Can Imipenem-Relebactam (Recarbrio) Be Used for Carbapenem-Resistant Klebsiella?
Yes, imipenem-relebactam is an effective treatment option for carbapenem-resistant Klebsiella pneumoniae infections, particularly those producing KPC carbapenemases, and should be considered as an alternative when first-line agents (ceftazidime-avibactam or meropenem-vaborbactam) are unavailable. 1, 2
First-Line Treatment Hierarchy for Carbapenem-Resistant Klebsiella
For KPC-producing carbapenem-resistant K. pneumoniae, ceftazidime-avibactam 2.5g IV q8h or meropenem-vaborbactam 4g IV q8h remain the preferred first-line options with strong recommendations and moderate certainty of evidence. 1, 2
Imipenem-cilastatin-relebactam 1.25g IV q6h is recommended as an alternative therapy when first-line options are unavailable, with conditional recommendation and low certainty of evidence. 1, 2
Mechanism and Activity Profile
Relebactam is a beta-lactamase inhibitor that protects imipenem from degradation by certain serine beta-lactamases including KPC, SHV, TEM, CTX-M, P99 (AmpC-type), and PDC carbapenemases. 3
In vitro studies demonstrate that relebactam restores imipenem susceptibility against 98% of KPC-producing K. pneumoniae isolates at ≤2 mg/L, lowering the imipenem MIC50 from 32 to 0.25 mg/L and MIC90 from >64 to 1 mg/L. 4
The FDA label confirms that vaborbactam (the comparator agent in meropenem-vaborbactam) protects meropenem from degradation by KPC carbapenemases, and similar activity is demonstrated by relebactam for imipenem. 5, 3
Critical Limitations and Resistance Mechanisms
Imipenem-relebactam is NOT active against metallo-beta-lactamases (MBLs such as NDM, VIM, IMP), some oxacillinases with carbapenemase activity, or certain GES alleles. 3
For MBL-producing strains, the combination of ceftazidime-avibactam plus aztreonam is recommended instead, with 70-90% efficacy. 2, 6
Reduced activity of imipenem-relebactam (occurring in approximately 2% of KPC-producing isolates) is associated with chromosomal factors including ompK35 disruption and/or mutated ompK36 porin mutations. 4
Imipenem-relebactam provides only weak potentiation against K. pneumoniae producing OXA-48-like carbapenemases, making it a poor choice for these specific resistance mechanisms. 4
Dosing and Administration
The standard dose is imipenem-cilastatin-relebactam 1.25g IV every 6 hours (imipenem 500mg + cilastatin 500mg + relebactam 250mg per dose). 3
Dose adjustment is mandatory for renal impairment: patients with CrCl 30-59 mL/min require 2.2-fold higher AUC exposure without adjustment, necessitating dose reduction per FDA labeling. 3
For end-stage renal disease patients on hemodialysis, imipenem-relebactam should be administered after the hemodialysis session, as all three components are removed by dialysis with extraction coefficients of 66-87% for imipenem, 46-56% for cilastatin, and 67-87% for relebactam. 3
Treatment Duration by Infection Type
- Bloodstream infections: 7-14 days 2
- Complicated urinary tract infections: 5-7 days 2
- Hospital-acquired/ventilator-associated pneumonia: 10-14 days 2, 6
- Complicated intra-abdominal infections: 5-7 days 2
Combination Therapy Considerations
For critically ill patients with severe CRKP infections and high mortality risk (INCREMENT score 8-15), combination therapy with two or more in vitro active antibiotics is strongly recommended, with adjusted HR 0.56 (95% CI 0.34-0.91) for 30-day mortality reduction. 1, 2
Monotherapy with newer agents like imipenem-relebactam is sufficient for non-severe infections in patients without septic shock. 2
Essential Diagnostic Requirements Before Treatment
Rapid molecular testing must be obtained immediately to identify the specific carbapenemase type (KPC vs OXA-48 vs MBL) because each class requires distinct treatment strategies. 1, 2
Among carbapenem-resistant K. pneumoniae, KPC remains the most common carbapenemase (47.4%), followed by MBLs (20.6%) and OXA-48-like enzymes (19.0%). 1
Time from blood culture collection to initiation of active antibiotic therapy directly influences outcomes in critically ill patients with KPC-producing K. pneumoniae bloodstream infections, making rapid diagnostics critical. 1
Clinical Outcomes and Comparative Efficacy
Initial adequate antibiotic therapy is the only independent factor protecting against death in CRKP bacteremia (p=0.02), with mortality rates reaching 71% in high-risk hematological patients when therapy is delayed or inadequate. 7
Traditional antibiotic regimens (colistin-based combinations) result in approximately one in three patients dying and <70% achieving clinical/microbiological response, highlighting the superiority of newer agents. 1
Common Pitfalls to Avoid
Do not use imipenem-relebactam for MBL-producing strains—this will result in treatment failure. 3
Do not assume activity against OXA-48 producers—relebactam provides only weak potentiation against these enzymes. 4
Do not forget renal dose adjustments—failure to adjust for renal function leads to toxicity and suboptimal outcomes. 3
Do not delay therapy while awaiting susceptibility results in critically ill patients—empiric coverage based on local epidemiology and rapid molecular testing is essential. 1, 7
Infectious disease consultation is highly recommended for all carbapenem-resistant Klebsiella infections to optimize antibiotic selection and dosing strategies. 2