Search Results (450)

Antimicrobial resistance (AMR) represents one of the most urgent global health threats, significantly impacting patient outcomes, healthcare systems, and economic sustainability. Rapid and accurate antimicrobial susceptibility testing (AST) are essential to guide targeted therapy, reduce inappropriate antimicrobial use, and support antimicrobial stewardship programs. However, conventional phenotypic AST methods, including broth microdilution, disk diffusion, agar dilution, and gradient strip tests, remain labor-intensive and require prolonged turnaround times, often delaying optimal therapeutic decisions. Although automated commercial platforms such as VITEK 2, BD Phoenix, MicroScan WalkAway, and Sensititre ARIS have improved laboratory workflow and standardization, they still rely on culture-based approaches and typically require 16–36 h to generate minimum inhibitory concentration (MIC) results. In recent years, several innovative rapid phenotypic AST technologies have emerged, aiming to significantly shorten the time to susceptibility results while maintaining high accuracy. This review provides an overview of currently available rapid automated phenotypic platforms for MIC determination, including VITEK^® Reveal™, ASTar, FASTinov^®AST, QuickMIC^®, and the Accelerate Pheno^® system. These systems employ advanced technologies such as volatile organic compound detection, flow cytometry, microfluidics, real-time imaging, and morphokinetic cellular analysis to deliver susceptibility results within a few hours directly from positive blood cultures. We summarize their technical principles, antibiotics and pathogens included, performances, and current limitations. Overall, the implementation of rapid phenotypic AST tools has the potential to substantially improve clinical decisions, optimize antimicrobial therapy, and contribute to fight AMR. Full article

Background/Objectives: The Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM) conducts longitudinal monitoring of antimicrobial resistance (AMR) in indicator bacteria from food-producing animals. For Escherichia coli from healthy pigs, slaughterhouse-based sampling has been conducted for approximately a decade, yielding a substantial accumulation of MIC data. While JVARM reporting has traditionally focused on annual resistance proportions by drug, the availability of long-term data enables investigation of cross-drug relationships, including MIC similarity and co-resistance patterns. This study aimed to (i) identify the co-resistance structure among antimicrobial agents using MIC- and phenotype-based similarity measures and (ii) identify drug resistances most strongly associated with multidrug resistance (MDR). Methods: We analyzed broth microdilution MIC data obtained annually for E. coli isolates from healthy pigs in the JVARM program in Japan between 2012 and 2023. Antimicrobial resistance was classified from MIC results and annual resistance prevalence was calculated for each antimicrobial. For the co-resistance and MDR analyses, isolate-level data were pooled across the full study period. To identify co-resistance structure, we performed hierarchical clustering using (i) correlation-based similarity of MIC profiles and (ii) Jaccard similarity of binary resistance profiles (resistant/susceptible classification). Multidrug resistance (MDR; ≥3 antimicrobial classes) was further modeled using XGBoost with each drug resistance as a predictive feature, and feature contributions were evaluated using gain, permutation importance, and SHAP values. We also examined how SHAP-based attributions varied when the outcome definition was set to ≥1-, ≥2-, or ≥3-class resistance. Results: Within the study period, resistance remained highest for tetracycline and moderate for streptomycin, ampicillin, sulfamethoxazole–trimethoprim, and chloramphenicol, whereas resistance to other agents was low. MIC-based correlation analysis revealed coordinated variation among ampicillin, sulfamethoxazole–trimethoprim, streptomycin, chloramphenicol, and tetracycline. Separately, Jaccard similarity of binary resistance profiles identified two closely positioned co-resistance groupings (Ampicillin/Streptomycin/Tetracycline and chloramphenicol/sulfamethoxazole–trimethoprim). Ampicillin was identified as the medoid in both MIC-based and resistance-profile similarity spaces, with streptomycin also positioned near the center in both structures. In the XGBoost model for MDR (≥3 classes), ampicillin resistance was consistently the highest-contributing feature when evaluated by gain, permutation importance, and SHAP. When we examined how SHAP-based attributions varied across outcome definitions (≥1-, ≥2-, and ≥3-class resistance), feature importance largely followed resistance prevalence at ≥1–≥2 classes (tetracycline highest) but shifted at ≥3 classes to ampicillin as the top feature. Conclusions: Both MIC-based and phenotype-based analyses revealed co-resistance structures. Under the MDR definition used in this study, explainable machine-learning analyses showed that ampicillin resistance emerged as a leading resistance feature associated with MDR. Because these findings are associative rather than causal, further work will be needed to clarify mechanisms. These findings have important implications for antimicrobial resistance control in the Japanese pig sector, indicating that stewardship strategies may need to be tailored according to antimicrobial class and underlying co-resistance structure. Full article

Bloodstream infections (BSIs) are associated with substantial morbidity, mortality, and healthcare costs. Conventional diagnostics are limited by delayed results, often postponing appropriate antimicrobial therapy. This review aimed to evaluate the clinical and economic value of rapid microbiological diagnostics in BSI management. A state-of-the-art evidence synthesis was conducted using structured searches of PubMed/MEDLINE, Scopus, Web of Science, EconLit, and Google Scholar (2013–2025). Eligible studies included economic evaluations and clinical studies reporting downstream economic or resource-use outcomes. Screening and data extraction were performed by two reviewers, and findings were narratively synthesized. Fifty-nine studies were included. Rapid diagnostics consistently reduced time to pathogen identification and targeted therapy compared to conventional methods. Molecular platforms provided results within hours, while MALDI-TOF enabled identification within 30–60 min after culture positivity. Clinical benefits included earlier therapy optimization, reduced mortality, and shorter hospital stays, particularly when combined with antimicrobial stewardship programs (ASPs). Economic evaluations demonstrated improved cost-effectiveness, including reduced hospitalization, ICU utilization, and antimicrobial costs. MALDI-TOF with stewardship showed notable cost savings and improved outcomes. However, results varied depending on implementation context, infrastructure, and workflow integration. Rapid microbiological diagnostics offer significant clinical and economic benefits in BSI management, particularly when integrated with stewardship programs. Context-specific implementation is essential to maximize their value across healthcare systems. Full article

Anti-inflammatory agents, antipyretics, and antibiotics are commonly used to manage fever and pain associated with infectious diseases in both adults and children. Despite their effectiveness, inappropriate and unnecessary prescriptions remain widespread, leading to adverse patient outcomes and, in the case of antibiotics, contributing to antimicrobial resistance. Addressing these issues requires effective stewardship programs focused on educating healthcare professionals and the public on evidence-based guidelines for optimal prescribing practices. This paper explores the five “A”s fundamental to infection management in pediatric and adult patients: appropriateness, abuse, antipyretics, anti-inflammatory agents, and antibiotics. Through a comprehensive literature review, expert perspectives, and clinical guidelines, the study evaluates the roles of anti-inflammatory agents (e.g., ibuprofen), antipyretics (e.g., paracetamol), and antibiotics in clinical practice, highlighting best practices for their use. Current guidelines emphasize that antipyretics should only be administered when fever is accompanied by significant discomfort or pain, as fever itself plays a role in the immune response. Based on the available literature, experts also suggest that paracetamol should be preferred as a first-line antipyretic due to its favorable safety profile, while ibuprofen should be used with caution, particularly during respiratory infections, varicella, and severe bacterial infections, due to its potential to exacerbate complications. According to experts, special consideration is also required for patients with renal or gastrointestinal comorbidities to prevent toxicity. Regarding antibiotics, prescriptions should be limited to clear evidence of bacterial infection to avoid unnecessary patient exposure and the development of antimicrobial resistance. Stewardship programs underscore the importance of selecting the right agent, optimizing dosing, and introducing shorter treatment regimens where supported by evidence, to improve therapeutic outcomes while minimizing resistance risks. Ultimately, this paper provides practical, evidence-based recommendations to support rational prescribing of antipyretics, anti-inflammatory drugs, and antibiotics, aiming to optimize patient outcomes, prevent unnecessary toxicity, and contribute to global efforts against antimicrobial resistance. Full article

Background/Objectives: Multidrug-resistant (MDR) Gram-negative bacteria represent a significant public health concern worldwide, particularly in resource-limited settings. In Ghana’s Tamale Metropolis, limited data exist on the prevalence and trends of MDR bacteria, posing challenges to effective antimicrobial stewardship. Methods: This study analyzed microbiological data from 2020 to 2023 to address these knowledge gaps. Results: Among the 4859 clinical samples analyzed, 1570 (33.7%) yielded Gram-negative bacterial isolates, with an MDR prevalence of 40.6%. The most frequently isolated organisms were Klebsiella spp. (28.9%) and Escherichia coli (20.4%). Resistance to cephalosporins (51%) and ciprofloxacin (46%) was particularly pronounced, highlighting the diminishing efficacy of commonly used antibiotics. Older adults (aged 60 years and above) presented the highest MDR prevalence, reflecting the vulnerability of this demographic group. Conclusion:These findings underscore the urgent need for enhanced antimicrobial stewardship programs, improved infection prevention and control measures, and continuous resistance monitoring to combat the growing threat of MDR bacteria in the region. Strengthening laboratory capacity and adherence to strict antibiotic usage policies are crucial for reducing the burden of MDR infections and improving patient outcomes. Full article

The inaugural Pennsylvania One Health Consortium Annual Meeting brought together partners from universities, state agencies, public health, veterinary, agriculture, industry, and community organizations to align around a shared One Health agenda. The program highlighted zoonotic threats, antimicrobial stewardship, wildlife and ecosystem health, invasive species, and climate-sensitive hazards. Participants affirmed privacy-preserving data exchange, projects integrating genomic epidemiology with field and environmental surveillance, cross-disciplinary education, and transparent governance, concluding with a phased roadmap for an integrated statewide One Health framework. Full article

Introduction: Clostridioides difficile (C. difficile) is a major cause of antibiotic-associated diarrhea and healthcare-associated infections, with rising global incidence and severity due to the emergence of hypervirulent strains. Methods: This review synthesizes recent literature on the epidemiology, pathogenesis, diagnostic approaches, and therapeutic strategies related to C. difficile infection (CDI). Sources were selected from peer-reviewed journals, clinical guidelines, and emerging research between 2020 and 2025. Results: Advances in molecular diagnostics have improved the accuracy and speed of CDI detection. New therapeutic options such as fidaxomicin offer narrower-spectrum antibiotic activity with reduced recurrence rates. Fecal microbiota transplantation (FMT) has emerged as a highly effective option for recurrent CDI. Preventive efforts, including antibiotic stewardship programs and early-phase vaccine trials, show potential in reducing infection rates. Discussion: The management of CDI is evolving rapidly with the integration of precision diagnostics, targeted therapies, and microbiome-based interventions. Preventive strategies are critical, particularly in healthcare settings where C. difficile persists in the environment. Continued research and coordinated public health efforts are essential to reduce disease burden, improve outcomes, and limit transmission. Conclusions: Clostridioides difficile infections remain a major healthcare challenge with rising incidence and recurrent cases. Fidaxomicin has become the preferred first-line therapy. Microbiota-based therapies (like FMT, Rebyota, and Vowst) and Lipopolysaccharide Binding Protein (LBP) are highly effective for recurrent CDI prevention. Diagnostic strategies have improved with multi-step testing, enhancing accuracy and reducing overtreatment. Future focus lies in vaccines, targeted antimicrobials, and stricter prevention through antibiotic stewardship and hygiene. Full article

Background/Objectives: The impact of antimicrobial susceptibility testing methodology on the categorization and positioning of cefiderocol and aztreonam-avibactam against metallo-β-lactamase (MBL)-producing Gram-negative bacilli remains unclear. This study aimed to evaluate the in vitro activity of cefiderocol and aztreonam-avibactam against clinical MBL-producing isolates and to assess the agreement between different cefiderocol susceptibility testing methods. Methods: A total of 299 non-duplicate clinical MBL-producing Gram-negative isolates were collected from clinical samples between 2022 and 2025. Antimicrobial susceptibility testing was performed using broth microdilution, disc diffusion, and gradient strip diffusion according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Carbapenemase genes were identified by immunochromatography and multiplex PCR. Categorical agreement and error rates between cefiderocol testing methods were analyzed. Results:Klebsiella pneumoniae was the predominant species, mainly producing NDM alone or in combination with OXA-48-like carbapenemases. Aztreonam-avibactam demonstrated complete activity against all Enterobacterales isolates (262/262, 100%) and high activity against Pseudomonas spp. (33/37, 89%). Cefiderocol susceptibility among Enterobacterales varied markedly depending on the testing method. Disc diffusion yielded 14% susceptibility (37/262), which increased to 52% (136/262) after ATU resolution, whereas broth microdilution showed 85% susceptibility (224/262). This resulted in low categorical agreement (42%) and a high rate of major errors (58%), with no very major errors detected. Cefiderocol activity did not differ substantially across carbapenemase types and was highest against VIM-producing Pseudomonas spp. Conclusions: Aztreonam-avibactam showed consistent in vitro activity against MBL-producing Enterobacterales, whereas cefiderocol activity was strongly influenced by the susceptibility testing methodology. Disc diffusion substantially underestimated cefiderocol susceptibility compared with broth microdilution. These findings highlight the critical impact of testing methodology on cefiderocol categorization and support the therapeutic role of last-line agents in the management of MBL-producing Gram-negative infections, with direct implications for clinical microbiology laboratories and antimicrobial stewardship programs. Full article

Background/Objectives: Carbapenem-resistant Acinetobacter spp. represent an emerging concern in human medicine; however, their epidemiology and genetic backgrounds in companion animals in Japan remain unclear. This study aimed to determine the prevalence of carbapenem resistance among Acinetobacter spp. isolated from diseased dogs and cats and elucidate the underlying genetic mechanisms. Methods: In this surveillance study conducted as part of the Japanese Veterinary Antimicrobial Resistance Monitoring (JVARM) program, 139 isolates were collected from diseased companion animals across Japan (84 from dogs and 55 from cats) during 2020, 2021 and 2023. Antimicrobial susceptibility testing was performed for seven antimicrobials and carbapenem-resistant isolates (meropenem MIC ≥ 8 μg/mL) underwent whole-genome sequencing to identify resistance genes, genomic contexts, and associated mobile genetic elements. Results: Resistance rates to all tested antimicrobials were below 20%. Meropenem resistance was detected in three isolates: one from a dog and two from cats. These resistant strains were identified as A. radioresistens, A. proteolyticus, and A. johnsonii, all harboring carbapenemase genes. The A. radioresistens isolate carried chromosomal bla_OXA-23, the A. proteolyticus isolate carried bla_OXA-58, and the A. johnsonii isolate possessed a plasmid containing bla_NDM-1 and bla_OXA-58. This represents the first report of bla_NDM-1-harboring Acinetobacter isolate from companion animals in Japan. Conclusions: Carbapenem-resistant Acinetobacter spp. remain rare in companion animals in Japan; however, insertion sequence mobility may promote resistance gene dissemination. As carbapenems are not approved for veterinary use in Japan, strict antimicrobial stewardship and appropriate hygiene management are essential. Full article

Background/Objectives: Data on antimicrobial resistance (AMR) in goat-derived E. coli within the Gulf Cooperation Council (GCC) region remain limited, and are largely restricted to studies conducted in Saudi Arabia and the UAE, with no published reports from Qatar. This study provides the first baseline characterization of AMR and extended-spectrum β-lactamase (ESBL) profiles of E. coli isolated from goats in Qatar. Methods: A total of 280 fecal samples were collected from goats across nine locations in Qatar (140 healthy and 140 diseased goats; 12 samples did not yield E. coli cultures). A selective agar medium was used to isolate E. coli, and the isolates were subsequently confirmed using the VITEK^® 2 Compact system. Antimicrobial susceptibility testing was performed to determine resistance profiles, and PCR assays were used to detect ESBL-associated genes. Results: 268 E. coli isolates were recovered from 280 samples. AMR analysis revealed a high prevalence of tetracycline resistance among E. coli isolates (53%), consistently observed across all nine sampling locations. Ampicillin resistance was also widespread. AMR was detected in isolates from both healthy and diseased goats; however, gentamicin resistance was found exclusively in the isolates from diseased animals. Overall, 44 isolates (16%) were classified as multidrug resistant (MDR), while nine isolates (3%) demonstrated ESBL production based on cefotaxime resistance. MDR and ESBL-producing E. coli were detected across all nine locations and in both healthy and diseased animals, with MDR strains occurring more frequently than ESBL producers. PCR analysis identified ESBL-associated genes, namely, bla_CTX-M in nine isolates and bla_TEM in three isolates. Conclusions: Goats in Qatar harbor multidrug-resistant and ESBL-producing E. coli, highlighting their role as AMR reservoirs within a One Health framework. The high resistance rates to commonly used antibiotics, particularly tetracycline and ampicillin, across health statuses and geographic locations suggest potential influences of local management practices and environmental factors. The detection of ESBL genes, notably bla_CTX-M and bla_TEM, underscores the need for prudent antimicrobial use and the implementation of integrated One Health surveillance programs to mitigate potential public health risks and to support national AMR surveillance and antimicrobial stewardship efforts across the region. Full article

The development of antimicrobial resistance (AMR) and the emergence of multiresistant pathogens represent a growing global threat to both human and animal health. Beyond the excessive and improper use of antimicrobials in human medicine, irrational use in veterinary medicine, agriculture, and aquaculture significantly contributes to the selection and spread of resistant microorganisms, which can enter the food chain and reach humans through food consumption or handling. Based on results from a recent meta-analysis, the prevalence of antimicrobial-resistant foodborne pathogens in food samples exceeds 10%. The veterinary sector is of particular concern, as a large proportion of antimicrobials are used in animal production, generating strong selective pressure and favoring the dissemination of AMR along the food chain. In an increasingly interconnected global context, resistant pathogens and resistance determinants can disseminate rapidly across sectors and national borders, making strategies confined to a single sector insufficient; therefore, effectively addressing AMR requires a One Health approach encompassing the human, veterinary, and environmental domains. Key mitigation strategies include strengthening antimicrobial stewardship programs, also in animal production, reducing routine prophylactic use of antimicrobials, and improving surveillance, coordinated across sectors and, where possible, further supported by advanced technologies such as artificial intelligence and machine learning. Further efforts are also needed to improve microbiological diagnostics, particularly through rapid and molecular methods, to support timely, targeted therapies and reduce inappropriate empirical treatments. In parallel, investment in new therapeutic options, including innovative molecules, drug combinations, and alternative approaches, remains crucial to effectively countering the growing burden of antimicrobial resistance. Full article

Antimicrobial resistance (AMR) is one of the most pressing global public health challenges, compromising the effectiveness of standard antibiotic therapies and increasing morbidity, mortality, and healthcare costs. The scarcity of new antibiotics has driven research into alternative strategies to restore or enhance the effectiveness of existing drugs. Natural compounds, including polyphenols, alkaloids, terpenes and terpenoids, antimicrobial peptides, and microbial secondary metabolites, exhibit multitarget activities such as membrane disruption, efflux pump inhibition, biofilm suppression, and quorum sensing interference. In parallel, synthetic and semi-synthetic small-molecule inhibitors have been rationally designed to target specific resistance determinants, including β-lactamases, efflux systems, quorum sensing pathways, and stress-induced mutagenesis mechanisms such as the SOS response and DNA repair processes. These agents act as adjuvants, restoring susceptibility or reducing bacterial virulence without exerting strong selective pressure. The integration of natural bioactive compounds and targeted small-molecule inhibitors represents a promising complementary strategy for conventional antibiotics. Further pharmacological and clinical investigations are required to translate these approaches into effective tools within antimicrobial stewardship programs and broader public health strategies aimed at mitigating the global burden of AMR. This narrative review analyses the recent literature on natural compounds and synthetic or semi-synthetic small-molecule inhibitors with documented activity against antimicrobial resistance mechanisms. Full article

Rapid diagnostic tests enable earlier pathogen identification in bloodstream infections compared with conventional culture-based methods and may improve clinical and economic outcomes, particularly when integrated with antimicrobial stewardship programs. Evidence suggests that while mortality benefits are context-dependent, rapid diagnostics can optimize antibiotic use and hospital resource allocation. The present study aimed to evaluate the clinical and economic impact of rapid diagnostic approaches compared with conventional microbiological culture in patients with confirmed bacteremia or fungemia hospitalized in a tertiary care setting in Bulgaria. A retrospective observational study was conducted between January 2015 and August 2020 at University Hospital “St. George,” Plovdiv. A total of 115 patients with confirmed bacteremia or fungemia were included and allocated to either a rapid diagnostic testing group (n = 77) or a standard culture group (n = 38). Mortality rates were comparable between groups (54.5% vs. 55.3%; OR 0.97, 95% CI 0.45–2.12; p = 0.942). Median length of stay was 20 days (12–35) in the rapid-test group versus 16 days (10–31) in the culture group (p = 0.505). Targeted antibiotic therapy duration was longer in the rapid-test group (median 12 vs. 6 days; p = 0.070). Median direct hospital costs were BGN 2319.40 versus BGN 1855.52, and indirect costs were BGN 19,388.80 versus BGN 15,511.04 (both p = 0.505). Diagnostic costs were significantly higher in the rapid-testing group (BGN 55.00 vs. BGN 38.00; p = 0.002). Rapid diagnostic testing produced clinical outcomes comparable to standard culture while demonstrating context-dependent economic differences in hospital resource utilization. Conclusions: Rapid diagnostic testing for bloodstream infections provides clinical outcomes comparable to standard culture-based methods while offering potential economic differences associated with the diagnostic strategy. When combined with antimicrobial stewardship interventions, rapid diagnostics support optimized antibiotic use and more efficient hospital resource utilization in critically ill patients. Full article

Background/Objectives: Antimicrobial resistance (AMR) is a major global public health threat, particularly in hospitals. Antimicrobial Stewardship Programs (ASPs) aim to optimize prescribing, reduce unnecessary exposure to broad-spectrum agents, and mitigate resistance. This study evaluated the clinical, ecological, and economic impact of an ASP implemented in January 2021 in a high-complexity hospital in Brazil, focusing on antimicrobial consumption, temporal trends in bacterial susceptibility, and direct antimicrobial-related costs. Methods: A quasi-experimental pre–post study using an interrupted time-series design was conducted in the adult intensive care unit from January 2019 to December 2023. Antimicrobial consumption was measured as Defined Daily Doses per 1000 patient-days (DDD/1000-PD) for ceftriaxone, meropenem, piperacillin–tazobactam, vancomycin, and polymyxin B. Temporal trends were assessed using Joinpoint regression, and pre- and post-intervention periods were compared using Student’s or Mann–Whitney tests. Susceptibility data were interpreted according to BrCAST standards. Results: Significant and sustained reductions were observed for all agents except polymyxin B. Susceptibility improved or stabilized among key Gram-negative pathogens, with a significant increase in aggregated Gram-negative susceptibility after 2021, while intrinsically resistant organisms showed limited change. Annual antimicrobial costs decreased by approximately USD 174,000. Conclusions: The ASP was associated with reduced broad-spectrum antimicrobial use, favorable ecological trends, and substantial cost savings. Full article

Background: Early and adequate empiric antibiotic therapy is essential in the treatment of pneumonia and sepsis and may influence the clinical outcome. Aims and Objectives: This retrospective before–after study aimed to appraise the impact of a local Antibiotic Stewardship Program (ASP—written guidelines and antibiotic restriction) on antibiotic (AB) use and clinical outcomes in patients requiring intensive care due to pneumonia and sepsis. Methods: This study was conducted as a single-center, retrospective observational study in the intensive care unit (ICU) of a pulmonology department of a tertiary care center. Data were collected for the pre-intervention period between January 2018 and May 2022 and for the ASP period between June 2022 and March 2024. In addition to descriptive statistics and univariable methods, interrupted time series (ITS) analysis was used to assess AB use and length of stay in the ICU before and after ASP implementation, using a segmented linear regression with a fixed breakpoint and continuous (hinge) specification. Results: The patients admitted to the ICU with pneumonia and sepsis were mainly men (58/101, 57.4% and 84/128, 65.6%), the need for intensive care increased with age, and most of the patients belonged to 65+ age group in both study phases (69/101, 68.3% and 75/128, 58.6%). The majority of the patients had four or more comorbidities (58/101, 57.4% and 52/128, 40.6%). In-hospital mortality was relatively high (42.6% and 41.4%), with most of the patients losing their lives in the ICU (33/43, 76.7% and 37/53, 69.8%). Significant increase in guideline-adherent agent selection (34.5%) and use of combination therapy (35.0%) was observed, while the use of fluoroquinolones decreased significantly (−31.1%). In the after period, a significant decrease in the number of patients using restricted ABs (−53.3%) was observed. In one-third of these cases (10/34, 29.4% and 16/40, 40%), two to four multidrug-resistant pathogens (MDRs) were detected simultaneously, resulting in a significant increase in direct costs (10.5%) in the ICU. The inappropriate use of AB therapy was relatively low in the presence of MDRs in both phases (2/34, 5.9% and 6/40, 15%). In the ASP period, guideline adherence was associated with slightly better clinical outcomes (30-day mortality: −0.8%; length of stay: −22.6%) in pneumonia and sepsis. The ITS analyses after the ASP implementation showed a weak downward trend and before it a slight increasing trend. Conclusions: ASP implementation in the ICU resulted in a significant improvement in the appropriate use of ABs, and guideline adherence led to slightly better clinical outcomes. Our results suggest that ASP may offer improved antimicrobial resistance with a sustained long-term effect. Full article