Background/Objectives: The COVID-19 pandemic accelerated the inappropriate use of antibiotics, amplifying the global threat of antimicrobial resistance (AMR), particularly in resource-limited healthcare settings. This study investigated AMR patterns in a tertiary care hospital, focusing on the impact of the COVID-19 pandemic on invasive bacterial pathogens. Methods: This retrospective observational study was conducted at the University Clinical Centre of the Republic of Srpska, analyzing AMR data from invasive bacterial isolates collected between 2015 and 2024, and assessing correlations between antibiotic utilization and resistance patterns during the study periods. Results: Among 4718 invasive bacterial isolates, Acinetobacter spp. (26.7%) and K. pneumoniae (20.8%) were the most prevalent. A significant increase in invasive isolates was observed during the COVID-19 period, particularly for K. pneumoniae (p = 0.003), P. aeruginosa (p = 0.017), Acinetobacter spp. (p = 0.013), and E. faecium (p = 0.028). The highest multidrug-resistant (MDR) rates were observed in Acinetobacter spp. (97% during COVID-19) and K. pneumoniae (>80% post-COVID-19). Resistance increased significantly in K. pneumoniae to cephalosporins, fluoroquinolones, and carbapenems, and in P. aeruginosa and Acinetobacter spp. to carbapenems, while P. aeruginosa resistance to aminoglycosides declined. Strong correlations were found between carbapenems use and Acinetobacter spp. resistance (r = 0.861, p = 0.001), and vancomycin use and E. faecalis resistance (r = 0.798, p = 0.006). Moderate correlations were also observed between carbapenems use and resistance of K. pneumoniae and P. aeruginosa. Conclusions: These findings highlight the profound impact of the COVID-19 pandemic on AMR dynamics, particularly among Gram-negative pathogens, and underscore the urgent need for strengthened antimicrobial stewardship and targeted surveillance to curb the spread of MDR pathogens, especially in resource-limited hospitals.

During veno-venous extracorporeal membrane oxygenation (vv ECMO) therapy, antimicrobial drugs are frequently used, and appropriate dosing is challenging due to there being limited data to support the dosage. Linezolid is effective against multidrug-resistant Gram-positive pathogens frequently isolated in ECMO patients. In total, 53 steady-state linezolid levels were obtained following 600 mg intravenous (IV) injections every 8 h, and these were used to develop a population pharmacokinetic (PopPK) model in patients with COVID-19-associated acute respiratory distress syndrome (CARDS) on vv ECMO. The data were analyzed using a nonlinear mixed-effects modelling approach. Monte Carlo simulation generated 5000 patients’ individual PK parameters and corresponding concentration–time profiles using the PopPK model, following the administration of 600 mg/8 h (a higher-than-standard dosing) and 600 mg/12 h (standard). The probabilities of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) and the cumulative fraction of responses (CFR) for three pathogens were calculated and compared between the two dosing scenarios. Linezolid 600 mg/8 h was predicted to achieve greater than or equal to 85%Tf>MIC in at least 90% of the patients with CARDS on vv ECMO compared to only approximately two thirds of the patients after dosing every 12 h at a minimal inhibitory concentration (MIC) of 2 mg/L. In addition, for the same MIC, fAUC₂₄/MIC ≥ 80 was achieved in almost three times the number of patients following an 8-h versus a 12-h interval. PopPK simulation predicted that a significantly higher proportion of the patients with CARDS on vv ECMO would achieve the PK/PD targets following the 8-h dosing interval compared to standard linezolid dosing. Nevertheless, the safety concern, in particular, for thrombocytopenia, with higher-than-standard linezolid dosage is reasonable, and consequently, monitoring is essential.

Background/Objectives: Improper use of systemic antibiotics remains a significant concern in hospital settings, contributing to increased antimicrobial resistance and suboptimal clinical outcomes. The COVID-19 pandemic exacerbated this issue. This study aimed to evaluate long-term trends in antibiotic utilization in low-resource settings at a tertiary care teaching hospital, focusing specifically on the changes before, during, and after the COVID-19 pandemic. Methods: This retrospective observational study analyzed antibiotic utilization data from the University Clinical Centre of the Republic of Srpska over ten years (2015–2024). Antibiotic consumption was expressed in defined daily doses (DDD) per 100 bed-days, and compared across three periods: pre-COVID-19 (2015–2019), COVID-19 (2020–2022), and post-COVID-19 (2023–2024). Additionally, antibiotic use was categorized according to the WHO AWaRe classification. Results: Antibiotic utilization peaked during the COVID-19 period, with the highest rate observed in 2021 (91.5 DDD/100 bed-days), despite a decrease in hospital admissions. The most frequently used antibiotics were cephalosporins, penicillins, and metronidazole. A significant increase in the use of azithromycin, meropenem, piperacillin/tazobactam, vancomycin, and colistin was noted during the COVID-19 and post-COVID-19 periods (p < 0.05), along with a notable decline in penicillin use. Watch and Reserve antibiotic use rose significantly (p < 0.05), while Access group use fell from 67% to 49.2%. Conclusions: These findings underscore the lasting impact of the COVID-19 pandemic on antibiotic prescribing patterns and emphasize the urgent need for strengthened antimicrobial stewardship efforts to ensure rational antibiotic use and combat antimicrobial resistance.