Control and management of MRSA

Transcription

1 Control and management of MRSA Daniel Kaul M.D. Associate Professor Director, ID Fellowship Program and Transplant ID service Division of Infec?ous Diseases University of Michigan Topics MRSA an?microbial therapy? Role and limita?on of newer agents Emerging issues with vancomycin Is anything beger than vancomycin? Nosocomial pneumonia Blood stream infec?on Treatment route and dura?on for MRSA blood stream infec?ons Update on community- acquired MRSA Op?ons for refractory MRSA bacteremia Agents with reliable activity against MRSA Drug Comments Cau.ons Vancomcyin Caution with MIC > 1.0 ug/ml Much less expensive Renal failure with higher troughs and/or recent impurities Linezolid (Zyvox ) Daptomycin (Cubicin ) Superior to vancomycin for MRSA pneumonia Excellent bioavailability Not for pneumonia At least = to vancomycin for blood stream infections Resistance Serotonin syndrome, neuropathy Cytopenias (common) Poor GI tolerance (oral) Rare rhabdo (monitor CPK) Eosinphilic pneumonia

2 Agents with reliable activity against MRSA Drug Comments Cau.ons Dalfopristin/Quinopristin Very difficult to deliver at home (Synercid ) May be potent when combined with vancomycin Phlebitis requires central access Myalgias/arthralgias Tigecycline (Tygacil ) Broad spectrum activity (excludes Pseudomonas and other some other GNR) Increased mortality in clinical trials Nausea Not effective for blood stream infections Agents with reliable activity against MRSA Drug Comments Cau.ons Ceftaroline (Teflaro ) Like ceftriaxone + MRSA and MDR S. pneumonia Approved for SSTI and CAP Similar to other cephalosporins Telavancin (Vibativ ) Lipoglycopeptide (similar to vancomycin) Active against (VRSA, VRE) Approved cssti Renal toxicity Agents with variable activity against MRSA Drug Comments Cau.ons Clindamycin Bacteriostatic (not for endovascular infections) HA-MRSA often resistant Diarrhea Poor tolerance > 300 mg po qid Rifampin Never monotherapy (resistance) Potent p450 induction (multiple drug interactions) Doxycycline TMP/SMX HA-MRSA often resistant Not appropriate for invasive infections HA-MRSA often resistant GI intolerance Rash 2 nd or 3 rd line agent for invasive infections Cytopenias Renal toxicity

3 Tigecycline associated with increased mortality in pooled analysis hgp:// (March 22, 2012) Hospital- acquired pneumonia MRSA first or second most common pathogen in most centers Early, effec?ve treatment results in improved outcome Empiric treatment typically includes MRSA ac?ve agent Debate over last decade vancomycin versus linezolid Daptomycin,?gecycline not approriate Recently completed randomized trial comparing linezolid to vancomycin Linezolid verus vancomycin MRSA HA- pneumonia Hospital acquired or health care- associated pneumonia Culture posi?ve for MRSA Randomized to Linezolid or Vancomycin (15 mg/kg twice daily) for days GNR coverage un?l culture nega?ve Local adjustment of vancomycin dose Primary outcome Clinical cure Symptoms, radiology (no progression), no need for addi?onal an?bio?cs

4 Study population Pa.ent enrollment 1225 pa?ents enrolled 224 in each arm in mitt (many without MRSA on culture) 170 s in each arm in per protocol analysis Linezolid superior to vancomycin for nosocomial pneumonia No difference in 60 day mortality Subgroup analysis Outcomes not beger with higher vancomycin troughs Outcomes not worse with MIC > 1 ug/ml Clinical Response Linezolid Vancomycin

5 MRSA pneumonia treatment Linezolid likely superior No difference in mortality noted Unexpected nephrotoxicity associated with vancomycin $$$$$$ linezolid > vancomycin (drug cost) Comple?on therapy at home with oral linezolid Results likely extend to CA- MRSA pneumonia Consider linezolid for significant MRSA pneumonia (nosocomial or community- acquired) MIC drift and vancomycin efcicacy heteroresistance, VISA, VRSA hvisa (mixed popula?on, hard to iden?fy in lab, may be associated with improved outcome) VISA uncommon (MIC 4-8 ug/ml) VRSA very rare (MIC > 8ug/ml) Breakpoint for vancomycin lowered to <= 2 from <=4 in 2006 Never use vancomycin if MIC > 2 ug/ml Less than 1% of MRSA isolates in most hospitals Consider alterna?ve agent or change to another agent if MIC = 2 ug/ml Vancomycin MIC 2.0 INCREASED MORTALITY

6 Vancomycin MIC 2.0 ug/ml This will be listed as sensi?ve Further micro tes?ng (e.g., E- test) indicated but variably available If clinical failure or ongoing serious infec?on (par?cularly blood stream infec?on) change to alterna?ve agent Vancomycin dosing Typical dose mg/kg/dose (2-3 doses a day) Consider load (25-30 mg/kg) in cri?cally ill Troughs (but not peaks) should be monitored (prior to 4 th or 5 th dose) Troughs < 10 ug/ml associated with clinical failure Typical goal trough ug/ml Severe infec?ons- consider trough ug/ml Limited data to support this May be more nephrotoxic than previously thought Trough > 15 ug/ml associated with increased toxicity but not clearly with beger outcome Caution with vancomycin dosing (recommendations may be too high)

7 Renal failure more common with vancomycin Vancomycin Trough (ug/ml) Renal toxicity (%) < 15 18% % > 20 37% Case 68 year old man with a history of diabetes mellitus admit ted with 2 months of back pain significant worsened over past 72 hours Difficulty ambula?ng and unable to sleep Pain radiates down lateral aspects legs to knees No fever and no leucocytosis Blood cultures obtained Posi?ve for gram posi?ve cocci in clusters MRI Lumbar Spine Degenerative changes T2 FS T1

8 Case Slight improvement in back pain Blood cultures persistently posi?ve for 6 days on vancomycin Trans- esophageal echocardiogram without evidence of endocardi?s Discharge diagnosis (hospital day #10) Back pain secondary to degenera?ve joint disease Urinary tract infec?on S. aureus bacteremia of unknown source 2 weeks of vancomycin and PCP follow up in 2 weeks Case Re- admiged to another hospital 11 days later with increasing weakness, numbness from waist down. Barely able to liq either thigh from the bed Vancomycin had been changed to daptomycin at the subacute rehabilita?on facility T7-8 T9-10

9 MRI T- L SPINE Disci?s/osteomyeli?s at T7- T8 and T9- T10 levels with marked paravertebral phlegmon, microabscesses, and a ventral epidural phlegmon from T8 to T11 Compression of the thoracic cord with findings sugges?ve of cord edema/ischemia Moderate to severe DJD of lumbar spine Required surgery to decompress (ischemic necrosis of spinal cord) Regained only par?al neurologic func?on Case Further history obtained Undergone hip replacement 6 months earlier Staph infec?on of hip wound treated with vancomycin followed by TMP/SMX (Bactrim) Teaching points S. aureus is a high destruc?ve and s?cky organism Prolonged S. aureus bacteremia requires vigorous examina?on for metasta?c areas Bacteremia may occur without fever and leucocytosis (par?cularly in the elderly) Two week dura?on of treatment for S. aureus bacteremia can only be considered in uncomplicated cases Brief dura?on of bacteremia (< 48 hours) Must document clearance of bacteremia Rapid response to therapy (defervescence within 72 hours) No endocardi?s and no prosthesis Oqen removable focus

10 Where does S. aureus like to go Lumbar spine > thoracic or cervical spine Oqen with extension to epidural space Psoas muscle Cardiac valves Large joints Eyes Anything possible Pericardium Thyroid Long bones brain Community- acquired MRSA Clinical syndrome CA- MRSA Fridkin et al. NEJM Volume 352:

11 A Clone of Methicillin- Resistant Staphylococcus aureus among Professional Football Players Volume 352: February 3, 2005 Number 5 MRSA St. Louis Rams NEJM 352:

12 Cultures obtained from 422 pa?ents presen?ng with skin and soq?ssue infec?ons at 11 Emergency Medicine Departments CA- MRSA (epidemiology) CA- MRSA (risk factors)

13 CA- MRSA antibiotics Fridkin et al. NEJM Volume 352: Clindamycin: inducible resistance in some CA- MRSA Inducible clindamycin resistance Lab s need to perform D- test to confirm ini?al sensi?vity to clindamycin CA- MRSA decolonization Nasal decoloniza?on mupirocin twice daily for 5 10 days AND Bleach baths (¼ cup per ¼ tub) for 15 minutes twice weekly for 2-3 months (preferred) OR Chlorhexidine (Hibclens) 3 X week for 2 weeks (drying) IF REFRACTORY Rifampin + doxy/clinda/tmp/smx for two weeks

14 CA- MRSA (teaching points) CA- MRSA typically presents as purulent soq?ssue infec?on Drainage is more important than medical treatment An?microbials indicated if significant surrounding erythema Linezolid (cost), TMP/SMX, doxycycline, clindamycin More invasive disease may occur: Necro?zing pneumonia Endovascular infec?on decoloniza?on Case 81 year old man with severe angina undergoes coronary artery bypass graqing 3 weeks post- opera?vely develops sternal wound infec?on Limited bedside debridement reveals MRSA and blood cultures are posi?ve Not a candidate for sternal debridement and flap placement Asymptoma?c but remains bacteremic for 12 weeks Evalua?on/treatment op?ons? Daptomycin non- inferior to standard therapy for Staph aureus bacteremia

15 Daptomycin may be superior to vancomycin if MIC > 1.0 ug/mi for bloodstream infection Refractory MRSA bacteremia (> 7-10 days) Evaluate for persistant source Heart valves Joints Any place that hurts Check MIC with E- test or equivalent for vancomcyin High dose daptomycin (10 mg/kg daily) Combina?on therapy Rifampin 600 mg daily Linezolid 600 mg twice daily TMP/SMX 5 mg/kg every 12 hours Aminoglycoside (probably best to avoid ) Quinopris?n/dalfopris?n + vancomycin (in vitro data) Telavancin 10 mg/kg daily Infection control basics Hand hygiene universal Contact precau?ons Most ins?tu?ons use for MRSA An?microbial stewardship Ins?tu?onal monitoring Intensified measures Cohor?ng opt out isola?on

16 Summary Vancomycin least expensive and most widely used Cau?on renal failure with higher troughs and if MIC > 1.0 ug/ml Linezolid superior for nosocomial pneumonia Daptomycin non- inferior for bacteremia MRSA is s?cky (heart valves, large joints, vertebral spine) 4-6 weeks of intravenous treatment unless brief bacteremia without deep seated focus Community- acquired MRSA most common purulent soq?ssue infec?on Invasive syndromes do occur