Publications

OBJECTIVES To describe the burden of extended-spectrum β-lactamase (ESBL) Enterobacteriaceae in veterans with spinal cord injury or disorder (SCI/D), to identify risk factors for ESBL acquisition, and to assess impact on clinical outcomes DESIGN Retrospective case-case-control study PATIENTS AND SETTING Veterans with SCI/D and utilization at a Veterans' Affairs medical center from January 1, 2012, to December 31, 2013. METHODS Patients with a positive culture for ESBL Klebsiella pneumoniae, Escherichia coli, or Proteus mirabilis were matched with patients with non-ESBL organisms by organism, facility, and level of care and to uninfected controls by facility and level of care. Inpatients were also matched by time at risk. Univariate and multivariate matched models were assessed for differences in risk factors and outcomes. RESULTS A total of 492 cases (62.6% outpatients) were matched 1:1 with each comparison group. Recent prior use of fluoroquinolones and prior use of third- and fourth-generation cephalosporins were independently associated with ESBL compared to the non-ESBL group (adjusted odds ratio [aOR], 2.61; 95% confidence interval [CI], 1.77-3.84; P<.001 for fluoroquinolones and aOR, 3.86; 95% CI, 2.06-7.25; P<.001 for third- and fourth-generation cephalosporins) and the control group (aOR, 2.10; 95% CI, 1.29-3.43; P = .003 for fluoroquinolones; and aOR, 3.31; 95% CI, 1.56-7.06; P=.002 for third- and fourth-generation cephalosporins). Although there were no differences in mortality rate, the ESBL group had a longer post-culture length of stay (LOS) than the non-ESBL group (incidence rate ratio, 1.36; 95% CI, 1.13-1.63; P=.001). CONCLUSIONS All SCI/D patients with ESBL were more likely to have had recent exposure to fluoroquinolones or third- and fourth-generation cephalosporins, and hospitalized patients were more likely to have increased post-culture LOS. Programs targeted toward reduced antibiotic use in SCI/D patients may prevent subsequent ESBL acquisition. Infect Control Hosp Epidemiol 2016;37:768-776.

OBJECTIVE: To characterize the use of tumor necrosis factor-α inhibitors (TNFIs) in children with juvenile idiopathic arthritis (JIA) and young adults with rheumatoid arthritis (RA).

METHODS: Patients with incident JIA or RA were identified by using the Truven Health MarketScan Commercial Claims and Encounters database from 2009 to 2013. The incident diagnosis was defined as no prior claims with a JIA/RA code and no JIA/RA medications recorded during the previous 6 months. TNFI use patterns were examined, including switching among TNFIs, adherence, persistence, and time from diagnosis to TNFI use. Earlier TNFI treatment without prior use of traditional disease-modifying antirheumatic drugs (DMARDs) and use of specific TNFIs were analyzed by age group.

RESULTS: Of 6929 children and young adults with new diagnoses of JIA/RA, 18.6% were treated with TNFIs. In these TNFI users, 39.1% received earlier TNFI therapy without prior use of DMARDs. The use of TNFIs was higher in patients diagnosed between 2012 and 2013 than that in patients diagnosed between 2009 and 2011 (hazard ratio 1.13, 95% confidence interval 1.00-1.28). Etanercept was the most commonly used, especially by children aged < 12 (75.5%) and adolescents aged 12 to 17 (62.5%) years. Adherence measured as mean proportion of days covered ranged from 70.4% to 93.2% for individual TNFI agents. Only about 60% of patients continuously took TNFIs for 12 months. When switching occurred, switching from etanercept to adalimumab was the most common pattern.

CONCLUSION: Earlier TNFI therapy was observed in 39.1% of children and young adults taking TNFIs. In addition, the time to the first TNFI prescription became shorter over the study period. Future research should evaluate the long-term effectiveness and safety of this more aggressive TNFI therapy.

OBJECTIVES: Although antibiotic prescriptions are decreasing in the United States, broad-spectrum prescribing is increasing. It is unknown if decreases observed in national antibiotic prescribing differ by provider group. Understanding prescribing trends over time by provider group can be helpful for customizing antimicrobial stewardship efforts. Therefore, the purposes of this study were to describe outpatient antibiotic prescribing by provider group overall and adjusted for population and number of providers. In addition, trends in prescribing by class and seasonal variation are described by provider group over 6 years.

DESIGN: Cross-sectional observation of outpatient antibiotic prescriptions.

SETTING AND PARTICIPANTS: A population-level analysis of U.S. prescribing from 2005 to 2010 with the use of the IMS Health Xponent dataset.

MAIN OUTCOME MEASURES: Number and rates of prescriptions dispensed overall and by provider group.

RESULTS: The majority (81.0%) of antibiotics were prescribed by physicians, followed by dentists (10.4%), nurse practitioners (NPs; 4.5%), and physician assistants (PAs; 4.2%). The percentage of antibiotic prescriptions decreased for physicians, but increased significantly for NPs and PAs. Provider-based and population-based prescribing rates decreased for physicians and dentists and increased for NPs and PAs. Penicillins were prescribed most frequently by all provider groups, decreasing for physicians and dentists. Increased prescribing of broad-spectrum agents was observed for NPs and PAs. With the exception of dentists, antibiotic prescriptions were higher in winter than in summer, with the largest seasonal increase by NPs.

CONCLUSION: Over 6 years, antibiotic prescriptions overall and for broad-spectrum agents decreased for physicians and increased for NPs and PAs. Thus, increasing trends in the US of broad-spectrum antibiotic prescriptions can be attributed to midlevel providers. Interventions should be designed to reverse increasing prescribing trends, especially of broad-spectrum agents prescribed by NPs and PAs. Stewardship efforts should also be targeted towards dentists, since this group prescribes a higher proportion of antibiotics compared with midlevel providers.

STUDY DESIGN: Retrospective observational study of bacterial susceptibilities in Veterans with SCI/D as compared to a general patient population.

OBJECTIVES: The purpose of this project was to evaluate the prevalence and susceptibility of bacteria isolated from spinal cord injury and disorder (SCI/D) patients as compared with a general patient population and determine whether a SCI/D-specific antibiogram, a report of bacterial susceptibilities used to guide empiric antibiotic selection, would be a useful stewardship tool.

SETTING: Veterans Affairs Medical Center located in Cook county, IL, USA.

METHODS: Microbiology reports from 1 October 2012 to 30 September 2013 were compiled into a SCI/D-specific antibiogram and compared to a non-SCI/D antibiogram.

RESULTS: Persons with positive cultures and SCI/D were younger and had a higher Charlson Index as compared to non-SCI/D patients (P<0.0001 for both). Five thousand one hundred and thirty-one unique isolate cultures were evaluated (SCI/D=23.0%). Frequencies of pathogens isolated in SCI/D and non-SCI/D differed. Methicillin-resistant Staphylococcus aureus occurred more frequently in SCI/D (27.8% vs 55.4%; P<0.0001). Gram-negatives had generally lower susceptibilities in SCI/D and a higher frequency of organisms producing extended-spectrum Beta-lactamases (17.6% vs 5.0%; P<0.0001), carbapenem-resistant Enterobacteriaceae (2.4% vs 0.5%; P<0.0001), carbapenem resistance (7.6% vs 2.4%; P<0.0001) and isolates resistant to ⩾3 antibiotic classes (60.7% vs 28.0%; P=0.0001).

CONCLUSION: Different pathogens with poorer susceptibilities are isolated in SCI/D. Thus an SCI/D-specific antibiogram reflective of resistance patterns in these patients may increase the appropriateness of empiric antibiotic selection. The frequency of multi-drug resistant organisms in cultures obtained from patients with SCI/D is worrisome.

BACKGROUND: Early initiation of tumor necrosis factor-alpha inhibitor (TNFI) therapy for children and young adults with inflammatory bowel disease (IBD) is not well described.

METHODS: We conducted a retrospective cohort study of children and young adults (≤24 yr) newly diagnosed with IBD using health insurance claims from 2009 to 2013. The conventional "step-up" approach was defined as TNFI initiation >30 days after first IBD medication prescription, whereas the "top-down" approach was defined as new TNFI prescription within 30 days of first IBD medication prescription. Switching rates, time to initiation, discontinuation, and adherence to TNFIs were compared between the 2 strategies.

RESULTS: A total of 11,962 IBD patients were identified. Among 3300 TNFI users, 1298 (39.3%) were treated with the top-down approach, whereas 2002 (60.7%) were treated with the step-up approach. Top-down approach use increased from 31.4% to 49.8% during the 5-year period, and under this approach, most patients were treated with TNFIs alone. Time to TNFI initiation was shorter for patients diagnosed in more recent years. Patients treated with the top-down strategy had lower rates of corticosteroid use (32.5% versus 94.2%) compared with step-up treatment but presented a higher rate of TNFI discontinuation. The 2 strategies both exhibited high adherence (mean proportion of days covered: 83.7%-95.4%).

CONCLUSIONS: Early TNFI initiation increased over time for children and young adults with IBD and was related to lower rates of corticosteroid use compared with the conventional approach. However, the higher rate of TNFI discontinuation under the top-down approach requires further examination.

IMPORTANCE: Antibiotic therapy is the cornerstone of medical management for community-acquired pneumonia.

OBJECTIVE: To assess the associations between 3 key aspects of antibiotic therapy (optimal time to antibiotic initiation, initial antibiotic selection, and criteria for the transition from intravenous to oral therapy) and short-term mortality in adults hospitalized with community-acquired pneumonia.

EVIDENCE REVIEW: Bibliographic databases of MEDLINE, EMBASE, and the Cochrane Collaboration were searched for studies of adults hospitalized with radiographically confirmed community-acquired pneumonia published from January 1, 1995, until November 5, 2015.

FINDINGS: Twenty studies (17 observational and 3 randomized trials) met eligibility criteria. Among 8 observational studies identified, the 4 largest (study populations of 2878 to 1,170,022) found that antibiotic initiation within 4 to 8 hours of hospital arrival was associated with relative reductions of 5% to 43% in mortality; the 4 smallest studies (study populations of 451 to 2076) found no associations between the timing of antibiotic initiation and mortality. One cluster randomized trial (n = 1737) demonstrated noninferiority of β-lactam monotherapy (n = 506) vs β-lactam plus macrolide combination therapy (n = 566), with an absolute adjusted difference of 2.5% (90% CI, -0.6% to 5.2%) in 90-day mortality favoring β-lactam monotherapy. A second randomized trial (n = 580) failed to demonstrate noninferiority of β-lactam monotherapy vs β-lactam plus macrolide combination therapy, with an absolute difference of 7.6% (1-sided 90% CI upper limit, 13.0%) in attainment of clinical stability on hospital day 7 favoring β-lactam plus macrolide combination therapy. Six of 8 observational studies (study populations of 1188 to 24,780) found that β-lactam plus macrolide combination therapy was associated with relative reductions of 26% to 68% in short-term mortality and all 3 observational studies (study populations of 2068 to 24,780) reported that fluoroquinolone monotherapy was associated with relative reductions of 30% to 43% in mortality compared with β-lactam monotherapy. One randomized trial (n = 302) reported significantly reduced hospital length of stay (absolute difference, 1.9 days; 95% CI, 0.6 to 3.2 days), but no differences in treatment failure when objective clinical criteria were used to decide when to transition patients from intravenous to oral therapy.

CONCLUSIONS AND RELEVANCE: In adults hospitalized with community-acquired pneumonia, antibiotic therapy consisting of β-lactam plus macrolide combination therapy or fluoroquinolone monotherapy initiated within 4 to 8 hours of hospital arrival was associated with lower adjusted short-term mortality, supported predominantly by low-quality observational studies. One randomized trial supports the use of objective clinical criteria to guide the transition from intravenous to oral antibiotic therapy.

When possible, chronic noncancer pain (CNCP) in older adults should be managed by nonpharmacologic modalities in conjunction with nonopioid analgesics. If moderate-to-severe pain persists despite these approaches, however, nonparenteral opioids may be considered as adjunctive therapy. This article reviews the epidemiology of opioid use and their effectiveness for CNCP in older adults and summarizes important age-related changes in opioid pharmacokinetics and pharmacodynamics that increase the risks of adverse effects in the elderly. Finally, to assist clinicians with selecting appropriate therapy, the article concludes with an evidence-based approach to optimize opioid prescribing in older adults with CNCP.