# Patterns of Antibiotic Use in Hospitalized COVID-19 Patients and Association with Secondary Infections and Outcomes

**Authors:** Diana-Maria Mateescu, Ana-Olivia Toma, Dragos-Mihai Gavrilescu, Adrian-Cosmin Ilie, Eduard Florescu, Ovidiu Rosca, Cristian Oancea, Stela Iurciuc, Camelia-Oana Muresan, Alexandra Enache

PMC · DOI: 10.3390/antibiotics15030240 · Antibiotics · 2026-02-25

## TL;DR

This study finds that widespread antibiotic use in hospitalized COVID-19 patients is linked to secondary infections and worse outcomes, emphasizing the need for better antibiotic stewardship.

## Contribution

The study identifies specific antibiotic prescribing patterns associated with secondary infections and poor outcomes in hospitalized COVID-19 patients.

## Key findings

- 88.4% of hospitalized COVID-19 patients received antibiotics, mostly empirically within 24 hours of admission.
- Antibiotic exposure was independently linked to secondary infections and worse clinical outcomes like ICU admission and mortality.
- Use of Watch/Reserve antibiotics and prolonged therapy increased the risk of multidrug-resistant secondary infections.

## Abstract

Background/Objectives: Antibiotic exposure is highly prevalent in patients hospitalized with COVID-19, yet the relationship between specific prescribing patterns, microbiologically confirmed secondary infections, and clinical outcomes remains incompletely understood, particularly in settings with high antimicrobial resistance. Methods: This single-center retrospective observational cohort included 395 consecutive adults hospitalized with RT-PCR-confirmed COVID-19 in a tertiary infectious diseases hospital. Data on demographics, comorbidities, baseline disease severity, antimicrobial prescribing (timing, WHO AWaRe class, duration, monotherapy/combination, escalation/de-escalation), microbiological results, and outcomes were extracted from electronic records and the microbiology information system. The primary outcome was microbiologically confirmed secondary infection; secondary outcomes were ICU admission, invasive mechanical ventilation, length of stay, and in-hospital mortality. Multivariable logistic regression and survival analyses assessed associations between antibiotic exposure and outcomes. Results: Overall, 88.4% of patients received systemic antibiotics, predominantly initiated within 24 h of admission and mostly empirical; 58.7% received combination regimens, with frequent use of Watch/Reserve agents. Secondary infections occurred in 28.4% of patients, were hospital-acquired in 82.1%, and involved multidrug-resistant organisms in 41.1% of cases. Any antibiotic exposure was independently associated with secondary infection (adjusted odds ratio, aOR 2.15; 95% CI 1.42–3.27), while prolonged therapy (≥7 days), Watch/Reserve use, and early initiation showed additional risk gradients. Antibiotic exposure was also associated with higher odds of ICU admission, invasive mechanical ventilation, prolonged hospitalization, and in-hospital mortality after adjustment. Conclusions: In this real-world COVID-19 cohort, broad and largely empirical antibiotic use was common and strongly associated with hospital-acquired, often multidrug-resistant secondary infections and worse clinical outcomes. These findings highlight the need for reinforced antimicrobial stewardship focusing on restrictive early broad-spectrum use, AWaRe-guided agent selection, systematic 48–72 h reassessment with de-escalation, and minimization of treatment duration.

## Linked entities

- **Diseases:** COVID-19 (MONDO:0100096)

## Full-text entities

- **Genes:** IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}
- **Diseases:** lymphopenia (MESH:D008231), viral illness (MESH:D014777), AMR (MESH:C565965), organ dysfunction (MESH:D009102), bloodstream and urinary tract infections (MESH:D014552), HAP (MESH:D000077299), coagulation (MESH:D001778), arterial hypertension (MESH:D000081029), Bloodstream infection (MESH:D018805), bacterial pneumonia (MESH:D018410), enterocolitis (MESH:D004760), nosocomial infection (MESH:D003428), diarrhea (MESH:D003967), fever (MESH:D005334), hypothermia (MESH:D007035), Infectious Diseases (MESH:D003141), thromboembolic (MESH:D013923), immune dysregulation (OMIM:614878), respiratory illness (MESH:D012140), pleural effusion (MESH:D010996), colonization (MESH:D003108), respiratory deterioration (MESH:D012131), MDRO (MESH:D018088), COVID-19 (MESH:D000086382), ischemic heart disease (MESH:D017202), Coma (MESH:D003128), Chronic kidney disease (MESH:D051436), Inflammatory (MESH:D007249), Co (MESH:D060085), bacterial superinfection (MESH:D015163), injury to (MESH:D014947), septic shock (MESH:D012772), respiratory secondary infections (MESH:D012141), leukocytosis (MESH:D007964), Infection (MESH:D007239), Clostridioides difficile infection (MESH:D003015), pyuria (MESH:D011776), bacteremia (MESH:D016470), bacterial (MESH:D001424), pneumonia (MESH:D011014), obesity (MESH:D009765), type 1 and type 2 diabetes (MESH:D003924), Cardiovascular disease (MESH:D002318), leukopenia (MESH:D007970), immune dysfunction (MESH:D007154), critical illness (MESH:D016638), dysbiosis (MESH:D064806), endothelial (MESH:D005642), VAP (MESH:D053717), Diabetes mellitus (MESH:D003920), chronic obstructive pulmonary disease (MESH:D029424), HAIs (MESH:D006255), Pulmonary complications (MESH:D008171), cardiac arrest (MESH:D006323), purulent (MESH:D003234)
- **Chemicals:** bilirubin (MESH:D001663), vancomycin (MESH:D014640), piperacillin-tazobactam (MESH:D000077725), remdesivir (MESH:C000606551), moxifloxacin (MESH:D000077266), OXA-48 (-), meropenem (MESH:D000077731), oxygen (MESH:D010100), favipiravir (MESH:C462182), ceftriaxone (MESH:D002443), carbapenem (MESH:D015780)
- **Species:** Pseudomonas aeruginosa (species) [taxon 287], Acinetobacter baumannii (species) [taxon 470], Klebsiella pneumoniae (species) [taxon 573], gut metagenome (species) [taxon 749906], Clostridioides difficile (species) [taxon 1496], Homo sapiens (human, species) [taxon 9606], Enterococcus faecium (species) [taxon 1352]

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## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC13024623/full.md

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Source: https://tomesphere.com/paper/PMC13024623