24 MRSA Yamaki Flashcards
What are the two commonly divided classifications of MRSA?
Hospital Acquired (HA) vs. Community Acquired (CA)
What is the most common burden of MRSA disease in the US?
Bacteremia
What is the definition of HA-MRSA?
MRSA being identified after 48 hours of admission to a hospital or does not meet criteria for CA-MRSA. Skilled nursing facility (SNF) transfer. Ventilator associated pneumoniae (VAP). Catheter associated infections (PVC/CVC)
What is the epidemiology of HA-MRSA?
Emerged shortly after methicillin introduction. Initially majority of all MRSA infection were nosocomial (until CA-MRSA emerged)
What are the at risk groups for HA-MRSA?
Hospitalized patients. Patients w/ intravenous catheters, prosthetic devices. Surgical wounds. On ventilators
What is the definition of CA-MRSA?
Persons have no significant medical history in past year (hospitalization, admission to nursing home/skilled nursing home or hospice, dialysis, surgery)
What are the at risk groups for CA-MRSA?
Correctional fascilities. Military. Close contacts in families. Athletic teams. MSM. Daycares. Native Americans, Pacific Islanders
What cassettes do HA-MRSA bacteria have?
SCCmec I, II, III (larger, can carry more resistant genes)
What cassettes do CA-MRSA bacteria have?
SCCmec IV, V (smaller, less resistant genes)
What are the genetic characteristics of CA-MRSA?
Methicillin resistance conferred by mecA gene (SCCmec types IV and V, rarely multi-drug resistant). ACME. Accessory gene regulator (agr) type I or III
What is ACME?
Arginine Catabolic Mobile Element. Found in USA300 strains of CA-MRSA only. Enables use of arginine as an energy source. Depletion of Arginine –> Decrease in NO production. ACME gene deletion –> less virulence
What is “Pathogenicity”?
The capability of a pathogen to cause disease
What is “Virulence”?
The degree in ability of a pathogen to cause disease
What does Protein A (pathogenicity factor) do?
Evades immune system by binding to Fc portion of IgG antibodies
What does FnbA/FnbB (pathogenicity factor) do?
Fibronectin binding proteins. Recognize and bind to sites containing fibronectin
What does Coagulase (pathogenicity factor) do?
Converts fibrinogen to fibrin –> clotting. May protect bacteria from immune system recognition and elimination
What does ClfA/ClfB (pathogenicity factor) do?
Clumping factor. Membrane bound coagulase
What are the virulence factors associated with MRSA?
a-Hemolysin. Panton-Valentine Leukocidin (PVL). Phenol-Soluble Modulins (PSMs). Toxic Shock Syndrome Toxin (TSST-1)
What is a-Hemolysin (Hla)?
Heptameric pore forming toxin produced by nearly all S. aureus strains. Lysis of RBCs –> Fe. Up-regulated in CA-MRSA. Studies demonstrated it may play a role in pneumonia. Demonstrated protection with vaccine directed against Hla. Never give someone with an infection iron
What is Panton-Valentine Leukocidin (PVL)?
Bi-component pore forming toxin encoded by prophage, targets PMNs. Common in CA-MRSA strains, rare in HA-MRSA. Significant association with invasive skin infections. Linked to necrotizing pneumonia. High concentrations cause lysis of PMNs, low concentrations cause apoptosis of mitochondria
What is Phenol-Solubule Modulins (PSMs)?
Two groups alpha and Beta. Four types a-PSMs (pore forming in PMNs) and two B-PSMs (biofilm). Up-regulated peptides in CA-MRSA vs. HA-MRSA
What treatment is used for MRSA in severe, invasive infection?
IV therapy. Vancomycin remains as 1st line empiric treatment (alternative agents need to be considered based on site of infection, MIC, development of nephrotoxicity). Step down to oral therapy once patient stable, tolerating POs
What are the antibiotics used for treatment of MRSA?
Vancomycin (trough 15-20). Daptomycin (6mg/kg IV Q24h). Linezolid (600mg IV Q12h). Synercid (7.5mg/kg IV Q8h). All of these can be used with AGs or Rifampin for synergy
What are some cautions with Vancomycin use?
Acute Kidney Injury
What are some cautions with Daptomycin use?
NOT to use in pneumonia
What are some cautions with Linezolid (Zyvox) use?
SSRI/MAOI DDI; bone marrow suppression
What are some cautions with Tigecycline (Tygacil)?
NOT to use in bacteremia, pneumonia
What are some cautions with Synercid?
3A4 DDI; arthralgia/myalgia
What are some cautions with Ceftaroline?
Nausea
What are some cautions with Telavancin?
Nephrotoxic > vanco, QT prolongation, teratogenic
What are some characteristics of Pneumonia caused by MRSA?
Commonly caused by HA-MRSA (HAP), reports of CA-MRSA causing severe necrotizing pneumonia. Can arise from prolonged bacteremia. Need adequate drug perfusion of lung tissue
What treatment options are there for Pneumonia caused by MRSA?
Vanco trough 15-20 d/t protein binding and its large structure –> difficult lung perfusion. Linezolid good alternative
What should NOT be used in Pneumonia caused by MRSA?
Daptomycin is an absolute NO (lung surfactant binds molecule). Tigecycline (doesn’t penetrate lung fluid enough for high MIC organisms)
What is the outline for treatment of MRSA bloodstream infections that are BSI (catheter-related)?
Removal of catheter/prosthetic material (risk relapse). 14 day course if: catheter removed, endocarditis excluded, no implanted prostheses, Cx (-) after ~3 days/defervesces w/i 72 hrs. No symptoms of metastatic infection
What is the outline for treatment of MRSA bloodstream infections that are Endocarditis (TEE/TEE+)?
Remove catheter/prosthetic material. Typical duration 4-6 weeks
What medications are used for the treatment of MRSA bloodstream infections?
Daptomycin, Vancomycin, Linezolid. NO tigecycline
What what MIC do you want to avoid Vancomycin use?
> 2
What is Vancomycin therapy like for MRSA?
High dose therapy (target trough 15-20). Time dependent killing, maximal effect = 5x MIC. Empiric high-dose –> higher initial response. Consider loading dose. Treatment failure if MIC > 2. Increased risk of nephrotoxicity
What is cross resistance of Vanco and Dapto like?
Has been observed even without prior exposure to daptomycin. Thought to be due to increased cell wall thickness
When should you start having considerations for alternative therapy (from vancomycin)?
Strains with high MIC > 1 (w/ pneumonia treatment). Slow response (>48-72hrs) or failure with vancomycin therapy. Risk for nephrotoxicity. Infections d/t VISA/VRSA
What is the treatment of MRSA SSTIs like?
MRSA should be considered in differential diagnosis if patient presents with SSTI. The “spider bite” complaint –> Furuncles and abscesses. Incision and drainage (cure rates > 85%) is primary therapy
When should antibiotics be given in MRSA SSTIs?
Progressing SSTI or if associated with cellulitis. Abcesses > 5cm. S/Sx of systemic illness. Co-morbid conditions (i.e. immunosuppressed). Location (i.e. difficult for I&D or near major vessels)
What does I&D stand for?
Incision and drainage
What is the outpatient treatment of MRSA SSTI like?
Typically most patients with SSTI (mild infections) can be managed with PO antibiotics. Outpatient/oral therapy. Assess progress in 48hrs. Duration of therapy: 7-14 days
What are the antibiotic treatment choices for MRSA SSTI?
Clindamycin. Bactrim. Doxycycline. Rifapmin (in combination with any of the previous). Linezolid
What is the MOA of Clindamycin?
Inhibits protein synthesis by binding to 50S ribosomal protein
How is Clindamycin typically dosed?
150-450mg PO Q8h
What are the ADRs associated with Clindamycin?
Super infection with C. diff associated disease
What is the MOA of Linezolid?
Protein synthesis inhibitor. Binds to large ribosomal subunit, inhibits initiation of translation to some extent
What is the dosage of Linezolid like?
600mg Q12h
What are the ADRs/SE of Linezolid?
Thrombocytopenia/myelosuppression, peripheral neuropathy, optic neuropathy
What is the MOA of Bactrim?
Inhibition of synthesis of dihydrofolic acid and folic acid, ultimately inhibits formation of thymine and uracil
What is the dosage of Bactrim like?
5-10mg/kg/day (TMP) in divided doses, typically 800/160 (DS) 1-2 tabs Q12h
What are the ADRs/SE of Bactrim?
Sulfa allergy, bone marrow suppression
What is the MOA of Doxycycline?
Binds to 30S ribosome blocks A-site
What is the dosage of Doxycycline?
100mg Q12h x 10 days
What are the ADRs/SE of Doxycycline?
Photosensitivity, hepatotoxicity
What is the MOA of Rifampin?
Protein synthesis inhibitor, prevents RNA polymerase activity
What should ALWAYS be done with Rifampin?
ALWAYS use in combination with another anti-MRSA agent due to rapid development of resistance
What is the dosing of Rifampin like?
300mg PO Q8h (synergy) usually w/ Bactrim
What are the ADRs/SE of Rifampin?
Elevated LFTs and Tbili, orange discoloration of sweat, saliva, urine, CONTACT lens
What is the transmission of MRSA like?
MRSA exposure from human to human. Skin to skin contact. Pets as carriers of MRSA. Report any skin sore or boil (red, swollen bumps like spider bites, sometimes with pus) that don’t heal easily to healthcare provider
