Gram Stain-Guided Antibiotics: Effective, May Combat Spread of Multidrug-Resistant Pathogens

Colorized SEM of four spherical methicillin-resistant Staphylococcus aureus
Colorized SEM of four spherical methicillin-resistant Staphylococcus aureus
Researchers compared the effect of Gram stain-guided antibiotics with guideline-based antibiotics for the treatment of patients with ventilator-associated pneumonia.

Among patients with ventilator-associated pneumonia (VAP), Gram stain-guided antibiotic therapy was noninferior to guideline-based therapy and may combat the spread of multidrug-resistant pathogens, according to findings from a study published in JAMA Network Open.

Researchers compared the clinical response of guideline-based and Gram stain-guided antibiotic therapies for patients with VAP. In this open-label, noninferiority, randomized clinical trial ( NCT03506113), patients (N=206) aged 15 years and older with a diagnosis of VAP and a modified clinical pulmonary infection score of 5 and higher were enrolled from the intensive care units (ICU) of 12 tertiary referral hospitals in Japan. After stratification by history of chronic obstructive pulmonary disease, traumatic brain injury, post-cardiopulmonary arrest syndrome, and hospitalizations requiring antibiotic therapy, patients were randomly assigned in a 1:1 fashion to receive either Gram-stain guided or guideline-based antibiotic therapy.

Patients (n=103) in the Gram stain-guided antibiotic therapy group received treatment on the basis of results of Gram staining from an endotracheal aspirate. Patients (n=103) in the guideline-based therapy group received an antipseudomonal agent in combination with an anti-methicillin-resistant Staphylococcus aureus (MRSA) agent according to the 2016 VAP guidelines.

Clinical assessments were performed at baseline and at each subsequent day throughout therapy, as well as at a follow-up visit 7 days after therapy was completed. The clinical response rate at the follow-up visit was the primary outcome. Secondary outcomes included 28-day mortality; 28-day ICU-free days; 28-day ventilator-free days; proportions of antipseudomonal agents and anti-MRSA agents as initial antibiotic therapies; coverage rate of initial antibiotic therapies; de-escalation rate; antibiotic therapy days; and adverse events.

The median patient age was 69 (IQR, 54-78), and 79 (76.7%) and 74 (71.8%) patients from the Gram stain and guideline-based groups, respectively, achieved the primary outcome (risk difference, 0.05; 95% CI, -0.07 to 0.17; P <.001 for noninferiority). Compared with patients in the guideline-based group, fewer patients in the Gram stain group received antipseudomonal (30.1%; 95% CI, 21.5-39.9; P <.001) and anti-MRSA agents (38.8%; 95% CI, 29.4-48.9; P <.001).

The difference in the 28-day cumulative incidence of mortality between the Gram stain and guideline therapy groups was statistically insignificant (13.6% vs 17.5%, respectively; P =.39). Group differences also were insignificant for ICU-free days, ventilator-free days, and adverse events. The escalation of antibiotics based on culture results occurred in 7 (6.8%) and 1 (1.0%) patients in the Gram stain and guideline therapy groups, respectively (P =.03).

Study limitations included the open-label design, the small sample size, and the potential lack of generalizability.

The researchers concluded, “[these] findings reinforce the potential use of Gram staining in the critical care setting to ameliorate the spread of [multidrug-resistant] pathogens.”

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 


Yoshimura J, Yamakawa K, Ohta Y, et al. Effect of gram stain-guided initial antibiotic therapy on clinical response in patients with ventilator-associated pneumonia: the GRACE-VAP randomized clinical trial. JAMA Netw Open. 2022;5(4):e226136. doi:10.1001/jamanetworkopen.2022.6136

This article originally appeared on Infectious Disease Advisor