Synergistic Meropenem/Vaborbactam Plus Fosfomycin Treatment of KPC Producing <i>K. pneumoniae</i> Septic Thrombosis Unresponsive to Ceftazidime/Avibactam: From the Bench to the Bedside
Alessandra Oliva,
Ambrogio Curtolo,
Lorenzo Volpicelli,
Francesco Cogliati Dezza,
Massimiliano De Angelis,
Sara Cairoli,
Donatella Dell’Utri,
Bianca Maria Goffredo,
Giammarco Raponi,
Mario Venditti
Affiliations
Alessandra Oliva
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Ambrogio Curtolo
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Lorenzo Volpicelli
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Francesco Cogliati Dezza
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Massimiliano De Angelis
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Sara Cairoli
Biochemistry Laboratory, Department of Specialist Pediatrics, Bambino Gesù Children’s Hospital, 00165 Rome, Italy
Donatella Dell’Utri
Department of Anesthesia and Critical Care Medicine, Policlinico Umberto I, 00161 Rome, Italy
Bianca Maria Goffredo
Biochemistry Laboratory, Department of Specialist Pediatrics, Bambino Gesù Children’s Hospital, 00165 Rome, Italy
Giammarco Raponi
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Mario Venditti
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Gram-negative bacilli septic thrombosis (GNB-ST) represents a subtle and often misleading condition, potentially fatal if not recognized early and requiring prolonged antimicrobial therapy and anticoagulation. Herein, reported for the first time, is a very challenging case of Klebsiella producing carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) ST unresponsive to ceftazidime/avibactam (CZA) relapsed first with meropenem/vaborbactam (MVB) monotherapy and subsequently cured with MVB plus fosfomycin (FOS) combination. The present case highlights the possibility of CZA underexposure on the infected thrombus and the risk of in vivo emergence of CZA resistance in the setting of persistent bacteremia and sub-optimal anticoagulation. Pharmacokinetic analyses showed that both MVB and FOS were in the therapeutic range. In vitro studies demonstrated a high level of MVB + FOS synergism that possibly allowed definitive resolution of the endovascular infection.
