Abstract
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.
Session: 250. Treatment of AMR Infections
Saturday, October 6, 2018: 12:30 PM