**Background:** Antimicrobial resistance is a global threat, and primary care accounts for 80% of antibiotic prescriptions in developed countries, with up to 50% deemed inappropriate. In Singapore, antimicrobial stewardship programs exist in hospitals but are lacking in primary care. The COVID-19 pandemic altered healthcare-seeking behavior and prescription patterns. This study aimed to examine antibiotic prescription patterns in Singapore's public primary care clinics from 2018–2021, identify care gaps, and explore associated factors.
**Methods:** A retrospective observational study was conducted using electronic health records from 6 public primary care clinics (National University Polyclinics) in Singapore. Data from 2018–2021 were extracted, including patient demographics, visit diagnoses (ICD-10), antibiotic name/class, and prescriber information. Patients >21 years prescribed an oral or topical antibiotic were included; those on long-term antibiotics (>14 days) were excluded. Oral antibiotic prescriptions were categorized by diagnosis (respiratory, skin, genitourinary, gastrointestinal, infectious disease, dental, undefined). Antibiotics were classified using the 2021 WHO AWaRe system. A tiered ranking logic system assigned each prescription to one diagnosis category. Segmented regression analysis assessed trends before/after the COVID-19 pandemic peak (April 2020). Chi-square tests and logistic regression identified factors associated with care gaps.
**Key Results:** A total of 141,944 oral and 108,357 topical antibiotics were prescribed over 3,278,562 patient visits. The overall oral antibiotic prescription rate was 4.33%, decreasing from 5.11% in 2018 to 3.38% in 2021. Segmented regression showed a significant reduction of 1926.8 prescriptions (p<0.01) after April 2020. Oral antibiotics were most prescribed for respiratory (29.6%), skin/soft tissue (28.9%), and genitourinary (15.2%) conditions. By 2021, skin (37.7%) and genitourinary (20.2%) conditions overtook respiratory conditions (10.8%) due to an 84% reduction in respiratory antibiotic prescriptions. The proportion of antibiotics prescribed for undefined conditions (non-infectious diagnoses) rose from 10.8% (2018) to 17.2% (2021). Factors associated with undefined-condition prescriptions included female gender (OR 1.12, 95% CI 1.08–1.15), diabetes mellitus (OR 1.34, 95% CI 1.29–1.40), chronic kidney disease (OR 1.31, 95% CI 1.26–1.37), and accredited family physician (OR 1.16, 95% CI 1.12–1.20). Use of Access group antibiotics increased from 85.6% (2018) to 92.1% (2021), mainly due to reduced clarithromycin use. Watch group antibiotic prescriptions were associated with male gender (OR 1.26, 95% CI 1.19–1.35), gastrointestinal (OR 28.5, 95% CI 24.1–33.8), respiratory (OR 11.9, 95% CI 10.6–13.3), and genitourinary conditions (OR 10.2, 95% CI 9.07–11.4), as well as locally trained physicians (OR 1.22, 95% CI 1.14–1.30). Topical skin antibiotic prescriptions with non-skin diagnoses increased from 35.2% (2018) to 40.1% (2021). Dual oral and topical antibiotic prescriptions for skin conditions occurred in 35.8% of cases, associated with younger age (OR 0.994, 95% CI 0.993–0.995), female gender (OR 1.13, 95% CI 1.08–1.18), and overseas-trained physicians (OR 1.18, 95% CI 1.13–1.24).
**Clinical Implications:** This study provides the first comprehensive analysis of antibiotic prescribing in Singapore's public primary care. The significant reduction in antibiotic prescriptions during the COVID-19 pandemic suggests that public health measures and altered patient behavior can influence prescribing. However, persistent care gaps—inaccurate diagnosis coding, high Watch group antibiotic use for genitourinary/gastrointestinal conditions, and dual antibiotic use for skin infections—highlight areas for improvement. Updated antimicrobial guidelines, academic detailing, and decision support tools are needed to optimize antibiotic use and combat antimicrobial resistance in primary care.