Daily defined dose-costs have a stronger influence on antibacterial drug prescriptions in Germany than bacterial resistance: economic factors are more important than scientific evidence.

Previous research from our group revealed a strong association between daily defined dose (DDD)-costs and -prescriptions of antibacterial drugs in Germany ( https://pubmed.ncbi.nlm.nih.gov/38842562/ ; https://pubmed.ncbi.nlm.nih.gov/39042156/ ). These data indicate that low costs are major driver of high prescription numbers. This study examines the relationship between bacterial resistance and DDD-prescriptions of antibacterial drugs using data from the Arzneiverordnungsreport (AVR) from 2008 to 2022 and the Antibiotic Resistance Surveillance (ARS) statistics provided by the Robert Koch Institute (RKI). We hypothesized that semi-rational or irrational prescribing behavior of antibacterial drugs is evident in Germany, i.e., prescriptions are driven to a greater extents by low DDD-costs than bacterial resistance. A bivariate correlation analysis was performed to test these models. Our data point to irrational prescribing behavior for amoxicillin, cefuroxime axetil, doxycycline, nitrofurantoin, ciprofloxacin, and clarithromycin. For amoxicillin clavulanic acid and sulfamethoxazole-trimethoprim, data point to semi-rational prescribing. For no antibacterial drug, a model pointing to rational drug prescribing was found. In conclusion, our study shows that DDD-costs exert a more significant influence on DDD-prescriptions than bacterial resistance, indicating that economic factors, rather than scientific evidence, primarily drive antibacterial drug prescriptions in outpatient settings in Germany. It will be important to conduct similar studies on the prescription of antibacterial drugs in other countries. It will also be important to study the relation between DDD-costs and -prescriptions for other drug classes and assess the scientific basis for these relations.

Trends and geographical variations in outpatient antimicrobial consumption in Ireland in relation to socio-economic deprivation.

Background: Different factors have been associated with changes in antimicrobial consumption rates in Ireland, however the relationship between socio-economic deprivation and antimicrobial consumption has not been explored. The presented ecological analysis explores the temporal and geographical variation in outpatient antimicrobial consumption and socio-economic deprivation in Ireland from January 2015 to March 2022. Method: Deprivation index (DI) was used as a socio-economic proxy. A multilevel mixed model was applied to explore temporal variation and analyse the longitudinal antimicrobial consumption (DID) in relation to DI. Furthermore, maps were generated based on antimicrobial consumption rates, and spatial autocorrelation analyses were carried out to study geographical variation in antimicrobial consumption rates. Results: The antimicrobial consumption rates per month varied from 26.2 DID (January 2015) to 22.1 DID (March 2022) showing an overall reduction of 16 %. Overall, total antimicrobial consumption in the multilevel model showed a consistent correlation with higher DI score (6.6 (95%CI 3.9 to 9.3)), and winter season (3.6 (95%CI 3.2 to 3.9)). In contrast, before COVID-19 showed significant lower antimicrobial consumption rates compared to during COVID-19 (-4.0 (95%CI -4.7 to -3.23)). No consistent trends were observed for geographical variation between areas. Conclusion: Antimicrobial consumption rates decreased from 2015 to 2021 in Ireland. No geographical patterns were observed in antimicrobial consumption rates but associations between deprivation and antimicrobial consumption rates were observed.

Prescriber-level surveillance of outpatient antimicrobial consumption to enable targeted antimicrobial stewardship: a nationwide observational study, Switzerland, 2015 to 2022.

BackgroundIn Europe and other high-income countries, antibiotics are mainly prescribed in the outpatient setting, which consists of primary, specialist and hospital-affiliated outpatient care. Established surveillance platforms report antimicrobial consumption (AMC) on aggregated levels and the contribution of the different prescriber groups is unknown.AimTo determine the contribution of different prescribers to the overall outpatient AMC in Switzerland.MethodsWe conducted a retrospective observational study using claims data from one large Swiss health insurance company, covering the period from 2015 to 2022. We analysed antibiotic prescriptions (ATC code J01) prescribed in the Swiss outpatient setting. Results were reported as defined daily doses per 1,000 inhabitants per day (DID) and weighted according to the total population of Switzerland based on census data.ResultsWe analysed 3,663,590 antibiotic prescriptions from 49 prescriber groups. Overall, AMC ranged from 9.12 DID (2015) to 7.99 DID (2022). General internal medicine (40.1% of all prescribed DID in 2022), hospital-affiliated outpatient care (20.6%), group practices (17.3%), paediatrics (5.4%) and gynaecology (3.7%) were the largest prescriber groups. Primary care accounted for two-thirds of the prescribed DID. Quantity and type of antibiotics prescribed varied between the prescriber groups. Broad-spectrum penicillins, tetracyclines and macrolides were the most prescribed antibiotic classes.ConclusionPrimary care contributed considerably less to AMC than anticipated, and hospital-affiliated outpatient care emerged as an important prescriber. Surveillance at the prescriber level enables the identification of prescribing patterns within all prescriber groups, offering unprecedented visibility and allowing a more targeted antibiotic stewardship according to prescriber groups.

DDD-costs have a strong influence on antibacterial drug prescription in Germany: a differentiated correlation analysis from 1985 to 2022.

Antibacterial drugs are vital in modern medicine, and understanding the factors influencing their prescriptions is essential for maintaining their effectiveness and accessibility. This study investigates the hypothesis that costs significantly impact the prescriptions of antibacterial drugs, a factor previously underrecognized. To investigate this, we conducted correlation analyses on defined daily dose (DDD-) prescriptions and DDD-costs for the 15 most prescribed antibacterial drugs in Germany in 2022, using data from the Arzneimittelverordnungsreport (Drug Prescription Report) (1985-2022). The analysis focused on the periods 1985-2022, 1985-2011, and 2012-2022. Our findings revealed significant correlations between DDD-prescriptions and -costs for nearly all drugs over the entire period (1985-2022), with strong negative correlations for amoxicillin (- 0.941), cefuroxime axetil (- 0.900), clindamycin (- 0.800), nitrofurantoin (- 0.895), and cefaclor (- 0.819). From 1985 to 2011, only significant negative correlations were observed. In 2012-2022, significant correlations included both negative and positive, with strong positive correlations for ciprofloxacin (0.950) and clarithromycin (0.962). Overall, DDD-costs showed a persistent and strong correlation with DDD-prescriptions, particularly in the earlier period. This influence appears to diminish slightly in recent years, suggesting other factors might become more significant as DDD-costs plateau. Notably, amoxicillin, amoxicillin clavulanic acid, and nitrofurantoin consistently exhibited strong cost-prescription correlations throughout the entire period. While correlation does not imply causation, the significant and strong correlations, coupled with logical explanations, support the hypothesis that costs are a primary factor in prescribing patterns. Further research is needed to establish causality and examine other potential systemic factors affecting antibacterial drug prescriptions.

Effects of pay-for-performance based antimicrobial stewardship on antimicrobial consumption and expenditure: An interrupted time series analysis.

Objectives: To evaluate the impact of pay-for-performance on antimicrobial consumption and antimicrobial expenditure in a large teaching hospital in Guangzhou, China. Methods: We collected data from hospital information system from January 2018 through September 2022 in the inpatient wards. Antimicrobial consumption was evaluated using antibiotic use density (AUD) and antibiotic use rate (AUR). The economic impact of intervention was assessed by antimicrobial expenditure percentage. The data was analyzed using interrupted time series (ITS) analysis. Results: Following the implementation of the intervention, immediate decreases in the level of AUD were observed in Department of Hematology Unit 3 (ß = -66.93 DDDs/100PD, P = 0.002), Urology (ß = -32.80 DDDs/100PD, P < 0.001), Gastrointestinal Surgery Unit 3 (ß = -11.44 DDDs/100PD, P = 0.03), Cardiac Surgery (ß = -14.30 DDDs/100PD, P = 0.01), ICU, Unit 2 (ß = -81.91 DDDs/100PD, P = 0.02) and Cardiothoracic Surgery ICU (ß = -41.52 DDDs/100PD, P = 0.05). Long-term downward trends in AUD were also identified in Organ Transplant Unit (ß = -1.64 DDDs/100PD, P = 0.02). However, only Urology (ß = -6.56 DDDs/100PD, P = 0.02) and Gastrointestinal Surgery Unit 3 (ß = -8.50 %, P = 0.01) showed an immediate decrease in AUR, and long-term downward trends in AUR were observed in Pediatric ICU (ß = -1.88 %, P = 0.05) and ICU Unit 1 (ß = -0.55 %, P = 0.02). Conclusion: This study demonstrates that the adoption of pay-for-performance effectively reduces antibiotic consumption in specific departments of a hospital in Guangzhou in the short term. However, it is important to recognize that the long-term impact of such interventions is often limited. Additionally, it should be noted that the overall effectiveness of the intervention across the entire hospital was not significant.

Drug Utilization Review of Monitored Parenteral Antimicrobials in a Tertiary Care Private Hospital in Cebu City.

Background: Based on the 2017-2020 annual report of the Department of Health-Antimicrobial Resistance Surveillance Program, significant resistance patterns have been observed for common disease-causing pathogens. In the hospital setting, antimicrobial stewardship programs have been implemented to optimize the use of antimicrobials. Drug utilization review studies provide essential feedback to improve prescribing and use of medications. Objectives: This study aimed to review drug utilization of monitored parenteral antimicrobials among patients admitted from January to December 2019. Methods: The study employed a retrospective, cross-sectional, descriptive research design. A retrospective chart review of drugs administered to patients was conducted. Results: A total of 821 patients charts met the inclusion criteria. The patients' ages ranged from 18 to 98 years old and 52% were females. General Internal Medicine practitioners (28%) were the top prescribers of monitored parenteral antimicrobials primarily for the management of moderate-risk community-acquired pneumonia (39%). They were mostly indicated for empirical treatment of infections (94%) and were given for an average of 5.73 days.Only 58% of the total cases had orders for culture and sensitivity testing. Of which, principally 47% had colony cultures. Blood (29%) and sputum (27%) were the most common specimens taken for culture and sensitivity testing. The microorganisms often isolated were Escherichia coli (19%), Klebsiella pneumoniae (18%), and Staphylococcus aureus (9%). In addition, extended-spectrum beta lactamase-producing gram-negative pathogens (4%) and methicillin-resistant S. aureus (1%) were also isolated. All the microorganisms isolated showed most resistance to ampicillin (81%) and most susceptibility to colistin (100%). There were drug therapy-related problems encountered. There was one case of an adverse drug reaction (0.1%) and two cases of contraindications (0.2%). Therapeutic duplication was also observed in 5% of the cases. Moreover, 39% had instances of drug-drug interactions.Piperacillin-tazobactam had the highest consumption (79.50 defined daily doses/1,000-patient days) among the monitored parenteral antimicrobials.Some prescriptions were deemed inappropriate upon evaluation. 12% of cases were inappropriate based on the justification indicator. As for the critical indicators, duration of therapy (78%) was the main reason. Only four components of the DUE criteria indicators have met or exceeded the established threshold level.The cost analysis indicated that the total actual cost of therapy with the monitored parenteral antimicrobials amounted to ₱17,645,601.73. Considering Department of Health National Antibiotic Guidelines recommendations, ideal total cost of treatment was ₱14,917,214.29. Potential cumulative cost savings of ₱2,728,387.44 could have been achieved for patients admitted last 2019. Conclusion: Consumption of piperacillin-tazobactam was relatively high as compared to the other monitored parenteral antimicrobials covered in this study. Physicians at the study site seldom prescribe monitored parenteral antimicrobials as recommended by the National Antibiotic Guidelines. This is evidenced in the incidence of inappropriate therapy regimens, with inapt duration of therapy as the leading explanation.From the patient's perspective, the main economic implication was on the direct medical costs, particularly the increased cost of the actual antimicrobial therapy prescribed to manage various infections. Adherence of physicians to the established guidelines and selection of the most cost-effective therapy could have resulted in considerable cost savings.

Automated surveillance of antimicrobial consumption in intensive care, northern Sweden: an observational case study.

BACKGROUND: The digitalization of information systems allows automatic measurement of antimicrobial consumption (AMC), helping address antibiotic resistance from inappropriate drug use without compromising patient safety. OBJECTIVES: Describe and characterize a new automated AMC surveillance service for intensive care units (ICUs), with data stratified by referral clinic and linked with individual patient risk factors, disease severity, and mortality. METHODS: An automated service collecting data from the electronic medical record was developed, implemented, and validated in a healthcare region in northern Sweden. We performed an observational study from January 1, 2018, to December 31, 2021, encompassing general ICU care for all ≥18-years-olds in a catchment population of 270000 in secondary care and 900000 in tertiary care. We used descriptive analyses to associate ICU population characteristics with AMC outcomes over time, including days of therapy (DOT), length of therapy, defined daily doses, and mortality. RESULTS: There were 5608 admissions among 5190 patients with a median age of 65 (IQR 48-75) years, 41.2% females. The 30-day mortality was 18.3%. Total AMC was 1177 DOTs in secondary and 1261 DOTs per 1000 patient days and tertiary care. AMC varied significantly among referral clinics, with the highest total among 810 general surgery admissions in tertiary care at 1486 DOTs per 1000 patient days. Case-mix effects on the AMC were apparent during COVID-19 waves highlighting the need to account for case-mix. Patients exposed to more than three antimicrobial drug classes (N = 242) had a 30-day mortality rate of 40.6%, with significant variability in their expected rates based on admission scores. CONCLUSION: We introduce a new service and instructions for automating local ICU-AMC data collection. The versatile long-term ICU-AMC metrics presented, covering patient factors, referral clinics and mortality outcomes, are expected to be beneficial in refining antimicrobial drug use.

Evaluation of Surveillance Strategies of Antimicrobial Consumption in Animals.

The aim of this paper is to explore and assess various strategies for monitoring antimicrobial consumption (AMC) in animals, within the context of the One Health approach. Recent studies have shed light on the limited surveillance and data collection for AMC in animals. Using the United States Center for Disease Control and Prevention Policy Analytical Framework, we assess global, national, and farm-level surveillance strategies on public health impact and feasibility using evidence from primary, secondary, and grey literature. From this, we identify key policy mechanisms that support the adoption of surveillance while providing specific recommendations. We find that a global strategy, though valuable for benchmarking and policy guidance, faces participation and data visibility challenges. National-level surveillance offers direct inputs into national action plans but struggles with data uniformity and comparability. Farm-level surveillance, while resource-intensive, provides the most granular data for informing specific interventions. We advocate for a multi-faceted approach to AMC surveillance, emphasizing that legal mandates and financial incentives are crucial for encouraging surveillance participation, along with international cooperation for enhancing participation and data quality. Drawing parallels with public reporting challenges in other sectors can provide valuable lessons on how to address data collection, analysis, and reporting barriers.

The effect of the COVID-19 pandemic on the incidence and resistance of Gram-negative bacilli and antimicrobial consumption in the intensive care units of a referral hospital in Buenos Aires.

BACKGROUND: There was a reported increase in the antimicrobial consumption in hospitals during the COVID-19 pandemic, accompanied by an increase in infections due to multidrug-resistant (MDR) bacteria. METHODS: This retrospective time series study from intensive care units in Buenos Aires examined changes in antibiotic consumption (defined daily doses/1000 patients/day), the incidence of Gram-negative bacilli (GNB) and the mechanism of resistance. Antibiotics were categorised into group 1 (agents against MDR GNB) and group 2 (agents against non-MDR infections). Bacteriological samples included respiratory samples and blood cultures. Periods were divided into pre-pandemic (July 2019 to March 2020) and pandemic (April 2020 to March 2022). Correlation coefficients (r) were analysed and the Mann-Whitney test was performed to compare both periods. RESULTS: During the study period, GNB incidence, group 1 antibiotic consumption and resistance mechanisms increased, whereas antibiotics decreased in group 2. A significant positive correlation was seen between the consumption of antibiotics in group 1 and the incidence of GNB (r = 0.63; P < 0.001) and resistance (r = 0.52; P = 0.002). Significant differences were found between pre-pandemic and pandemic periods regarding the medians of group 1 consumption (520 [408-570] vs. 753 [495-851] DDD/1000 patients/day; P = 0.029), incidence of GNB (12 [10-13] vs. 43 [25-52.5] cases/month; P < 0.001) and resistance mechanisms (5 [4-8] vs. 17 [10-25] cases/month; P < 0.001), extended-spectrum beta lactamases (2 [1-2] vs. 6 [3-8] cases/month; P < 0.001) and metallo-beta-lactamases (0 [0-0] vs. 6 [1.75-8.5] cases/month; P < 0.001). CONCLUSION: During the COVID-19 pandemic, the rise in GNB incidence and the amount of resistance mechanisms significantly correlated with the increase in consumption of agents against MDR strains.

Could traces of fluoroquinolones in food induce ciprofloxacin resistance in Escherichia coli and Klebsiella pneumoniae? An in vivo study in Galleria mellonella with important implications for maximum residue limits in food.

We hypothesized that the residual concentrations of fluoroquinolones allowed in food (acceptable daily intake-ADIs) could select for ciprofloxacin resistance in our resident microbiota. We developed models of chronic Escherichia coli and Klebsiella pneumoniae infection in Galleria mellonella larvae and exposed them to ADI doses of ciprofloxacin via single dosing and daily dosing regimens. The emergence of ciprofloxacin resistance was assessed via isolation of the target bacteria in selective agar plates. Exposure to as low as one-tenth of the ADI dose of the single and daily dosing regimens of ciprofloxacin resulted in the selection of ciprofloxacin resistance in K. pneumoniae but not E. coli. This resistance was associated with cross-resistance to doxycycline and ceftriaxone. Whole genome sequencing revealed inactivating mutations in the transcription repressors, ramR and rrf2, as well as mutations in gyrA and gyrB. We found that ciprofloxacin doses 10-fold lower than those classified as acceptable for daily intake could induce resistance to ciprofloxacin in K. pneumoniae. These results suggest that it would be prudent to include the induction of antimicrobial resistance as a significant criterion for determining ADIs and the associated maximum residue limits in food.IMPORTANCEThis study found that the concentrations of ciprofloxacin/enrofloxacin allowed in food can induce de novo ciprofloxacin resistance in Klebsiella pneumoniae. This suggests that it would be prudent to reconsider the criteria used to determine "safe" upper concentration limits in food.

Evaluation of Hospital Antimicrobial Stewardship Programs: Implementation, Process, Impact, and Outcomes, Review of Systematic Reviews.

Antimicrobial Stewardship Programs (ASP) were introduced in healthcare as a public health priority to promote appropriate prescribing of antimicrobials, to reduce adverse events related to antimicrobials, as well as to control the escalating challenges of antimicrobial resistance. To deliver aimed outcome objectives, ASPs involve multiple connected implementation process measures. A systematic review was conducted to evaluate both concepts of ASPs. Guided by PRISMA frames, published systematic reviews (SR) focusing on ASPs restricted to secondary and tertiary healthcare were evaluated over the past 10 years involving all age groups. Out of 265 identified SR studies, 63 met the inclusion criteria. The majority were conducted in Europe and North America, with limited studies from other regions. In the reviewed studies, all age groups were examined, although they were conducted mainly on adults when compared to children and infants. Both process and outcomes measures of ASPs were examined equally and simultaneously through 25 different concepts, dominated by efficacy, antimicrobial resistance, and economic impact, while information technology as well as role of pharmacy and behavioral factors were equally examined. The main broad conclusions from the review were that, across the globe, ASPs demonstrated effectiveness, proved efficacy, and confirmed efficiency, while focused evaluation advocated that developed countries should target medium- and small-sized hospitals while developing countries should continue rolling ASPs across healthcare facilities. Additionally, the future of ASPs should focus on embracing evolving information technology to bridge the gaps in knowledge, skills, and attitude, as well as to enhance appropriate decision making.

Does selective digestive decontamination (SDD) increase antibiotic resistance? Long-term comparison of two intensive care units (with and without SDD) of the same tertiary hospital.

PURPOSE: The aim of this study was to to compare the antimicrobial resistance rate and its relationship with the antibiotic consumption in two separate Intensive Care Units (ICUs) of the same hospital, one with and other without selective decontamination of the digestive tract (SDD). METHODS: We performed a retrospective study in the two ICUs of the Araba University Hospital. Trauma and neurosurgical patients are admitted to the SDD-ICU, and general digestive surgery patients go to the no SDD-ICU. From 2014 to 2018 we analyzed the number of isolates, and the bacterial resistance trends of 47 antimicrobial-microorganism combinations. Additionally, antimicrobial consumption was estimated in both ICUs. Resistance rates were also compared with those reported in ENVIN-HELICS Spanish national registry. RESULTS: In the ICU with SDD protocol, there was a significant decrease in the resistance of E. coli to amoxicillin/clavulanic acid and in the resistance of E. faecalis to high concentration of gentamycin and high concentration of streptomycin. A significant increase of resistance of Staphylococcus coagulasa negative (CoNS) to linezolid in the no SDD-ICU was also detected. Overall, the level of resistance in the SDD-ICU was lower or of the same order than in the ICU without SDD and that reported in the Spanish national registry. CONCLUSIONS: SDD had neither a clinically relevant impact on emergence and spread of resistance, nor in the overall systemic antimicrobial use. The patient type rather than the SDD protocol showed to condition the ecology and therefore, the resistance rate in the ICUs.

Antimicrobial consumption and resistance in bacteria from humans and food-producing animals: Fourth joint inter-agency report on integrated analysis of antimicrobial agent consumption and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals in the EU/EEA JIACRA IV - 2019-2021.

The fourth joint inter-agency report on integrated analysis of antimicrobial consumption (AMC) and the occurrence of antimicrobial resistance (AMR) in bacteria from humans and food-producing animals (JIACRA) addressed data obtained by the Agencies' EU-wide surveillance networks for 2019-2021. The analysis also sought to identify whether significant trends in AMR and AMC were concomitant over 2014-2021. AMC in both human and animal sectors, expressed in mg/kg of estimated biomass, was compared at country and European level. In 2021, the total AMC was assessed at 125.0 mg/kg of biomass for humans (28 EU/EEA countries, range 44.3-160.1) and 92.6 mg/kg of biomass for food-producing animals (29 EU/EEA countries, range 2.5-296.5). Between 2014 and 2021, total AMC in food-producing animals decreased by 44%, while in humans, it remained relatively stable. Univariate and multivariate analyses were performed to study associations between AMC and AMR for selected combinations of bacteria and antimicrobials. Positive associations between consumption of certain antimicrobials and resistance to those substances in bacteria from both humans and food-producing animals were observed. For certain combinations of bacteria and antimicrobials, AMR in bacteria from humans was associated with AMR in bacteria from food-producing animals which, in turn, was related to AMC in animals. The relative strength of these associations differed markedly between antimicrobial class, microorganism and sector. For certain antimicrobials, statistically significant decreasing trends in AMC and AMR were concomitant for food-producing animals and humans in several countries over 2014-2021. Similarly, a proportion of countries that significantly reduced total AMC also registered increasing susceptibility to antimicrobials in indicator E. coli from food-producing animals and E. coli originating from human invasive infections (i.e., exhibited 'complete susceptibility' or 'zero resistance' to a harmonised set of antimicrobials). Overall, the findings suggest that measures implemented to reduce AMC in food-producing animals and in humans have been effective in many countries. Nevertheless, these measures need to be reinforced so that reductions in AMC are retained and further continued, where necessary. This also highlights the importance of measures that promote human and animal health, such as vaccination and better hygiene, thereby reducing the need for use of antimicrobials.

The unseen use of antimicrobials: Drivers of human antibiotic use in a community in Thailand and implications for surveillance.

We investigated sociocultural and economic drivers of human antimicrobial use (AMU) in Thailand through ethnographic research, interviews, focus groups and a cross-sectional survey. This community-based study generated findings clustered around three key themes: treatment-seeking practices, medicine use, and interpretation of biomedical constructs. Participants sought care from public health facilities for chronic conditions, but medicines from the private sector were considered more powerful and were preferred for acute complaints. Many antibiotics were unrecognised as such by consumers due to the practice at private healthcare facilities of dispensing repackaged medicines without identifying labels. This unseen use of antibiotics is probably driven by economic drivers including market competition in the private sector, policy implementation drivers whereby rational drug use policies mainly target the public sector, behavioural drivers relating to treatment seeking-practices, and sociocultural drivers that influenced participants' understanding of medical terms and concepts. Participants regarded antibiotics as reducing inflammation and were uncertain about the distinctions between anti-inflammatories, antibiotics, and pain relievers. Antimicrobial Resistance (AMR) was understood as a form of drug tolerance to be remedied by changing the medicine. Community surveys may not provide accurate estimates of AMU where people are unable to distinguish antibiotics reliably from other medicines.

Trends in inpatient antimicrobial consumption using days of therapy and days of antibiotic spectrum coverage: A nationwide claims database study in Japan.

INTRODUCTION: Days of antibiotic spectrum coverage (DASC), a novel metric for both antimicrobial volume and spectrum, was proposed to measure inpatient antimicrobial consumption in 2022. The DASC may better reflect efforts toward antimicrobial stewardship; however, no previous study has described the distribution of trends in DASC in hospitals or the association between the trend in DASC and days of therapy (DOT). This study assessed trends in antimicrobial consumption for inpatients at acute care hospitals in Japan using the DOT and DASC. METHODS: This retrospective observational study used the nationwide administrative inpatient claims database of Japanese acute care hospitals between 2014 and 2018. The prescriptions of all antibiotics were identified to calculate DOT/1000 patient-days, DASC/1000 patient-days, and DASC/DOT. We described the five-year trend in these metrics and examined the association between the trends in DOT and DASC. RESULTS: In total, 26,301,685 admissions from 634 hospitals were included. The DOT/1000 patient-days and DASC/1000 patient-days increased significantly by 6.1% and 5.6%, respectively. The DASC/DOT ratio did not change significantly (P = 0.35). Moreover, there was little correlation between DOT/1000 patient-days and DASC/DOT (R2 = 0.01). There was also little correlation between the five-year changes in DOT/1000 patient-days and those in DASC/DOT (R2 = 0.02). CONCLUSIONS: It may be difficult to assess trends in the antibiotic spectrum using DASC alone. However, the combination of DOT as a quantity indicator and DASC/DOT as a spectrum indicator may allow for a more appropriate evaluation of stewardship efforts.

Clinical and Microbiological Impact of Implementing a Decision Support Algorithm through Microbiologic Rapid Diagnosis in Critically Ill Patients: An Epidemiological Retrospective Pre-/Post-Intervention Study.

BACKGROUND: Data on the benefits of rapid microbiological testing on antimicrobial consumption (AC) and antimicrobial resistance patterns (ARPs) are scarce. We evaluated the impact of a protocol based on rapid techniques on AC and ARP in intensive care (ICU) patients. METHODS: A retrospective pre- (2018) and post-intervention (2019-2021) study was conducted in ICU patients. A rapid diagnostic algorithm was applied starting in 2019 in patients with a lower respiratory tract infection. The incidence of nosocomial infections, ARPs, and AC as DDDs (defined daily doses) were monitored. RESULTS: A total of 3635 patients were included: 987 in the pre-intervention group and 2648 in the post-intervention group. The median age was 60 years, the sample was 64% male, and the average APACHE II and SOFA scores were 19 points and 3 points. The overall ICU mortality was 17.2% without any differences between the groups. An increase in the number of infections was observed in the post-intervention group (44.5% vs. 17.9%, p < 0.01), especially due to an increase in the incidence of ventilator-associated pneumonia (44.6% vs. 25%, p < 0.001). AC decreased from 128.7 DDD in 2018 to 66.0 DDD in 2021 (rate ratio = 0.51). An increase in Pseudomonas aeruginosa susceptibility of 23% for Piperacillin/tazobactam and 31% for Meropenem was observed. CONCLUSION: The implementation of an algorithm based on rapid microbiological diagnostic techniques allowed for a significant reduction in AC and ARPs without affecting the prognosis of critically ill patients.

Rebound in community antibiotic consumption after the observed decrease during the COVID-19 pandemic, EU/EEA, 2022.

We observed a rebound in consumption of antibacterials for systemic use (ATC J01) in the community sector in the European Union/European Economic Area during 2021 and 2022, after an observed decrease between 2019 and 2020. The rates in 2022 returned to pre-COVID-19-pandemic levels and were exceeded in 13 countries. Although these patterns could partly be a result of changes in disease transmission during the study period, it could also reflect a lost opportunity to strengthen and reinforce prudent antibiotic use.

Antimicrobial consumption surveillance in Uganda: Results from an analysis of national import data for the human health sector, 2018-2021.

BACKGROUND: The surveillance of antimicrobial consumption (AMC) is critical to developing appropriate antimicrobial stewardship interventions. It is a key component of World Health Organization's (WHO) Global Action Plan on Antimicrobial Resistance and the Uganda Antimicrobial Resistance National Action Plan 2018-2023. Our study's objective was to determine the national consumption of all antimicrobials. METHODS: Data on all imported antimicrobials were retrieved from paper-based records and entered in the web-based National Drug Authority (NDA) management information system from 2021. The import data for the year is a proxy for nationwide consumption because they account for 95% of all medical products. The NDA authorizes all imports to the country regardless of final distribution in the supply chain. The data were analyzed in accordance with WHO Anatomical Therapeutic Chemical codes and defined daily dose (DDD) methodology. We also retrieved consumption data for 2018, 2019, and 2020 that were previously submitted by Uganda to WHO's Global Antimicrobial Resistance and Use Surveillance System. RESULTS: In 2021, the average DDD per 1000 inhabitants was 29.02 for all antimicrobials; 80.7% of antimicrobials consumed were oral. Penicillins (27.6%) were the most consumed antimicrobial class, followed by sulfonamides and trimethoprim (15.5%). Based on WHO's Access, Watch, and Reserve (AWaRe) antibiotic classification, 62.91% of AMC was from the access class, with watch class averaging 14.51% in the period 2018-2021. Watch class AMC spiked in 2021 (34.2%) during COVID-19 pandemic compared to 2020 (24.29%). Azithromycin and ciprofloxacin were the most consumed watch class antimicrobials in 2021. CONCLUSIONS: The relatively high consumption of injectable antimicrobials and year over year increase in watch class AMC requires urgent stewardship interventions. Further work is needed to establish a system for longitudinal AMC surveillance that is well resourced and funded to overcome the challenges of estimation and provide more accurate data on consumption and use patterns.

Productivity parameters, antimicrobial consumption, and prevalence of enteric pathogens before and after intramuscular vaccination against Lawsonia intracellularis in naturally infected Danish weaner and finisher pig herds.

In Danish pig production, gastro-intestinal diseases account for most of the antimicrobials (AM) used in growing pigs. Diarrhoea is most frequently caused by Lawsonia intracellularis (LI), Brachyspira pilosicoli (BP), E coli fimbria type F4 (F4) and E. coli fimbria type F18 (F18). With a new LI vaccine available from 2019, it was relevant to investigate the effect of this vaccine in a Danish field study including both weaner and finisher sites. The aim was to evaluate the efficacy of Porcilis® Lawsonia Vet. in naturally LI-infected pig herds by comparing of productivity parameters, AM consumption and dynamics of enteric pathogens over two 6-months periods before and after LI vaccination. Further, faecal sock samples were collected from each site before and after vaccination and analysed by qPCR for excretion levels of LI, BP, F18 and F4. In total, 28 weaner and 41 finisher sites were included in the study. Vaccination reduced Feed Conversion Ratio by 0.12 Feed Unit/kg (p = 0.029) and 0.08 Feed Unit/kg (p = 0.005) in weaners and finishers, respectively. Increased Average Daily Weight Gain of 45.6 gr./day (p < 0.001) was found in the finishers. Mortality risk fell by 8.8% in weaners (RR = 0.912; p < 0.001). AM prescriptions for oral group treatments were reduced by 38.8% active compound/kg pig produced (p = 0.005) or 33.3% Weighted Animal Daily Doses per 100 animals per day in finishers (p = 0.004). LI prevalence was reduced in weaners and finishers (both p < 0.001) and BP prevalence was reduced in finishers (p = 0.043). Mean excretion levels of LI and BP decreased at weaner sites (-1.32 and -1.02 log(10) copies/gr faeces, respectively; both p < 0.001) and at finisher sites (-1.04 and -1.16 log(10) copies/gr faeces, respectively; both p < 0.001). Prevalence and excretion levels of F18 and F4 were unaffected by LI vaccination. In conclusion, vaccination against LI using Porcilis® Lawsonia Vet. improved productivity parameters, cut AM consumption, and reduced prevalence and excretion levels of LI and BP in naturally LI-infected pig herds.