Treatment of mrsa infection

management

1. Treatment of MRSA Infection Dr Saurav Misra

2. Staphylococcus aureus Gram positive cocci Staphule : “grape like clusters” Facultative aerobic Resistant to desiccation Optimal temp: 30-37 deg Celsius Neutral pH Coagulase positive Ubiquitous colonizers of human skin & mucus membranes

3. Clinical manifestations Skin & soft tissue infections Musculoskeletal infections Respiratory tract infections Bacteremia & its complications Infective Endocarditis Device-related infections Toxic Shock Syndrome, Food poisoning

4. Evolution of Drug Resistance in S. aureus

5. MRSA - mechanism of resistance Modifying enzymes Degrading enzymes Alteration of Target Efflux pumps

6. Global prevalence of MRSA

7. Risk factors for MRSA infection Age < 2 yrs, > 65yrs Athletes Injection drug users Homosexual men, Military personnel Blacks Pet owners, Pig farmers Crowded places Recent influenza like illness/severe pneumonia Longer hospitalization ICU admission/ Invasive procedures Irrationale use of antibiotics!.

8. Prevention of MRSA infection Hand washing Isolation Rationale use of antibiotics

9. Drugs for MRSA SSI Clindamycin Doxycycline Minocycline Tedizolid TMP/SMX Daptomycin Linezolid Vancomycin Tigecycline Quinpristin/Dalfopristin

10. Cephalosporin - Ceftobiprole Fifth generation cephalosporin Active component of prodrug ceftobiprolemedocaril Structurally engineered to allow binding to PBP-2a expressed by the mecA cassettes Active against MRSA, VISA, VRSA Use – HAP & CAP, ABSSI Approved on October, 2013 in Europe

11. Lipoglycopeptide Dalbavancin Inhibit cell wall synthesis by forming a stable complex between the heptapeptide backbone & D-Ala-D-Ala Second generation semi-synthetic lipoglycopeptide Long half life &extensive protein binding Approved in May 2014

12. Glycopeptide Oritavancin Inhibits transpeptidation & transglycosylation Also blocks utilization of D-ala-D-ala or D-ala-D-lac PG precursors Concentration dependent activity & prolonged half life – single dose treatment Approved in Aug 2014

13. Carbapenems Tomopenem (CS-023) Good activity against MRSA with a low rate of spontaneous resistance HAP & cSSI Phase II Razupenem New parenteral carbepenem for the treatment of cSSI Phase II

14. Streptogramin - Linoprostin/Flopristin (NXL-103) Linoprostin/ Flopristin (70:30) Derived from Streptomyces pristinaspiralis Flopristin blocks an early step of protein synthesis by forming a bond with a ribosome, prevent elongation Linopristin blocks a later step by preventing the extension of peptide chains & causing incomplete release of chains. Phase II- for treatment of acute bacterial SSSI

15. Ketolide Modithromycin ( EDP-420) Bridged bicyclic ketolide Half life is 2-3 times longer than clarithromycin & telithromycin Once daily dose for CAP PHASE II

16. Fluoroquinolone Delafloxacin (RX3341) Novel broad spectrum IV and oral route Phase III Avarofloxacin / Acorafloxacin (JNJ-Q2) Available in IV & oral formulations For CAP & SSI Phase III Nemonoxacin (TG-873870) Low propensity for development of resistance Phase II

17. Pleuromutilins MOA- Interferes with bacterial protein synthesis via a specific interaction with 23s RNA Lefamulin (BC-3781) First systemically available pleuromutilin for human use Highly active against MRSA, VRE Excellent resistant profile Oral & IV availability Phase III

18. Pagibaximab Chimeric monoclonal antibody Directed against lipoteichoic acid (LTA) moiety LTA is an important structural component of cell wall of Staph aureus Prevention of staphylococcal sepsis in infants with low birth weight Phase III

19. IDSA Guidelines on the Treatment of MRSA Infections in Adults and Children

20. Conclusion Treatment of MRSA bacteremia requires prompt source control and initiation of active antimicrobial therapy. Vancomycin remains the initial antibiotic of choice for the treatment of patients with MRSA bacteremia and endocarditis  The need for antibiotics that are more efficacious than vancomycin has never been greater. Fortunately, several agents have become available for the treatment of MRSA. 

21. References Rodvold KA, McConeghy. Methicillin resistant Staphylococcus aureus therapy: Past, Present, and Future.CID. 2016;58:20S-7S. Michio Kurosu, Shajila Siricilla, Katsuhiko Mitachi. Advances in MRSA drug discovery. Expert Opin Drug Discov. 2016 Sept;8(9):1095-116. Bassetti M, Merelli M, Temperino C, Astilean A. New antiobitics for bad bugs: where are we? Annals of clinical microbiol antimicrobiol.2015;12:1-15. IDSA Guidelines on the Treatment of MRSA Infections in Adults and Children.2011.

22. References Kumar K, Chopra S. New drugs for methicillin-resistant Staphylococcus aureus : an update. JAntimicrob Chemotherap. 2013; 68:1–6. Gould M, Bal A. New antibiotic agents in the pipeline and how they can help overcome microbial resistance. Virulence. 2013;4(2):185-91. Fernebro J. Fighting bacterial infections- Future treatment options. Drug resistance updates. 2011;14:125-39. Katzung-Text book of basic and clinical pharmacology 12 th edition. Harrison`s principles of Internal medicine.18 th edition.