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Case report: rapid in vivo resistance mechanism shifts in multiple carbapenem-resistant Pseudomonas aeruginosa strains after esophagectomy in an immunocompromised patient: a case report
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DOI:10.1007/s10096-025-05366-4.png)
Abstract
En 中文
Carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses growing therapeutic challenges, particularly in critically ill, immunocompromised patients. More concerning is the rapid shift in resistance mechanisms—such as from non–MBL to metallo-β-lactamase (MBL) producers—within days, which can render initial targeted therapy ineffective. Male in his seventies with esophageal cancer underwent chemoradiotherapy followed by dual immune checkpoint inhibitor therapy, resulting in profound immune dysfunction. After a complex esophagectomy complicated by anastomotic leakage, he developed severe pneumonia while receiving mechanical ventilation, extracorporeal membrane oxygenation (ECMO), and continuous renal replacement (CRRT). Aspergillus fumigatus was first isolated from bronchoalveolar lavage on postoperative day (POD) 4. On POD 12, CRPA with OprD loss and AmpC overexpression was subsequently isolated, as confirmed by antimicrobial susceptibility testing (AST); no other bacterial species were detected. Treatment with ceftazidime/avibactam combined with intravenous amikacin and polymyxin B, together with adjuncts inhaled tobramycin, produced only transient improvement. By POD 15, repeated culture revealed a distinct CRPA isolate producing a VIM-type MBL. Therapy was promptly switched to aztreonam (2 g, q8h) plus ceftazidime/avibactam (2.5 g, q8h), alongside polymyxin B (1 million U, q12h), high-dose amikacin(15 mg/kg), fosfomycin (4 g, q8h), and inhaled tobramycin (300 mg, bid), leading to clinical recovery and microbiologic clearance. This case underscores the need for enhanced mechanism-based surveillance of antimicrobial resistance and adaptive antimicrobial management in high-risk patients. The rapid within-host replacement and emergence of an non-MBL to MBL CRPA highlights the necessity for frequent cultures and rapid carbapenemase testing to guide timely, targeted therapy. Rapid transition in CRPA resistance mechanisms — from non–MBL to VIM-type MBL production — was observed within only 3 days in a critically ill postoperative patient. Sequential mixed-strain CRPA infections occurred in the setting of profound immunosuppression, disrupted anatomical barriers, and prolonged advanced life support (MV, ECMO, CRRT). Mechanism-guided escalation from ceftazidime–avibactam–based therapy to aztreonam–ceftazidime–avibactam combination, plus adjunctive agents, achieved clinical and microbiological clearance. Highlights the importance of early and repeated microbiological surveillance, rapid carbapenemase detection, and PK/PD optimization in high-risk ICU patients.
Keywords:
Carbapenem-resistant Pseudomonas aeruginosa
Immunocompromised patient
Post-esophagectomy anastomotic leak infection
Mixed-strain infection
Rapid resistance mechanism shift
Mechanism-guided antimicrobial therapy
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