The Resistance Paradox in COVID-19 Ventilator-Associated Pneumonia: A Retrospective Study on Rapid Molecular Stewardship

Bălan et al., Antibiotics, doi:10.3390/antibiotics15030236, Feb 2026
Retrospective 52 mechanically ventilated ICU patients showing a "resistance paradox" in COVID-19-associated Ventilator-Associated Pneumonia (VAP), with significantly higher carbapenem resistance and fluoroquinolone resistance, despite fewer traditional multidrug-resistant risk factors at admission.
The COVID-19 VAP phenotype was distinguished by near-universal corticosteroid use, very high PPI use, and prolonged NIV exposure
The increased risk in COVID-19 likely reflects pandemic protocols with widespread use of corticosteroids and PPIs:
Immune suppression from corticosteroids: corticosteroids impair the body's natural immune response, making COVID-19 patients significantly more vulnerable to developing secondary bacterial infections like Ventilator-Associated Pneumonia (VAP).
Airway colonization from PPIs: high utilization of PPIs causes hypochlorhydria, a reduction in stomach acid. This lack of acidity allows bacteria to survive and colonize the aerodigestive tract, creating a direct pathway for lung superinfections.
Study covers proton pump inhibitors and dexamethasone.
Bălan et al., 24 Feb 2026, retrospective, Romania, peer-reviewed, 8 authors, study period January 2020 - December 2021. Contact: tmmagdas@gmail.com (corresponding author), balan.andrei@umfcluj.ro, tranca.sebastian@umfcluj.ro, aurda@umfcluj.ro.
The Resistance Paradox in COVID-19 Ventilator-Associated Pneumonia: A Retrospective Study on Rapid Molecular Stewardship
Andrei Mihai Bălan, Tudor-Mihai Magdaș, Andrada Elena Urda-Cîmpean, Constantin Bodolea, Andrada Nemeș, Lucreția Avram, Dana Crișan, Sebastian Trancă
Antibiotics, doi:10.3390/antibiotics15030236
Background/Objectives: The COVID-19 pandemic complicated the diagnosis of Ventilator-Associated Pneumonia (VAP), leading to empiric antibiotic overuse due to the difficulty in distinguishing viral progression from bacterial superinfection. However, it remains unclear whether COVID-19-associated VAP displays a distinct antimicrobial resistance profile compared to classical VAP. Methods: This monocentric, retrospective cohort study primarily investigated differences in clinical phenotypes and antibiotic resistance profiles between patients with VAP-COVID (n = 26) and non-COVID-VAP (n = 26). Logistic regression was used to identify factors associated with the COVID-19 phenotype and predictors of antimicrobial resistance. As a secondary objective, we evaluated the diagnostic efficacy of a multiplex Point-of-Care PCR (POC-PCR) system (n = 22) compared to standard culture (n = 26) regarding turnaround time and resistance detection. Results: Patients with VAP-COVID exhibited significantly higher resistance rates to carbapenems (76.9% vs. 50%, p = 0.04) and fluoroquinolones (88.5% vs. 61.5%, p = 0.02) despite fewer traditional risk factors at admission. The clinical profile of the VAP-COVID group was distinguished by a significantly lower incidence of parapneumonic pleural effusion (19.2% vs. 84.6%, p < 0.001) and a higher median Neutrophil-to-Lymphocyte Ratio (41.36 vs. 9.63, p < 0.001). Regarding diagnostic speed, POC-PCR significantly reduced the time to result validation compared to standard culture (~1 h vs. ~62.5 h, p < 0.001). Conclusions: VAP in COVID-19 patients presents a distinct microbiological profile characterized by higher antimicrobial resistance. In this context, the integration of rapid molecular diagnostics may support earlier microbiological guidance compared to standard methods.
Funding: The current study received no funding. Institutional Review Board Statement: The study protocol complied with the ethical guidelines of the 1975 Declaration of Helsinki (revised) and was approved by the hospital's Ethics Committee (Approval no. 7/2020). Informed Consent Statement: Informed consent was waived due to the retrospective and observational nature of the study. All patient data were anonymized prior to analysis. Conflicts of Interest: The authors declare no conflicts of interest. Abbreviations
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DOI record: { "DOI": "10.3390/antibiotics15030236", "ISSN": [ "2079-6382" ], "URL": "http://dx.doi.org/10.3390/antibiotics15030236", "abstract": "<jats:p>Background/Objectives: The COVID-19 pandemic complicated the diagnosis of Ventilator-Associated Pneumonia (VAP), leading to empiric antibiotic overuse due to the difficulty in distinguishing viral progression from bacterial superinfection. However, it remains unclear whether COVID-19-associated VAP displays a distinct antimicrobial resistance profile compared to classical VAP. Methods: This monocentric, retrospective cohort study primarily investigated differences in clinical phenotypes and antibiotic resistance profiles between patients with VAP-COVID (n = 26) and non-COVID-VAP (n = 26). Logistic regression was used to identify factors associated with the COVID-19 phenotype and predictors of antimicrobial resistance. As a secondary objective, we evaluated the diagnostic efficacy of a multiplex Point-of-Care PCR (POC-PCR) system (n = 22) compared to standard culture (n = 26) regarding turnaround time and resistance detection. Results: Patients with VAP-COVID exhibited significantly higher resistance rates to carbapenems (76.9% vs. 50%, p = 0.04) and fluoroquinolones (88.5% vs. 61.5%, p = 0.02) despite fewer traditional risk factors at admission. The clinical profile of the VAP-COVID group was distinguished by a significantly lower incidence of parapneumonic pleural effusion (19.2% vs. 84.6%, p &lt; 0.001) and a higher median Neutrophil-to-Lymphocyte Ratio (41.36 vs. 9.63, p &lt; 0.001). Regarding diagnostic speed, POC-PCR significantly reduced the time to result validation compared to standard culture (~1 h vs. ~62.5 h, p &lt; 0.001). Conclusions: VAP in COVID-19 patients presents a distinct microbiological profile characterized by higher antimicrobial resistance. 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Late treatment
is less effective
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