What is the treatment for Ventilator-Associated Pneumonia (VAP) caused by Acinetobacter baumannii complex, given resistance to multiple antibiotics, including Ampicillin (Ampicillin)/Sulbactam, Ceftriaxone, Ciprofloxacin, Imipenem, Meropenem, Piperacillin (Piperacillin)/Tazobactam, and Trimethoprim (Trimethoprim)/Sulfamethoxazole, but susceptibility to Cefiderocol?

From the Guidelines

For treating ventilator-associated pneumonia (VAP) caused by this multidrug-resistant Acinetobacter baumannii complex, I recommend using sulbactam/durlobactam as the primary treatment option, considering the susceptibility results and recent guidelines. Based on the provided evidence, particularly from 1 and 1, sulbactam has shown efficacy against Acinetobacter baumannii, especially when used in appropriate dosages. The recommended dosage for sulbactam is 3 grams every 8 hours, infused over 4 hours, for 7-14 days depending on clinical response, as suggested by 1. Dose adjustment may be needed for renal impairment.

Key points to consider:

• Cefiderocol, despite being susceptible, has limited evidence supporting its use for CRAB infections, as noted in 1, which advises against its use based on low-certainty evidence.
• The organism shows resistance to all other tested antibiotics, including carbapenems, fluoroquinolones, and other beta-lactams, making treatment challenging.
• Consider obtaining infectious disease consultation given the highly resistant nature of this pathogen.
• Supportive care measures, including optimizing ventilator settings, pulmonary toilet, and monitoring for clinical improvement, are essential components of management.
• Combination therapy could be considered in severe cases, but there is limited evidence to support specific combinations for CRAB infections, as discussed in 1.

Given the complexity and resistance profile of this infection, careful monitoring and adjustment of the treatment plan as necessary are crucial. The choice of sulbactam/durlobactam is based on the best available evidence and guidelines, prioritizing morbidity, mortality, and quality of life outcomes.

From the FDA Drug Label

A total of 177 hospitalized adults with documented Acinetobacter baumannii-calcoaceticus complex infections were randomized and treated in a multicenter, active-controlled, investigator-unblinded, independent assessor-blinded, non-inferiority, phase 3 trial (Trial 1, NCT03894046). Patients were treated with either XACDURO (1 g sulbactam and 1 g durlobactam, or renally adjusted dose) intravenously over 3 hours every 6 hours (n = 91) or colistin 2.5 mg/kg (or renally adjusted dose) intravenously over 30 minutes every 12 hours after an initial loading dose of colistin 2. 5 to 5 mg/kg (n = 86). The primary efficacy endpoint for the study was 28-day all-cause mortality in the patients who received any amount of study medication with a confirmed baseline infection with carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRABC microbiologically modified intent to treat (m-MITT) population) Clinical cure rates in the CRABC m-MITT population at the Test of Cure (TOC) Visit that was 7 days (±2 days) after the end of treatment were 39/63 (61.9%) for XACDURO versus 25/62 (40.3%) for colistin.

The treatment for Ventilator-associated Pneumonia (VAP) caused by Acinetobacter baumannii complex is XACDURO (sulbactam and durlobactam), as it has shown non-inferiority to colistin in terms of 28-day all-cause mortality and clinical cure rates in patients with carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex infections 2.

• Key points:
  • XACDURO was administered intravenously over 3 hours every 6 hours.
  • Clinical cure rates were 61.9% for XACDURO versus 40.3% for colistin.
  • XACDURO was non-inferior to colistin with regard to Day 28 all-cause mortality.

From the Research

Treatment Options for Acinetobacter baumannii Complex Causing VAP

• The given antibiotic susceptibility test results show that the Acinetobacter baumannii complex is resistant to multiple antibiotics, including Ampicillin/Sulbactam, Ceftriaxone, Ciprofloxacin, Imipenem, Meropenem, Piperacillin/Tazobactam, and Trimethoprim/Sulfamethoxazole, but susceptible to Cefiderocol 3, 4.
• A study published in 2019 found that the combination of sulbactam with etilmicin or levofloxacin, and meropenem with etilmicin or levofloxacin, were effective in treating Acinetobacter baumannii ventilator-associated pneumonia (VAP) 3.
• Another study published in 2021 found that cefiderocol was effective as a rescue therapy for carbapenem-resistant Acinetobacter baumannii and other Gram-negative infections in intensive care unit patients, with a 30-day clinical success rate of 70% and a survival rate of 90% 4.
• A 2022 study found that colistin-based treatment regimens, including ampicillin/sulbactam and rifampicin, were used to treat COVID-19 patients with carbapenem-resistant Acinetobacter baumannii VAP, with a 28-day survival rate of 35% 5.
• A 2019 study found that the mortality rate due to drug-resistant Acinetobacter baumannii VAP was high, but not associated with the A. baumannii resistance profile, and that female gender, SOFA score, and RBC transfusion were independent predictors of in-hospital mortality 6.

Recommended Treatment Regimens

• Sulbactam combined with etilmicin or levofloxacin, and meropenem combined with etilmicin or levofloxacin, may be effective treatment regimens for Acinetobacter baumannii VAP 3.
• Cefiderocol may be considered as a rescue therapy for carbapenem-resistant Acinetobacter baumannii and other Gram-negative infections in intensive care unit patients 4.
• Colistin-based treatment regimens, including ampicillin/sulbactam and rifampicin, may be used to treat COVID-19 patients with carbapenem-resistant Acinetobacter baumannii VAP 5.