, R.S. Community-associated methicillin-resistant Staphylococcus aureus: Epidemiology and clinical consequences of an emerging epidemic. Clin. Microbiol. Rev. 2010, 23, 616–687. [Google Scholar] [CrossRef] [PubMed]
- Cookson, B. Five decades of MRSA: Controversy and uncertainty continues. Lancet 2011, 378, 1291–1292. [Google Scholar] [CrossRef]
- King, M.D.; Humphrey, B.J.; Wang, Y.F.; Kourbatova, E.V.; Ray, S.M.; Blumberg, H.M. Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections. Ann. Intern. Med. 2006, 144, 309–317. [Google Scholar] [CrossRef] [PubMed]
- Moellering, R.C. MRSA: The first half century. J. Antimicrob. Chemother. 2012, 67, 4–11. [Google Scholar] [CrossRef] [PubMed]
- Redgrave, L.S.; Sutton, S.B.; Webber, M.A.; Piddock, L.J.V. Fluoroquinolone resistance: Mechanisms, impact on bacteria, and role in evolutionary success. Trends Microbiol. 2014, 22, 438–445. [Google Scholar] [CrossRef] [PubMed]
- Jacoby, G.A. Mechanisms of Resistance to Quinolones. Clin. Infect. Dis. 2005, 41, S120–S126. [Google Scholar] [CrossRef]
- Dukic, V.M.; Lauderdale, D.S.; Wilder, J.; Daum, R.S.; David, M.Z. Epidemics of Community-Associated Methicillin-Resistant Staphylococcus aureus in the United States: A Meta-Analysis. PLoS ONE 2013, 8, e52722. [Google Scholar] [CrossRef]
- Chapman, A.L.N. Outpatient parenteral antimicrobial therapy. BMJ 2013, 346, f1585. [Google Scholar] [CrossRef] [PubMed]
- Laupland, K.B.; Valiquette, L. Outpatient parenteral antimicrobial therapy. Can. J. Infect. Dis. Med. Microbiol. 2013, 24, 9–11. [Google Scholar] [CrossRef]
- Peton, V.; Le Loir, Y. Staphylococcus aureus in veterinary medicine. Infect. Genet. Evol. 2014, 21, 602–615. [Google Scholar] [CrossRef] [PubMed]
- Cuny, C.; Wieler, L.H.; Witte, W. Livestock-Associated MRSA: The Impact on Humans. Antibiotics (Basel) 2015, 4, 521–543. [Google Scholar] [CrossRef] [PubMed]
- Cuny, C.; Köck, R.; Witte, W. Livestock associated MRSA (LA-MRSA) and its relevance for humans in Germany. Int. J. Med. Microbiol. 2013, 303, 331–337. [Google Scholar] [CrossRef]
- Dorado-García, A.; Bos, M.E.; Graveland, H.; Cleef, B.A.V.; Verstappen, K.M.; Kluytmans, J.A.; Wagenaar, J.A.; Heederik, D.J. Risk factors for persistence of livestock-associated MRSA and environmental exposure in veal calf farmers and their family members: An observational longitudinal study. BMJ Open 2013, 3, e003272. [Google Scholar] [CrossRef]
- Sharma, M.; Nunez-Garcia, J.; Kearns, A.M.; Doumith, M.; Butaye, P.R.; Argudín, M.A.; Lahuerta-Marin, A.; Pichon, B.; AbuOun, M.; Rogers, J.; et al. Livestock-Associated Methicillin Resistant Staphylococcus aureus (LA-MRSA) Clonal Complex (CC) 398 Isolated from UK Animals belong to European Lineages. Front. Microbiol. 2016, 7. [Google Scholar] [CrossRef]
- Kevorkijan, B.K.; Petrovič, Ž.; Kocuvan, A.; Rupnik, M. MRSA diversity and the emergence of LA-MRSA in a large teaching hospital in Slovenia. Acta Microbiol. Immunol. Hung. 2019, 1–12. [Google Scholar] [CrossRef]
- Butaye, P.; Argudín, M.A.; Smith, T.C. Livestock-Associated MRSA and Its Current Evolution. Curr. Clin. Microbiol. Rep. 2016, 3, 19–31. [Google Scholar] [CrossRef]
- Gajdács, M.; Spengler, G.; Urbán, E. Identification and Antimicrobial Susceptibility Testing of Anaerobic Bacteria: Rubik’s Cube of Clinical Microbiology? Antibiotics 2017, 6, 25. [Google Scholar] [CrossRef]
- Lawson, P.A.; Citron, D.M.; Tyrrell, K.L.; Finegold, S.M. Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O’Toole 1935) Prevot 1938. Anaerobe 2016, 40, 95–99. [Google Scholar] [CrossRef]
- Khan, F.Y.; Elzouki, A.-N. Clostridium difficile infection: A review of the literature. Asian Pac. J. Trop. Med. 2014, 7, S6–S13. [Google Scholar] [CrossRef]
- MacFadden, D.R.; Lipsitch, M.; Olesen, S.W.; Grad, Y. Multidrug-resistant Neisseria gonorrhoeae: Implications for future treatment strategies. Lancet Infect. Dis. 2018, 18, 599. [Google Scholar] [CrossRef]
- Rupp, M.E.; Fey, P.D. Extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae: Considerations for diagnosis, prevention and drug treatment. Drugs 2003, 63, 353–365. [Google Scholar] [CrossRef] [PubMed]
- Doi, Y.; Paterson, D.L. Carbapenemase-Producing Enterobacteriaceae. Semin. Respir. Crit. Care Med. 2015, 36, 74–84. [Google Scholar] [PubMed]
- CDC The biggest antibiotic-resistant threats in the U.S. Available online: https://www.cdc.gov/drugresistance/biggest_threats.html (accessed on 27 March 2019).
- Nasim, J.; Witek, K.; Kincses, A.; Abdin, A.Y.; Żesławska, E.; Marć, M.A.; Gajdács, M.; Spengler, G.; Nitek, W.; Latacz, G.; et al. Pronounced activity of aromatic selenocyanates against multidrug resistant ESKAPE bacteria. New J. Chem. 2019, 15. [Google Scholar] [CrossRef]
- Abbas, M.; Paul, M.; Huttner, A. New and improved? A review of novel antibiotics for Gram-positive bacteria. Clin. Microbiol. Infect. 2017, 23, 697–703. [Google Scholar] [CrossRef] [PubMed]
- Gajdács, M. The Concept of an Ideal Antibiotic: Implications for Drug Design. Molecules 2019, 24, 892. [Google Scholar] [CrossRef] [PubMed]
- Singh, S.B.; Young, K.; Silver, L.L. What is an “ideal” antibiotic? Discovery challenges and path forward. Biochem. Pharmacol. 2017, 133, 63–73. [Google Scholar] [CrossRef]
- Campanini-Salinas, J.; Andrades-Lagos, J.; Mella-Raipan, J.; Vasquez-Velasquez, D. Novel Classes of Antibacterial Drugs in Clinical Development, a Hope in a Post-antibiotic Era. Curr. Top. Med. Chem. 2018, 18, 1188–1202. [Google Scholar] [CrossRef]
- Kasim, N.A.; Whitehouse, M.; Ramachandran, C.; Bermejo, M.; Lennernäs, H.; Hussain, A.S.; Junginger, H.E.; Stavchansky, S.A.; Midha, K.K.; Shah, V.P.; et al. Molecular properties of WHO essential drugs and provisional biopharmaceutical classification. Mol. Pharm. 2004, 1, 85–96. [Google Scholar] [CrossRef] [PubMed]
- Prioritization of Pathogens to Guide Discovery, Research and Development of New Antibiotics for Drug Resistant Bacterial Infections, Including Tuberculosis. Available online: http://www.who.int/medicines/areas/rational_use/prioritization-of-pathogens/en/ (accessed on 27 March 2019).
- Stefani, S.; Chung, D.R.; Lindsay, J.A.; Friedrich, A.W.; Kearns, A.M.; Westh, H.; Mackenzie, F.M. Meticillin-resistant Staphylococcus aureus (MRSA): Global epidemiology and harmonisation of typing methods. Int. J. Antimicrob. Agents 2012, 39, 273–282. [Google Scholar] [CrossRef] [PubMed]
- Stevens, A.M.; Hennessy, T.; Baggett, H.C.; Bruden, D.; Parks, D.; Klejka, J. Methicillin-Resistant Staphylococcus aureus Carriage and Risk Factors for Skin Infections, Southwestern Alaska, USA. Emerg. Infect. Dis. 2010, 16, 797–803. [Google Scholar] [CrossRef] [PubMed]
- Sollid, J.U.E.; Furberg, A.S.; Hanssen, A.M.; Johannessen, M. Staphylococcus aureus: Determinants of human carriage. Infect. Genet. Evol. 2014, 21, 531–541. [Google Scholar] [CrossRef]
- McConeghy, K.W.; Mikolich, D.J.; LaPlante, K.L. Agents for the decolonization of methicillin-resistant Staphylococcus aureus. Pharmacotherapy 2009, 29, 263–280. [Google Scholar] [CrossRef] [PubMed]
- Lai, C.F.; Liao, C.H.; Pai, M.F.; Chu, F.Y.; Hsu, S.P.; Chen, H.Y.; Yang, J.Y.; Chiu, Y.L.; Peng, Y.S.; Chang, S.C.; et al. Nasal Carriage of Methicillin-resistant Staphylococcus aureus Is Associated with Higher All-Cause Mortality in Hemodialysis Patients. Clin. J. Am. Soc. Nephrol. 2011, 6, 167–174. [Google Scholar] [CrossRef]
- Dulon, M.; Peters, C.; Schablon, A.; Nienhaus, A. MRSA carriage among healthcare workers in non-outbreak settings in Europe and the United States: A systematic review. BMC Infect. Dis. 2014, 14, 363. [Google Scholar] [CrossRef]
- Safdar, N.; Narans, L.; Gordon, B.; Maki, D.G. Comparison of Culture Screening Methods for Detection of Nasal Carriage of Methicillin-Resistant Staphylococcus aureus: A Prospective Study Comparing 32 Methods. J. Clin. Microbiol. 2003, 41, 3163–3166. [Google Scholar] [CrossRef]
- Ábrók, M.; Lázár, A.; Szécsényi, M.; Deák, J.; Urbán, E. Combination of MALDI-TOF MS and PBP2’ latex agglutination assay for rapid MRSA detection. J. Microbiol. Methods 2018, 144, 122–124. [Google Scholar] [CrossRef]
- Wolk, D.M.; Marx, J.L.; Dominguez, L.; Driscoll, D.; Schifman, R.B. Comparison of MRSASelect Agar, CHROMagar Methicillin-Resistant Staphylococcus aureus (MRSA) Medium, and Xpert MRSA PCR for Detection of MRSA in Nares: Diagnostic Accuracy for Surveillance Samples with Various Bacterial Densities. J. Clin. Microbiol. 2009, 47, 3933–3936. [Google Scholar] [CrossRef]
- Leclercq, R.; Cantón, R.; Brown, D.F.J.; Giske, C.G.; Heisig, P.; MacGowan, A.P.; Mouton, J.W.; Nordmann, P.; Rodloff, A.C.; Rossolini, G.M.; et al. EUCAST expert rules in antimicrobial susceptibility testing. Clin. Microbiol. Infect. 2013, 19, 141–160. [Google Scholar] [CrossRef] [PubMed]
- Clinical and Laboratory Standards Institute (CLSI). Available online: https://clsi.org/standards/products/microbiology/ (accessed on 10 September 2017).
- Broekema, N.M.; Van, T.T.; Monson, T.A.; Marshall, S.A.; Warshauer, D.M. Comparison of Cefoxitin and Oxacillin Disk Diffusion Methods for Detection of mecA-Mediated Resistance in Staphylococcus aureus in a Large-Scale Study. J. Clin. Microbiol. 2009, 47, 217–219. [Google Scholar] [CrossRef] [PubMed]
- Wolk, D.M.; Struelens, M.J.; Pancholi, P.; Davis, T.; Della-Latta, P.; Fuller, D.; Picton, E.; Dickenson, R.; Denis, O.; Johnson, D.; et al. Rapid Detection of Staphylococcus aureus and Methicillin-Resistant S. aureus (MRSA) in Wound Specimens and Blood Cultures: Multicenter Preclinical Evaluation of the Cepheid Xpert MRSA/SA Skin and Soft Tissue and Blood Culture Assays. J. Clin. Microbiol. 2009, 47, 823–826. [Google Scholar] [CrossRef]
- Benagli, C.; Rossi, V.; Dolina, M.; Tonolla, M.; Petrini, O. Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for the Identification of Clinically Relevant Bacteria. PLoS ONE 2011, 6, e16424. [Google Scholar] [CrossRef] [PubMed]
- Shore, A.C.; Deasy, E.C.; Slickers, P.; Brennan, G.; O’Connell, B.; Monecke, S.; Ehricht, R.; Coleman, D.C. Detection of staphylococcal cassette chromosome mec type XI carrying highly divergent mecA, mecI, mecR1, blaZ, and ccr genes in human clinical isolates of clonal complex 130 methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 2011, 55, 3765–3773. [Google Scholar] [CrossRef]
- Murray, B.E. The life and times of the Enterococcus. Clin. Microbiol. Rev. 1990, 3, 46–65. [Google Scholar] [CrossRef]
- Hakenbeck, R. Transformation in Streptococcus pneumoniae: Mosaic genes and the regulation of competence. Res. Microbiol. 2000, 151, 453–456. [Google Scholar] [CrossRef]
- Deurenberg, R.H.; Stobberingh, E.E. The evolution of Staphylococcus aureus. Infect. Genet. Evol. 2008, 8, 747–763. [Google Scholar] [CrossRef]
- Ito, T.; Kuwahara-Arai, K.; Katayama, Y.; Uehara, Y.; Han, X.; Kondo, Y.; Hiramatsu, K. Staphylococcal Cassette Chromosome mec (SCCmec) analysis of MRSA. Methods Mol. Biol. 2014, 1085, 131–148. [Google Scholar]
- Rolo, J.; Worning, P.; Nielsen, J.B.; Bowden, R.; Bouchami, O.; Damborg, P.; Guardabassi, L.; Perreten, V.; Tomasz, A.; Westh, H.; et al. Evolutionary Origin of the Staphylococcal Cassette Chromosome mec (SCCmec). Antimicrob. Agents Chemother. 2017, 61, 1042–1046. [Google Scholar] [CrossRef]
- Baig, S.; Johannesen, T.B.; Overballe-Petersen, S.; Larsen, J.; Larsen, A.R.; Stegger, M. Novel SCCmec type XIII (9A) identified in an ST152 methicillin-resistant Staphylococcus aureus. Infect. Genet. Evol. 2018, 61, 74–76. [Google Scholar] [CrossRef] [PubMed]
- Otto, M. Next-generation sequencing to monitor the spread of antimicrobial resistance. Genome. Med. 2017, 9. [Google Scholar] [CrossRef] [PubMed]
- Kuroda, M.; Ohta, T.; Uchiyama, I.; Baba, T.; Yuzawa, H.; Kobayashi, I.; Cui, L.; Oguchi, A.; Aoki, K.; Nagai, Y.; et al. Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Lancet 2001, 357, 1225–1240. [Google Scholar] [CrossRef]
- Otto, M. MRSA virulence and spread. Cell. Microbiol. 2012, 14, 1513–1521. [Google Scholar] [CrossRef] [PubMed]
- Adler, A.; Temper, V.; Block, C.S.; Abramson, N.; Moses, A.E. Panton-Valentine Leukocidin–producing Staphylococcus aureus. Emerg. Infect. Dis. 2006, 12, 1789–1790. [Google Scholar] [CrossRef] [PubMed]
- Bhatta, D.R.; Cavaco, L.M.; Nath, G.; Kumar, K.; Gaur, A.; Gokhale, S.; Bhatta, D.R. Association of Panton Valentine Leukocidin (PVL) genes with methicillin resistant Staphylococcus aureus (MRSA) in Western Nepal: A matter of concern for community infections (a hospital based prospective study). BMC Infect. Dis. 2016, 16. [Google Scholar] [CrossRef]
- Özekinci, T.; Dal, T.; Yanık, K.; Özcan, N.; Can, Ş.; Tekin, A.; Yıldırım, H.İ.; Kandemir, İ. Panton-Valentine leukocidin in community and hospital-acquired Staphylococcus aureus strains. Biotechnol. Biotechnol. Equip. 2014, 28, 1089–1094. [Google Scholar] [CrossRef]
- Ballhausen, B.; Kriegeskorte, A.; Schleimer, N.; Peters, G.; Becker, K. The mecA Homolog mecC Confers Resistance against β-Lactams in Staphylococcus aureus Irrespective of the Genetic Strain Background. Antimicrob. Agents Chemother. 2014, 58, 3791–3798. [Google Scholar] [CrossRef]
- Paterson, G.K.; Harrison, E.M.; Holmes, M.A. The emergence of mecC methicillin-resistant Staphylococcus aureus. Trends Microbiol. 2014, 22, 42–47. [Google Scholar] [CrossRef]
- Ariza-Miguel, J.; Hernández, M.; Fernández-Natal, I.; Rodríguez-Lázaro, D. Methicillin-Resistant Staphylococcus aureus Harboring mecC in Livestock in Spain. J. Clin. Microbiol. 2014, 52, 4067–4069. [Google Scholar] [CrossRef]
- Saunders, N.A.; Holmes, A. Multilocus sequence typing (MLST) of Staphylococcus aureus. Methods Mol. Biol. 2007, 391, 71–85. [Google Scholar]
- He, Y.; Xie, Y.; Reed, S. Pulsed-field gel electrophoresis typing of Staphylococcus aureus isolates. Methods Mol. Biol. 2014, 1085, 103–111. [Google Scholar]
- Bosch, T.; de Neeling, A.J.; Schouls, L.M.; Van der Zwaluw, K.W.; Kluytmans, J.A.; Grundmann, H.; Huijsdens, X.W. PFGE diversity within the methicillin-resistant Staphylococcus aureus clonal lineage ST398. BMC Microbiol. 2010, 10, 40. [Google Scholar] [CrossRef]
- Kwon, S.S.; Hong, S.K.; Kim, M.S.; Yong, D.; Lee, K. Performance of Matrix-Assisted Laser Desorption Ionization Time-of-Fight Mass Spectrometry for Rapid Discrimination of Methicillin-Resistant Staphylococcus aureus (MRSA): First Report of a Relation Between Protein Peaks and MRSA spa Type. Ann. Lab. Med. 2017, 37, 553–555. [Google Scholar] [CrossRef]
- Koreen, L.; Ramaswamy, S.V.; Graviss, E.A.; Naidich, S.; Musser, J.M.; Kreiswirth, B.N. spa Typing Method for Discriminating among Staphylococcus aureus Isolates: Implications for Use of a Single Marker to Detect Genetic Micro- and Macrovariation. J. Clin. Microbiol. 2004, 42, 792–799. [Google Scholar] [CrossRef]
- Hallin, M.; Friedrich, A.W.; Struelens, M.J. spa typing for epidemiological surveillance of Staphylococcus aureus. Methods Mol. Biol. 2009, 551, 189–202. [Google Scholar]
- Croxatto, A.; Prod’hom, G.; Greub, G. Applications of MALDI-TOF mass spectrometry in clinical diagnostic microbiology. FEMS Microbiol. Rev. 2012, 36, 380–407. [Google Scholar] [CrossRef]
- Manukumar, H.M.; Umesha, S. MALDI-TOF-MS based identification and molecular characterization of food associated methicillin-resistant Staphylococcus aureus. Sci. Rep. 2017, 7. [Google Scholar] [CrossRef]
- Cunningham, S.A.; Chia, N.; Jeraldo, P.R.; Quest, D.J.; Johnson, J.A.; Boxrud, D.J.; Taylor, A.J.; Chen, J.; Jenkins, G.D.; Drucker, T.M.; et al. Comparison of Whole-Genome Sequencing Methods for Analysis of Three Methicillin-Resistant Staphylococcus aureus Outbreaks. J. Clin. Microbiol. 2017, 55, 1946–1953. [Google Scholar] [CrossRef]
- Bhambri, S.; Kim, G. Use of Oral Doxycycline for Community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) Infections. J. Clin. Aesthet. Dermatol. 2009, 2, 45–50. [Google Scholar]
- Cadena, J.; Nair, S.; Henao-Martinez, A.F.; Jorgensen, J.H.; Patterson, J.E.; Sreeramoju, P.V. Dose of Trimethoprim-Sulfamethoxazole To Treat Skin and Skin Structure Infections Caused by Methicillin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 2011, 55, 5430–5432. [Google Scholar] [CrossRef]
- Archer, G.L.; Coughter, J.P.; Johnston, J.L. Plasmid-encoded trimethoprim resistance in staphylococci. Antimicrob. Agents Chemother. 1986, 29, 733–740. [Google Scholar] [CrossRef]
- Tennent, J.M.; Young, H.K.; Lyon, B.R.; Amyes, S.G.; Skurray, R.A. Trimethoprim resistance determinants encoding a dihydrofolate reductase in clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci. J. Med. Microbiol. 1988, 26, 67–73. [Google Scholar] [CrossRef]
- Larsen, T. Occurrence of doxycycline resistant bacteria in the oral cavity after local administration of doxycycline in patients with periodontal disease. Scand. J. Infect. Dis. 1991, 23, 89–95. [Google Scholar] [CrossRef]
- Handzlik, J.; Matys, A.; Kieć-Kononowicz, K. Recent Advances in Multi-Drug Resistance (MDR) Efflux Pump Inhibitors of Gram-Positive Bacteria S. aureus. Antibiotics (Basel) 2013, 2, 28–45. [Google Scholar] [CrossRef]
- Felicetti, T.; Cannalire, R.; Burali, M.S.; Massari, S.; Manfroni, G.; Barreca, M.L.; Tabarrini, O.; Schindler, B.D.; Sabatini, S.; Kaatz, G.W.; et al. Searching for Novel Inhibitors of the S. aureus NorA Efflux Pump: Synthesis and Biological Evaluation of the 3-Phenyl-1,4-benzothiazine Analogues. ChemMedChem. 2017, 12, 1293–1302. [Google Scholar] [CrossRef]
- Truong-Bolduc, Q.C.; Bolduc, G.R.; Okumura, R.; Celino, B.; Bevis, J.; Liao, C.H.; Hooper, D.C. Implication of the NorB Efflux Pump in the Adaptation of Staphylococcus aureus to Growth at Acid pH and in Resistance to Moxifloxacin. Antimicrob. Agents Chemother. 2011, 55, 3214–3219. [Google Scholar] [CrossRef]
- Spengler, G.; Kincses, A.; Gajdacs, M.; Amaral, L. New Roads Leading to Old Destinations: Efflux Pumps as Targets to Reverse Multidrug Resistance in Bacteria. Molecules 2017, 22. [Google Scholar] [CrossRef]
- Klinker, K.P.; Borgert, S.J. Beyond Vancomycin: The Tail of the Lipoglycopeptides. Clin. Ther. 2015, 37, 2619–2636. [Google Scholar] [CrossRef]
- Brunton, L.; Chabner, B.A.; Knollman, B. Goodman & Gillman’s The Pharmacological Basis of Therapeutics, 12th ed.; McGraw-Hill: New York, NY, USA, 2011. [Google Scholar]
- Moore, C.L.; Lu, M.; Cheema, F.; Osaki-Kiyan, P.; Perri, M.B.; Donabedian, S.; Haque, N.Z.; Zervos, M.J. Prediction of Failure in Vancomycin-Treated Methicillin-Resistant Staphylococcus aureus Bloodstream Infection: A Clinically Useful Risk Stratification Tool. Antimicrob. Agents Chemother. 2011, 55, 4581–4588. [Google Scholar] [CrossRef]
- Bruniera, F.R.; Ferreira, F.M.; Saviolli, L.R.; Bacci, M.R.; Feder, D.; da Luz Gonçalves Pedreira, M.; Sorgini Peterlini, M.A.; Azzalis, L.A.; Campos Junqueira, V.B.; et al. The use of vancomycin with its therapeutic and adverse effects: A review. Eur. Rev. 2015, 19, 694–700. [Google Scholar]
- Gardete, S.; Tomasz, A. Mechanisms of vancomycin resistance in Staphylococcus aureus. J. Clin. Invest. 2014, 124, 2836–2840. [Google Scholar] [CrossRef] [PubMed]
- McGuinness, W.A.; Malachowa, N.; DeLeo, F.R. Vancomycin Resistance in Staphylococcus aureus. Yale J. Biol. Med. 2017, 90, 269–281. [Google Scholar] [PubMed]
- Weinstein, R.A.; Fridkin, S.K. Vancomycin-Intermediate and -Resistant Staphylococcus aureus: What the Infectious Disease Specialist Needs to Know. Clin. Infect. Dis. 2001, 32, 108–115. [Google Scholar] [CrossRef] [PubMed]
- Allen, N.E.; LeTourneau, D.L.; Hobbs, J.N. Molecular interactions of a semisynthetic glycopeptide antibiotic with D-alanyl-D-alanine and D-alanyl-D-lactate residues. Antimicrob. Agents Chemother. 1997, 41, 66–71. [Google Scholar] [CrossRef] [PubMed]
- Liu, C.; Chambers, H.F. Staphylococcus aureus with Heterogeneous Resistance to Vancomycin: Epidemiology, Clinical Significance, and Critical Assessment of Diagnostic Methods. Antimicrob. Agents Chemother. 2003, 47, 3040–3045. [Google Scholar] [CrossRef]
- Szabó, J. hVISA/VISA: Diagnostic and therapeutic problems. Expert Rev. Anti-Infect. Ther. 2009, 7, 1–3. [Google Scholar] [CrossRef]
- Guskey, M.T.; Tsuji, B.T. A comparative review of the lipoglycopeptides: Oritavancin, dalbavancin, and telavancin. Pharmacotherapy 2010, 30, 80–94. [Google Scholar] [CrossRef]
- Allen, N.E.; Nicas, T.I. Mechanism of action of oritavancin and related glycopeptide antibiotics. FEMS Microbiol. Rev. 2003, 26, 511–532. [Google Scholar] [CrossRef]
- Biedenbach, D.J.; Arhin, F.F.; Moeck, G.; Lynch, T.F.; Sahm, D.F. In vitro activity of oritavancin and comparator agents against staphylococci, streptococci and enterococci from clinical infections in Europe and North America, 2011–2014. Int. J. Antimicrob. Agents 2015, 46, 674–681. [Google Scholar] [CrossRef]
- Leach, K.L.; Swaney, S.M.; Colca, J.R.; McDonald, W.G.; Blinn, J.R.; Thomasco, L.M.; Gadwood, R.C.; Shinabarger, D.; Xiong, L.; Mankin, A.S. The site of action of oxazolidinone antibiotics in living bacteria and in human mitochondria. Mol. Cell 2007, 26, 393–402. [Google Scholar] [CrossRef]
- Falagas, M.E.; Vardakas, K.Z. Benefit-risk assessment of linezolid for serious gram-positive bacterial infections. Drug Saf. 2008, 31, 753–768. [Google Scholar] [CrossRef]
- Long, K.S.; Vester, B. Resistance to Linezolid Caused by Modifications at Its Binding Site on the Ribosome. Antimicrob. Agents Chemother. 2012, 56, 603–612. [Google Scholar] [CrossRef]
- Stefani, S.; Bongiorno, D.; Mongelli, G.; Campanile, F. Linezolid Resistance in Staphylococci. Pharmaceuticals (Basel) 2010, 3, 1988–2006. [Google Scholar] [CrossRef]
- Steenbergen, J.N.; Alder, J.; Thorne, G.M.; Tally, F.P. Daptomycin: A lipopeptide antibiotic for the treatment of serious Gram-positive infections. J. Antimicrob. Chemother. 2005, 55, 283–288. [Google Scholar] [CrossRef]
- Mensa, B.; Howell, G.L.; Scott, R.; DeGrado, W.F. Comparative Mechanistic Studies of Brilacidin, Daptomycin, and the Antimicrobial Peptide LL16. Antimicrob. Agents Chemother. 2014, 58, 5136–5145. [Google Scholar] [CrossRef]
- Lalani, T.; Boucher, H.W.; Cosgrove, S.E.; Fowler, V.G.; Kanafani, Z.A.; Vigliani, G.A.; Campion, M.; Abrutyn, E.; Levine, D.P.; Price, C.S.; et al. Outcomes with daptomycin versus standard therapy for osteoarticular infections associated with Staphylococcus aureus bacteraemia. J. Antimicrob. Chemother. 2008, 61, 177–182. [Google Scholar] [CrossRef]
- Tran, T.T.; Munita, J.M.; Arias, C.A. Mechanisms of drug resistance: Daptomycin resistance. Ann. N. Y. Acad. Sci. 2015, 1354, 32–53. [Google Scholar] [CrossRef]
- Anderson, S.D.; Gums, J.G. Ceftobiprole: An extended-spectrum anti-methicillin-resistant Staphylococcus aureus cephalosporin. Ann. Pharmacother. 2008, 42, 806–816. [Google Scholar] [CrossRef] [PubMed]
- Kisgen, J.; Whitney, D. Ceftobiprole, a Broad-Spectrum Cephalosporin with Activity against Methicillin-Resistant Staphylococcus aureus (MRSA). P.T. 2008, 33, 631–641. [Google Scholar]
- Duplessis, C.; Crum-Cianflone, N.F. Ceftaroline: A New Cephalosporin with Activity against Methicillin-Resistant Staphylococcus aureus (MRSA). Clin. Med. Rev. Ther. 2011, 3. [Google Scholar] [CrossRef]
- Farrell, D.J.; Flamm, R.K.; Sader, H.S.; Jones, R.N. Spectrum and potency of ceftaroline tested against leading pathogens causing skin and soft-tissue infections in Europe (2010). Int. J. Antimicrob. Agents 2013, 41, 337–342. [Google Scholar] [CrossRef] [PubMed]
- Livermore, D.M.; Mushtaq, S.; Warner, M.; James, D.; Kearns, A.; Woodford, N. Pathogens of skin and skin-structure infections in the UK and their susceptibility to antibiotics, including ceftaroline. J. Antimicrob. Chemother. 2015, 70, 2844–2853. [Google Scholar] [CrossRef] [PubMed]
- Fritsche, T.R.; Sader, H.S.; Jones, R.N. Antimicrobial activity of ceftobiprole, a novel anti–methicillin-resistant Staphylococcus aureus cephalosporin, tested against contemporary pathogens: Results from the SENTRY Antimicrobial Surveillance Program (2005–2006). Diagn. Microbiol. Infect. Dis. 2008, 61, 86–95. [Google Scholar] [CrossRef]
- Bérenger, R.; Bourdon, N.; Auzou, M.; Leclercq, R.; Cattoir, V. In vitro activity of new antimicrobial agents against glycopeptide-resistant Enterococcus faecium clinical isolates from France between 2006 and 2008. Med. Mal. Infect. 2011, 41, 405–409. [Google Scholar] [CrossRef]
- Urbán, E.; Stone, G.G. Impact of EUCAST ceftaroline breakpoint change on the susceptibility of methicillin-resistant Staphylococcus aureus isolates collected from patients with complicated skin and soft tissue infections. Clin. Microbiol. Infect. 2019. [Google Scholar] [CrossRef] [PubMed]
- Chan, L.C.; Basuino, L.; Diep, B.; Hamilton, S.; Chatterjee, S.S.; Chambers, H.F. Ceftobiprole- and Ceftaroline-Resistant Methicillin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 2015, 59, 2960–2963. [Google Scholar] [CrossRef] [PubMed]
- Tong, S.Y.C.; Nelson, J.; Paterson, D.L.; Fowler, V.G.; Howden, B.P.; Cheng, A.C.; Chatfield, M.; Lipman, J.; Van Hal, S.; O’Sullivan, M.; et al. CAMERA2—combination antibiotic therapy for methicillin-resistant Staphylococcus aureus infection: Study protocol for a randomised controlled trial. Trials 2016, 17. [Google Scholar] [CrossRef]
- Livermore, D.M. Tigecycline: What is it, and where should it be used? J. Antimicrob. Chemother. 2005, 56, 611–614. [Google Scholar] [CrossRef]
- Florescu, I.; Beuran, M.; Dimov, R.; Razbadauskas, A.; Bochan, M.; Fichev, G.; Dukart, G.; Babinchak, T.; Cooper, C.A.; Ellis-Grosse, E.J.; et al. Efficacy and safety of tigecycline compared with vancomycin or linezolid for treatment of serious infections with methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci: A Phase 3, multicentre, double-blind, randomized study. J. Antimicrob. Chemother. 2008, 62. [Google Scholar] [CrossRef]
- Koomanachai, P.; Crandon, J.L.; Banevicius, M.A.; Peng, L.; Nicolau, D.P. Pharmacodynamic Profile of Tigecycline against Methicillin-Resistant Staphylococcus aureus in an Experimental Pneumonia Model. Antimicrob. Agents Chemother. 2009, 53, 5060–5063. [Google Scholar] [CrossRef]
- Dixit, D.; Madduri, R.P.; Sharma, R. The role of tigecycline in the treatment of infections in light of the new black box warning. Expert. Rev. Anti-Infect. Ther. 2014, 12, 397–400. [Google Scholar] [CrossRef]
- Solomkin, J.S.; Gardovskis, J.; Lawrence, K.; Montravers, P.; Sway, A.; Evans, D.; Tsai, L. IGNITE4: Results of a Phase 3, Randomized, Multicenter, Prospective Trial of Eravacycline vs. Meropenem in the Treatment of Complicated Intra-Abdominal Infections. Clin. Infect. Dis. 2018. [Google Scholar] [CrossRef]
- Sutcliffe, J.A.; O’Brien, W.; Fyfe, C.; Grossman, T.H. Antibacterial Activity of Eravacycline (TP-434), a Novel Fluorocycline, against Hospital and Community Pathogens. Antimicrob. Agents Chemother. 2013, 57, 5548–5558. [Google Scholar] [CrossRef]
- Dougherty, J.A.; Sucher, A.J.; Chahine, E.B.; Shihadeh, K.C. Omadacycline: A New Tetracycline Antibiotic. Ann. Pharmacother. 2018. [Google Scholar] [CrossRef]
- Villano, S.; Steenbergen, J.; Loh, E. Omadacycline: Development of a novel aminomethylcycline antibiotic for treating drug-resistant bacterial infections. Future Microbiol. 2016, 11, 1421–1434. [Google Scholar] [CrossRef]
- Florindo, C.; Costa, A.; Matos, C.; Nunes, S.L.; Matias, A.N.; Duarte, C.M.M.; Rebelo, L.P.N.; Branco, L.C.; Marrucho, I.M. Novel organic salts based on fluoroquinolone drugs: Synthesis, bioavailability and toxicological profiles. Int. J. Pharm. 2014, 469, 179–189. [Google Scholar] [CrossRef]
- Candel, F.J.; Peñuelas, M. Delafloxacin: Design, development and potential place in therapy. Drug Des. Dev. Ther. 2017, 11, 881–891. [Google Scholar] [CrossRef]
- McCurdy, S.; Lawrence, L.; Quintas, M.; Woosley, L.; Flamm, R.; Tseng, C.; Cammarata, S. In Vitro Activity of Delafloxacin and Microbiological Response against Fluoroquinolone-Susceptible and Nonsusceptible Staphylococcus aureus Isolates from Two Phase 3 Studies of Acute Bacterial Skin and Skin Structure Infections. Antimicrob. Agents Chemother. 2017, 61. [Google Scholar] [CrossRef]
- Flamm, R.K.; Rhomberg, P.R.; Huband, M.D.; Farrell, D.J. In Vitro Activity of Delafloxacin Tested against Isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Antimicrob. Agents Chemother. 2016, 60, 6381–6385. [Google Scholar] [CrossRef]
- Park, H.-S.; Kim, H.-J.; Seol, M.J.; Choi, D.R.; Choi, E.C.; Kwak, J.H. In Vitro and In Vivo Antibacterial Activities of DW-224a, a New Fluoronaphthyridone. Antimicrob. Agents Chemother. 2006, 50, 2261–2264. [Google Scholar] [CrossRef] [PubMed]
- Lauderdale, T.L.; Shiau, Y.R.; Lai, J.F.; Chen, H.C.; King, C.H.R. Comparative In Vitro Activities of Nemonoxacin (TG-873870), a Novel Nonfluorinated Quinolone, and Other Quinolones against Clinical Isolates. Antimicrob. Agents Chemother. 2010, 54, 1338–1342. [Google Scholar] [CrossRef] [PubMed]
- Park, H.S.; Oh, S.H.; Kim, H.S.; Choi, D.R.; Kwak, J.H. Antimicrobial Activity of Zabofloxacin against Clinically Isolated Streptococcus pneumoniae. Molecules 2016, 21, 1562. [Google Scholar] [CrossRef] [PubMed]
- Daneman, N.; Lu, H.; Redelmeier, D.A. Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study. BMJ Open 2015, 5, e010077. [Google Scholar] [CrossRef] [PubMed]
- Laue, H.; Weiss, L.; Bernardi, A.; Hawser, S.; Lociuro, S.; Islam, K. In vitro activity of the novel diaminopyrimidine, iclaprim, in combination with folate inhibitors and other antimicrobials with different mechanisms of action. J. Antimicrob. Chemother. 2007, 60, 1391–1394. [Google Scholar] [CrossRef] [PubMed]
- Sincak, C.A.; Schmidt, J.M. Iclaprim, A novel diaminopyrimidine for the treatment of resistant gram-positive infections. Ann. Pharmacother. 2009, 43, 1107–1114. [Google Scholar] [CrossRef] [PubMed]
- Parenti, M.A.; Hatfield, S.M.; Leyden, J.J. Mupirocin: A topical antibiotic with a unique structure and mechanism of action. Clin. Pharm. 1987, 6, 761–770. [Google Scholar] [PubMed]
- Poovelikunnel, T.; Gethin, G.; Humphreys, H. Mupirocin resistance: Clinical implications and potential alternatives for the eradication of MRSA. J. Antimicrob. Chemother. 2015, 70, 2681–2692. [Google Scholar] [CrossRef] [PubMed]
- Chen, H.J.; Hung, W.C.; Tseng, S.P.; Tsai, J.C.; Hsueh, P.R.; Teng, L.J. Fusidic Acid Resistance Determinants in Staphylococcus aureus Clinical Isolates. Antimicrob. Agents Chemother. 2010, 54, 4985–4991. [Google Scholar] [CrossRef]
- Dobie, D.; Gray, J. Fusidic acid resistance in Staphylococcus aureus. Arch. Dis. Child. 2004, 89, 74–77. [Google Scholar] [CrossRef]
- Paukner, S.; Riedl, R. Pleuromutilins: Potent Drugs for Resistant Bugs-Mode of Action and Resistance. Cold Spring Harb. Perspect. Med. 2017, 7. [Google Scholar] [CrossRef]
- Jacobs, M.R. Retapamulin: A semisynthetic pleuromutilin compound for topical treatment of skin infections in adults and children. Future Microbiol. 2007, 2, 591–600. [Google Scholar] [CrossRef]
- Paukner, S.; Sader, H.S.; Ivezic-Schoenfeld, Z.; Jones, R.N. Antimicrobial Activity of the Pleuromutilin Antibiotic BC-3781 against Bacterial Pathogens Isolated in the SENTRY Antimicrobial Surveillance Program in 2010. Antimicrob. Agents Chemother. 2013, 57, 4489–4495. [Google Scholar] [CrossRef]
- Sader, H.S.; Paukner, S.; Ivezic-Schoenfeld, Z.; Biedenbach, D.J.; Schmitz, F.J.; Jones, R.N. Antimicrobial activity of the novel pleuromutilin antibiotic BC-3781 against organisms responsible for community-acquired respiratory tract infections (CARTIs). J. Antimicrob. Chemother. 2012, 67, 1170–1175. [Google Scholar] [CrossRef]
- Sai, N.; Laurent, C.; Strale, H.; Denis, O.; Byl, B. Efficacy of the decolonization of methicillin-resistant Staphylococcus aureus carriers in clinical practice. Antimicrob. Resist. Infect. Control 2015, 4, 56. [Google Scholar] [CrossRef]
- Kumar, P.; Kizhakkedathu, J.N.; Straus, S.K. Antimicrobial Peptides: Diversity, Mechanism of Action and Strategies to Improve the Activity and Biocompatibility In Vivo. Biomolecules 2018, 8. [Google Scholar] [CrossRef]
- Scott, R.W.; Tew, G.N. Mimics of Host Defense Proteins; Strategies for Translation to Therapeutic Applications. Curr. Top. Med. Chem. 2017, 17, 576–589. [Google Scholar] [CrossRef]
- Even, S.; Charlier, C.; Nouaille, S.; Ben Zakour, N.L.; Cretenet, M.; Cousin, F.J.; Gautier, M.; Cocaign-Bousquet, M.; Loubière, P.; Le Loir, Y. Staphylococcus aureus virulence expression is impaired by Lactococcus lactis in mixed cultures. Appl. Environ. Microbiol. 2009, 75, 4459–4472. [Google Scholar] [CrossRef]
- Cegelski, L.; Marshall, G.R.; Eldridge, G.R.; Hultgren, S.J. The biology and future prospects of antivirulence therapies. Nat. Rev. Microbiol. 2008, 6, 17–27. [Google Scholar] [CrossRef]
- Gao, P.; Ho, P.L.; Yan, B.; Sze, K.H.; Davies, J.; Kao, R.Y.T. Suppression of Staphylococcus aureus virulence by a small-molecule compound. Proc. Natl. Acad. Sci. USA 2018, 115, 8003–8008. [Google Scholar] [CrossRef]
- Amaral, L.; Martins, A.; Spengler, G.; Molnar, J. Efflux pumps of Gram-negative bacteria: What they do, how they do it, with what and how to deal with them. Front Pharmacol. 2014, 4. [Google Scholar] [CrossRef]
- Tegos, G.P.; Haynes, M.; Jacob Strouse, J.; Khan, M.M.T.; Bologa, C.G.; Oprea, T.I.; Sklar, L.A. Microbial Efflux Pump Inhibition: Tactics and Strategies. Curr. Pharm. Des. 2011, 17, 1291–1302. [Google Scholar] [CrossRef]
- Wright, G.D. Something old, something new: Revisiting natural products in antibiotic drug discovery. Can. J. Microbiol. 2014, 60, 147–154. [Google Scholar] [CrossRef]
- Brown, D.G.; Lister, T.; May-Dracka, T.L. New natural products as new leads for antibacterial drug discovery. Bioorg. Med. Chem. Lett. 2014, 24, 413–418. [Google Scholar] [CrossRef]
- Golkar, Z.; Bagasra, O.; Pace, D.G. Bacteriophage therapy: A potential solution for the antibiotic resistance crisis. J. Infect. Dev. Ctries. 2014, 8, 129–136. [Google Scholar] [CrossRef]
- Love, M.J.; Bhandari, D.; Dobson, R.C.J.; Billington, C. Potential for Bacteriophage Endolysins to Supplement or Replace Antibiotics in Food Production and Clinical Care. Antibiotics (Basel) 2018, 7. [Google Scholar] [CrossRef]
- Clowry, J.; Irvine, A.D.; McLoughlin, R.M. Next-generation anti-Staphylococcus aureus vaccines: A potential new therapeutic option for atopic dermatitis? J. Allergy Clin. Immunol. 2019, 143, 78–81. [Google Scholar] [CrossRef]
- Deresinski, S. Antistaphylococcal vaccines and immunoglobulins: Current status and future prospects. Drugs 2006, 66, 1797–1806. [Google Scholar] [CrossRef]
- Takahashi, D.; Shukla, S.K.; Prakash, O.; Zhang, G. Structural determinants of host defense peptides for antimicrobial activity and target cell selectivity. Biochimie 2010, 92, 1236–1241. [Google Scholar] [CrossRef]
- Park, I.Y.; Cho, J.H.; Kim, K.S.; Kim, Y.-B.; Kim, M.S.; Kim, S.C. Helix stability confers salt resistance upon helical antimicrobial peptides. J. Biol. Chem. 2004, 279, 13896–13901. [Google Scholar] [CrossRef]
- Ahn, M.; Jacob, B.; Gunasekaran, P.; Murugan, R.N.; Ryu, E.K.; Lee, G.; Hyun, J.-K.; Cheong, C.; Kim, N.-H.; Shin, S.Y.; et al. Poly-lysine peptidomimetics having potent antimicrobial activity without hemolytic activity. Amino Acids 2014, 46, 2259–2269. [Google Scholar] [CrossRef]
- Cruz, J.; Flórez, J.; Torres, R.; Urquiza, M.; Gutiérrez, J.A.; Guzmán, F.; Ortiz, C.C. Antimicrobial activity of a new synthetic peptide loaded in polylactic acid or poly(lactic-co-glycolic) acid nanoparticles against Pseudomonas aeruginosa, Escherichia coli O157:H7 and methicillin resistant Staphylococcus aureus (MRSA). Nanotechnology 2017, 28, 135102. [Google Scholar] [CrossRef] [PubMed]
- Ganz, T. Defensins: Antimicrobial peptides of innate immunity. Nat. Rev. Immunol. 2003, 3, 710–720. [Google Scholar] [CrossRef] [PubMed]
- Wilmes, M.; Sahl, H.-G. Defensin-based anti-infective strategies. Int. J. Med. Microbiol. 2014, 304, 93–99. [Google Scholar] [CrossRef] [PubMed]
- Schmelcher, M.; Donovan, D.M.; Loessner, M.J. Bacteriophage endolysins as novel antimicrobials. Future Microbiol. 2012, 7, 1147–1171. [Google Scholar] [CrossRef]
- Lin, D.M.; Koskella, B.; Lin, H.C. Phage therapy: An alternative to antibiotics in the age of multi-drug resistance. World J. Gastrointest Pharmacol. Ther. 2017, 8, 162–173. [Google Scholar] [CrossRef]
- Bergler, H.; Fuchsbichler, S.; Högenauer, G.; Turnowsky, F. The enoyl-[acyl-carrier-protein] reductase (FabI) of Escherichia coli, which catalyzes a key regulatory step in fatty acid biosynthesis, accepts NADH and NADPH as cofactors and is inhibited by palmitoyl-CoA. Eur. J. Biochem. 1996, 242, 689–694. [Google Scholar] [CrossRef]
- Schiebel, J.; Chang, A.; Lu, H.; Baxter, M.V.; Tonge, P.J.; Kisker, C. Staphylococcus aureus FabI: Inhibition, Substrate Recognition and Potential Implications for In Vivo Essentiality. Structure 2012, 20, 802–813. [Google Scholar] [CrossRef]
- Hibbitts, A.; O’Leary, C. Emerging Nanomedicine Therapies to Counter the Rise of Methicillin-Resistant Staphylococcus aureus. Materials (Basel) 2018, 11. [Google Scholar] [CrossRef]
- Knetsch, M.L.W.; Koole, L.H. New Strategies in the Development of Antimicrobial Coatings: The Example of Increasing Usage of Silver and Silver Nanoparticles. Polymers 2011, 3, 340–366. [Google Scholar] [CrossRef]
- Seil, J.T.; Webster, T.J. Antibacterial effect of zinc oxide nanoparticles combined with ultrasound. Nanotechnology 2012, 23, 495101. [Google Scholar] [CrossRef] [PubMed]
- Azam, A.; Ahmed, A.S.; Oves, M.; Khan, M.; Memic, A. Size-dependent antimicrobial properties of CuO nanoparticles against Gram-positive and -negative bacterial strains. Int. J. Nanomedicine 2012, 7, 3527–3535. [Google Scholar] [CrossRef] [PubMed]
- Qiu, Z.; Yu, Y.; Chen, Z.; Jin, M.; Yang, D.; Zhao, Z.; Wang, J.; Shen, Z.; Wang, X.; Qian, D.; et al. Nanoalumina promotes the horizontal transfer of multiresistance genes mediated by plasmids across genera. Proc. Natl. Acad. Sci. USA 2012, 109, 4944–4949. [Google Scholar] [CrossRef] [PubMed]
- Imamura, H.; Ohtake, N.; Jona, H.; Shimizu, A.; Moriya, M.; Sato, H.; Sugimoto, Y.; Ikeura, C.; Kiyonaga, H.; Nakano, M.; et al. Dicationic dithiocarbamate carbapenems with anti-MRSA activity. Bioorg. Med. Chem. 2001, 9, 1571–1578. [Google Scholar] [CrossRef]
- Livermore, D.M.; Mushtaq, S.; Warner, M. Activity of the anti-MRSA carbapenem razupenem (PTZ601) against Enterobacteriaceae with defined resistance mechanisms. J. Antimicrob. Chemother. 2009, 64, 330–335. [Google Scholar] [CrossRef] [PubMed]
- Sunagawa, M.; Itoh, M.; Kubota, K.; Sasaki, A.; Ueda, Y.; Angehrn, P.; Bourson, A.; Goetschi, E.; Hebeisen, P.; Then, R.L. New anti-MRSA and anti-VRE carbapenems; synthesis and structure-activity relationships of 1beta-methyl-2-(thiazol-2-ylthio)carbapenems. J. Antibiot. 2002, 55, 722–757. [Google Scholar] [CrossRef]
- Zhou, M.; Chen, J.; Liu, Y.; Hu, Y.; Liu, Y.; Lu, J.; Zhang, S.; Yu, Y.; Huang, X.; Yang, Q.; et al. In Vitro Activities of Ceftaroline/Avibactam, Ceftazidime/Avibactam, and Other Comparators Against Pathogens From Various Complicated Infections in China. Clin. Infect. Dis. 2018, 67, S206–S216. [Google Scholar] [CrossRef]
- Lahiri, S.D.; Johnstone, M.R.; Ross, P.L.; McLaughlin, R.E.; Olivier, N.B.; Alm, R.A. Avibactam and Class C β-Lactamases: Mechanism of Inhibition, Conservation of the Binding Pocket, and Implications for Resistance. Antimicrob. Agents Chemother. 2014, 58, 5704–5713. [Google Scholar] [CrossRef]
- Luo, M.L.; Leenay, R.T.; Beisel, C.L. Current and future prospects for CRISPR-based tools in bacteria. Biotechnol. Bioeng. 2016, 113, 930–943. [Google Scholar] [CrossRef]
- Yanagihara, K.; Tashiro, M.; Fukuda, Y.; Ohno, H.; Higashiyama, Y.; Miyazaki, Y.; Hirakata, Y.; Tomono, K.; Mizuta, Y.; Tsukamoto, K.; et al. Effects of short interfering RNA against methicillin-resistant Staphylococcus aureus coagulase in vitro and in vivo. J. Antimicrob. Chemother. 2006, 57, 122–126. [Google Scholar] [CrossRef]
- Spellberg, B. The future of antibiotics. Crit. Care 2014, 18, 228. [Google Scholar] [CrossRef]
- Gajdács, M.; Handzlik, J.; Sanmartín, C.; Domínguez-Álvarez, E.; Spengler, G. Prediction of ADME properties for selenocompounds with anticancer and efflux pump inhibitory activity using preliminary computational methods (article in Hungarian). Acta Pharm. Hung. 2018, 88, 67–74. [Google Scholar]
- Aung, A.K.; Haas, D.W.; Hulgan, T.; Phillips, E.J. Pharmacogenomics of antimicrobial agents. Pharmacogenomics 2014, 15, 1903–1930. [Google Scholar] [CrossRef]
- Weng, Z.; DeLisi, C. Protein therapeutics: Promises and challenges for the 21st century. Trends Biotechnol. 2002, 20, 29–35. [Google Scholar] [CrossRef]
- Ruppé, E.; Burdet, C.; Grall, N.; de Lastours, V.; Lescure, F.-X.; Andremont, A.; Armand-Lefèvre, L. Impact of antibiotics on the intestinal microbiota needs to be re-defined to optimize antibiotic usage. Clin. Microbiol. Infect. 2018, 24, 3–5. [Google Scholar] [CrossRef]
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