# Evaluation of the In Vitro Synergistic Activity of Ceftazidime/Avibactam Against Stenotrophomonas maltophilia Strains in Planktonic and Biofilm Cell Cultures

## TL;DR

This study shows that combining ceftazidime/avibactam with other antibiotics can effectively fight Stenotrophomonas maltophilia in both free-floating and biofilm forms.

## Contribution

The study introduces new evidence of synergistic effects of ceftazidime/avibactam with other antibiotics against S. maltophilia.

## Key findings

- CZA was four times more efficient against 37 S. maltophilia strains compared to ceftazidime.
- CZA combinations with LVX, AMK, or CS showed synergistic effects in 57-100% of tested strains.
- CZA combinations inhibited S. maltophilia biofilm formation and had MPC values 8–16 times the MIC.

## Abstract

Background/Objectives: Stenotrophomonas maltophilia (SM) is a significant cause of hospital-acquired infections in immunocompromised and critical care patients. This study investigates the impact of combining ceftazidime/avibactam (CZA) with conventional antibiotics on SM obtained from various sources in planktonic and biofilm cell cultures. Methods: Using broth microdilution, the MICs of different antibiotics, including CZA, were determined on 37 SM strains. CZA’s bactericidal and synergistic effectiveness were examined through in vitro time–kill curve tests with tigecycline (TGC), chloramphenicol (CHL), levofloxacin (LVX), colistin (CS), and amikacin (AMK). In addition, synergistic activity was investigated against SM biofilm cell cultures, and antibiotic Mutant Prevention Concentrations (MPCs) were tested against SM isolates. Results: Compared to ceftazidime (CAZ), CZA was four times more efficient against 37 SM strains. Unlike TGC and CHL, CS, AMK, and CZA had 2–4 times higher MBCs than MICs. All studied antibiotics were bactericidal at 1× or 4× MIC doses against SM bacteria, except for CZA. The combinations of CZA with LVX and CZA with AMK or CS demonstrated synergistic effects in four out of seven (57%) strains and in three out of seven (43%) strains, respectively, when tested at doses equivalent to the MIC. Moreover, all antibiotic combinations with CZA showed a synergistic effect at dosages four times the MIC. Additionally, CZA and the tested drugs synergistically inhibited SM biofilm formation, and MPC values were 8–16 times the MIC. Conclusions: The results of this study indicate that combining CZA with LVX and CS was more effective against SM strains. These combinations might provide alternatives for treating SM pathogens in both planktonic and biofilm cell cultures.