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      Association of 30-Day Mortality With Oral Step-Down vs Continued Intravenous Therapy in Patients Hospitalized With Enterobacteriaceae Bacteremia

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          Abstract

          This cohort study compares the 30-day mortality among hospitalized patients with Enterobacteriaceae bacteremia treated with oral step-down therapy vs intravenous therapy. Is conversion to oral therapy associated with effective treatment of Enterobacteriaceae bloodstream infections? In this multicenter cohort study of 1478 unique patients with Enterobacteriaceae bacteremia, no difference in 30-day mortality or recurrent bacteremia was observed between patients converted to early, oral step-down therapy and propensity score–matched patients who continued to receive intravenous antibiotics for the duration of therapy. Oral step-down therapy appears to be a potential treatment approach for adults with Enterobacteriaceae bacteremia after the source is controlled and clinical improvement is observed. Conversion to oral therapy for Enterobacteriaceae bacteremia has the potential to improve the quality of life of patients by improving mobility, eliminating catheter-associated discomfort, decreasing the risk for noninfectious and infectious catheter-associated adverse events, and decreasing health care costs. To compare the association of 30-day mortality with early oral step-down therapy vs continued parenteral therapy for the treatment of Enterobacteriaceae bloodstream infections. This retrospective multicenter cohort study included a 1:1 propensity score–matched cohort of 4967 unique patients hospitalized with monomicrobial Enterobacteriaceae bloodstream infection at 3 academic medical centers from January 1, 2008, through December 31, 2014. Eligibility criteria included appropriate source control measures, appropriate clinical response by day 5, active antibiotic therapy from day 1 until discontinuation of therapy, availability of an active oral antibiotic option, and ability to consume other oral medications or feeding. Statistical analysis was performed from March 2, 2018, to June 2, 2018. Oral step-down therapy within the first 5 days of treatment of Enterobacteriaceae bacteremia. The main outcome was 30-day all-cause mortality. Of the 2161 eligible patients, 1185 (54.8%) were male and 1075 (49.7%) were white; the median (interquartile range [IQR]) age was 59 (48-68) years. One-to-one propensity-score matching yielded 1478 patients, with 739 in each study arm. Sources of bacteremia included urine (594 patients [40.2%]), gastrointestinal tract (297 [20.1%]), central line-associated (272 [18.4%]), pulmonary (58 [3.9%]), and skin and soft tissue (41 [2.8%]). There were 97 (13.1%) deaths in the oral step-down group and 99 (13.4%) in the intravenous (IV) group within 30 days (hazard ratio [HR], 1.03; 95% CI, 0.82-1.30). There were no differences in recurrence of bacteremia within 30 days between the groups (IV, 6 [0.8%]; oral, 4 [0.5%]; HR, 0.82 [0.33-2.01]). Patients transitioned to oral step-down therapy were discharged from the hospital an average of 2 days (IQR, 1-6) sooner than patients who continued to receive IV therapy (5 days [IQR, 3-8 days] vs 7 days [IQR, 4-14 days]; P  < .001). In this study, 30-day mortality was not different among hospitalized patients who received oral step-down vs continued parenteral therapy for the treatment of Enterobacteriaceae bloodstream infections. The findings suggest that transitioning to oral step-down therapy may be an effective treatment approach for patients with Enterobacteriaceae bacteremia who have received source control and demonstrated an appropriate clinical response. Early transition to oral step-down therapy may be associated with a decrease in the duration of hospital stay for patients with Enterobacteriaceae bloodstream infections.

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          Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update

          Purpose To provide an updated joint ASCO/Infectious Diseases Society of American (IDSA) guideline on outpatient management of fever and neutropenia in patients with cancer. Methods ASCO and IDSA convened an Update Expert Panel and conducted a systematic review of relevant studies. The guideline recommendations were based on the review of evidence by the Expert Panel. Results Six new or updated meta-analyses and six new primary studies were added to the updated systematic review. Recommendation Clinical judgment is recommended when determining which patients are candidates for outpatient management, using clinical criteria or a validated tool such as the Multinational Association of Support Care in Cancer risk index. In addition, psychosocial and logistic considerations are outlined within the guideline. The panel continued to endorse consensus recommendations from the previous version of this guideline that patients with febrile neutropenia receive initial doses of empirical antibacterial therapy within 1 hour of triage and be monitored for ≥ 4 hours before discharge. An oral fluoroquinolone plus amoxicillin/clavulanate (or clindamycin, if penicillin allergic) is recommended as empirical outpatient therapy, unless fluoroquinolone prophylaxis was used before fever developed. Patients who do not defervesce after 2 to 3 days of an initial, empirical, broad-spectrum antibiotic regimen should be re-evaluated and considered as candidates for inpatient treatment. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .
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            Comparing the Outcomes of Adults With Enterobacteriaceae Bacteremia Receiving Short-Course Versus Prolonged-Course Antibiotic Therapy in a Multicenter, Propensity Score–Matched Cohort

            Among adults receiving short-course (6–10 days) vs prolonged-course (11–16 days) antibiotic therapy for Enterobacteriaceae bacteremia, no difference in 30-day mortality or recurrent bacteremia was observed. Short-course antibiotic therapy may be protective against the emergence of multidrug-resistant bacteria. Background The recommended duration of antibiotic treatment for Enterobacteriaceae bloodstream infections is 7–14 days. We compared the outcomes of patients receiving short-course (6–10 days) vs prolonged-course (11–16 days) antibiotic therapy for Enterobacteriaceae bacteremia. Methods A retrospective cohort study was conducted at 3 medical centers and included patients with monomicrobial Enterobacteriaceae bacteremia treated with in vitro active therapy in the range of 6–16 days between 2008 and 2014. 1:1 nearest neighbor propensity score matching without replacement was performed prior to regression analysis to estimate the risk of all-cause mortality within 30 days after the end of antibiotic treatment comparing patients in the 2 treatment groups. Secondary outcomes included recurrent bloodstream infections, Clostridium difficile infections (CDI), and the emergence of multidrug-resistant gram-negative (MDRGN) bacteria, all within 30 days after the end of antibiotic therapy. Results There were 385 well-balanced matched pairs. The median duration of therapy in the short-course group and prolonged-course group was 8 days (interquartile range [IQR], 7–9 days) and 15 days (IQR, 13–15 days), respectively. No difference in mortality between the treatment groups was observed (adjusted hazard ratio [aHR], 1.00; 95% confidence interval [CI], .62–1.63). The odds of recurrent bloodstream infections and CDI were also similar. There was a trend toward a protective effect of short-course antibiotic therapy on the emergence of MDRGN bacteria (odds ratio, 0.59; 95% CI, .32–1.09; P = .09). Conclusions Short courses of antibiotic therapy yield similar clinical outcomes as prolonged courses of antibiotic therapy for Enterobacteriaceae bacteremia, and may protect against subsequent MDRGN bacteria.
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              Medication administration through enteral feeding tubes.

              An overview of enteral feeding tubes, drug administration techniques, considerations for dosage form selection, common drug interactions with enteral formulas, and methods to minimize tube occlusion is given. Enteral nutrition through a feeding tube is the preferred method of nutrition support in patients who have a functioning gastrointestinal tract but who are unable to be fed orally. This method of delivering nutrition is also commonly used for administering medications when patients cannot swallow safely. However, several issues must be considered with concurrent administration of oral medications and enteral formulas. Incorrect administration methods may result in clogged feeding tubes, decreased drug efficacy, increased adverse effects, or drug-formula incompatibilities. Various enteral feeding tubes are available and are typically classified by site of insertion and location of the distal tip of the feeding tube. Liquid medications, particularly elixirs and suspensions, are preferred for enteral administration; however, these formulations may be hypertonic or contain large amounts of sorbitol, and these properties increase the potential for adverse effects. Before solid dosage forms are administered through the feeding tube, it should be determined if the medications are suitable for manipulation, such as crushing a tablet or opening a capsule. Medications should not be added directly to the enteral formula, and feeding tubes should be properly flushed with water before and after each medication is administered. To minimize drug-nutrient interactions, special considerations should be taken when administering phenytoin, carbamazepine, warfarin, fluoroquinolones, and proton pump inhibitors via feeding tubes. Precautions should be implemented to prevent tube occlusions, and immediate intervention is required when blockages occur. Successful drug delivery through enteral feeding tubes requires consideration of the tube size and placement as well as careful selection and appropriate administration of drug dosage forms.
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                Author and article information

                Journal
                JAMA Internal Medicine
                JAMA Intern Med
                American Medical Association (AMA)
                2168-6106
                January 22 2019
                Affiliations
                [1 ]Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore
                [2 ]Medical Student, Department of Medicine, University of Maryland School of Medicine, Baltimore
                [3 ]Department of Medicine, Johns Hopkins University School of Medicine, Baltimore
                [4 ]Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore
                [5 ]Department of Medicine, Perelman School of Medicine, University of Pennsylvania
                [6 ]Department of Pharmacy, The Johns Hopkins Hospital, Baltimore
                [7 ]Medical Student, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore
                Article
                10.1001/jamainternmed.2018.6226
                927b97ae-a96d-4726-8b4d-4384136bcb12
                © 2019
                History

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