Treatment and diagnosis of severe KPC-producing Klebsiella pneumoniae infections: a perspective on what has changed over last decades

Abstract

Antimicrobial resistance is a global health threat. Among Gram-negative bacteria, resistance to carbapenems, a class of β-lactam antibiotics, is usually a proxy for difficult-to-treat resistance, since carbapenem-resistant organisms are often resistant to many classes of antibiotics. Carbapenem resistance in the Gram-negative pathogen Klebsiella pneumoniae is mostly due to the production of carbapenemases, enzymes able to hydrolyze carbapenems, and K. pneumoniae carbapenemase (KPC)-type enzymes are overall the most prevalent carbapenemases in K. pneumoniae . In the last decade, the management of severe infections due to KPC-producing K. pneumoniae (KPC-Kp) in humans has presented many peculiar challenges to clinicians worldwide. In this perspective, we discuss how the treatment of severe KPC-Kp infections has evolved over the last decades, guided by the accumulating evidence from clinical studies, and how recent advances in diagnostics have allowed to anticipate identification of KPC-Kp in infected patients. KEY MESSAGES In the last decade, the management of severe infections due to KPC-Kp has presented many peculiar challenges to clinicians worldwide Following the introduction in clinical practice of novel β-lactam/β-lactamase inhibitor combinations and novel β-lactams active against KPC-producing bacteria, the management of severe KPC-Kp infections has witnessed a remarkable evolution Treatment of severe KPC-Kp infections is a highly dynamic process, in which the wise use of novel antimicrobials should be accompanied by a continuous refinement based on evolving clinical evidence and laboratory diagnostics

Mutations in ompK36 differentially impact in vitro synergy of meropenem/vaborbactam and ceftazidime/avibactam in combination with other antibiotics against KPC-producing Klebsiella pneumoniae

“…The development of the novel β-lactam/β-lactamase inhibitor (BL/BLI) agents ceftazidime/avibactam and meropenem/vaborbactam has changed the therapeutic landscape against infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC- Kp ) over the last decade. 1 Prior to the availability of BL/BLI agents, expert guidelines recommended polymyxin-based combinations as salvage therapy against carbapenem-resistant bacteria. 1 , 2 Now, both the IDSA and ESCMID recommend either ceftazidime/avibactam or meropenem/vaborbactam as monotherapy for the treatment of infections caused by carbapenem-resistant Enterobacterales (including KPC- Kp ), without preference for either agent.…”

“… 1 Prior to the availability of BL/BLI agents, expert guidelines recommended polymyxin-based combinations as salvage therapy against carbapenem-resistant bacteria. 1 , 2 Now, both the IDSA and ESCMID recommend either ceftazidime/avibactam or meropenem/vaborbactam as monotherapy for the treatment of infections caused by carbapenem-resistant Enterobacterales (including KPC- Kp ), without preference for either agent. 3–5 Other recently approved agents like imipenem/relebactam and cefiderocol demonstrate excellent in vitro activity against KPC- Kp ; however, real-world clinical data to support guideline recommendations are lacking.…”

Clinical Outcome of Cefiderocol for Infections with Carbapenem-Resistant Organisms

“…Cefiderocol is a novel cephalosporin that is currently FDA-approved for the treatment of patients with serious gram-negative bacterial infections [7,8]. Cefiderocol has potent in vitro efficacy against CRE, CRAB, DTR-P and S. maltophilia [3,6,9,10]. However, the current available data on clinical outcome and efficacy of cefiderocol are limited.…”

The Etiology, Antibiotic Therapy and Outcomes of Bacteremic Skin and Soft-Tissue Infections in Onco-Hematological Patients

“…The last update of the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of SSTIs was published in 2014, almost ten years ago [6]. Since then, the global epidemiology of bacterial infections has changed, with an increase in Gramnegatives and a worrisome emergence of antimicrobial resistance [7]. These developments are of paramount importance in cancer patients, who are particularly prone to infections by resistant bacteria due to repeated cycles of antibiotics, prolonged hospitalizations and immunosuppression [8].…”