Oral ß-Lactams, Fluoroquinolones, or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Uncomplicated Escherichia coli or Klebsiella Species Bacteremia From a Urinary Tract Source.

Background: Fluoroquinolones (FQs) are effective for oral step-down therapy for gram-negative bloodstream infections but are associated with unfavorable toxic effects. Robust data are lacking for trimethoprim-sulfamethoxazole (TMP-SMX) and high-bioavailability ß-lactams (HBBLs). Methods: In this multicenter observational cohort study, we simulated a 3-arm registry trial using causal inference methods to compare the effectiveness of FQs, TMP-SMX, or HBBLs for gram-negative bloodstream infections oral step-down therapy. The study included adults treated between January 2016 and December 2022 for uncomplicated Escherichia coli or Klebsiella species bacteremia of urinary tract origin who were who were transitioned to an oral regimen after ≤4 days of effective intravenous antibiotics. Propensity weighting was used to balance characteristics between groups. 60-day recurrence was compared using a multinomial Cox proportional hazards model with probability of treatment weighting. Results: Of 2571 patients screened, 648 (25%) were included. Their median age (interquartile range) was 67 (45-78) years, and only 103 (16%) were male. Characteristics were well balanced between groups. Compared with FQs, TMP-SMX had similar effectiveness (adjusted hazard ratio, 0.91 [95% confidence interval, .30-2.78]), and HBBLs had a higher risk of recurrence (2.19 [.95-5.01]), although this difference was not statistically significant. Most HBBLs (70%) were not optimally dosed for bacteremia. A total antibiotic duration ≤8 days was associated with a higher recurrence rate in select patients with risk factors for failure. Conclusions: FQs and TMP-SMX had similar effectiveness in this real-world data set. HBBLs were associated with higher recurrence rates but suboptimal dosing may have contributed. Further studies are needed to define optimal BL dosing and duration to mitigate treatment failures.

Excellence in Antibiotic Stewardship: A mixed methods study comparing High, Medium, and Low Performing Hospitals.

BACKGROUND: Despite antibiotic stewardship programs existing in most acute care hospitals, there continues to be variation in appropriate antibiotic use. While existing research examines individual prescriber behavior, contextual reasons for variation are poorly understood. METHODS: We conducted an explanatory, sequential mixed methods study of a purposeful sample of 7 hospitals with varying discharge antibiotic overuse. For each hospital, we conducted surveys, document analysis, and semi-structured interviews with antibiotic stewardship and clinical stakeholders. Data were analyzed separately and mixed during the interpretation phase, where each hospital was examined as a case, with findings organized across cases using a strengths, weaknesses, opportunities, and threats framework to identify factors accounting for differences in antibiotic overuse across hospitals. RESULTS: Surveys included 85 respondents. Interviews included 90 respondents (31 hospitalists, 33 clinical pharmacists, 14 stewardship leaders, 12 hospital leaders). On surveys, clinical pharmacists at hospitals with lower antibiotic overuse were more likely to report feeling: respected by hospitalist colleagues (p=0.001), considered valuable team members (p=0.001), comfortable recommending antibiotic changes (p=0.02). Based on mixed-methods analysis, hospitals with low antibiotic overuse had four distinguishing characteristics: a) robust knowledge of and access to antibiotic stewardship guidance, b) high quality clinical pharmacist-physician relationships, c) tools and infrastructure to support stewardship, and d) highly engaged Infectious Diseases physicians who advocated stewardship principles. CONCLUSION: This mixed-method study demonstrates the importance of organizational context for high performance in stewardship and suggests improving antimicrobial stewardship requires attention to knowledge, interactions, and relationships between clinical teams and infrastructure that supports stewardship and team interactions.

Antibiotic prescribing for adults with group A streptococcal bacteremia in a large healthcare system.

Purpose: Limited data exist regarding treatment of invasive group A streptococcal (GAS) infections, including safety and efficacy of oral (PO) step-down therapy. We sought to describe current prescribing practices and clinical outcomes for patients with GAS bacteremia across a large health system, including a prespecified subset of patients who stepped down to PO antibiotics. Methods: This retrospective cohort study included adult patients with a positive blood culture for GAS between July 2018 and July 2021. Primary outcomes included frequency of PO step-down, total duration of therapy, duration of intravenous (IV) therapy prior to PO switch, and antimicrobial selection. Secondary outcomes included length of stay (LOS), mortality, adverse events, and clinical failure leading to readmission within 90 days. Results: In total, 280 patients met inclusion criteria. Of these, 46.7% were stepped down to PO antibiotics. Median total duration of therapy was 15 days. Median duration of IV therapy prior to PO switch was 5 days. The predominant definitive antibiotic choice was a beta-lactam. Median LOS was 5 days. Ninety-day mortality was 16.7%. One patient developed an occluded line and one developed Clostridioides difficile-associated diarrhea within 90 days. Ninety-day readmission due to clinical failure was 12.5%. Among cases of uncomplicated skin and soft tissue source, mortality (6.1% vs 2.4%) and readmission (15.2% vs 16.9%) were similar between definitive IV and PO groups. Conclusions: Group A streptococcal bacteremia is a severe infection with a high readmission and mortality rate. Use of PO step-down therapy was common with similar readmission and mortality rates compared with definitive IV therapy.

Beyond antibiotic prescribing rates: first-line antibiotic selection, prescription duration, and associated factors for respiratory encounters in urgent care.

Objective: Assess urgent care (UC) clinician prescribing practices and factors associated with first-line antibiotic selection and recommended duration of therapy for sinusitis, acute otitis media (AOM), and pharyngitis. Design: Retrospective cohort study. Participants: All respiratory UC encounters and clinicians in the Intermountain Health (IH) network, July 1st, 2019-June 30th, 2020. Methods: Descriptive statistics were used to characterize first-line antibiotic selection rates and the duration of antibiotic prescriptions during pharyngitis, sinusitis, and AOM UC encounters. Patient and clinician characteristics were evaluated. System-specific guidelines recommended 5-10 days of penicillin, amoxicillin, or amoxicillin-clavulanate as first-line. Alternative therapies were recommended for penicillin allergy. Generalized estimating equation modeling was used to assess predictors of first-line antibiotic selection, prescription duration, and first-line antibiotic prescriptions for an appropriate duration. Results: Among encounters in which an antibiotic was prescribed, the rate of first-line antibiotic selection was 75%, the recommended duration was 70%, and the rate of first-line antibiotic selection for the recommended duration was 53%. AOM was associated with the highest rate of first-line prescriptions (83%); sinusitis the lowest (69%). Pharyngitis was associated with the highest rate of prescriptions for the recommended duration (91%); AOM the lowest (51%). Penicillin allergy was the strongest predictor of non-first-line selection (OR = 0.02, 95% CI [0.02, 0.02]) and was also associated with extended duration prescriptions (OR = 0.87 [0.80, 0.95]). Conclusions: First-line antibiotic selection and duration for respiratory UC encounters varied by diagnosis and patient characteristics. These areas can serve as a focus for ongoing stewardship efforts.

Impact of a Multifaceted Intervention on Antibiotic Prescribing for Cystitis and Asymptomatic Bacteriuria in 23 Community Hospital Emergency Departments.

Background: Urinary tract infections (UTIs) are over-diagnosed and over-treated in the emergency department (ED) leading to unnecessary antibiotic exposure and avoidable side effects. However, data describing effective large-scale antimicrobial stewardship program (ASP) interventions to improve UTI and asymptomatic bacteriuria (ASB) management in the ED are lacking. Methods: We implemented a multifaceted intervention across 23 community hospital EDs in Utah and Idaho consisting of in-person education for ED prescribers, updated electronic order sets, and implementation/dissemination of UTI guidelines for our healthcare system. We compared ED UTI antibiotic prescribing in 2021 (post-intervention) to baseline data from 2017 (pre-intervention). The primary outcomes were the percent of cystitis patients prescribed fluoroquinolones or prolonged antibiotic durations (>7 days). Secondary outcomes included the percent of patients treated for UTI who met ASB criteria, and 14-day UTI-related readmissions. Results: There was a significant decrease in prolonged treatment duration for cystitis (29% vs 12%, P < .01) and treatment of cystitis with a fluoroquinolone (32% vs 7%, P < .01). The percent of patients treated for UTI who met ASB criteria did not change following the intervention (28% pre-intervention versus 29% post-intervention, P = .97). A subgroup analysis indicated that ASB prescriptions were highly variable by facility (range 11%-53%) and provider (range 0%-71%) and were driven by a few high prescribers. Conclusions: The intervention was associated with improved antibiotic selection and duration for cystitis, but future interventions to improve urine testing and provide individualized prescriber feedback are likely needed to improve ASB prescribing practice.

Implementation of an Antibiotic Stewardship Initiative in a Large Urgent Care Network.

Importance: Urgent Care (UC) encounters result in more inappropriate antibiotic prescriptions than other outpatient setting. Few stewardship interventions have focused on UC. Objective: To evaluate the effectiveness of an antibiotic stewardship initiative to reduce antibiotic prescribing for respiratory conditions in a UC network. Design, Setting, and Participants: This quality improvement study conducted in a UC network with 38 UC clinics and 1 telemedicine clinic included 493 724 total UC encounters. The study compared the antibiotic prescribing rates of all UC clinicians who encountered respiratory conditions for a 12-month baseline period (July 1, 2018, through June 30, 2019) with an intervention period (July 1, 2019, through June 30, 2020). A sustainability period (July 1, 2020, through June 30, 2021) was added post hoc. Interventions: Stewardship interventions included (1) education for clinicians and patients, (2) electronic health record (EHR) tools, (3) a transparent clinician benchmarking dashboard, and (4) media. Occurring independently but concurrent with the interventions, a stewardship measure was introduced by UC leadership into the quality measures, including a financial incentive. Main Outcomes and Measures: The primary outcome was the percentage of UC encounters with an antibiotic prescription for a respiratory condition. Secondary outcomes included antibiotic prescribing when antibiotics were not indicated (tier 3 encounters) and first-line antibiotics for acute otitis media, sinusitis, and pharyngitis. Interrupted time series with binomial generalized estimating equations were used to compare periods. Results: The baseline period included 207 047 UC encounters for respiratory conditions (56.8% female; mean [SD] age, 30.0 [21.4] years; 92.0% White race); the intervention period included 183 893 UC encounters (56.4% female; mean [SD] age, 30.7 [20.8] years; 91.2% White race). Antibiotic prescribing for respiratory conditions decreased from 47.8% (baseline) to 33.3% (intervention). During the initial intervention month, a 22% reduction in antibiotic prescribing occurred (odds ratio [OR], 0.78; 95% CI, 0.71-0.86). Antibiotic prescriptions decreased by 5% monthly during the intervention (OR, 0.95; 95% CI, 0.94-0.96). Antibiotic prescribing for tier 3 encounters decreased by 47% (OR, 0.53; 95% CI, 0.44-63), and first-line antibiotic prescriptions increased by 18% (OR, 1.18; 95% CI, 1.09-1.29) during the initial intervention month. Antibiotic prescriptions for tier 3 encounters decreased by an additional 4% each month (OR, 0.96; 95% CI, 0.94-0.98), whereas first-line antibiotic prescriptions did not change (OR, 1.00; 95% CI, 0.99-1.01). Antibiotic prescribing for respiratory conditions remained stable in the sustainability period. Conclusions and relevance: The findings of this quality improvement study indicated that a UC antibiotic stewardship initiative was associated with decreased antibiotic prescribing for respiratory conditions. This study provides a model for UC antibiotic stewardship.

Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis.

BACKGROUND: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients. METHODS: We searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 and 35 post enrollment; comparisons used proportional odds ratios. Harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator. The data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions. RESULTS: Eight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We did not find evidence of a difference in COVID-19 ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and found no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively). CONCLUSIONS: The findings of this individual participant data meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.

Harnessing the Power of Health Systems and Networks for Antimicrobial Stewardship.

Twenty of 21 health systems and network-based antimicrobial stewardship programs (ASPs) who were invited participated in a questionnaire, a webinar, and focus groups to understand implementation strategies for system-wide antimicrobial stewardship. Four centralized ASPs structures emerged. Of participating organizations, 3 (15%) confirmed classification as collaborative, 3 (15%) as centrally coordinated, 3 (15%) as in between or in transition between centrally coordinated and centrally led, 8 (40%) as centrally led, 2 (10%) as collaborative, consultative network. One (5%) organization considered themselves to be a hybrid. System-level stewardship responsibilities varied across sites and generally fell into 6 major categories: building and leading a stewardship community, strategic planning and goal setting, development of validated data streams, leveraging tools and technology for stewardship interventions, provision of subject-matter expertise, and communication/education. Centralized ASPs included in this study most commonly took a centrally led approach and engaged in activities tailored to system-wide goals.

Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis.

Background: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients. Methods: We searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 and 35 post enrollment; comparisons used proportional odds ratios. Harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator. The data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions. Results: Eight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We did not find evidence of a difference in COVID-19 ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and found no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively). Conclusions: The findings of this individual participant data meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.

Interventions to optimize antimicrobial stewardship.

Developing and improving an antimicrobial stewardship program successfully requires evaluation of numerous factors. As technology progresses and our understanding of antimicrobial resistance grows, careful consideration should be taken to ensure that a program meets the needs of the institution and is achievable given the available resources. In this review, we explore fundamental initiatives and strategies for both new and established antimicrobial stewardship programs, including the specific areas to target and key elements required for sustainable implementation.

Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with COVID-19 (HAHPS): Results of a Randomized, Active Comparator Trial.

RATIONALE: The COVID-19 pandemic struck an immunologically naïve, globally interconnected population. In the face of a new infectious agent causing acute respiratory failure for which there were no known effective therapies, rapid, often pragmatic trials were necessary to evaluate potential treatments, frequently starting with medications that are already marketed for other indications. Early in the pandemic, hydroxychloroquine and azithromycin were two such candidates. OBJECTIVE: Assess the relative efficacy of hydroxychloroquine and azithromycin among hospitalized patients with COVID-19. METHODS: We performed a randomized clinical trial of hydroxychloroquine vs. azithromycin among hospitalized patients with COVID-19. Treatment was 5 days of study medication. The primary endpoint was the COVID Ordinal Outcomes scale at day 14. Secondary endpoints included hospital-, ICU-, and ventilator-free days at day 28. The trial was stopped early after enrollment of 85 patients when a separate clinical trial concluded that a clinically important effect of hydroxychloroquine over placebo was definitively excluded. Comparisons were made a priori using a proportional odds model from a Bayesian perspective. RESULTS: We enrolled 85 patients at 13 hospitals over 11 weeks. Adherence to study medication was high. The estimated odds ratio for less favorable status on the ordinal scale for hydroxychloroquine vs. azithromycin from the primary analysis was 1.07, with a 95% credible interval from 0.63 to 1.83 with a posterior probability of 60% that hydroxychloroquine was worse than azithryomycin. Secondary outcomes displayed a similar, slight preference for azithromycin over hydroxychloroquine. QTc prolongation was rare and did not differ between groups. The twenty safety outcomes were similar between arms with the possible exception of post-randomization onset acute kidney injury, which was more common with hydroxychloroquine (15% vs. 0%). Patients in the hydroxychloroquine arm received remdesivir more often than in the azithromycin arm (19% vs. 2%). There was no apparent association between remdesivir use and acute kidney injury. CONCLUSIONS: While early termination limits the precision of our results, we found no suggestion of substantial efficacy for hydroxychloroquine over azithromycin. Acute kidney injury may be more common with hydroxychloroquine than azithromycin, although this may be due to the play of chance. Differential use of remdesivir may have biased our results in favor of hydroxychloroquine. Our results are consistent with conclusions from other trials that hydroxychloroquine cannot be recommended for inpatients with COVID-19; azithromycin may merit additional investigation. CLINICAL TRIAL REGISTRATION: This trial was prospectively registered (NCT04329832) before enrollment of the first patient.

Hydroxychloroquine versus Azithromycin for Hospitalized Patients with Suspected or Confirmed COVID-19 (HAHPS). Protocol for a Pragmatic, Open-Label, Active Comparator Trial.

Coronavirus disease (COVID-19) is a potentially fatal illness with no proven therapy beyond excellent supportive care. Treatments are urgently sought. Adaptations to traditional trial logistics and design to allow rapid implementation, evaluation of trials within a global trials context, flexible interim monitoring, and access outside traditional research hospitals (even in settings where formal placebos are unavailable) may be helpful. Thoughtful adaptations to traditional trial designs, especially within the global context of related studies, may also foster collaborative relationships among government, community, and the research enterprise. Here, we describe the protocol for a pragmatic, active comparator trial in as many as 300 patients comparing two current "off-label" treatments for COVID-19-hydroxychloroquine and azithromycin-in academic and nonacademic hospitals in Utah. We developed the trial in response to local pressures for widespread, indiscriminate off-label use of these medications. We used a hybrid Bayesian-frequentist design for interim monitoring to allow rapid, contextual assessment of the available evidence. We also developed an inference grid for interpreting the range of possible results from this trial within the context of parallel trials and prepared for a network meta-analysis of the resulting data. This trial was prospectively registered (ClinicalTrials.gov Identifier: NCT04329832) before enrollment of the first patient.Clinical trial registered with www.clinicaltrials.gov (NCT04329832).

Antibiotic Prescribing Variability in a Large Urgent Care Network: A New Target for Outpatient Stewardship.

Improving antibiotic prescribing in outpatient settings is a public health priority. In the United States, urgent care (UC) encounters are increasing and have high rates of inappropriate antibiotic prescribing. Our objective was to characterize antibiotic prescribing practices during UC encounters, with a focus on respiratory tract conditions. This was a retrospective cohort study of UC encounters in the Intermountain Healthcare network. Among 1.16 million UC encounters, antibiotics were prescribed during 34% of UC encounters and respiratory conditions accounted for 61% of all antibiotics prescribed. Of respiratory encounters, 50% resulted in antibiotic prescriptions, yet the variability at the level of the provider ranged from 3% to 94%. Similar variability between providers was observed for respiratory conditions where antibiotics were not indicated and in first-line antibiotic selection for sinusitis, otitis media, and pharyngitis. These findings support the importance of developing antibiotic stewardship interventions specifically targeting UC settings.

Collaborative Antimicrobial Stewardship: Working with Hospital and Health System Administration.

Successful antimicrobial stewardship programs rely on engagement with hospital administrators. Antimicrobial stewards should understand the unique pressures and demands of hospital and health system administration and be familiar with key terminology and regulatory requirements. This article provides guidance on strategies for engaging hospital and health system administration to support antimicrobial stewardship, including recommendations for designing a successful antimicrobial stewardship program structure, pitching resource requests, setting meaningful and measurable goals, achieving and communicating results, and fostering ongoing relationships with hospital and health system administration.

Antimicrobial Stewardship in Community Hospitals.

Antibiotic stewardship programs are needed in all health care facilities, regardless of size and location. Community hospitals that have fewer resources may have different priorities and require different strategies when defining antibiotic stewardship program components and implementing interventions. By following the Centers for Disease Control and Prevention Core Elements and using the strategies suggested in this article, readers should be able to design, develop, participate in, or improve antibiotic stewardship programs within community hospitals.

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

Background: Studies on the implementation of antibiotic stewardship programs (ASPs) in small hospitals are limited. Accreditation organizations now require all hospitals to have ASPs. Methods: 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. Results: 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. Conclusions: Only the most intensive ASP intervention was associated with reduction in total and broad-spectrum antibiotic use when compared with baseline. Clinical Trials Registration: NCT03245879.

Broad- versus Narrow-Spectrum Oral Antibiotic Transition and Outcomes in Health Care-associated Pneumonia.

RATIONALE: Guidelines recommend a switch from intravenous to oral antibiotics once patients who are hospitalized with pneumonia achieve clinical stability. However, little evidence guides the selection of an oral antibiotic for patients with health care-associated pneumonia, especially where no microbiological diagnosis is made. OBJECTIVES: To compare outcomes between patients who were transitioned to broad- versus narrow-spectrum oral antibiotics after initially receiving broad-spectrum intravenous antibiotic coverage. METHODS: We performed a secondary analysis of an existing database of adults with community-onset pneumonia admitted to seven Utah hospitals. We identified 220 inpatients with microbiology-negative health care-associated pneumonia from 2010 to 2012. After excluding inpatient deaths and treatment failures, 173 patients remained in which broad-spectrum intravenous antibiotics were transitioned to an oral regimen. We classified oral regimens as broad-spectrum (fluoroquinolone) versus narrow-spectrum (usually a ß-lactam). We compared demographic and clinical characteristics between groups. Using a multivariable regression model, we adjusted outcomes by severity (electronically calculated CURB-65), comorbidity (Charlson Index), time to clinical stability, and length of intravenous therapy. MEASUREMENTS AND MAIN RESULTS: Age, severity, comorbidity, length of intravenous therapy, and clinical response were similar between the two groups. Observed 30-day readmission (11.9 vs. 21.4%; P = 0.26) and 30-day all-cause mortality (2.3 vs. 5.3%; P = 0.68) were also similar between the narrow and broad oral antibiotic groups. In multivariable analysis, we found no statistically significant differences for adjusted odds of 30-day readmission (adjusted odds ratio, 0.56; 95% confidence interval, 0.06-5.2; P = 0.61) or 30-day all-cause mortality (adjusted odds ratio, 0.55; 95% confidence interval, 0.19-1.6; P = 0.26) between narrow and broad oral antibiotic groups. CONCLUSIONS: On the basis of analysis of a limited number of patients observed retrospectively, our findings suggest that it may be safe to switch from broad-spectrum intravenous antibiotic coverage to a narrow-spectrum oral antibiotic once clinical stability is achieved for hospitalized patients with health care-associated pneumonia when no microbiological diagnosis is made. A larger retrospective study with propensity matching or regression-adjusted test of equivalence or ideally a prospective comparative effectiveness study will be necessary to confirm our observations.

Risk Factors for Non-Therapeutic Initial Steady-State Vancomycin Trough Concentrations in Children and Adolescents Receiving High Empiric Doses of Intravenous Vancomycin.

BACKGROUND: Achieving vancomycin troughs of 15-20 µg/mL remains challenging in children. Our objective was to identify risk factors associated with non-therapeutic initial vancomycin troughs in children. METHODS: We conducted a retrospective cohort study of children who received intravenous vancomycin with at least one initial steady-state trough obtained. Patients who achieved therapeutic troughs (15-20 µg/mL in the 20-mg/kg/dose sub-cohort and 10-15 µg/mL in the 15-mg/kg/dose sub-cohort) were compared with those with subtherapeutic troughs (<15 and <10 µg/mL, respectively) and supratherapeutic troughs (>20 and >15 µg/mL, respectively) separately to determine risk factors associated with non-therapeutic troughs. RESULTS: A total of 153 vancomycin courses in 140 patients met study eligibility criteria. Of 45 patients who received 20 mg/kg/dose of empiric vancomycin, 60, 16, and 24% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2 increase in initial creatinine clearance (CrCl) was associated with a 47% increase in the odds of an initial subtherapeutic trough (adjusted odds ratio [aOR] 1.47; 95% CI 0.98-2.22). Of 108 patients who received 15 mg/kg/dose of empiric vancomycin, 62, 19, and 19% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2 increase in initial CrCl was associated with an 18% increase in the odds of an initial subtherapeutic trough (aOR 1.18; 95% CI 1.02-1.37). CONCLUSION: Achieving vancomycin troughs of 15-20 µg/mL for severe Gram-positive infections continues to be challenging in children, even at higher empiric doses of 20 mg/kg/dose IV every 6-8 h. Children with higher initial CrCls are particularly susceptible to subtherapeutic initial steady-state vancomycin troughs.

Antibiotic Use in Small Community Hospitals.

BACKGROUND: Antibiotic use and misuse is driving drug resistance. Much of US healthcare takes place in small community hospitals (SCHs); 70% of all US hospitals have <200 beds. Antibiotic use in SCHs is poorly described. We evaluated antibiotic use using data from the National Healthcare and Safety Network antimicrobial use option from the Centers for Disease Control and Prevention. METHODS: We used Intermountain Healthcare's monthly antibiotic use reports for 19 hospitals from 2011 to 2013. Hospital care units were categorized as intensive care, medical/surgical, pediatric, or miscellaneous. Antibiotics were categorized based on spectrum of coverage. Antibiotic use rates, expressed as days of therapy per 1000 patient-days (DOT/1000PD), were calculated for each SCH and compared with rates in large community hospitals (LCHs). Negative-binomial regression was used to relate antibiotic use to predictor variables. RESULTS: Total antibiotic use rates varied widely across the 15 SCHs (median, 436 DOT/1000PD; range, 134-671 DOT/1000PD) and were similar to rates in 4 LCHs (509 DOT/1000PD; 406-597 DOT/1000PD). The proportion of patient-days spent in the respective unit types varied substantially within SCHs and had a large impact on facility-level rates. Broad-spectrum antibiotics accounted for 26% of use in SCHs (range, 8%-36%), similar to the proportion in LCHs (32%; range, 26%-37%). Case mix index, proportion of patient-days in specific unit types, and season were significant predictors of antibiotic use. CONCLUSIONS: There is substantial variation in patterns of antibiotic use among SCHs. Overall usage in SCHs is similar to usage in LCHs. Small hospitals need to become a focus of stewardship efforts.