Eradiaction of Resistant Organisms: Can we do it and does it help? Noah Lechtzin, MD; MHS Director, Adult CF Program
Outline Evidence resistant organisms are bad MRSA, B cepacia, Pseudomonas, Fungal infections Evidence that organisms can be eradicated Data on PA eradication, cepacia eradication, MRSA eradication and outcomes
Resistant Organisms are not Rare in CF Cystic Fibrosis Foundation Patient Registry Annual Data Report: 2014
Prevalence of MRSA in Cystic Fibrosis 30 25 20 15 11.8 14.6 17.2 18.9 21.2 22.6 23.7 25.7 26.5 10 5 0 2.1 4 1996 1999 2003 2004 2005 2006 2007 2008 2009 2010 2012 Cystic Fibrosis Foundation Patient Registry Annual Data Report: 1996-2012
43% more rapid decline in those with persistent MRSA Am J Respir Crit Care Med 2008;178(8):814 21
25% more rapid rate of decline of FEV 1 % predicted after persistent MRSA infection, compared to the time period before MRSA infection Dasenbrook, AJRCCM 2008
MRSA in the respiratory tract of CF patients is associated with worse survival Dasenbrook EC, et al. JAMA 2010;303 (23):2386 92.
Median estimated age of survival is 6.2 years less in the MRSA group Dasenbrook. JAMA 2010
Risk of death remains 1.27 times greater, even with adjustment for known contributors to mortality. Dasenbrook. JAMA 2010
Not just marker of disease severity MRSA associated with an increased risk of death compared to MSSA Increased risk of death associated with persistent MRSA vs. MRSA clearance Dasenbrook. JAMA 2010
Dorothy Anderson Graduated from Johns Hopkins in 1926 August 1938 CYSTIC FIBROSIS OF THE PANCREAS AND ITS RELATION TO CELIAC DISEASE: A CLINICAL AND PATHOLOGIC STUDY
Impact of other resistant organisms
Liverpool Epidemic Strain of PA Leads to Worse Outcomes
Worse Outcomes in LES Patients
Burkholderia cenocepacia patient to patient transmission, rapid fall in lung function, shorter survival after transplant Chaparro et al. AJRCCM 2001; 163:43-48 Courtney et al. J. CF. 2004; 3:93-98
Lessons learned from Pseudomonas aeruginosa EPIC 5 year follow up 172 of 249 (69%) sustained eradication Sustained eradicators had 74% less chance of developing chronic Pseudomonas 57% reduced risk of mucoidy Less antipseudomonal antibiotic use in eradicators No difference in lung function or exacerbation rate Entire cohort was generally healthy
We Can Eradicate MRSA Dual agents better than single Rifampin/Fusidic Acid particularly good Hall et al. Respiratory Medicine 2015
Success of MRSA Treatment in CF
STAR-too Trial New MRSA infection tx d with TMP/Sulfa + rifampin vs. observation N=48 28 day culture results: 81% negative in treatment arm 22% in observation arm 60% reduction in exacerbations in treatment arm Stopped early Goss et al, NACFC 2015
Persistent MRSA Eradication Protocol (PMEP) Jennings M, Boyle M, Callahan,K, Weaver D, Dasenbrook E. Eradication Strategy for Persistent Methicillin-Resistant Staphylococcus aureus infect ion in Individuals with Cystic Fibrosis: Rationale and Design of the PMEP Randomized Clinical Trial. Trials 2014, 15:223 Study Objective: Evaluate the Safety and Efficacy of a 28-day course of inhaled vancomycin, in combination with oral antibiotics, in eliminating MRSA from the respiratory tract of individuals with CF and persistent MRSA infection
PMEP Trial Randomized trial of Inhaled Vancomycin vs placebo Everyone receives oral antibiotics & decontamination Two positive cultures 6 months apart & 50% of cultures positive for MRSA in last 2 years Endpoint: % MRSA free 30 days after protocol Enrolled ~27 of 40 patients
Can we eradicate B. cepacia? Survey of practice in the UK Case series of new B. cepacia cases in Manchester 12 of 17 adult centers routinely attempted eradication Usually IV antibiotics for 2-6 weeks ± oral or inhaled antibiotics 7 of 19 (37%) of cases were successfully eradicated Horsley et al. Frontiers celluar & infection microbiology 2011
What about fungal infections? Scedosporium sp. 2 nd most common filamentous fungi in CF (2-10%) Difficult resistance patterns: S. apiospermum and S. prolificans resistant to amphotericin and voriconazole Recent study using CF Foundation Registry
Scedosporium is associated with more exacerbations Study Population Scedo + Scedo - P-value Age 26.2 27.4 0.004 F508 del 51.9% 46.9% 0.03 BMI 21.2 22.4 <0.001 Panc Insuf. 90.1% 86.5% 0.18 Inhaled Abx 82.7% 69% <0.001
Association between Scedosporium infection and pulmonary exacerbations/year Odds ratio 95% confidence interval P-value Scedosporium-positive 1.64 1.27, 2.14 <0.001 Baseline age 0.95 0.94, 0.96 <0.001 Baseline FEV1 % predicted 0.96 0.95, 0.96 <0.001 Female 1.84 1.67, 2.03 <0.001 PI 1.72 1.43, 2.08 <0.001 F508 homozygous 1.24 1.05, 1.47 0.01 BMI 0.97 0.95, 0.98 <0.001 Pseudomonas aeruginosa 1.51 1.34, 1.69 <0.001
Johns Hopkins Adult Experience with Scedoporium species May be under identified Nine patients with positive cultures 2013 to 2016 Seven treated with antifungals Three (33%) cleared cultures
Conclusions Resistant organisms are common in CF Resistant organisms are frequently associated with poor clinical outcomes Loss of lung function and shortened survival Eradication can be accomplished but success is variable Attempts should be made after initial culture Outcomes after eradication need further study