Changes In Antibiotic Use Research Articles

Associations Between Antibiotic Stewardship Policies and Antibiotic Use in U.S. Nursing Homes

<h3>Background</h3> Nursing homes (NHs) are implementing antibiotic stewardship programs due to recent federal regulations. We sought to evaluate if NH antibiotic stewardship policies change antibiotic use in NH residents. <h3>Methods</h3> Antibiotic stewardship policy data were collected from nationally-representative samples of NHs in 2013 and 2017. An aggregate antibiotic stewardship intensity index, ranging from 0-100, was calculated from five antibiotic stewardship policy measures. Survey data were merged with concurrent MDS 3.0 data and antibiotic use was defined as a one-day prevalence from annual and quarterly assessments. Multivariable models, overall and stratified by infection type, were used to estimate antibiotic use as a function of antibiotic stewardship intensity, NH and resident characteristics, and time. The total adjusted change in antibiotic use was calculated as the difference in predicted use after setting time and stewardship intensity to 2013 values and then to 2017 values, adjusting for 2017 characteristics. The isolated contribution of antibiotic stewardship intensity was calculated as the predicted antibiotic use when time is set to 2013 and policy intensity to 2017 divided by the total adjusted change in antibiotic use. <h3>Results</h3> Data from 584,540 resident assessments from 1,825 NHs were analyzed. On average, antibiotic stewardship intensity in NHs increased significantly from 2013 to 2017 (µ=33.08 to µ=67.94, p < 0.001). The observed prevalence of antibiotic use decreased by 2.9% (8.29% to 8.05%, p=0.001). The total adjusted decline in antibiotic use given similar characteristics was 5.3% from 2013 to 2017. Increases in policy intensity accounted for 37% of this decline. Antibiotic stewardship intensity was negatively associated with antibiotic use overall and in cases with active diagnoses of urinary tract infection or septicemia. <h3>Conclusions</h3> Improved antibiotic stewardship programs have resulted in a modest decline in antibiotic use, suggesting that the full extent of the translation from antibiotic stewardship policy to practice remains to be seen.

Antibiotic stewardship and its implications for agricultural animal-human relationships: Insights from an intensive dairy farm in England

Abstract The concept of antibiotic stewardship has recently gained prominence in UK and EU policy and practice as part of wider efforts to reduce antibiotic use in agriculture and respond to concerns about antimicrobial resistance. The purpose of the paper is to provide initial insights into what antibiotic stewardship might mean in practice for agricultural animal-human relationships, particularly within intensive systems. We do this by firstly outlining the anticipated implications for agricultural animals by different stakeholders. Secondly, we develop the concept of heterogeneous biosocial collectivities through engagement with the literatures on care and thirdly we apply this concept to one case study (intensive dairy) farm to explore empirically how animal-human relationships are changing in response to antibiotic stewardship. Three on-farm heterogeneous biosocial collectivities are identified, each of which coheres around a particular problem of life associated with distinctive practices of care and antibiotic use resulting in collectivity-specific responses to antibiotic stewardship. These collectivities are: the calf collectivity and the problem of immunodeficient life; the milking cow collectivity and the problem of ‘stoic’ life; the dry cow collectivity and the problem of fatigued life. In conclusion we point to: the uneven effects for animal-human relationships of changes in antibiotic use including in particular practices of care and their consequences; an intensification of human control over animals with variable implications for their health and welfare. The analysis raises questions for future research, in particular the need to test the assumption that reducing antibiotic use will stimulate systemic change in intensive animal agriculture towards sustainable, high-welfare, and more extensive systems of production.

Trends, seasonality and the association between outpatient antibiotic use and antimicrobial resistance among urinary bacteria in the Netherlands.

To determine trends, seasonality and the association between community antibiotic use and antimicrobial resistance (AMR) in Escherichia coli and Klebsiella pneumoniae in urinary tract infections. We analysed Dutch national databases from January 2008 to December 2016 regarding antibiotic use and AMR for nitrofurantoin, trimethoprim, fosfomycin and ciprofloxacin. Antibiotic use was expressed as DDD/1000 inhabitant-days (DID) and AMR was expressed as the percentage of resistance from total tested isolates. Temporal trends and seasonality were analysed with autoregressive integrated moving average (ARIMA) models. Each antibiotic use-resistance combination was cross-correlated with a linear regression of the ARIMA residuals. The trends of DID increased for ciprofloxacin, fosfomycin and nitrofurantoin, but decreased for trimethoprim. Similar trends were found in E. coli and K. pneumoniae resistance to the same antibiotics, except for K. pneumoniae resistance to ciprofloxacin, which decreased. Resistance levels peaked in winter/spring, whereas antibiotic use peaked in summer/autumn. In univariate analysis, the strongest and most significant cross-correlations were approximately 0.20, and had a time delay of 3-6 months between changes in antibiotic use and changes in resistance. In multivariate analysis, significant effects of nitrofurantoin use and ciprofloxacin use on resistance to these antibiotics were found in E. coli and K. pneumoniae, respectively. There was a significant association of nitrofurantoin use with trimethoprim resistance in K. pneumoniae after adjusting for trimethoprim use. We found a relatively low use of antibiotics and resistance levels over a 9 year period. Although the correlations were weak, variations in antibiotic use for these four antibiotics were associated with subsequent variations in AMR in urinary pathogens.

Change in Antibiotic Use in Secondary and Tertiary Hospitals Nationwide After a National Antimicrobial Stewardship Campaign Was Launched in China, 2011-2016: An Observational Study.

An antimicrobial stewardship campaign was launched in 2011 by the Ministry of Health. This study aimed to assess the achievements and trends in the clinical use of antibiotics in secondary and tertiary hospitals following this campaign in China. This observational study analyzed nationwide hospital antibiotic procurement and consumption data and antibiotic-resistance surveillance data based on claims filed in 2010-2016. After a 6-year national campaign, the proportion of outpatients and surgical patients who received antibiotic treatment decreased from 19.5% to 8.5% and from 97.9% to 38.3%, respectively. The intensity of antibiotic use among inpatients decreased from 85.3±29.8 defined daily dosage (DDD) per 100 patient days to 48.5±8.0 DDD per 100 patient days. Moreover, the antibiotic procurement expenditure among hospitals declined from 22.3% of total drug procurement costs in 2010 to 12.1% in 2016, although total drug procurement costs doubled during that time. The incidence of methicillin-resistant Staphylococcus aureus isolates also dropped (from 54.4% in 2010 to 34.4% in 2016), as did the proportion of carbapenem-resistant Pseudomonas aeruginosa isolates (from 30.8% to 22.3%). The 6-year campaign successfully reduced antibiotic consumption and irrational drug use in Chinese hospitals which was associated with declines in the prevalence of common antibiotic-resistant bacteria.

Catchment-scale export of antibiotic resistance genes and bacteria from an agricultural watershed in central Iowa.

Antibiotics are administered to livestock in animal feeding operations (AFOs) for the control, prevention, and treatment of disease. Manure from antibiotic treated livestock contains unmetabolized antibiotics that provide selective pressure on bacteria, facilitating the expression of anti-microbial resistance (AMR). Manure application on row crops is an agronomic practice used by growers to meet crop nutrient needs; however, it can be a source of AMR to the soil and water environment. This study in central Iowa aims to directly compare AMR indicators in outlet runoff from two adjacent (221 to 229 ha) manured and non-manured catchments (manure comparison), and among three catchments (600 to 804 ha) with manure influence, no known manure application (control), and urban influences (mixed land use comparison). Monitored AMR indicators included antibiotic resistance genes (ARGs) ermB, ermF (macrolide), tetA, tetM, tetO, tetW (tetracycline), sul1, sul2 (sulfonamide), aadA2 (aminoglycoside), vgaA, and vgaB (pleuromutilin), and tylosin and tetracycline resistant enterococci bacteria. Results of the manure comparison showed significantly higher (p<0.05) tetracycline and tylosin resistant bacteria from the catchment with manure application in 2017, but no differences in 2018, possibly due to changes in antibiotic use resulting from the Veterinary Feed Directive. Moreover, the ARG analysis indicated a larger diversity of ARGs at the manure amended catchment. The mixed land use comparison showed the manure amended catchment had significantly higher (p<0.05) tetracycline resistant bacteria in 2017 and significantly higher tylosin resistant bacteria in 2017 and 2018 than the urban influenced catchment. The urban influenced catchment had significantly higher ermB concentrations in both sampling years, however the manure applied catchment runoff consisted of higher relative abundance of total ARGs. Additionally, both catchments showed higher AMR indicators compared to the control catchment. This study identifies four ARGs that might be specific to AMR as a result of agricultural sources (tetM, tetW, sul1, sul2) and optimal for use in watershed scale monitoring studies for tracking resistance in the environment.

Impact of FDA black box warning on fluoroquinolone and alternative antibiotic use in southeastern US hospitals.

We analyzed antibiotic use data from 29 southeastern US hospitals over a 5-year period to determine changes in antibiotic use after the fluoroquinolone US Food and Drug Administration (FDA) advisory update in 2016. Fluoroquinolone use declined both before and after the FDA announcement, and the use of select, alternative antibiotics increased after the announcement.Fluoroquinolones are among the 4 most commonly prescribed antibiotic classes.1,2 Postmarketing reports of serious adverse events linked to fluoroquinolones include tendonitis, neuropathy, hypoglycemia, psychiatric side effects, and possible aortic vessel rupture, leading to safety label changes in July 2008 and August 2013.3 In July 2016, the US Food and Drug Administration (FDA) strengthened the "black box" warning following an initial safety announcement in May 2016, recommending avoidance of fluoroquinolones for uncomplicated infections such as acute exacerbation of chronic bronchitis, uncomplicated urinary tract infections, and acute bacterial sinusitis.4 Concerns over safety and the association with Clostridiodes difficile infection have led inpatient antimicrobial stewardship programs (ASPs) to develop initiatives to promote avoidance of quinolones. The objective of this study was to quantify the effect of the 2016 FDA "black box" update on inpatient antibiotic use among a cohort of southeastern US hospitals.

PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP): study protocol for a randomised controlled trial

BackgroundDifferentiating infection from inflammation in acute pancreatitis is difficult, leading to overuse of antibiotics. Procalcitonin (PCT) measurement is a means of distinguishing infection from inflammation as levels rise rapidly in response to a pro-inflammatory stimulus of bacterial origin and normally fall after successful treatment. Algorithms based on PCT measurement can differentiate bacterial sepsis from a systemic inflammatory response. The PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP) trial tests the hypothesis that a PCT-based algorithm to guide initiation, continuation and discontinuation of antibiotics will lead to reduced antibiotic use in patients with acute pancreatitis and without an adverse effect on outcome.MethodsThis is a single-centre, randomised, controlled, single-blind, two-arm pragmatic clinical and cost-effectiveness trial. Patients with a clinical diagnosis of acute pancreatitis will be allocated on a 1:1 basis to intervention or standard care. Intervention will involve the use of a PCT-based algorithm to guide antibiotic use. The primary outcome measure will be the binary outcome of antibiotic use during index admission. Secondary outcome measures include: safety non-inferiority endpoint all-cause mortality; days of antibiotic use; clinical infections; new isolates of multiresistant bacteria; duration of inpatient stay; episode-related mortality and cause; quality of life (EuroQol EQ-5D); and cost analysis. A 20% absolute change in antibiotic use would be a clinically important difference. A study with 80% power and 5% significance (two-sided) would require 97 patients in each arm (194 patients in total): the study will aim to recruit 200 patients. Analysis will follow intention-to-treat principles.DiscussionWhen complete, PROCAP will be the largest randomised trial of the use of a PCT algorithm to guide initiation, continuation and cessation of antibiotics in acute pancreatitis. PROCAP is the only randomised trial to date to compare standard care of acute pancreatitis as defined by the International Association of Pancreatology/American Pancreatic Association guidelines to patients having standard care but with all antibiotic prescribing decisions based on PCT measurement.Trial registrationInternational Standard Randomised Controlled Trial Number, ISRCTN50584992. Registered on 7 February 2018.

Changes in antibiotic use following implementation of a telehealth stewardship pilot program.

Starting in 2016, we initiated a pilot tele-antibiotic stewardship program at 2 rural Veterans Affairs medical centers (VAMCs). Antibiotic days of therapy decreased significantly (P&lt;.05) in the acute and long-term care units at both intervention sites, suggesting that tele-stewardship can effectively support antibiotic stewardship practices in rural VAMCs.

Trends and patterns of outpatient and inpatient antibiotic use in China's hospitals: data from the Center for Antibacterial Surveillance, 2012-16.

Data surveillance and policy interventions can optimize antibiotic use, but few studies have focused on the changes in antibiotic use after a strict antibiotic stewardship policy was implemented in China in 2012. Based on the Center for Antibacterial Surveillance, data were collected from general hospitals in two provinces of China. Using indicators (e.g. percentage of antibiotic use and proportion of antibiotic costs) recommended by the WHO, this study aimed to identify trends and patterns of systemic antibiotic (Anatomical Therapeutic Chemical code J01) use in hospitals in 2012-16 and to explore inappropriate antibiotic use. This study obtained 282479 outpatient prescriptions and 86070 inpatient records from 52 hospitals. The percentage of antibiotic use in outpatients and non-surgical and surgical inpatients significantly declined from 20.17%, 41.92% and 74.15% in 2012 to 12.94%, 33.88% and 69.03% in 2016, respectively. Among antibiotic prescriptions and records, the percentage of antibiotic combination therapy, the percentage of antibiotic use for prophylaxis and the proportion of antibiotic costs showed a decreasing trend over time. However, in 2016, the percentage of antibiotic use for surgical prophylaxis was still >80%, with more than one-third involving inappropriate timing of antibiotic usage according to the predefined criteria. In non-surgical inpatients, the usage rates in acute upper respiratory infections, diarrhoea in children <5 years and fever or cough symptoms all exceeded 55%. A significant downward trend in antibiotic use was identified in China's hospitals, which indicates that policy intervention might reduce the overuse of antibiotics. Furthermore, strengthening appropriate antibiotic use should be the focus of antibiotic stewardship.

Comparing prescribing and dispensing databases to study antibiotic use: a validation study of the Electronic Medical Record Administrative data Linked Database (EMRALD).

Monitoring and studying community antibiotic use is a critical component in combating rising antimicrobial resistance. To validate an electronic medical record dataset containing antibiotic prescriptions and to quantify some important differences between prescribing and dispensing databases. We evaluated antibiotics prescribed and dispensed to patients ≥65 years of age during 2011-15. We compared the EMRALD prescribing database with the validated Ontario Drug Benefit (ODB) dispensing database. Using ODB as the gold standard and limiting to EMRALD physicians, we calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) with 95% CIs. We also compared the relative change in antibiotic use prescribed by all physicians to this population over time between the databases using Poisson regression models. In this population, 74% of all antibiotics dispensed were from non-EMRALD physicians. Trends in use were discordant over time. When we limited ODB to EMRALD prescribers only to assess the validity of EMRALD data, we observed good sensitivity and excellent specificity for correctly identifying antibiotics at 85% (95% CI 84%-85%) and 98% (95% CI 98%-98%), respectively. The PPV was 78% (95% CI 78%-78%) and the NPV was 99% (95% CI 99%-99%). All performance measures were higher among the highest prescribing physicians. We demonstrated EMRALD is well suited for studying antibiotic prescribing by EMRALD physicians. However, due to the frequency with which patients receive antibiotic prescriptions from their non-primary care physicians, we caution against the use of non-population-based prescribing databases to infer antibiotic use rates or trends over time.

857. A Tele-Antibiotic Stewardship Program Influences Antibiotic Use at 2 Rural Veterans Affairs Medical Centers

BackgroundTelehealth offers the possibility of supporting antibiotic stewardship in settings with limited access to people with infectious diseases (ID) expertise. Previously, we described preliminary results from a pilot project that used the Veterans Affairs (VA) telehealth system to facilitate a Videoconference Antimicrobial Stewardship Team (VAST) which connected a multidisciplinary team from a rural VA medical center (VAMC) with ID physicians at a remote site to support antibiotic stewardship. Here, we present 3 distinct metrics to assess the influence of the VAST on antibiotic use at 2 intervention sites.MethodsOutcomes assessed antibiotic use in the hospital and long-term care units of 2 rural VAMCs in the year before and after VAST implementation, allowing for a 1-month wash-in period in the first month of the VAST. Using VA databases, we determined 3 metrics: the rate of antibiotic use (days of therapy per 1,000 bed days of care); the mean length of therapy (days); and the mean patient antibiotic spectrum index (ASI), a measure of antibiotic spectrum increasing from narrow to broad. Using segmented regression on monthly measures of each metric with a knot at the wash-in month (gray square), we calculated predicted values (solid lines), and confidence intervals (dashed lines) to examine trends before (black squares) and after (white squares) implementing the VAST.ResultsThe rate of antibiotic use, mean length of therapy, and ASI decreased at Site A. As indicated in the figure, the effect was more pronounced in long-term care compared with the hospital, where the VAST sustained but did not accelerate downward trends. At Site B, the most notable influence of the VAST was on the ASI for the hospital and long-term care units.ConclusionThe VAST is a feasible, sustainable program that is effective at inducing change in antibiotic use at 2 VAMCs. The influence of the VAST differed between the 2 sites and, at Site A had a more pronounced effect on the long-term care compared with hospital units. These distinct metrics capture changes in overall antibiotic use, length of therapy, and agent selection. Tele-antibiotic stewardship programs hold potential to improve antibiotic use at facilities with limited access to people with antibiotic stewardship expertise. Disclosures All authors: No reported disclosures.

1804. Impact of Susceptibility Testing Method on Antibiotic Selection for Methicillin-Resistant Staphylococcus Aureus (MRSA) Bacteremia

BackgroundThe selection of intravenous (IV) antibiotics for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia can be influenced by the vancomycin minimum inhibitory concentration (MIC). This study explores the changes in antibiotic use and inpatient mortality for patients with MRSA bacteremia after switching the MIC testing methods.MethodsAt University of Kentucky Medical Center, Etest™ was implemented in November 2013 for all Staphylococcus aureus blood isolates. In April 2016, this was changed to Phoenix™ automated system. Data regarding antibiotic usage for patients with MRSA bacteremia were collected from July 2014 to December 2015 (Etest™) and September 2016 to March 2017 (Phoenix™). Only patients started on IV vancomycin were included. Daptomycin and ceftaroline use was monitored by the antimicrobial stewardship team with focus on guideline adherence.ResultsA total of 119 and 62 patients were identified before and after switching to Phoenix™. MICs of 2 μg/mL were significantly decreased (P < 0.001) after changing to Phoenix™ (Table 1). Daptomycin use (alone or in combination) decreased from 37% (44/119) to 21% (13/62) (P = 0.013). Ceftaroline use (alone or in combination) decreased from 32% (38/119) to 19% (12/62) (P = 0.036). The reason for escalation in 13 of 44 (30%) patients with daptomycin and 6 of 38 (16%) patients with ceftaroline was an MIC of 2 μg/mL. Overall, IV vancomycin use (alone or in combination) increased from 50% (60/119) to 69% (43/62) (P = 0.007). All-cause inpatient mortality was 16% (19/119) before and 10% (6/62) (P = 0.24) after switching to Phoenix.Table 1:Difference in MIC Data and Antibiotic UtilizationParametersEtest™ (n = 119) n (%)Phoenix™ (n = 62) n (%) P-ValueMIC = 2 μg/mL56 (47)2 (3)<0.001MIC = 1.5 μg/mL37 (31)N/AN/AMIC ≤1 μg/mL26 (22)60 (97)<0.001IV vancomycin60 (50)43 (69)0.007Daptomycin44 (37)13 (21)0.013Ceftaroline38 (32)12 (19)0.036Other antibioticsa4 (3)4 (6)0.27All-cause inpatient mortality19 (16)6 (10)0.24 aInclude linezolid and trimethoprim/sulfamethoxazole.ConclusionA switch in vancomycin susceptibility testing from Etest™ to Phoenix™ automated system was associated with a significant decrease in daptomycin and ceftaroline use and an increase in IV vancomycin use without any change in all-cause inpatient mortality.Disclosures All authors: No reported disclosures.

The Relative Impact of Community and Hospital Antibiotic Use on the Selection of Extended-spectrum Beta-lactamase-producing Escherichia coli.

Antibiotic stewardship programs have traditionally focused on reducing hospital antibiotic use. However, reducing community antibiotic prescribing could have substantial impacts in both hospital and community settings. We developed a deterministic model of transmission of extended-spectrum beta-lactamase-producing Escherichia coli in both the community and hospitals. We fit the model to existing, national-level antibiotic use and resistance prevalence data from Sweden. Across a range of conditions, a given relative change in antibiotic use in the community had a greater impact on resistance prevalence in both the community and hospitals than an equivalent relative change in hospital use. However, on a per prescription basis, changes in antibiotic use in hospitals had the greatest impact. The magnitude of changes in prevalence were modest, even with large changes in antimicrobial use. These data support the expansion of stewardship programs/interventions beyond the walls of hospitals, but also suggest that such efforts would benefit hospitals themselves.

Ventilator-Associated Pneumonia (VAP): Are we ready to let go of the old definitions

Background: In 2013 the NHSH implemented major changes in the VAP definition. Reviewing episodes became easier and faster and it eliminated most of the subjective interpretation of data. We started implementing this new definition in January 2017 but continued to use the old definition as well. Objectives: Assess the impact of the new NHSN definitions to calculate the VAP rates in our hospital. Analyze whether the changes in the VAP rates trends are reflected in antibiotic consumption. Methods & Materials: Descriptive Study. Retrospective analysis of the VAP rates in Intensive Care Unit (ICU) and Coronary Care Unit (CCU). Daily data from active surveillance, microbiology reports and electronic medical records review. Antibiotic consumption in ICU and CCU: DDD Defined Daily Dose. D/P: every 100 days/patient Results: VAP Rates (per1000 days ventilator) 2013-2016 old definition and 2017 old and new definition. ICU: 2013: 4.02, 2014 6.27 2015 3.42, 2016 4.12 2017 old 2.65, new:0. CCU: 2013: 12.41, 2014 9.9, 2015 10.23, 2016: 8, 2017 old: 2.8 new: 0. Antibiotic consumption: CCU DDD 2016 D/P 27.4, 2017 39.09. ICU DDD 2016 D/P 91,39 2017 95.43. We observed a statistically significant increase in antibiotic consumption in the ICC from 2016 to 2017(p ≤ 0.001). In the ICU there was there was no significant decrease in antibiotic consumption, with a tendency to rise for this period. Conclusion: Although we observed a decreasing tendency in VAP these years, the abrupt fall in VAP rates after the introduction of the new NHSN definitions seems to reflect a definition biass more than an improvement in the care provided to our patients.We have observed no significant change in antibiotic use to match the changes in VAP rates.It can be a big risk to use a definition that gives us a false sense of security, leading us to more relaxed behaviour in terms of prevention. For the time being, we consider useful to use both definitions to calculate VAP rates and dentify this risk.

Trends in outpatient antibiotic use and prescribing practice among US older adults, 2011-15: observational study

ObjectiveTo identify temporal trends in outpatient antibiotic use and antibiotic prescribing practice among older adults in a high income country.DesignObservational study using United States Medicare administrative claims in 2011-15.SettingMedicare, a...

Antibiotic use on German pig farms - A longitudinal analysis for 2011, 2013 and 2014.

To study antibiotic use in livestock in a temporal context with the development of antimicrobial resistance, long-term changes in antibiotic use must be mapped and their possible causes must be explored. Therefore, the present work assesses the changes in antibiotic use over time in German livestock husbandry. In addition, factors associated with antibiotic use were analyzed to identify possible strategies for further reducing antimicrobial usage. For 2011, 2013 and 2014, antibiotic usage data were collected and examined within the VetCAb project. Three hundred participating pig holdings provided information on their antibiotic use based on obligatory application and delivery forms (ADFs) filled in by their veterinarian as well as information on their current stabling capacities for each production type held. Data on sow, piglet, weaner and fattening pig holdings were described separately, using the semi-annual treatment frequency (TF) to measure antibiotic consumption. Multiple linear mixed models were used to investigate the effects of time, farm size, region and farm management category on the treatment frequency. The study yielded significant time changes with p-values below 0.001 in antibiotic administration with a decreasing median TF in piglets from 3.8 in the first half of 2011 (IQR = 1.1–10.6) to 1.7 in the second half of 2014 (IQR = 0.2–4.5) and in fattening pigs from 5.1 in the first half of 2011 (IQR = 0.2–15.4) to 0.7 in the second half of 2014 (IQR = 0.1–6.7). Meanwhile the TF fluctuated between 8.2 and 12.2 in weaners during the observational period (IQRs between zero (lower quartile) and 37.9 (upper quartile)). Piglet, weaner and fattening pig holdings belonging to the upper third of the holdings in size used significantly more antibiotics than the other holdings investigated. Particularly for weaner and fattening pig holdings, a higher TF was noted for farms without breeding units. The region was only a significant factor in weaners. In conclusion, for 2011, 2013 and 2014, the present study shows a clear reduction in antibiotic treatment frequency in German pig holdings. In addition, the association with various factors such as herd size and farm organization on the antibiotic usage frequency is indisputable. Therefore, these factors should be included in monitoring systems and considered when evaluating intervention measures.

Strength of the association between antibiotic use and hemolytic uremic syndrome following Escherichia coli O157:H7 infection varies with case definition

BackgroundThe veracity of the association between antibiotic use and hemolytic uremic syndrome (HUS) caused by Escherichia coli O157:H7 has been a topic of debate. We postulated that criteria used to define HUS affect this association. MethodsWe reviewed 471 hospitalized E. coli O157:H7 cases reported in Washington State, 2005–2014, to determine HUS status by various case definitions and antibiotic treatment. We used age-adjusted logistic regression models to estimate the effect of treatment on HUS status according to four common, but heterogeneous, definitions: the Council of State and Territorial Epidemiologists (CSTE) definition, hematology-focused and age-focused definitions from the literature, and hospital diagnosis. ResultsInter-annual variation in antibiotic use was high, but no meaningful change in antibiotic use was observed over this ten-year period. Thirteen percent of cases <18 years-old received antibiotics, compared to 54% of cases ≥18 years-old. The CSTE, hematology-focused, age-focused, and hospital diagnosis definitions identified 149, 57, 74, and 89 cases of HUS, respectively. The association between antibiotic treatment and HUS varied by definition: CSTE odds ratio (OR) 1.57 [95% confidence interval (CI) 0.98, 2.55]; hematology-focused OR 1.73 (95% CI 0.83, 3.54); age-focused OR 2.29 (95% CI 1.20, 4.39); and hospital diagnosis OR 1.94 (95% CI 1.01, 3.72). ConclusionsEach definition yielded an estimate of the association in the direction of increased risk of HUS with antibiotics. While the range of OR point estimates was relatively small, confidence intervals for two HUS definitions crossed the null and two did not, potentially altering the inference an investigator makes. Discrepant reports of the association between antibiotic use and HUS in the literature might be due in part to the choice of HUS definition, and a consistent definition of HUS should be adopted for research and public health purposes.

Impact of Implementing Antibiotic Stewardship Programs in 15 Small Hospitals: A Cluster-Randomized Intervention.

Studies on the implementation of antibiotic stewardship programs (ASPs) in small hospitals are limited. Accreditation organizations now require all hospitals to have ASPs. The objective of this cluster-randomized intervention was to assess the effectiveness of implementing ASPs in Intermountain Healthcare's 15 small hospitals. Each hospital was randomized to 1 of 3 ASPs of escalating intensity. Program 1 hospitals were provided basic antibiotic stewardship education and tools, access to an infectious disease hotline, and antibiotic utilization data. Program 2 hospitals received those interventions plus advanced education, audit and feedback for select antibiotics, and locally controlled antibiotic restrictions. Program 3 hospitals received program 2 interventions plus audit and feedback on the majority of antibiotics, and an infectious diseases-trained clinician approved restricted antibiotics and reviewed microbiology results. Changes in total and broad-spectrum antibiotic use within programs (intervention versus baseline) and the difference between programs in the magnitude of change in antibiotic use (eg, program 3 vs 1) were evaluated with mixed models. Program 3 hospitals showed reductions in total (rate ratio, 0.89; confidence interval, .80-.99) and broad-spectrum (0.76; .63-.91) antibiotic use when the intervention period was compared with the baseline period. Program 1 and 2 hospitals did not experience a reduction in antibiotic use. Comparison of the magnitude of effects between programs showed a similar trend favoring program 3, but this was not statistically significant. Only the most intensive ASP intervention was associated with reduction in total and broad-spectrum antibiotic use when compared with baseline. NCT03245879.

Why sensitive bacteria are resistant to hospital infection control.

Background: Large reductions in the incidence of antibiotic-resistant strains of Staphylococcus aureus and Clostridium difficile have been observed in response to multifaceted hospital-based interventions. Reductions in antibiotic-sensitive strains have been smaller or non-existent. It has been argued that since infection control measures, such as hand hygiene, should affect resistant and sensitive strains equally, observed changes must have largely resulted from other factors, including changes in antibiotic use. We used a mathematical model to test the validity of this reasoning. Methods: We developed a mechanistic model of resistant and sensitive strains in a hospital and its catchment area. We assumed the resistant strain had a competitive advantage in the hospital and the sensitive strain an advantage in the community. We simulated a hospital hand hygiene intervention that directly affected resistant and sensitive strains equally. The annual incidence rate ratio ( IRR) associated with the intervention was calculated for hospital- and community-acquired infections of both strains. Results: For the resistant strain, there were large reductions in hospital-acquired infections (0.1 ≤ IRR ≤ 0.6) and smaller reductions in community-acquired infections (0.2≤ IRR ≤ 0.9). These reductions increased in line with increasing importance of nosocomial transmission of the strain. For the sensitive strain, reductions in hospital acquisitions were much smaller (0.6 ≤ IRR ≤ 0.9), while communityacquisitions could increase or decrease (0.9 ≤ IRR ≤ 1.2). The greater the importance of the community environment for the transmission of the sensitive strain, the smaller the reductions. Conclusions: Counter-intuitively, infection control interventions, including hand hygiene, can have strikingly discordant effects on resistant and sensitive strains even though they target them equally, following differences in their adaptation to hospital and community-based transmission. Observed lack of effectiveness of control measures for sensitive strains does not provide evidence that infection control interventions have been ineffective in reducing resistant strains.

Why sensitive bacteria are resistant to hospital infection control

Background: Large reductions in the incidence of antibiotic-resistant strains of Staphylococcus aureus and Clostridium difficile have been observed in response to multifaceted hospital-based interventions. Reductions in antibiotic-sensitive strains have been smaller or non-existent. It has been argued that since infection control measures, such as hand hygiene, should affect resistant and sensitive strains equally, observed changes must have largely resulted from other factors, including changes in antibiotic use. We used a mathematical model to test the validity of this reasoning. Methods: We developed a mechanistic model of resistant and sensitive strains in a hospital and its catchment area. We assumed the resistant strain had a competitive advantage in the hospital and the sensitive strain an advantage in the community. We simulated a hospital hand hygiene intervention that directly affected resistant and sensitive strains equally. The annual incidence rate ratio ( IRR) associated with the intervention was calculated for hospital- and community-acquired infections of both strains. Results: For the resistant strain, there were large reductions in hospital-acquired infections (0.1 ≤ IRR ≤ 0.6) and smaller reductions in community-acquired infections (0.2 ≤ IRR ≤ 0.9). These reductions increased in line with increasing importance of nosocomial transmission of the strain. For the sensitive strain, reductions in hospital acquisitions were much smaller (0.6 ≤ IRR ≤ 0.9), while communityacquisitions could increase or decrease (0.9 ≤ IRR ≤ 1.2). The greater the importance of the community environment for the transmission of the sensitive strain, the smaller the reductions. Conclusions: Counter-intuitively, infection control interventions, including hand hygiene, can have strikingly discordant effects on resistant and sensitive strains even though they target them equally, following differences in their adaptation to hospital and community-based transmission. Observed lack of effectiveness of control measures for sensitive strains does not provide evidence that infection control interventions have been ineffective in reducing resistant strains.