Implications For Antibiotic Stewardship Research Articles

High Prevalence of ESBL Genes in Commensal Escherichia coli of the Urinary Tract: Implications for Antibiotic Stewardship among Residents of Ghanaian Elderly Nursing Care Homes

High Prevalence of ESBL Genes in Commensal Escherichia coli of the Urinary Tract: Implications for Antibiotic Stewardship among Residents of Ghanaian Elderly Nursing Care Homes

First Fever between Lymphodepletion and Day 30 after CAR-T Cell Therapy: Patterns, Origins, and Implications in Lymphoma Patients

Introduction: Fever is a common adverse event associated with chimeric antigen receptor-T cell (CAR-T cell) therapy and serves as the hallmark of cytokine release syndrome (CRS). However, limited data are available on competing and contributing etiologies of fever. Thus, we aimed to investigate the causes, risk factors, and implications of fever in CAR-T cell recipients in the period with the most profound immunosuppression: between lymphodepletion (LD) and day 30 after infusion. Methods: In this single-center retrospective analysis, we studied 304 non-Hodgkin lymphoma patients (80% large B-cell lymphoma, 11% mantle cell lymphoma, 4% follicular lymphoma) treated with CD19-CAR-T cells (48% axi-cel, 23% tisa-cel, 23% liso-cel, 6% brexu-cel) between 2016 and 2023. First fever was defined as a temperature of 38°C or higher between LD and day 30 after CD19-CAR-T cells. Patients experiencing fever were routinely cultured, following institutional guidelines. Additional workup, including respiratory virus PCR panel, stool gastrointestinal PCR panel, Clostridioides difficile PCR, urine culture, chest x-ray, and fungal infection assessment, was done at the medical team's discretion. A contributing infectious source for the fever was considered if there was a positive test in the workup within 72 hours of the initial fever. Results: Fever occurred in 232/304 (76%) of patients between LD and day 30 after CAR-T cell infusion. The median time from LD to first fever was 5 days (range 2-13) and from CAR-T infusion to first fever was 2 days (range: LD initiation to 16). Of patients who had not developed a fever up to the day of infusion (n=271), 199 (73%) experienced a fever between infusion (day 0) and day 30. The primary etiology of fever between LD and day 30 was CRS (n=159/232, 68.5%), with 54% experiencing grade 2 or higher. An infectious source was identified in 52/232 (22%) of all patients and 35/194 (18%) of the subgroup developing CRS. Leading infectious etiologies were gastrointestinal (GI), bloodstream, and respiratory infections in 20 (38%), 14 (27%), and 11 (21%) of patients, respectively (Figure A). The most frequent pathogens identified were Clostridioides difficile for GI tract infections (10/20), Enterobacteriaceae for bloodstream infections (8/14), and common upper respiratory viruses, such as Rhinovirus and Parainfluenzavirus (10/16). Importantly, in patients developing fever after infusion, an infectious source was identified in 42/199 (21%). Among them, 12/42 (29%) were bloodstream infections, and 10/42 (24%) were Clostridioides difficile infections requiring rapid antibiotic management. Of an array of potential risk factors, only pre-apheresis metabolic tumor volume was associated with an increased risk for an infectious cause of fever in a univariable logistic-regression model (p=0.029). Furthermore, an infectious source of fever, compared to a non-infectious cause, was associated with an increased risk of mortality (HR 1.60, 95%CI 1.02-2.51, p=0.039) in a multivariable Cox regression model adjusted for LDH range before lymphodepletion, age and CAR-T construct type (Figure B). Conclusions: This study represents one of the first and largest investigations into fever patterns and origins in CAR-T cell therapy recipients. Although fever is common, treatable infectious sources are infrequent. Our findings may have implications for antibiotic stewardship and fever management in CAR-T patients. Finally, the association between infectious fever and inferior survival warrants further investigation on the biological processes driving mortality.

Prevalence of methicillin and clindamycin resistant Staphylococcus species at a tertiary hospital in Tanzania: Implications for antibiotic stewardship and infection management

Methicillin and clindamycin resistance (constitutive and inducible) pose a common clinical challenge in treating Staphylococcal infections. This cross-sectional study, conducted at Muhimbili National Hospital (MNH) in Tanzania from April to June 2023, to assess the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and clindamycin-resistant Staphylococcus (S.) species by using a cefoxitin disk (30 μg) and the D-test method as per CLSI 2022 guidelines. Of the 361 clinical samples, 125 (34.6%) were culture-positive. Among Staphylococcus spp., S. aureus was 6% (12/125), while 33.6% (42/125) were coagulase-negative staphylococci (CoNS). Among the isolated S. aureus, 75% were resistant to methicillin, while 66.7% of the CoNS were resistant to methicillin. Further, 92% (11/12) of the S. aureus isolates were resistant to erythromycin, and 50% (6/12) were resistant to clindamycin. Among the CoNS, 83% (35/42) were resistant to erythromycin, and 52% (22/42) were resistant to clindamycin. The proportion of inducible macrolides lincosamide streptogramin B resistance (iMLSB), constitutive macrolides lincosamide streptogramin B resistance (cMLSB), and macrolides lincosamide streptgramin B methicillin susceptible (MS) phenotypes among S. aureus isolates was 16.7%, 41.7%, and 33.3%, respectively, and among CoNS was 19%, 35.7%, and 28.6%, respectively. The overall prevalence of iMLSB and cMLSB phenotypes was 18.5% (10/54) and 37% (20/54), respectively. Comparatively, MRSA had more resistance to ciprofloxacin than methicillin-susceptible S. aureus (MSSA) (88.9% vs. 33.3% p = 0.027), while methicillin-resistant coagulase-negative staphylococci (MR-CoNS) had significantly higher resistance to gentamicin (35.7% vs. 7.1% p= 0.005), and trimethoprim-sulfamethoxazole (78.6% vs. 50% p=0.007) than methicillin-susceptible coagulase-negative staphylococci (MS-CoNS). The high prevalence of methicillin and inducible clindamycin resistance in this study points out a potential rise in treatment failures, prolonged hospitalization, and limited treatment options. Thus, emphasizes the importance of antibiotic stewardship and laboratory-guided antibiotic decisions. To address the growing challenge of antibiotic resistance in Tanzania, it is advisable to implement stringent public health measures, including monitoring antibiotic usage, conducting educational initiatives, and raising awareness among patients and healthcare professionals.

One size doesn’t fit all: Lessons from a procalcitonin external quality assurance program

Sepsis accounts for approximately 20% of global deaths, and early diagnosis is a critical factor in intervention. Procalcitonin (PCT) is an established biomarker for bacterial infection and there are recognised intervals for clinical interpretation in the context of sepsis. Antibiotic therapy is indicated for PCT results >2.0 ng/mL and this has implications for antibiotic stewardship in the age of antibiotic resistance.

Postoperative Oral Antibiotics and Sinonasal Outcomes Following Endoscopic Transsphenoidal Surgery for Pituitary Tumors Study: A Multicenter, Prospective, Randomized, Double-Blinded, Placebo-Controlled Study.

Postoperative prophylactic antibiotics are commonly used in pituitary surgery, but evidence supporting their use is lacking, which has implications for antibiotic stewardship. To evaluate whether receipt of postoperative oral antibiotics results in superior sinonasal quality of life (QOL) compared with placebo among patients who undergo endoscopic endonasal transsphenoidal pituitary surgery. Patients were randomized to receive either oral placebo or cefdinir (trimethoprim-sulfamethoxazole in patients intolerant to cefdinir) for 7 d after surgery. They were monitored for 12 wk. The primary outcome measure was sinonasal QOL at 2 wk on the Anterior Skull Base Nasal Inventory-12. Supplementary end points included sinonasal QOL reported on the Sinonasal Outcome Test-22 and objective endoscopy scores to assess nasal healing according to the Lund-Kennedy method. A total of 461 patients were screened, 131 were randomized, and 113 (placebo arm: 55; antibiotic arm: 58) were analyzed. There was no clinically meaningful or statistically significant difference in sinonasal QOL at any measured time point (P≥.24) using either instrument. Nasal cavity endoscopy scores were not significantly different at 1 to 2 wk after surgery (P=.25) or at 3 to 4 wk after surgery (P=.08). Postoperative prophylactic oral antibiotics did not result in superior sinonasal QOL compared with placebo among patients who underwent standard endoscopic transsphenoidal surgery.

Antibiotic use practices of veterinarians and para-veterinarians and the implications for antibiotic stewardship in Nigeria.

The aim of this study was to describe the antibiotic use practices of veterinarians and para-veterinarians in Nigeria. An online survey was distributed during November through December 2018 via email and phone to veterinarians and para-veterinarians to collect information on antibiotic use practices. Data were downloaded into Excel and descriptive statistics were presented and analysed. The survey was completed by 390 respondents. Almost all respondents (98.5%, 384/390) recommended the use of antibiotics to treat animal patients, and of these, 93.2% (358/384) were veterinarians and 6.8% (26/384) were para-veterinarians. Most respondents reported commonly recommending the use of oxytetracycline (82.6%, 317/384), tylosin (44.5%, 171/384) and gentamycin (43.8%, 168/384). A third (32.0%, 122/384) of respondents did not undertake antimicrobial susceptibility testing (AST) prior to antibiotic treatment. At least 60% of the respondents recommended the use of antibiotics for the treatment of non-bacterial pathogens, including viral, helminth and fungal pathogens. Over 55% (217/390) were not aware of government-issued guidelines on antibiotic use in animals, although of those aware, 69% (74/107) utilised the guidelines. Across all respondents, the majority believed legislation or regulation by government can influence the use of antibiotics by animal health professionals. The study highlights areas that can be targeted as part of intervention strategies to promote antimicrobial stewardship by animal health professionals in Nigeria, including the need for increased use of AST as a tool for supporting disease management, increased awareness of appropriate antibiotic use and greater dissemination of antibiotic use guidelines and enforcement of relevant regulation by government authorities.

Clinical diagnosis and treatment of common respiratory tract infections in relation to microbiological profiles in rural health facilities in China: implications for antibiotic stewardship

BackgroundThis paper tries to describe prevalence and patterns of antibiotics prescription and bacteria detection and sensitivity to antibiotics in rural China and implications for future antibiotic stewardship.MethodsThe study was implemented in one village clinic and one township health center in each of four rural residential areas in Anhui Province, China. It used mixed-methods comprising non-participative observations, exit-survey and microbiological study. Observations were conducted to record clinical diagnosis and antibiotic prescription. Semi-structured questionnaire survey was used to collect patient’s sociodemographic information and symptoms. Sputum and throat swabs were collected for bacterial culture and susceptibility testing.ResultsA total of 1068 (51.0% male vs 49.0% female) patients completed the study with diagnosis of respiratory tract infection (326,30.5%), bronchitis/tracheitis (249,23.3%), pharyngitis (119,11.1%) and others (374, 35.0%). They provided 683 sputum and 385 throat swab specimens. Antibiotics were prescribed for 88% of the RTI patients. Of all the specimens tested, 329 (31%) were isolated with bacteria. The most frequently detected bacteria were K. pneumonia (24% in all specimens), H. influenza (16%), H. parainfluenzae (15%), P. aeruginosa (6%), S.aureus (5%), M. catarrhalis (3%) and S. pneumoniae (2%).ConclusionsThe study establishes the feasibility of conducting microbiological testing outside Tier 2 and 3 hospitals in rural China. It reveals that prescription of antibiotics, especially broad-spectrum and combined antibiotics, is still very common and there is a clear need for stewardship programs aimed at both reducing the number of prescriptions and promoting single and narrow-spectrum antibiotics.

Harnessing the wisdom of crowds can improve guideline compliance of antibiotic prescribers and support antimicrobial stewardship

Antibiotic overprescribing is a global challenge contributing to rising levels of antibiotic resistance and mortality. We test a novel approach to antibiotic stewardship. Capitalising on the concept of “wisdom of crowds”, which states that a group’s collective judgement often outperforms the average individual, we test whether pooling treatment durations recommended by different prescribers can improve antibiotic prescribing. Using international survey data from 787 expert antibiotic prescribers, we run computer simulations to test the performance of the wisdom of crowds by comparing three data aggregation rules across different clinical cases and group sizes. We also identify patterns of prescribing bias in recommendations about antibiotic treatment durations to quantify current levels of overprescribing. Our results suggest that pooling the treatment recommendations (using the median) could improve guideline compliance in groups of three or more prescribers. Implications for antibiotic stewardship and the general improvement of medical decision making are discussed. Clinical applicability is likely to be greatest in the context of hospital ward rounds and larger, multidisciplinary team meetings, where complex patient cases are discussed and existing guidelines provide limited guidance.

Ivacaftor Is Associated with Reduced Lung Infection by Key Cystic Fibrosis Pathogens. A Cohort Study Using National Registry Data.

Rationale: Ivacaftor can greatly improve clinical outcomes in people with cystic fibrosis (CF) and has been shown to have in vitro antibacterial properties, yet the long-term microbiological outcomes of treatment are unknown.Objectives: To investigate changes in respiratory microbiology associated with long-term ivacaftor use.Methods: This was a retrospective cohort study using data from the UK CF Registry 2011-2016. Primary outcome was the annual prevalence ratios for key CF pathogens between ivacaftor users and their contemporaneous comparators. Multivariable log-binomial regression models were designed to adjust for confounders. Changes in Pseudomonas aeruginosa status were compared between groups using nonparametric maximum likelihood estimate for the purposes of Kaplan-Meier approximation.Results: Ivacaftor use was associated with early and sustained reduction in P. aeruginosa rates (2016 adjusted prevalence ratio, 0.68; 95% confidence interval, 0.58-0.79; P < 0.001) via a combination of increased clearance in those with infection (ivacaftor: 33/87 [37.9%] vs. nonivacaftor: 432/1,872 [22.8%]; P < 0.001) and reduced acquisition in those without infection (49/134 [36.6%] vs. 1,157/2,382 [48.6%]; P = 0.01). The improved prevalence of P. aeruginosa infection was independent of reduced sampling in the ivacaftor cohort. Ivacaftor was also associated with reduced prevalence of Staphylococcus aureus and Aspergillus spp. but not Burkholderia cepacia complex.Conclusions: In this study, long-term ivacaftor use was associated with reduced infection with important CF pathogens including P. aeruginosa. These findings have implications for antibiotic stewardship and the need for ongoing chronic antimicrobial therapy in this cohort.

2653. Epidemiology and Risk Factors for Healthcare-Associated Viral Infections in Children

BackgroundHealthcare-associated viral infections (HA-VI) are common in hospitalized children and are increasingly recognized as a cause of preventable harm. Yet, epidemiology and modifiable risk factors related to pediatric HA-VI are currently poorly understood.MethodsWe performed a prospective case–control study to identify the risk factors and outcomes associated with pediatric HA-VI at a quaternary care children’s hospital between November 2016 and August 2018. Prospective surveillance for HA-VI was performed hospital-wide by certified infection preventionists using NHSN definitions. Cases were matched 1:1 to controls by age, duration of hospitalization, and hospital unit. We abstracted data from the electronic medical record and conducted semi-structured interviews with patient caregivers to identify potential exposures beginning 4 days prior to HA-VI identification date. We also measured length of antibacterial therapy (LOT) in the 7 days following enrollment.ResultsDuring the study period, we identified 143 eligible patients with HA-VI and enrolled 64 matched case–control pairs. In total, 79 viruses were identified among 64 case patients, of which 53 (67.1%) were respiratory viruses and 26 (32.9%) were GI. Case patients were more frequently exposed to a sick visitor, specifically either caregiver or sibling, compared with controls (18.8% vs. 9.4%; P = 0.20, Fisher exact test). During the exposure period, case patients also had a significantly higher number of hospital procedures performed when compared with controls (n = 320 vs. 232; X2 = 58.43, P < 0.001). Case, when compared with control, patients had a greater average LOT (2.89 vs. 1.08).ConclusionResults of study show that exposure to a sick visitor is a potentially modifiable risk factor for pediatric HA-VI. In addition, hospitalized children with HA-VI have increased exposure to antibacterial antibiotics when compared with matched controls. Prevention of pediatric HA-VI may have implications for antibiotic stewardship. Our findings suggest that hospital policies may need to be revised, with emphasis on visitor screening and partnership with families, to reduce the incidence of pediatric HA-VI during hospitalization.Disclosures All authors: No reported disclosures.

Lack of Pharmacokinetic Basis of Weight-Based Dosing and Intra-Operative Re-Dosing with Cefazolin Surgical Prophylaxis in Obese Patients: Implications for Antibiotic Stewardship.

Traditionally, there have been uniform antibiotic dosing guidelines for prophylaxis for clean-clean-contaminated surgery in both non-obese and obese adults. All other factors predisposing to surgical site infections (SSIs) being equal, over time, the preferred drug is cefazolin. The usual dose, given immediately pre-procedure, has been 1 g intravenously (IV) in non-penicillin-allergic patients, which has been highly effective, Recently, it has become common practice to use high-dose cefazolin; i.e., 3 g IV, in obese patients. This article reviews the literature on high-dose cefazolin prophylactic regimens in the obese from a pharmacokinetic (PK) point of view. There are no comparative studies to support this approach, which is based largely on the theory "more must be better." Weight-based dosing of cefazolin in the obese is flawed, because it does not take into account PK factors, which are critical in the obese. Cefazolin is a water-soluble (hydrophilic) antibiotic that does not penetrate adipose tissue regardless of IV dose. Importantly, adipose tissue is not a valid target tissue in clean-clean-contaminated SSI prophylaxis, as it does not become infected. Higher doses result in proportionately higher serum/non-adipose tissue concentrations, but adipose tissue concentrations are unaffected. Cefazolin displays time-dependent killing kinetics so that as long as serum/tissue concentrations are above the minimum inhibitory concentration (MIC) of SSI pathogens, there is no enhanced killing with higher concentrations relative to concentration-dependent antibiotics. Taking into account PK principles, a cefazolin 1 g IV bolus results in peak serum concentrations of ∼185 mcg/mL, provides at least six hours of intra-operative protection, aside from any post-antibiotic effects, and eliminates any rationale for intra-operative re-dosing for procedures lasting six hours or less. Some have argued that a cefazolin 3 g IV dose in the obese does not matter, as more must necessarily be better. However, from an antibiotic stewardship program (ASP) perspective, unneeded antibiotics are unnecessary. Moreover, the costs of cefazolin 1 g (IV push) at $0.75 versus 2 g (IV piggyback) at $ 6.83 can be significant in large centers using cefazolin prophylaxis for cardiothoracic, orthopedic, obstetric/gynecology, and bariatric surgery. Excessive antibiotics also expose the patient to potential adverse effects; i.e., Clostridium difficile. There is no dose-dependent or duration of exposure effect on resistance with one or two pre-operative or intra-operative doses. Well-done PK-based studies in obese patients clearly demonstrate the lack of benefit of using a 3-g dose or intra-operative re-dosing and show no incremental increase in adipose tissue concentrations with high doses. From an ASP point of view, antibiotic dosing recommendations should be reviewed and revised on the basis of PK principles that indicate that weight-based dosing has no basis for pre-operative prophylaxis in obese patients.

Reflex urine culture testing in an ambulatory urology clinic: Implications for antibiotic stewardship in urology.

To evaluate the performance characteristics of urinalysis and urine microscopy parameters for predicting urine culture results and to implement a reflex urine culture program. We reviewed the charts of all patients presenting to our clinic January-March 2013 and June-August 2014, excluding those who were catheter-dependent or with urinary diversions. We assessed the association of urinalysis and urine microscopy parameters on urine culture outcomes defining a positive urinalysis as nitrite-positive and/or the presence of ≥5 white blood cells per high-powered field with bacteria and a positive urine culture as ≥10000 colony-forming units/mL excluding diphtheroids. We carried out logistic regression to assess for predictors of positive urine culture to inform implementation of a reflex urine culture program. A total of 2764 patients were evaluated. Logistic regression using urinalysis variables identified positive nitrites (odds ratio 18.6, P<0.001) and large leukocyte esterase (odds ratio 41.8, P<0.001) as the strongest predictors of positive urine culture. Logistic regression using urine microscopy variables identified >50 white blood cells per high-powered field (odds ratio 13.6, P<0.001) and moderate/many bacteria (odds ratio 16.8, P<0.001) as the strongest predictors of positive urine culture. We used our positive urinalysis definition to implement the reflex urine culture program and noted a 60% reduction in urine culture rates over the first 3months of implementation. A urine positive for nitrites and/or ≥50 white blood cells per high powered field with bacteria seems to have a strong association with a positive urine culture and the best negative predictive value. A reflex urine culture program is an effective strategy to decrease the rates of unnecessary urine culture and their associated costs.

Lessons Learned in Antibiotic Stewardship: Fluoroquinolone Use in Pediatrics.

The use of fluoroquinolones differs dramatically between adult and pediatric patients. For adults, they are the leading class of antibiotics prescribed in ambulatory care visits whereas in children, they are the least frequently prescribed class. The reasons for this difference in practice likely relate to perceptions of their potential for harm. This highlights the impact of physicians' perception of direct patient harm in antibiotic decision making which has implications for antibiotic stewardship.

A modified method for measuring antibiotic use in healthcare settings: implications for antibiotic stewardship and benchmarking

To determine whether adjusting the denominator of the common hospital antibiotic use measurement unit (defined daily doses/100 bed-days) by including age-adjusted comorbidity score (100 bed-days/age-adjusted comorbidity score) would result in more accurate and meaningful assessment of hospital antibiotic use. The association between the monthly sum of age-adjusted comorbidity and monthly antibiotic use was measured using time-series analysis (January 2008 to June 2012). For the purposes of conducting internal benchmarking, two antibiotic usage datasets were constructed, i.e. 2004-07 (first study period) and 2008-11 (second study period). Monthly antibiotic use was normalized per 100 bed-days and per 100 bed-days/age-adjusted comorbidity score. Results showed that antibiotic use had significant positive relationships with the sum of age-adjusted comorbidity score (P = 0.0004). The results also showed that there was a negative relationship between antibiotic use and (i) alcohol-based hand rub use (P = 0.0370) and (ii) clinical pharmacist activity (P = 0.0031). Normalizing antibiotic use per 100 bed-days contributed to a comparative usage rate of 1.31, i.e. the average antibiotic use during the second period was 31% higher than during the first period. However, normalizing antibiotic use per 100 bed-days per age-adjusted comorbidity score resulted in a comparative usage rate of 0.98, i.e. the average antibiotic use was 2% lower in the second study period. Importantly, the latter comparative usage rate is independent of differences in patient density and case mix characteristics between the two studied populations. The proposed modified antibiotic measure provides an innovative approach to compare variations in antibiotic prescribing while taking account of patient case mix effects.

Long-Term Care Acquired Urinary Tract Infections' Antibiotic Resistance Patterns and Empiric Therapy: A Pilot Study

Long-term care (LTC) acquired urinary tract infections (UTIs) are increasingly resistant to antibiotics, and the selection of appropriate empiric antibiotic therapy can be challenging for clinicians. The purpose of this study is to describe LTC-acquired UTI empiric antibiotic prescription patterns and UTI resistance patterns among older adults admitted to an acute psychiatric facility. This retrospective study found that ciprofloxacin was the agent most often used for empiric therapy (76% of cases). However, LTC-acquired UTIs in the sample were susceptible to ciprofloxacin in only 31% of cases. The study has implications for antibiotic stewardship with recommendations for empiric antibiotic selection for LTC-acquired UTIs given the prevalence of fluoroquinolone-resistant bacterial strains in the LTC setting.

Hospital and Societal Costs of Antimicrobial‐Resistant Infections in a Chicago Teaching Hospital: Implications for Antibiotic Stewardship

Organisms resistant to antimicrobials continue to emerge and spread. This study was performed to measure the medical and societal cost attributable to antimicrobial-resistant infection (ARI). A sample of high-risk hospitalized adult patients was selected. Measurements included ARI, total cost, duration of stay, comorbidities, acute pathophysiology, Acute Physiology and Chronic Health Evaluation III score, intensive care unit stay, surgery, health care-acquired infection, and mortality. Hospital services used and outcomes were abstracted from electronic and written medical records. Medical costs were measured from the hospital perspective. A sensitivity analysis including 3 study designs was conducted. Regression was used to adjust for potential confounding in the random sample and in the sample expanded with additional patients with ARI. Propensity scores were used to select matched control subjects for each patient with ARI for a comparison of mean cost for patients with and without ARI. In a sample of 1391 patients, 188 (13.5%) had ARI. The medical costs attributable to ARI ranged from $18,588 to $29,069 per patient in the sensitivity analysis. Excess duration of hospital stay was 6.4-12.7 days, and attributable mortality was 6.5%. The societal costs were $10.7-$15.0 million. Using the lowest estimates from the sensitivity analysis resulted in a total cost of $13.35 million in 2008 dollars in this patient cohort. The attributable medical and societal costs of ARI are considerable. Data from this analysis could form the basis for a more comprehensive evaluation of the cost of resistance and the potential economic benefits of prevention programs.