High-Dose Inhaled Colistin-Aminoglycoside Combination Therapy in Critically Ill Patients With Multidrug-Resistant

Background: Multidrug-resistant Case Report: We describe three critically ill patients with HAP/VAP due to MDR PA. All received adjunctive high-dose inhaled colistin immediately followed by inhaled amikacin or tobramycin, in addition to systemic therapy. Dosing was individualized based on renal function. Nebulization was optimized using inspiratory-synchronized delivery. All patients demonstrated clinical improvement, reductions in inflammatory markers (though with a transient rise in one or more markers in two patients), radiologic resolution, and eventual microbiologic eradication, despite isolates reported as resistant to the aminoglycoside and colistin used in vitro. No nephrotoxicity, bronchospasm, or device-related complications were observed clinically, despite doses exceeding those commonly reported, although formal ototoxicity surveillance was not performed. However, because all patients also received concurrent systemic antibiotics, a specific causal contribution from inhaled therapy cannot be fully established. Conclusions: Dual inhaled colistin-aminoglycoside therapy may represent a pharmacokinetically rational adjunctive strategy in selected patients with MDR PA HAP/VAP. High intrapulmonary concentrations achieved through aerosolization may overcome resistance while maintaining acceptable systemic safety. Prospective PK-guided studies are warranted.