Critical Review of Double-Carbapenem Therapy for the Treatment of Carbapenemase-Producing Klebsiella pneumoniae

Objective: To review the clinical data on the effectiveness and safety of double carbapenem therapy (DCT) in patients infected with carbapenemase-producing Klebsiella pneumoniae (CP-Kp). Data Sources: A literature search was performed utilizing PubMed and EMBASE (from 1966 to May 2018); bibliographies of the retrieved articles were also searched. Study Selection and Data Extraction: Articles were included if they evaluated patients with infections caused by CP-Kp and were treated with DCT. Meeting abstracts, editorials, and animal and in vitro studies were excluded. Data Synthesis: The search strategy revealed 8 case reports and 6 clinical studies (total of 171 patients) that evaluated the administration of ertapenem followed by prolonged infusions of meropenem or doripenem. Most patients were critically ill and commonly had infections in the blood, lungs, and urine. Clinical and microbiological success were reported in 70% of the patients and mortality in 24%. Adverse events, which included mostly seizures, sodium disorders, and gastrointestinal symptoms, were reported in 16 patients; none required interruption of treatment. Relevance to Patient Care and Clinical Practice: This review evaluated the clinical experience of DCT in the treatment of CP-Kp infections, based on case reports and clinical studies, for the potential role of DCT as a therapeutic option. Conclusion: Despite the limited studies, current data suggest that DCT may be an effective and safe strategy to treat CP-Kp. However, large randomized controlled trials are necessary to clearly define the role of DCT.