1601 - Combination Therapy versus Monotherapy for Carbapenem-resistant Organisms: Is More Really Better?

Background: Carbapenem-resistant organisms (CROs) represent an urgent public health threat and associated with mortality rates up to 60%. Pharmacotherapy for these infections remain challenging and historically included multiple agents. Meropenem/vaborbactam and ceftazidime/avibactam are options to treat CRO infections as monotherapy; however, combination therapy is still frequently utilized. Data evaluating outcomes of patients who received combination therapy compared to those receiving monotherapy for CRO infections is limited.

Methods: This retrospective analysis was completed across 7 campuses at AdventHealth Orlando (AHO) from March 2018-October 2019. AHO implemented CRO PCR testing in March 2018, to identify carbapenemase producing CROs (CP-CROs). Inclusion criteria were hospitalization, age ≥ 18 years, culture with CP-CRO detected by PCR, and ≥ 72 hours of either monotherapy or combination therapy. Primary outcome was clinical success, defined as resolution of signs and symptoms of infection and absence of recurrent infection. Secondary outcomes included mean length of therapy, mean length of stay, inpatient mortality, adverse reactions and 30-day all cause readmissions.

Results: CRO was isolated 68 times in 59 unique patients (56% male, mean age 62 years). Most common sources included urine (41%), sputum (24%) and wound (22%). Commonly isolated organisms include K. pneumoniae (44%) and E. cloacae (29%). Thirty infections (44%) were polymicrobial and 28 patients (41%) had a secondary source of infection. Forty-three patients (63%) received definitive treatment therapy with a single antibiotic. Monotherapy treated patients had higher rates of treatment success (79% vs 68%, p=0.39), lower in-hospital mortality (4% vs 9%, p=0.066), less nephrotoxicity (6% vs 10%, p=0.084), shorter length of therapy (9.6 vs 13.4 days, p=0.034) and shorter hospital stay (20 vs 34 days, p=0.056). All-cause readmission rates were higher in the monotherapy group (18% vs 9%, p=0.78). Minimum inhibitory concentrations (MIC) were reported in 97% of patients.

Conclusion: Treatment with a single antibiotic for carbapenem-resistant infections can lead to treatment success, while minimizing adverse events, compared to utilizing combination therapy.