CA-MRSA Pneumonia Michael S. Niederman, M.D. Clinical Director Pulmonary and Critical Care Medicine New York Presbyterian Hospital Weill Cornell Medical Center Professor of Clinical Medicine Weill Cornell Medical College msn9004@med.cornell.edu
2 Clinical Presentation A 25 year old teacher with a flu-like illness along with malaise and myalgias, dry cough and low grade fever for 3 days. He went to an emergency room and was discharged with a diagnosis of viral illness On the 4 th day of illness, he developed higher fever, chills, right sided pleuritic chest pain, blood tinged sputum, and dyspnea Chest radiograph showed a right lower lobe density with a combination of infiltrate and possible effusion and the patient was referred to the hospital
CASE 1: Community Acquired Pneumonia (2) 3 On arrival, his WBC was 18,300/mm 3. Liver and renal function were normal. Sputum and blood cultures were sent. T= 101.9 degrees F, P=96, R= 28, BP=129/73 Shortly after arrival to the ED, he was started on intravenous moxifloxacin and ceftriaxone and sent for a CT scan of the chest.
CT Scan on admission (1) 4
5 Post-Operative Course Based on the findings of the CT scan, the patient was taken for immediate thoracotomy for drainage of pleural fluid and decortication. Based on the clinical presentation and pleural fluid findings, the patient was treated with linezolid 600 mg twice daily. He had a slow resolution of fever, but during his illness, there was a consideration of whether he had gangrenous lung. However, he responded gradually to antibiotic therapy and was discharged home on day 10, on oral linezolid, which he continued for a total of 4 weeks.
Pleural Fluid Culture 6
Sputum Culture 7
Post Operative CT Scan with chest tubes and necrosis 8
Followup Radiograph 10 months later 9
Differences Between CA-MRSA Pneumonia and MRSA in the HCAP Patient Distinguish CA-MRSA in previously healthy patients, from MRSA arising in the community in patients with HCAP risks. CA-MRSA uncommon and often post influenza or viral illness Wunderink R. Inf Dis Clin North Am 2013; 27:177-188 10
Clinical Features of CA-MRSA: Need a High Level of Suspicion 11 Often a serious illness, with necrotizing pneumonia, but not always. Usually in previously healthy patient. Wunderink R. Inf Dis Clin North Am 2013; 27:177-188
12 Incidence of CA-MRSA 2259 adults with radiographic CAP S. aureus (all types, not just MRSA) in 5% of ICU patients, 1% non-icu, 2% overall. Most often in winter Jain et al. NEJM 2015; 375:415
The Expanded Clinical Spectrum of CA- MRSA Demonstrated that not all CA-MRSA is severe necrotizing pneumonia 15 patients with CA-MRSA CAP in 28 months No seasonal pattern;1 prior influenza 7 with cavitary CXR 7 not to ICU; 7 with mechanical vent. 9 with pleural fluid, 5 with drainage 7 immune compromised 2 deaths, both immune compromised 14 got linezolid or clindamycin Did inhibition of protein synthesis improve outcomes? Lobo LJ, et al. Chest 2010; 138:130-36. CT more informative than CXR
14 Not All CA-MRSA Needs ICU Care 16 patients from Australia Symptoms for 1-21 days 8 multilobar consolidation, 7 necrotizing pneumonia, 5 empyema Mean delay of 69 hours until appropriate rx. Need high level of suspicion 9/16 with positive blood cultures Thomas R, et al. Respirology 2011; 16:926-931
Is Empiric MRSA Therapy Needed in All ICU-Admitted CAP? 621 with ICU admitted CAP in CAPO study 57 treated emprically for MRSA (vancomycin or linezolid) MRSA rx group sicker 20 proven MRSA, 35% mortality. 10 treated empirically. Same outcome empiric vs. late rx. No difference in-hospital mortality (25%), 28 day mortality, LOS, time to clinical stability with empiric MRSA rx. Griffin AT, et al. Infection 2012; DOI 10.1007/s15010-012-0363-1
PVL Positive S. Aureus Pneumonia: Role of Methicillin Resistance and Proper Therapy 133 with PVL positive Staphylococcal CAP 29 MRSA 104 MSSA 39% mortality, Methicillin resistance NOT a mortality predictor. 64% mechan vent. Hemoptysis assoc. with mortality. 33.7% got antitoxin (linezolid, clindamycin or rifampin), with reduced mortality (6.1% vs. 52.3%, p < 0.001) Sicot N, et al. Clin Microbiol Infect 2012; 19: E142-148
Toxin Inhibition in the Therapy of CA- MRSA by Linezolid Given Early Best therapy is unclear. Vancomycin is slowly bacteridal, and toxin release can continue Linezolid and clindamycin inhibit toxin production Beta-lactams kill rapidly and may eliminate toxin Cetaroline was effective in MRSA pneumonia with bacteremia, unresponsive to vancomycin Faris J, et al. Infect Dis Ther 2015; DOI 10.1007/s40121-015-0096-4 Rabbit model of USA 300 MRSA necrotizing pneumonia, using direct inoculation into the lung Linezolid w/i 1.5 hours after infection, reduced toxin production (PVL, alpha hemolysin), pro-inflammatory cytokines (IL-8) and mortality vs. vancomycin Diep BA, et al. CID 2013; 28:75-82 17
Toxin Inhibition in the Therapy of CA- MRSA Diep BA, et al. CID 2013; 28:75-82 18
Even With Appropriate Therapy (Of All Types), MRSA (VAP) Is Slow To Clinically Resolve Vidaur et al. Chest 2008; 133: 625-632.
Vancomycin vs. Linezolid Vancomycin. Glycopeptide, disrupts cell wall/peptidoglycan synthesis Pros: low resistance rates, years of experience Cons: slow increase in MICs (w/i sensitive range); poor lung penetration (12% serum levels); slowly bactericidal; nephrotoxicity with dose optimization May overcome poor penetration by synergy with rifampin Linezolid Pros: good lung penetration; IV/oral available; high bioavailability orally; no renal dose adjustment Cons: thrombocytopenia, optic neuritis, lactic acidosis (prolonged therapy); drug interactions (serotonin syndrome).? If effective in bacteremia/endocarditis Pletz MW, et al. Eur J Med Res 2010; 15:507-13 Linezolid, but not vancomycin reduces MRSA bacterial burden in ETT biofilm, in a pig model of MRSA pneumonia. Fernandez-Barat L, et al. Crit Care Med 2012; 40: 2385-89.
Vancomycin Trough Concentrations Predict Efficacy and Toxicity IDSA recommendations: Vancomycin trough of15-20 mg/l for MIC <1 mg/l. Higher MIC needs alternative treatment Rybak et al. CID 2009;49:325-327 31 patients with MRSA pneumonia Nephrotoxicity: increase Cr by 0.5 mg/dl or 50% from baseline Relationship of trough/mic with success, and trough levels with toxicity Suzuki Y et al. Chemotherapy 2012; 58:308-12 Toxicity Efficacy
Therapy of MRSA Pneumonia and Bacteremia 22 MRSA pneumonia with bacteremia may be complicated by endocarditis, and secondary seeding of the lung. What is the best therapy? Vancomycin may not eradicate lung source Linezolid may not eliminate endocarditis Daptomycin has a role in MRSA bacteremia but not MRSA pneumonia BUT daptomycin IS EFFECTIVE in septic emboli to the lung MAYBE use daptomycin with linezolid for MRSA pneumonia and bacteremia
Daptomycin/ Rifampin for Septic Pulmonary Emboli From Right Sided Endocarditis 4 patients with MRSA septic emboli, 3 not clearing on vancomycin Gomez EO, et al. Microb Drug Resist 2010; 16:241 23
New Therapy Options for CA- MRSA 24 Karampela I, et al. Minerva Anesthesiologica 2012; p. 930
25 Conclusions About CA-MRSA Pneumonia CA-MRSA pneumonia should be distinguished from MRSA in the community arising in HCAP patients Often necrotizing, but does not always need ICU care Associated with toxin production (so is MSSA) Slow to resolve Not all severe CAP patients need empiric MRSA therapy Optimal therapy unclear Role of toxin inhibition Therapy of pneumonia with bacteremia Maybe a role for new beta-lactams