UMEM Educational Pearls

Should we give a dose of antibiotics after intubating to reduce risk of VAP down the line? A multicenter RCT conducted in 2024 - the PROPHY-VAP Trial - found that a single dose of 2g ceftriaxone administered within 12 hours of intubation reduced VAP within the first week of hospitalization for patients intubated for airway protection due to TBI, stroke or SAH, with a VAP rate of 14% in the CTX group vs 32% in the VAP group (HR 0.60; 95% CI 0.38-0.95).

Click the link below for details and additional discussion

Additional Information

Details:

• The PROPHY-VAP trial included 345 patients across 9 university-affiliated ICUs in France.
• Inclusion:
  • Intubation for airway protection in the setting of neurologic injury, defined as TBI, ischemic or hemorrhagic stroke, or SAH
  • Intubation <12h and hospitalized <48h at the time of randomization
  • Expected mechanical ventilation >48h
  • No pre-existing infection or antibiotic therapy
• Exclusion:
  • Hospitalization within 30d
  • Beta lactam allergy
• Patients: Well-matched between groups, mostly hemorrhagic insults (hemorrhagic stroke, SAH, TBI), all with GCS <12 and majority GCS 4-8. 
• Intervention: Single dose of CTX 2g IV. Mean time from intubation to antibiotics was 7h.
• Primary Outcome: Early VAP (2-7d after intubation) was less common in the CTX group (14% vs. 32%; HR 0.60; 95% CI 0.38-0.95, p = 0.03).
• Secondary Outcomes: The CTX group had more antibiotic-free and ventilator-free days, lower mortality, and lower incidence of VAP at 28d.
• Safety Outcomes: C diff and MDR organism infection were not more common in the CTX group

Background: prior studies have investigated different antibiotic regimens in different groups. In 2023, the AMIKIHAL trial suggested that a 3d course of inhaled amikacin would reduce 28d risk of VAP among patients ventilated for >3d (not just neuro patients). In 2022, the SuDDICU trial suggested that “selective decontamination of the digestive tract” with a combination of IV abx, oral suspension of antibiotics, and topical abx to the oropharynx and buccal mucosa suggested a lower risk of in-hospital mortality in Baysian meta-analysis (though not in the primary study statistics). In 2005, the ANTHARTIC trial suggested a lower rate of VAP with a 2 days course of amoxicillin-clavulanate among patients admitted after OHCA.

Closing Thoughts: Together, these studies suggest that there may be a role for an early and short course of antibiotics for preventing VAP in a few patient populations. A single dose of CTX is easier and more benign than prior suggested regimens, and based on the available data, seems to offer benefit with minimal risk.

References

Dahyot-Fizelier C, Lasocki S, Kerforne T et al. Ceftriaxone to prevent early ventilator-associated pneumonia in patients with acute brain injury: a multicentre, randomised, double-blind, placebo-controlled, assessor-masked superiority trial. The Lancet Respiratory Medicine, 2024; 12, 375-385

Additional References

1. Ehrmann S, Barbier F, Demiselle J, Quenot JP, Herbrecht JE, Roux D, Lacherade JC, Landais M, Seguin P, Schnell D, Veinstein A, Gouin P, Lasocki S, Lu Q, Beduneau G, Ferrandiere M, Plantefève G, Dahyot-Fizelier C, Chebib N, Mercier E, Heuzé-Vourc'h N, Respaud R, Gregoire N, Garot D, Nay MA, Meziani F, Andreu P, Clere-Jehl R, Zucman N, Azaïs MA, Saint-Martin M, Gandonnière CS, Benzekri D, Merdji H, Tavernier E; Reva and CRICS-TRIGGERSEP F-CRIN Research Networks. Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia. N Engl J Med. 2023 Nov 30;389(22):2052-2062. 
2. The SuDDICU Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group. Effect of Selective Decontamination of the Digestive Tract on Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial. JAMA. 2022;328(19):1911–1921. doi:10.1001/jama.2022.17927
3. Acquarolo A, Urli T, Perone G, Giannotti C, Candiani A, Latronico N. Antibiotic prophylaxis of early onset pneumonia in critically ill comatose patients. A randomized study. Intensive Care Med. 2005 Apr;31(4):510-6. doi: 10.1007/s00134-005-2585-5. Epub 2005 Mar 8. PMID: 15754197.