Advisor: Dr. Stephanie Booth Methicillin resistant Staphylococcus aureus (MRSA): Epidemiology, mechanisms of resistance, types of infections and treatments Jenny Myskiw Msc Student Advisor: Dr. Stephanie Booth

Staphylococcus aureus Gram Positive bacteria First identified in the 1880s Causes a variety of illnesses, ranging from minor skin reactions to life threatening diseases Penicillin was introduced in the 1940s and commonly used as a treatment In 1959 methicillin was synthesized for use as a S. aureus treatment In 1880 a Scottish surgeon named Sir alexander ogston first described staphylococcus from pus In a knee joint Staphyl = bunch of grapes - greek Coccus = berry Aurum = gold 1984 german scientist High mortality rate of about 80% of individuals infected Colonized with no illness to the host Staphylococcus Aureus. Retrieved from https://zipcodezoo.com/monera/staphylococcus-aureus/

Staphylococcus aureus cont’d MRSA Skin Infections. Retrieved from https://www.webmd.com/skin-problems-and-treatments/ss/slideshow-closer-look-at-mrsa S. aureus is colonized on approximately 20-30% of the general population Less than 2% colonized with methicillin resistant staphylococcus aureus (MRSA) Often presents itself as skin rashes or boils In some cases, can infect bloodstream, lungs, heart, bones and joints

What is MRSA? Staphylococcus aureus infection that has become resistant to many antibiotics, mostly -lactams

-lactam Antibiotics These antibiotics inhibit cell wall synthesis causing cell damage and lysis a) Normal Peptidoglycan structure b) Peptidoglycan in the making: Amino acid chains need to be linked c) Penicillin Binding Proteins (PBP) connect these amino acid chains to complete peptidoglycan synthesis B-Lactams: Mechanisms of action and resistance. Stills were retrieved from Youtube video https://www.youtube.com/watch?v=qBdYnRhdWcQ

-lactam Antibiotics cont’d d) Peptidoglycan is complete e) -lactams covalently bind to PBPs, interfering with peptidoglycan synthesis B-Lactams: Mechanisms of action and resistance. Stills were retrieved from Youtube video https://www.youtube.com/watch?v=qBdYnRhdWcQ

Resistance Mechanisms Penicillin resistance for S. aureus -lactamase Prevents antibiotic from binding to the PBPs Methicillin resistance for S. aureus Expression of PBP2a Manages cross-linking that is normally carried out by PBP PBP2a is regulated through a foreign DNA fragment called the mec element Antibiotic Resistance. Retrieved from https://theconversation.com/we-know-why-bacteria-become-resistant-to-antibiotics-but-how-does-this-actually-happen-59891

MRSA Resistance Mechanism MecA: Encodes PBP2a MecR1: integral-membrane-zinc dependent sensor MecI: Transcriptional repressor Model of the salient features of mecA regulation. Retreived from “Mechanisms of Methicillin Resistance in Staphylococcus aureus” by S. Peacock et al. 2015, Annual Review of Biochemistry, 84:584  

Levels of Resistance Many MRSA isolates are heterogenous or heterotypic in their resistance to antibiotics Most bacteria from a culture exhibit low antibiotic resistance Minority of isolates will exhibit high resistance It is less common to have a colony all exhibit high homogenous resistance Stringent response seems to result in high-levels of homogenous antibiotic resistance Studies have shown MecA to be unaffected by the stringent response

HA-MRSA vs. CA-MRSA HA-MRSA CA-MRSA Healtchare. Retreived from https://www.europeis.com/en/health-care-in-latvia/   HA-MRSA MRSA isolates are identified 48-72 hours following admission into a healthcare facility Isolates are found in individuals who reside in long-term healthcare facilities CA-MRSA MRSA infections that have been acquired outside of a healthcare facility Individuals lack exposure to “Traditional” risk factors Community Antibiotic Resistance. Retreived from http://www.emro.who.int/health-topics/antimicrobial-resistance/index.html  

CA-MRSA HA-MRSA Typically infect a younger healthy population Typically infect an aging population Usually limited to -Lactam antibiotic resistance Multi-drug resistance is common Often carry genes for Panton-Valentine Leukocidin (PVL) Rarely carry genes for PVL Often are skin and soft tissue infections (SSTIs), in severe cases can cause necrotizing pneumonia Often are invasive infections (Bacteremia, pneumonia, UTIs, surgical wound infections)

HA-MRSA vs. CA-MRSA CANWARD study compared CA-MRSA and HA-MRSA infections in regards to epidemiology, antibiotic resistance, and demographics in Canada Overall Findings: MRSA isolates recovered from individuals decreased from 26.1% in 2007 to 19.3% in 2011 Majority of MRSA isolates are HA-MRSA CA-MRSA genotypes increased from 19.7% in 2007 to 36.4% in 2011

Changing epidemiology of methicillin-resistant Staphylococcus aureus in Canada. Nichol. A. et al. 2013. Journal of Antimicrobial Chemotherapy.68 Suppl 1: i50  

Molecular Classification of MRSA Canada identified epidemic clones found within the country and assigned names ranging from CMRSA1 to CMRSA10 HA-MRSA CMRSA 1,2,3,4,5,6,8, and 9 Most predominant type: CMRSA2 (58% of all MRSA isolates in Canada) Second most common type: CMRSA3/6 (decreased from over 10% to below 1% within the duration of the CANWARD study) CA-MRSA CMRSA7 and 10 CMRSA7 used to be the most common CA-MRSA infection in the 1990s, however has now been replaced as most common type by CMRSA10 CMRSA10 accounts for 22.1% of MRSA isolates within Canada

Prevention: 5 C’s from the Center for Disease Control Contact Cleanliness Compromised skin Contaminated objects Crowded areas If you think you have an S. aureus infection, get it checked as soon as possible Hand Hygiene. Retrieved from http://www.quest2fitness.info/importance-cleanliness-hygiene/ 

Treatment: Localized MRSA infections are treated with surgical incision and drainage of the abscesses, often accompanied by oral antibiotics Vancomycin is the drug of choice for MRSA infections Endocarditis infections (63% cure rate) Pneumonia (75% cure rate) Wound infections (90% cure rate) Vancomycin is being questioned due to: Poor pharmokinetic performance Increasing resistance from MRSA Poor penetration into certain tissues Variable minimum inhibitory concentrations (MICs) Vancomycin. Retrieved from https://www.henryschein.com/us-en/Shopping/ProductDetails.aspx?productid=2585707&CatalogName=MEDICAL  

Treatment cont’d: Vancomycin alternatives are needed The CANWARD study found the majority of MRSA isolates found within Canada were susceptible to tigecycline, and had not developed resistance to daptomycin, telavancin or linezolid However, the business of making antibiotics is not considered “lucrative” Discovery of new classes of antibacterials has stalled. World Health Organization (2012)  

Questions? Staph Cartoon. Retrieved from http://www.cartoonistgroup.com/subject/The-Antibiotic+Resistant-Comics-and-Cartoons.php