Cefiderocol (FDC) is a recently developed siderophore cephalosporin showing excellent antibacterial activity against Gram-negative bacteria, including Acinetobacter baumannii. By investigating a series of A. baumannii clinical isolates with elevated MICs of FDC, we showed that PER-like β-lactamases and, to a lesser extent, NDM-like β-lactamases, significantly contributed to reduced susceptibility to that antibiotic. Interestingly, we showed that combination of FDC with avibactam exhibited excellent activity against all multidrug-resistant isolates coproducing OXA-23 and PER-type β-lactamases.