In Vitro Antibiofilm Activity of Fosfomycin Alone and in Combination with Other Antibiotics against Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa

Background: Due to its rapid resistance development and ability to form biofilms, treatment of Pseudomonas aeruginosa infections is becoming more complicated by the day. Drug combinations may help reduce both resistance and biofilm formation. Methods: Using the microtiter plate assay, we investigated the in vitro inhibition of biofilm formation and the disruption of preformed biofilms in multidrug-resistant and extensively drug-resistant clinical isolates of P. aeruginosa in the presence of peak plasma levels of eight antipseudomonal antibiotics alone and in combination with fosfomycin: ceftazidime, piperacillin/tazobactam, cefepime, imipenem, gentamicin, amikacin, ciprofloxacin and colistin. Results: Combination therapy was significantly superior to monotherapy in its inhibition of biofilm formation. The highest inhibition rates were observed for combinations with colistin, cefepime and ceftazidime. Conclusion: Our results support fosfomycin combination therapy as an enhanced prophylactic option. Moreover, combinations with beta-lactam antibiotics and colistin demonstrated a more potent inhibition effect on biofilm formation than protein synthesis inhibitors.