BackgroundContinuous monitoring of antimicrobial resistance (AMR) in Uganda involves testing bacterial isolates from clinical samples at national and regional hospitals. Although the National Microbiology Reference Laboratory (NMRL) analyzes these isolates for official AMR surveillance data, there's limited integration into public health planning. To enhance the utilization of NMRL data to better inform drug selection and public health strategies in combating antibiotic resistance, we evaluated the trends and spatial distribution of AMR to common antibiotics used in Uganda.MethodsWe analyzed data from pathogenic bacterial isolates from blood, cerebrospinal, peritoneal, and pleural fluid from AMR surveillance data for 2018–2021. We calculated the proportions of isolates that were resistant to common antimicrobial classes. We used the chi-square test for trends to evaluate changes in AMR resistance over the study period.ResultsOut of 537 isolates with 15 pathogenic bacteria, 478 (89%) were from blood, 34 (6.3%) were from pleural fluid, 21 (4%) were from cerebrospinal fluid, and 4 (0.7%) were from peritoneal fluid. The most common pathogen was Staphylococcus aureus (20.1%), followed by Salmonella species (18.8%). The overall change in resistance over the four years was 63–84% for sulfonamides, fluoroquinolones macrolides (46–76%), phenicols (48–71%), penicillins (42–97%), β-lactamase inhibitors (20–92%), aminoglycosides (17–53%), cephalosporins (8.3–90%), carbapenems (5.3–26%), and glycopeptides (0–20%). There was a fluctuation in resistance of Staphylococcus aureus to methicillin (60%-45%) (using cefoxitin resistance as a surrogate for oxacillin resistance) Among gram-negative organisms, there were increases in resistance to tetracycline (29–78% p < 0.001), ciprofloxacin (17–43%, p = 0.004), ceftriaxone (8–72%, p = 0.003), imipenem (6–26%, p = 0.004), and meropenem (7–18%, p = 0.03).ConclusionThe study highlights a concerning increase in antibiotic resistance rates over four years, with significant increase in resistance observed across different classes of antibiotics for both gram-positive and gram-negative organisms. This increased antibiotic resistance, particularly to commonly used antibiotics like ceftriaxone and ciprofloxacin, makes adhering to the WHO's Access, Watch, and Reserve (AWaRe) category even more critical. It also emphasizes how important it is to guard against the growing threat of antibiotic resistance by appropriately using medicines, especially those that are marked for "Watch" or "Reserve."