Impact of a Systematic Pharmacist-Initiated Antibiotic Time-Out Intervention for Hospitalized Adults.

INTRODUCTION: Antibiotic time-outs (ATO) are a recommended antimicrobial stewardship action, but data assessing their impact are lacking. This study investigated the impact of a systematic, pharmacist initiated ATO intervention. METHODS: This pre-post study included inpatients on hospitalist and intensivist services receiving empiric antibiotics for ≥48 hours. The ATO was initiated by pharmacists after 48 hours of empiric therapy and the outcome was documented including antibiotic indication, plan, and duration. An electronic medical record (EMR) alert facilitated ATO completion and pharmacists and prescribers received education prior to implementation. The primary outcome was EMR documentation of an antibiotic plan by 72 hours. Secondary outcomes included antibiotic utilization and antibiotic therapy modifications by 2 hours. RESULTS: 399 patients were included, 199 pre- and 200 post-intervention. The most common indications were pneumonia (32%), intra-abdominal infection (20%) and urinary tract infection (19%), with no between-group differences. EMR documentation of an antibiotic plan significantly improved in the post-intervention group (19% vs. 79%, p<0.0001) as did modifications to antibiotic therapy. The median duration of in-hospital antibiotic therapy was similar between groups (4.0 vs. 4.0 days, p = 0.2499). Approximately 45% of patients in each group received discharge antibiotics and median duration of discharge antibiotic therapy prescribed was reduced (7 vs. 5 days in the pre- and post-intervention groups, respectively; p = 0.0140). DISCUSSION: Implementation of pharmacist initiated ATO was associated with improvements in supporting EMR documentation and antibiotic therapy modifications. These findings highlight an important role in which pharmacists can serve as part of a collaborative antibiotic stewardship team.

Comparison of Clinical Outcomes among Intensive Care Unit Patients Receiving One or Two Grams of Ceftriaxone Daily.

Intensive care unit (ICU) patients may experience ceftriaxone underexposure, but clinical outcomes data are lacking. The objective of this study was to determine the impact of ceftriaxone dosing on clinical outcomes among ICU patients without central nervous system (CNS) infection. A retrospective study of ICU patients receiving intravenous, empirical ceftriaxone for non-CNS infections was conducted. Patients ≥18 years of age who received ≤2 g of ceftriaxone daily for ≥72 h were included and categorized as receiving ceftriaxone 1 g or 2 g daily. The primary, composite outcome was treatment failure, defined as inpatient mortality and/or antibiotic escalation due to clinical worsening. Propensity score matching was performed based on the probability of receiving 2 g of ceftriaxone daily. Multivariable logistic regression determined the association between ceftriaxone dose and treatment failure in a propensity-matched cohort. A total of 212 patients were included in the propensity-matched cohort. The most common diagnoses (83.0%) were pneumonia and urinary tract infection. Treatment failure occurred in 17.0% and 5.7% of patients receiving 1 g and 2 g daily, respectively (P = 0.0156). Overall inpatient mortality was 8.5%. Ceftriaxone 2 g dosing was associated with a reduced likelihood of treatment failure (adjusted odds ratio [aOR] = 0.190; 95% confidence interval [CI] = 0.059 to 0.607). Other independent predictors of treatment failure included sequential organ failure assessment score (aOR = 1.440; 95% CI = 1.254 to 1.653) and creatinine clearance at 72 h from ceftriaxone initiation (aOR = 0.980; 95% CI = 0.971 to 0.999). Therefore, ceftriaxone at 2 g daily, when used as appropriate antimicrobial coverage, may be appropriate for ICU patients with lower mortality risk.

Jamestown Canyon virus encephalitis in a heart transplant patient.

Jamestown Canyon virus (JtCV) is an arbovirus and a member of the California serogroup. To our knowledge, all the cases of JtCV have been reported in immunocompetent patients since it was first detected in 1997. We report a case of JtCV encephalitis in a solid organ transplant patient. A 48-year-old woman from Wisconsin had multiple hospital admissions for symptoms of progressive confusion, visual hallucinations, and inability to perform self-care. Initial evaluation was significant for lymphocytes in cerebrospinal fluid (CSF), and multiple infectious and metabolic causes were excluded. Further investigation found JtCV IgM in serum, and CSF. The patient's clinical course was compatible with JtCV encephalitis, and she was treated with ribavirin in addition to reduction of her immunosuppressive medications. She showed gradual and significant improvement in her mental and functional status. JtCV can cause a variety of symptoms that range from a flu-like syndrome to encephalitis. There have been an increased number of reported cases in recent years which is attributed to increased physician awareness and the availability of laboratory testing. Optimal treatment is still not known.

Impact of an electronic best-practice advisory in combination with prescriber education on antibiotic prescribing for ambulatory adults with acute, uncomplicated bronchitis within a large integrated health system.

OBJECTIVE: To determine the impact of a passive, prescriber-directed, electronic best-practice advisory coupled with prescriber education on the rate of antibiotic prescribing for acute, uncomplicated bronchitis in ambulatory adults across a large health system. DESIGN: This study was a quasi-experiment examining antibiotic prescribing for ambulatory adults with acute bronchitis from January 1, 2016 through December 31, 2018. The intervention was implemented in December 2016 for emergency departments and urgent care clinics followed by ambulatory clinics in September 2017. SETTING: Outpatient settings across a health system, including 15 emergency departments, >30 urgent care clinics, and >150 ambulatory clinics. PARTICIPANTS: All adults with a primary diagnosis of acute bronchitis who were seen and discharged from a study site were included. INTERVENTIONS: A passive, prescriber-directed, best-practice advisory for treatment of acute bronchitis in the electronic health record and an optional, online education module regarding acute bronchitis. RESULTS: The study included 81,975 ambulatory adults with a primary diagnosis of acute bronchitis during the preintervention period (19.8% >65 years of age; 61.9% female) and 89,571 ambulatory adults during the postintervention period (16.5% >65 years of age; 61.1% female). Antibiotic prescribing rates decreased from 60.8% (49,877 of 81,975 patients) preintervention to 51.4% (46,018 of 89,571 patients) postintervention (absolute difference, 9.4%; P < .001). The largest reduction occurred in the emergency departments. CONCLUSIONS: An electronic best practice advisory combined with prescriber education was associated with a statistically significant reduction in antibiotic prescribing for adults with acute bronchitis. Future studies should incorporate patient education and address prescriber-reported barriers to appropriate antibiotic prescribing.

Examining the Relationship Between Vancomycin Area Under the Concentration Time Curve and Serum Trough Levels in Adults With Presumed or Documented Staphylococcal Infections.

BACKGROUND: Investigations of the relationship between vancomycin trough concentrations and area under the concentration time curve (AUC) are growing, but still limited. The authors sought to determine vancomycin exposure among hospitalized adults with presumed or confirmed invasive staphylococcal infections using 2-level pharmacokinetic monitoring to inform changes to an institutional vancomycin dosing protocol. METHODS: This was a retrospective observational study performed in 2 acute care hospitals. Adults prescribed vancomycin (therapeutic trough 15-20 mg/L) for a presumed or documented invasive staphylococcal infection were evaluated. Two steady-state serum vancomycin levels were used to determine each patient's 24-hour AUC to minimum inhibitory concentration ratio (AUC/MIC) using a non-Bayesian, equation-based approach. Patient demographics and crude clinical outcomes were also collected. RESULTS: Thirty-four patients were included in the study, with 2 patients having vancomycin levels drawn twice (36 sets of levels). Most patients were located in an intensive care unit (91.2%), and 85.3% of patients were prescribed vancomycin for bacteremia, pneumonia, or endocarditis. The mean ± SD vancomycin Cmin was 16.6 ± 6.1 mg/L, and the mean AUC/MIC was 588 ± 156 mg/L × hour. The rate of 24-hour vancomycin AUC/MIC target attainment was 91.2% (n = 31/34). Of the patients with a Cmin > 9 mg/L, 100% (n = 33) achieved AUC/MIC values >400 mg/L × hour and 93.9% were >500 mg/L × hour. There was a strong correlation between vancomycin Cmin and AUC24 hr (R = 0.731; P < 0.001). CONCLUSIONS: Targeting a vancomycin trough between 15 and 20 mg/L frequently resulted in an AUC/MIC greater than that thought to be necessary for efficacy optimization. Considering these findings alongside the practical challenges associated with wide-scale implementation of AUC monitoring, reducing the target trough as a means to prevent vancomycin overexposure warrants clinical consideration and further evaluation.

Risk assessment for infected endocarditis in Staphylococcus aureus bacteremia patients: When is transesophageal echocardiography needed?

AIMS: Echocardiography is the main technique for the diagnosis of endocarditis in patients with Staphylococcus aureus bacteremia (SAB), but a consensus about performing transthoracic echocardiography or transesophageal echocardiography (TEE) as first-line tests is currently lacking. Recently, a new scoring system has been proposed by Palraj et al. to guide the use of TEE in this population. Our aim was to validate this scoring system or modify it, if necessary. METHODS AND RESULTS: Data from SAB patients admitted from 2012 to 2014 were collected. We tested the Palraj scores to stratify patients' risk for endocarditis. Moreover, we analyzed our population to identify any other possible clinical predictors of endocarditis not included in the score. Endocarditis was diagnosed in 38 of 205 patients (18.5%). Palraj's score was effective in the detection of patients at high risk of endocarditis. In addition, we identified the presence of cardiac devices, prolonged bacteremia and intravenous drug abuse (IVDA) as elements strongly correlated with endocarditis. Two scoring systems (Day-1 and Day-5) were derived including IVDA as a variable. Using a Day-1 cut-off value ≥5 and a Day-5 cut-off value ≥2, the 'modified Palraj's score' showed sensitivities of 42.1% and 97.0% and specificities of 88.6% and 32.0% for Day-1 and Day-5 scores, respectively. CONCLUSION: We modify and expand upon an effective scoring system to identify SAB patients at high risk for endocarditis in order to guide use of TEE. The inclusion of IVDA in the criteria for the calculation of the scores improves its effectiveness.

Genetic diversity in Blastomyces dermatitidis: implications for PCR detection in clinical and environmental samples.

Blastomycosis is a serious and potentially fatal infection caused by the thermally dimorphic fungus Blastomyces dermatitidis. Polymerase chain reaction (PCR) assays targeting the BAD-1 virulence gene promoter have been developed to aid in the detection of the pathogen in clinical and environmental samples. However, little is known regarding the genetic diversity of B. dermatitidis and how this might affect the performance characteristics of these assays. We explored the genetic relatedness of 106 clinical and environmental isolates of B. dermatitidis using a previously described rDNA PCR restriction fragment length polymorphism (RFLP) assay. In addition, we looked for polymorphisms in the promoter region upstream of BAD-1. RFLP analysis showed that all isolates fell into one of five genotypic groups, designated A through E. Genotypic groups A and B predominated, comprising 50/106 (47.2%) and 51/106 (48.1%) of isolates, respectively. Three of 106 (2.8%) isolates were genotype C. Genotypes D and E represented novel genotypes and were each associated with single clinical isolates. PCR of the BAD-1 promoter revealed significant size differences among amplification products. Fifty-one of 106 isolates (50/50 RFLP genotypic group A and 1/51 genotypic group B) had amplicons of 663-bp, nearly twice the size of the expected product. Sequence analysis of amplification products from 17 representative isolates revealed four haplotypes and showed that the size disparity was due to two large insertions. Because these insertions were present in a high percentage of isolates, the utility of the PCR assays for diagnostic purposes could be affected. However, the novel RFLP genotypes and multiple BAD-1 haplotypes may prove useful as markers in population genetic studies.

Blastomycosis in urban southeastern Wisconsin.

PURPOSE: A previous study revealed a non-random distribution of blastomycosis cases by home site in urban Milwaukee County. This study was conducted to determine the proportion of cases with likely exposures solely in urban areas. METHODS: Records of 68 urban southeastern Wisconsin individuals, including 45 residents of Milwaukee, 19 from suburban Milwaukee County, and 4 from outside Milwaukee County, diagnosed with blastomycosis between January 2002 and July 2007 were studied using medical record reviews, case reports, and telephone interviews. Geographic Information Systems (GIS) proximity analysis was then used to compare the distance between case and control home sites to environmental risk factors. RESULTS: Of patients reporting their exposure history, 41 of 49 (84%) participated in outdoor work or leisure activities, and 12 of 47 (26%) engaged in fishing, hunting, camping, or hiking. Of the urban cases, 64 occurred among Milwaukee County residents; of those, 25 of 49 (51%) denied traveling, which suggests local urban exposure, and 8 of 11 (73%) specifically recalled urban waterway exposure prior to diagnosis. The 45 Milwaukee cases were concentrated on the north side of town and were closer to inland waterways than a random sample of 6528 controls (median 690 versus 1170 meters; P=0.003), but not closer to parks. CONCLUSION: Southeastern Wisconsin residents may acquire blastomycosis solely in their local urban area, sometimes without specific outdoor exposures. Proximity to inland waterways is associated with blastomycosis cases in urban areas, similar to rural areas of Wisconsin. Clinicians should include blastomycosis in appropriate differential diagnoses of symptomatic individuals, even in urban residents without travel history or history of significant outdoor exposures.

Acute pasteurella multocida in total knee arthroplasty.

Pasturella multocida is a rare cause of joint sepsis in total joint arthroplasty, and all case reports have identified a distant source of infection from an animal bite that has caused potential hematogenous seeding of the prosthesis. We report a case in which no potential distal wound source was found and the only likely etiology was local wound seeding from an old injury. In that injury, a saddle stirrup had caused a severe traumatic soft tissue injury as a horse had rolled over the patient. We draw attention to the fact that this particular bacteria is virulent in producing septic contamination of a total joint prosthesis, and aggressive treatment is indicated when such infection is identified.