2395. Mechanism-Based-Susceptibility Testing (MBST) Using Disc Diffusion Assays (DDA) to Guide Treatment of Multidrug- and Extensively Drug-Resistant Pseudomonas aeruginosa (MDR-XDR-Pa) in a Cystic Fibrosis (CF) Lung Transplant Recipient; Are We Ready for Combination Therapy vs. MDR-XDR-Pa?

Background Lung infections with MDR-XDR-Pa in patients with CF are challenging due to the emergence of antibiotic resistance. We applied MBST with DDA to guide combination antibiotic therapy in an 18-year-old woman with CF. We investigated if this approach can assist in choosing effective regimens. Methods Consecutive Pa respiratory isolates were collected between 12/16 and 3/18 and typed with MLST. After automated antibiotic susceptibility (AST) and Kirby-Bauer testing, we performed double or triple DDAs. Combinations were based on mechanisms (MBST) of anti-pseudomonal antibiotics (e.g., targeting of penicillin-binding proteins, β-lactamase inhibition, and cell membrane disruption). Results During therapy, 1859 antibiotic-days were administered. Fifteen Pa isolates, (9 sequence type (ST) 2100 and 1 ST463) with varying AST patterns were found (figure). MBST with DDA revealed active combinations for isolates resistant to individual antibiotics (table). These combinations led to a microbiological response permitting lung transplantation. Antibiotic regimens were also informed by allergies, clinical and radiologic findings. Conclusion Strains with evolving resistance profiles recapitulate the dynamic nature of respiratory infections in CF. Double or triple DDAs identified potential treatment options, e.g., vs. MDR-XDR Pa. MBST can support the management of challenging infections. Table: Antimicrobial combinations reflecting zones of inhibition by strain and date. CZA: ceftazidime–avibactam; C/T: ceftolozane-tazobactam; TOB: tobramycin; PMB: polymyxin B; FOF: fosfomycin; TZP: piperacillin–tazobactam; CIP: ciprofloxacin; IPM: imipenem; MEM: meropenem. Bold: largest zone Combinations + inhibition zones (mm) Strain Date Combo 1 Combo 2 Combo 3 1 February 23, 2017 CZA + TOB 35 PMB + IPM 38 FOF 40+ 2 April 8, 2017 CZA + TOB 31 FOF + CZA 35 PMB + C/T + MEM 39 3 May 27, 2017 FOF + TZP 40 C/T + TOB 37 PMB + CZA 33 4 June 7, 2017 FOF + TZP 15 PMB + CZA + IPM 22 C/T + IPM 24 5 August 3, 2017 FOF + TZP 18 PMB + CZA + IPM 38 C/T + IPM 42 6 August 7, 2017 FOF + TZP 19 PMB + IPM 21 7 August 21, 2017 FOF + TZP 32 FOF + CZA 26 CZA + TOB 22 8 August 24, 2017 FOF + TZP 28 PMB +I PM 35 C/T + IPM 39 9 October 15, 2017 FOF + IPM 30 PMB + IPM 30 C/T + IPM 30 10 November 30, 2017 PMB+CIP 19 PMB + CZA + IPM 25 PMB + FOF + IPM 25 11 December 9, 2017 FOF + TZP 30 PMB + IPM 25 12 January 15, 2018 PMB + IPM 23 13 January 25, 2018 PMB + IPM 26 14 February 21, 2018 FOF + TZP 20 PMB + CIP 21 15 March 4, 2018 C/T + IPM 21 CZA + IPM 23 Disclosures L. M. Abbo, Roche Diagnostics: Scientific Advisor, Consulting fee. M. I. Morris, Chimerix: Investigator and Scientific Advisor, Consulting fee and Research support. Merck: Investigator, Research grant.