RECARBRIO Gains FDA Clearance for Hospital-Acquired Pneumonia Treatment: Clinical Trial Results Show Promise

Merck has secured U.S. Food and Drug Administration approval for an expanded therapeutic indication of RECARBRIO (imipenem, cilastatin, and relebactam) targeting adults with hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). This supplemental new drug application authorization broadens RECARBRIO’s clinical utility in treating serious Gram-negative infections.

Clinical Evidence from RESTORE-IMI 2 Trial

The regulatory decision rests on data from the Phase 3 RESTORE-IMI 2 study, a multinational randomized controlled trial comparing RECARBRIO against standard piperacillin/tazobactam (PIP/TAZ) therapy. The trial enrolled 535 hospitalized adults across 113 sites, with participants randomized to receive either RECARBRIO 1.25 grams or PIP/TAZ 4.5 grams intravenously every six hours over 7 to 14 days.

Key Study Population Characteristics:

• Mean patient age: 60 years (43% aged ≥65 years)
• Female representation: 31%
• Ventilated patients at enrollment: 49%
• Mean APACHE II severity score: 15
• Polymicrobial infections: 22%

Efficacy Outcomes

RECARBRIO met both primary and secondary efficacy endpoints, demonstrating non-inferiority to the standard treatment approach.

28-Day All-Cause Mortality:

• RECARBRIO group: 15.9% (42 of 264 patients)
• PIP/TAZ comparator: 21.3% (57 of 267 patients)
• Treatment difference: -5.3% (95% CI: -11.9 to 1.2)

Clinical Response at Early Follow-Up (Days 7-14 post-therapy):

• RECARBRIO: 61% (161 of 264 patients)
• PIP/TAZ: 55.8% (149 of 267 patients)
• Treatment difference: 5% (95% CI: -3.2 to 13.2)

Among ventilated patients specifically, RECARBRIO demonstrated a favorable mortality signal. In the ventilated HABP/VABP subgroup, mortality was 19.7% with RECARBRIO versus 30.9% with PIP/TAZ (treatment difference: -11.2%, 95% CI: -21.6 to -0.5).

Targeted Bacterial Coverage

RECARBRIO is now indicated for infections caused by susceptible Gram-negative organisms including Acinetobacter calcoaceticus-baumannii complex, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens.

The drug’s mechanism combines imipenem (a carbapenem antibiotic) with cilastatin (a renal dehydropeptidase inhibitor) and relebactam (a beta-lactamase inhibitor). Relebactam protects imipenem from degradation by serine beta-lactamases including SHV, TEM, CTX-M, P99, PDC, and KPC variants—a critical advantage against resistant pathogens.

Safety Considerations

Serious adverse reactions occurred in 27% of RECARBRIO recipients versus 32% receiving PIP/TAZ. Adverse events leading to treatment discontinuation occurred in 5.6% with RECARBRIO compared to 8.2% with the comparator.

Most Frequently Reported Adverse Effects (≥4%):

• Elevated aspartate aminotransferase (11.7%)
• Anemia (10.5%)
• Elevated alanine aminotransferase (9.8%)
• Diarrhea (7.9%)
• Hypokalemia (7.9%)
• Hyponatremia (6.4%)
• Constipation (4.1%)
• Pyrexia (4.1%)
• Rash (4.1%)

Critical Safety Warnings: RECARBRIO carries contraindications in patients with severe hypersensitivity history. CNS adverse effects including seizures have been documented, particularly in patients exceeding recommended imipenem dosages or with underlying CNS pathology. Concomitant valproic acid use may increase seizure breakthrough risk. Clostridioides difficile-associated diarrhea remains a potential complication requiring clinical vigilance.

Expanded Clinical Applications

Beyond HABP/VABP, RECARBRIO retains FDA authorization for complicated urinary tract infections (cUTI including pyelonephritis) and complicated intra-abdominal infections (cIAI) in adult patients lacking adequate alternative treatment options. These indications were based on earlier trials with limited safety and efficacy datasets.

Clinical Significance

Hospital-acquired infections continue representing a substantial source of morbidity and mortality despite preventive advances. The emergence of multidrug-resistant Gram-negative organisms has constrained therapeutic options. RECARBRIO’s approval in HABP/VABP expands clinician armamentarium for this challenging patient population, particularly those requiring mechanical ventilation, where the trial demonstrated a numerical mortality benefit.