Days Of Inpatient Therapy Research Articles

Hospitalized cancer patients with comorbidities and low lymphocyte counts had poor clinical outcomes to immune checkpoint inhibitors.

BackgroundImmune checkpoint inhibitor (ICI) therapy has improved survivals with a favorable toxicity profile in a variety of cancer patients. We hypothesized that hospitalized cancer patients who have acute or chronic comorbidities may have suppressed immune systems and poor clinical outcomes to ICIs. The objective of this study was to explore clinical outcomes and predictive factors of hospitalized cancer patients who received ICI therapy at an NCI-designated Comprehensive Cancer Center.MethodsA retrospective review of electronic medical records was conducted for adult cancer patients who received an FDA-approved ICI during admission from 08/2016 to 01/2022. For each patient we extracted demographics, cancer histology, comorbidities, reasons for hospitalization, ICI administered, time from treatment to discharge, time from treatment to progression or death, and complete blood counts. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using the log-rank test. The 95% confidence interval for survival was calculated using the exact binomial distribution. Statistical significance was defined as 2-sided p<0.05.ResultsOf 37 patients identified, 2 were excluded due to lack of complete blood counts on admission. Average hospital stay was 24.2 (95% CI 16.5, 31.9) days. Ten (27.0%) patients died during the same hospitalization as treatment. Of those who followed up, 22 (59.5%) died within 90 days of inpatient therapy. The median PFS was 0.86 (95% CI 0.43, 1.74) months and median OS was 1.55 (95% CI 0.76, 3.72) months. Patients with ≥3 comorbidities had poorer PFS (2.4 vs. 0.4 months; p=0.0029) and OS (5.5 vs. 0.6 months; p=0.0006). Pre-treatment absolute lymphocyte counts (ALC) <600 cells/µL were associated with poor PFS (0.33 vs. 1.35 months; p=0.0053) and poor OS (0.33 vs. 2.34 months; p=0.0236). Pre-treatment derived neutrophil to lymphocyte ratio (dNLR) <4 was associated with good median PFS (1.6 vs. 0.4 months; p=0.0157) and OS (2.8 vs. 0.9 months; p=0.0375).ConclusionsAdministration of ICI therapy was associated with poor clinical outcomes and high rates of both inpatient mortality and 90-day mortality after inpatient ICI therapy. The presence of ≥3 comorbidities, ALC <600/μL, or dNLR >4 in hospitalized patients was associated with poor survival outcomes.

Low lymphocyte counts and association with clinical outcomes in hospitalized patients with cancer receiving immune checkpoint inhibitor therapy.

e14600 Background: Immune checkpoint inhibitors (ICIs) improve survivals in a variety of cancer patients by harnessing the immune system. Pre-treatment lymphopenia as measured by absolute lymphocyte counts (ALC) was associated with decreased progression-free survival (PFS) and overall survival (OS) in patients receiving ICIs. During hospitalization ICI treatment is often deferred and efficacy in this population is unclear. Our study explores outcomes and predictive factors for hospitalized patients who received ICI therapy. Methods: Cancer patients who received inpatient ICI were identified in the institutional pharmacy database from 08/2016 to 07/2021. Data were abstracted from electronic medical records. Data were summarized according to frequency and percentage for qualitative variables, and by mean ± standard deviation, median, and range for quantitative variables. The 95% confidence interval for survival was calculated using the exact binomial distribution. PFS and OS were estimated using the Kaplan–Meier method and compared using the log-rank test between groups. Receiver-operating characteristic (ROC) analysis was used to evaluate the discrimination ability of ALC for prognosis. Statistical significance was defined as 2-sided P &lt; 0.05. Results: Of 37 identified patients, 2 were excluded from the ALC analysis due to lack of blood counts. The most common cancer type treated was lung cancer (13, 35.1%). The majority of subjects were men (29, 78.4%) and the median age was 57 (21-79) years. Average hospital stay was 24.2 (95% CI 16.5, 31.9) days, and the most common reasons for admission were initiation of therapy (14, 37.8%) and infection (5, 13.5%). Reasons for inpatient treatment included convenience (6, 16.2%), disposition delays (6, 16.2%), initiation of therapy (13, 35.1%), and emergent or last resort measures (10, 27.0%). Most patients died during the study period, and 5 were alive at the time of data analysis. 10 patients died during the same hospitalization as treatment. Of those who followed up, 22 died within 90 days of inpatient therapy. The median PFS was 0.86 (95% CI 0.43, 1.74) months and median OS was 1.55 (95% CI 0.76, 3.72) months. Pre-treatment ALC &lt; 600 cells/µL were associated with poor PFS (0.33 vs. 1.35 months; HR 6.9, 95% CI 10.8-25.9, P = 0.0053) and poor OS (0.33 vs. 2.34 months; HR 4.66, 95% CI 1.2-17.5, P = 0.0236), respectively. Furthermore, patients with ALC &lt; 600 were less likely to receive a subsequent ICI dose than their counterparts. Conclusions: Administration of inpatient ICI therapy is associated with poor clinical outcomes and high rates of both inpatient mortality and death within 3 months of discharge. The presence of ALC &lt; 600/µL in hospitalized patients was associated with poor clinical outcomes.

56. High Frequencies of Adverse Drug Events with Intravenous vs Oral High-Dose Trimethoprim-Sulfamethoxazole: An Opportunity for Antibiotic Stewardship

BackgroundTrimethoprim-sulfamethoxazole (TMP-SMX) is a high-bioavailability antibiotic associated with potentially serious adverse drug events (ADE). The objective of this study was to evaluate the safety of intravenous (IV) and oral (PO) high-dose TMP-SMX.MethodsIRB-approved retrospective cohort of hospitalized patients from January 2016 to November 2020. Inclusion: ≥ 18 years old and > 72 hours of renally adjusted high-dose TMP-SMX defined as ≥ 5 mg/kg/day of TMP. Exclusion: prophylaxis. Endpoints during treatment: hyponatremia with sodium < 135 mmol/L, hyperkalemia with potassium > 5 mmol/L, serum creatinine increase of ≥ 0.3 mg/dL or 1.5-1.9 times from baseline, and fluid overload on physical exam. Descriptive and bivariate statistics were performed.ResultsEach group included 50 patients (Table 1). Intensive care unit patients comprised 82% IV TMP-SMX compared to 32% PO. Most common infection: respiratory tract 86% IV and 68.1% PO. Most common organisms were Stenotrophomonas maltophilia (52% IV and 18% PO) and Pneumocystis jiroveci (16.3% IV and 62% PO). Median (IQR) days of inpatient therapy: 6 (5-7.5) PO vs. 7.5 (6-11.3) IV. Median (IQR) days of total duration: 9 (6-21.5) PO vs. 12 (7.8-14) IV (p=0.93). IV group: 88% of patients received >1 liter of D5W daily. Median (IQR) liters of D5W daily was 1 (1-1.5). 56% had a diuretic added, and 38% had a diuretic dose increase. Majority of patients (78%) on IV were taking other oral medications. 100% patients experienced any adverse event with IV vs. 70% with PO (unAdjOR 2.43; 95% CI 1.89-3.13). Most common ADE in both groups: hyponatremia, hyperkalemia, and elevated creatinine. Hyponatremia: 92% with IV and 32% with PO (unAdjOR 24.44; 95% CI 7.50-79.68). Edema on physical exam, an ADE specific to IV TMP-SMX, was the third most common side effect in the IV group. Relative changes from baseline in sodium, potassium, and creatinine from those who experienced hyponatremia, hyperkalemia and elevated creatinine were listed in Table 2.Table 1. Baseline and Clinical Characteristics Table 2. Adverse Effects ConclusionPatients on IV TMP-SMX therapy were more likely to experience an ADE compared to PO, likely driven by the high volume of free water. Most patients on IV TMP-SMX were on other PO medications, suggesting a missed stewardship opportunity for IV to PO conversion to reduce patient harm.Disclosures Susan L. Davis, PharmD, Nothing to disclose Michael P. Veve, Pharm.D., Cumberland (Grant/Research Support)Paratek Pharmaceuticals (Research Grant or Support) Rachel Kenney, PharmD, Medtronic, Inc. (Other Financial or Material Support, spouse is an employee and shareholder)

105. Fluoroquinolone Stewardship at a Community Health-System: A Decade in Review

BackgroundFluoroquinolone stewardship is a common target for antimicrobial stewardship programs seeking to maintain or improve fluoroquinolone susceptibility rates. Additional benefits include reducing C. difficile infection rates, drug toxicities, and resistance to other antimicrobials as fluoroquinolones can co-select for resistance. The Norton Healthcare antimicrobial stewardship program was founded in 2011 and provides services at 4 adult hospitals with ~1600 beds. Main fluoroquinolone stewardship activities have included provider education, prospective audit and feedback, and guideline and order-set development. The purpose of this study was to describe the resistance and usage rates of fluoroquinolones over time. MethodsThis was a descriptive study examining individual adult hospital antibiograms from 2010 to 2020. Levofloxacin susceptibility rates to E. coli and P. aeruginosa were collated from annual antibiograms between 2010 and 2020 for outpatients and each adult hospital. Adult hospital resistance rates were aggregated and weighted accordingly to number of isolates per hospital per year. Additionally, levofloxacin and ciprofloxacin inpatient days of therapy (DOT) was collected since 2016 when DOT was first readily retrievable and was normalized per 1000 patient days to compare between different time points.ResultsOutpatient levofloxacin likelihood of activity against P. aeruginosa improved from 81% to 91%. Outpatient levofloxacin likelihood of activity against E. coli remained stable between 84 – 86% (Figure 1). Adult inpatient fluoroquinolone usage decreased by approximately 75% from 83.5 to 21.37 DOT/1000 patient days since 2016 (Figure 2). Adult inpatient levofloxacin likelihood of activity against P. aeruginosa improved from 53% to 83%. Adult inpatient levofloxacin likelihood of activity against E. coli improved from 65% to 75% (Figure 3). ConclusionThe Norton Healthcare antimicrobial stewardship program has been effective in reducing unnecessary fluoroquinolone usage and improving inpatient fluoroquinolone susceptibility rates. Future studies should examine opportunities to translate successes to the outpatient phase of care. Disclosures Ashley Wilde, PharmD, BCPS-AQ ID, Nothing to disclose Paul S. Schulz, MD, Gilead (Consultant, Speaker’s Bureau)Merck (Consultant, Speaker’s Bureau)

128. Development of an Analytics Dashboard to Monitor Antimicrobial Selection and Duration for Pneumonia

BackgroundAnalytical and visual tools can be used to monitor progress for a variety of ASP key performance indicators, but few data describe the process of building disease-state specific tools to retrospectively monitor antimicrobial choice and duration. We describe process and methods for development of a pneumonia dashboard.MethodsIn late 2019, the Carolina ASP began construction of a dashboard to monitor antimicrobial selection and duration in patients admitted with a diagnosis code (ICD-10) consistent with pneumonia. Data extracted from the medical record after discharge included: admission date and time, admission and discharge ICD-10s, inpatient orders and administrations for agents included in the NHSN Antimicrobial Use (AU) option, and antimicrobials ordered at discharge with associated ICD-10. Extracted data fields were validated using a one-month sample. Displays were constructed to trend selection during the first 48 hours of admission, inpatient days of therapy, and total length of therapy (sum of inpatient + outpatient days) for patients who received a discharge prescription for an antimicrobial included in the AU option that was associated with an ICD-10 consistent with pneumonia. Trends observed between Jan 2020 and Mar 2021 are reported. Results341 admissions were trended. Within the first two days of admission, monthly proportions of patients receiving an antimicrobial by category were: anti-MRSA therapies (vancomycin, linezolid), 0.20 to 0.75; broad spectrum beta-lactams (e.g., cefepime, pip/tazo), 0.40 to 0.81; CAP therapies (e.g., ceftriaxone, levofloxacin), 0.48 to 1.00 (Figure). Median inpatient duration of therapy was 5 days (IQR 3-8; range 1 to 68). Total length of therapy was median 6 days (IQR 4-10; range 1 to 68). Figure. Proportions of Patients Prescribed Antimicrobial Categories of Interest During the First 48 Hours of Admissions for Pneumonia. Legend: Anti-MRSA = vancomycin or linezolid; HAP abx = cefepime, piperacillin/tazobactam, ceftazidime, meropenem; CAP = ceftriaxone, azithromycin, ampicillin/sulbactam, amoxicillin/clavulanate, cefdinir, levofloxacin.ConclusionAutomated reports and visual tools can provide actionable insights for ASP practice. From this dashboard, we identified variable but high rates of anti-MRSA and broad-spectrum beta-lactam use within the first 48 hours of admission. The median inpatient and total length of therapy of 5 and 6 days, respectively, were similar to guideline-recommended durations. The up-front cost for building analytical tools can be substantial, but can be viewed as an investment if the metrics and methods are carefully selected. Disclosures All Authors: No reported disclosures

112. Impact of Respiratory Viral PCR Panels (RVP) and Serum Procalcitonin (PCT) on Antibiotic Days of Therapy (DOT) in Patients Admitted with Lower Respiratory Tract Infections (LRTI)

BackgroundIDSA advocates for the use of RVP and PCT to reduce inappropriate antibiotic use. These assays were implemented in our health system without formal antimicrobial stewardship intervention. Herein, we evaluated assay utilization and impact on antibiotic DOT in patients admitted with LRTI.MethodsRecords of patients admitted to our health system in January 2019 with a diagnosis of LRTI (ICD 10 codes: J13-22, J44, or J85) were reviewed. Patients < 18 years old, receiving active treatment at time of admission for a concurrent infection, or had a RVP or initial PCT ordered > 48 hours from admission were excluded. Patients were cohorted based on at least one test ordered (VPPC) vs neither (CTRL). The primary endpoint was total antibiotic DOT, including inpatient and outpatient. Secondary endpoints were hospital length of stay (LOS), 30 day readmission (30DR), and all cause mortality (ACM). Multivariate linear regression was used to determine variables associated with DOT.ResultsOf 294 patients included, 15 (5.1%), 84 (28.6%), and 43 (14.6%) had RVP alone, PCT alone, or both ordered, respectively, resulting in 142 (48.3%) patients in the VPPC group. Providers modified therapy based on PCT and RVP results in 39.4% (50/127) and 33.3% (7/21) of patients, respectively. Median (IQR) DOT was similar between VPPC and CTRL groups (7 [5–9] vs 7 [3–8] days; p=0.159), respectively. Inpatient DOT (4 [2–5] vs 3 [2–4] days; p=0.001) and LOS (99.5 vs 81.7 hours; p=0.001) were longer in the VPPC group. VPPC patients were more likely to receive anti-pseudomonal B-lactams (anti-PSA) (26.8 vs 16.4%; p=0.044) and anti-MRSA antibiotics (45.1 vs 34.9%; p=0.096). No difference in 30DR (13.4 vs 15.1%; p=0.793) or ACM (2.1 vs 3.3%; p=0.794) was observed. Variables significantly associated with increased DOT were non-ICU admission, positive chest X-ray, LOS, younger age, and receipt of anti-MRSA or anti-PSA antibiotics.ConclusionOver one month, RVP or PCT was ordered in nearly half of admitted LRTI patients in our health system, but modification of therapy based on results was infrequent. The unrestricted use of these tests without stewardship intervention did not impact overall antibiotic DOT, LOS, 30DR, or ACM. These data emphasize the need for additional intervention to enhance the clinical utility of these tests.Disclosures Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)bioMérieux (Research Grant or Support, Other Financial or Material Support, Speaker Honorarium)Melinta (Research Grant or Support)Merck & Co., Inc. (Research Grant or Support)Paratek (Speaker’s Bureau)Summit (Other Financial or Material Support, Research funding (clinical trials))

624. Significant Institutional Cost Savings from OPAT-Facilitated Discharge for Patients with Challenging Situations

BackgroundOutpatient parenteral antimicrobial therapy (OPAT) programs are becoming a standard of care, however, program cost justification remains a challenge. One area of focus for institutions is facilitating timely discharge from the inpatient setting, and difficult to discharge patients are a group with which OPAT teams can be particularly impactful.MethodsThis retrospective review identified patients intervened upon by the Nebraska Medicine OPAT team during the initial nine months after program implementation (4/1/19 - 12/31/19) for which routine efforts at discharge by primary teams had failed. Patients were planned for extended inpatient stays to complete the full duration of parenteral antibiotic therapy due to discharge issues given the therapy plan initially recommended by infectious disease consult teams. Outcomes evaluated included inpatient days of therapy avoided, associated financial metrics, and 30-day readmission rates. A matched cohort of patients with similar lengths-of-stay, infectious disease indications, medication use, and lack of major complications was identified to calculate a cost per inpatient day avoided.ResultsA total of 17 difficult to discharge patients were intervened on by the OPAT team, leading to avoidance of 429 planned inpatient days. Based on calculation from internal matched cohort data, these OPAT interventions avoided an estimated $943,000 in total inpatient costs. All-cause 30-day readmission was 24% (4 of 17 patients). Additionally, 15 of these therapy courses were shifted to hospital-associated outpatient infusion centers. Facilitation of enrollment for 11 of these patients in pharmaceutical manufacturer patient assistance programs resulted in replacement of outpatient medication totaling over $28,000 in value. Reimbursements for two additional patients through either governmental or private insurance generated over $11,000 in margin for the health system.ConclusionAttention to complex discharge facilitation by OPAT programs can be a significant contribution to program cost justification, while also transitioning patients to therapy plans that lead to similar clinical outcomes when compared to the overall OPAT population.Disclosures All Authors: No reported disclosures

Auditing use of antibiotics in Zimbabwean neonates

SummaryBackgroundNeonatal sepsis is a major cause of morbidity and mortality in low-income settings. As signs of sepsis are non-specific and deterioration precipitous, antibiotics are often used profusely in these settings where diagnostics may not be readily available. Harare Central Hospital, Zimbabwe, delivers 12000 babies per annum admitting ∼4800 to the neonatal unit. Overcrowding, understaffing and rapid staff turnover are consistent problems. Suspected sepsis is highly prevalent, and antibiotics widely used. We audited the impact of training and benchmarking intervention on rationalizing antibiotic prescription using local, World Health Organization-derived, guidelines as the standard.MethodsAn initial audit of admission diagnosis and antibiotic use was performed between 8th May - 6th June 2018 as per the audit cycle. An intern training programme, focusing on antimicrobial stewardship and differentiating between babies ‘at risk of’ versus ‘with’ clinically-suspected sepsis was instituted post-primary audit. Re-audit was conducted after 5 months.ResultsSepsis was the most common admitting diagnosis by interns at both time points but reduced at repeat audit (81% versus 59%, P<0.0001). Re-audit after 5 months demonstrated a decrease in antibiotic prescribing at admission and discharge. Babies prescribed antibiotics at admission decreased from 449 (98%) to 96 (51%), P<0.0001. Inpatient days of therapy (DOT) reduced from 1243 to 1110/1000 patient-days. Oral amoxicillin prescription at discharge reduced from 349/354 (99%) to 1% 1/161 (P<0.0001).ConclusionA substantial decrease in antibiotic use was achieved by performance feedback, training and leadership, although ongoing performance review will be key to ensuring safety and sustainability.

Post-discharge oral antimicrobial use among hospitalized patients across an integrated national healthcare network

ObjectivesAntimicrobial stewardship programmes have focused on reducing inappropriate inpatient antimicrobial prescribing, but several small studies have found a large portion of antimicrobial exposure occurs immediately after hospital discharge. In this study, we describe the prescribing of oral antimicrobials at hospital discharge across an integrated national healthcare system. At the hospital level, we also compare total inpatient antimicrobial use and post-discharge oral antimicrobial use. MethodsThis retrospective cross-sectional study used national administrative data to identify all acute-care admissions during 2014–2016 within the Veterans Health Administration (VHA). We evaluated inpatient days of therapy (DOT) and post-discharge DOT, defined as oral outpatient antimicrobials dispensed at the time of hospital discharge. At the hospital level, inpatient DOT/100 admissions were compared with post-discharge DOT/100 admissions using Spearman's rank-order correlation. ResultsThere were 1 681 701 acute-care admissions across 122 hospitals, and 335 369 (19.9%) were prescribed an oral antimicrobial at discharge. Fluoroquinolones (38.3%) were the most common post-discharge antimicrobial. At the hospital level, median inpatient antimicrobial use was 331.3 (interquartile range (IQR) 284.9–367.9) DOT/100 admissions and median post-discharge use was 209.5 (IQR 181.5–239.6) DOT/100 admissions. Thirty-nine per cent of the total duration of antimicrobial exposure occurred after discharge. At the hospital-level, the metrics of inpatient DOT/100 admissions and post-discharge DOT/100 admissions were weakly positively correlated with rho=0.44 (p < 0.001). ConclusionsA large proportion of antimicrobial exposure among hospitalized patients occurred immediately following discharge. Antimicrobial-prescribing at hospital discharge provides an opportunity for antimicrobial stewardship. Hospital-level stewardship metrics need to include both inpatient and post-discharge antimicrobial-prescribing to provide a comprehensive assessment of hospital-associated antimicrobial use.

Introduction of Procalcitonin Testing and Antibiotic Utilization for Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Background:The majority of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are triggered by nonbacterial causes, yet most patients receive antibiotics. Treatment guided by procalcitonin (PCT), a sensitive biomarker of bacterial infection, safely decreases antibiotic use in many controlled trials. We evaluated PCT implementation for inpatients with AECOPD at a large academic hospital.Methods:All patients admitted for AECOPD during the first 6 months of PCT-guided therapy were eligible for inclusion in this retrospective cohort study. Patients with PCT performed were compared with those without PCT. The primary outcome was antibiotic days of therapy (DOT). Secondary outcomes included 30-day readmission and mortality.Results:Of the 238 AECOPD admissions, 73 (31%) had PCT performed. Procalcitonin-tested patients were more likely to meet systemic inflammatory response syndrome (SIRS) criteria, require intensive care unit (ICU)-level care, and have a longer length of stay (LOS) compared with those without PCT. Even after adjustment for these factors, PCT-tested patients received more inpatient DOT and there was no difference in total DOT. However, a low PCT value (<0.25 ng/mL) was associated with a 25.5% (P ⩽ .001) decrease in intravenous (IV) antibiotic DOT. Guideline-recommended follow-up testing was rare (12%). Procalcitonin measurement had no effect on 30-day readmission or mortality.Conclusions:In this real-world analysis of inpatients with AECOPD, PCT-guided therapy was poorly adopted by providers and was not associated with a decrease in total antibiotic DOT. However, a low PCT level was associated with a 25.5% decrease in IV antibiotic DOT, suggesting increased comfort stepping down from IV to PO therapy.

Antibiotic treatment patterns, costs, and resource utilization among patients with community acquired pneumonia: a US cohort study

ABSTRACTObjectives: The current treatment options for patients with community-acquired pneumonia (CAP) often present a trade-off between the potential for treatment failure and safety concerns. We set out to investigate real-world outcomes associated with the use of currently available antimicrobial treatment options for CAP in both the outpatient and inpatient (non-intensive care unit [ICU]) settings.Methods: This claims-based retrospective study included adult patients diagnosed with CAP and treated with antibiotic therapies, including any oral fluoroquinolone, macrolide, or beta-lactam monotherapy in the outpatient setting, and intravenous (IV) levofloxacin or IV azithromycin/ceftriaxone in the inpatient setting. Generalized linear model (GLM) regression was used to determine total charges for inpatient stay, the length of stay, and days of inpatient therapy. For outpatients, rates of adverse events (AEs), treatment failure, and hospitalization were compared by type of initial antibiotic therapy using logistic regression multivariate models that controlled for baseline characteristics.Results: A total of 441,820 outpatients and 33,287 inpatients treated for CAP between 2007 and 2012 were included in this analysis. In the outpatient setting, fluoroquinolone therapy led to a higher rate of documented AEs (adjusted odds ratio [OR]: 1.23; 95% confidence interval [CI]: 1.20–1.25; p < 0.0001) but a lower rate of retreatment (adjusted OR: 0.9; 95% CI: 0.87–0.94; p < 0.0001) compared with macrolides. Both AEs and retreatment in these patients were associated with increased costs. For patients treated with the IV macrolide/beta-lactam combination compared with IV fluoroquinolone in the inpatient setting, a significantly longer length of stay in hospital (4.71 vs. 4.38 days; p < 0.0001) and greater overall costs ($3,535 more per stay; p < 0.0001) were observed.Conclusion: In both the inpatient and outpatient settings, the development of additional efficacious treatment options that have a reduced AE burden for patients with CAP may be warranted.

Impact of an Antimicroibal Stewardship Bundle of Rapid Identification of Methicillin Susceptibility and Active Intervention on Treatment of Staphylococcus aureus Bacteremia

Background Staphylococcus aureusbacteremia (SAB) is a major source of morbidity and mortality. Studies show rapid initiation of appropriate antibiotic therapy is essential to treatment and optimal therapy depends upon antibiotic susceptibility.MethodsUsing a quasi-experimental pre-post intervention study we evaluated a bundled antimicrobial stewardship rapid identification and susceptibility testing protocol. The pre-intervention group included all patients treated for SAB at our hospital between April and Sept 2015; the post-intervention group was between April and Sept 2016. We implemented combined rapid identification by MALDI-TOF with a modified immunochromatographic assay for penicillin–binding protein 2a to differentiate MSSA and MRSA. Identification and susceptibility results were communicated to the primary team per usual protocol and to an antimicrobial stewardship pharmacist for intervention. The primary outcome was time to optimal antibiotic therapy calculated as the difference in time from the first dose of antibiotic therapy to the discontinuation time of the non-optimal antibiotic, for patients receiving combination therapy or first dose of optimal therapy, determined using a predefined protocol developed in collaboration with the Infectious Diseases (ID) consult service. Additional outcomes included time to pathogen identification, time to ID consult, time to source control, length of hospital stay (LOS), intensive care unit LOS, inpatient-days of therapy, and in-hospital mortality. Outcomes were compared using the χ2 test, or Student’s t-test for independent samples.Results74 pre-intervention and 55 post-intervention patients were included. Time in days to optimal therapy (1.7 ± 1.2 vs.. 2.5 ± 1.6, P = 0.003), total time to pathogen identification (1.5 ± 0.5 vs.. 2.7 ± 0.6, P < 0.001) and time to ID consult (1.6 ± 1.5 vs.. 2.8 ± 2.4, P = <0.001) were significantly shorter in the intervention group. All other outcomes were not statistically significantly different between groups.ConclusionWe demonstrate significant improvement in time to pathogen identification, optimal therapy, and ID consult utilizing rapid pathogen identification and susceptibility testing coupled with antimicrobial stewardship pharmacist intervention.Disclosures E. Ernst, Merck Sharp and Dohme: Consultant, Consulting fee.

26-Year-Old Man With Nausea, Delirium, and Fever

Resident in Internal Medicine, Mayo School of Graduate Medical Education, Rochester, MN (H.L.T.); Advisor to resident and Consultant in Infectious Diseases, Mayo Clinic, Rochester, MN (L.M.B.). A 26-year-old-man who had been living in Indonesia until 4 months previously presented to our hospital for evaluation of fever, agitation, and altered mental status. He had been seen previously at another facility for vague abdominal pain, nausea, and fever. He had become subacutely agitated and was transferred to our institution because of altered mental status and vomiting. On admission, he was febrile (temperature, 39.3 C) and tachycardic (heart rate, 118 beats/ min); his blood pressure was 134/96 mm Hg, and his oxygen saturation was 100% while breathing room air. Physical examination findings were notable for intermittent altered mental status with restlessness, agitation, inattention, and pain with neck flexion and posterior neck palpation. Findings on work-up at the outside facility included a sodium level of 118 mmol/L and no abnormalities detected on head computed tomography (CT) and chest radiography. His pupils were mildly constricted but responded to light. Admission laboratory studies yielded a normal white blood cell count of 10.1 10/L and an improved sodium concentration of 133 mmol/L.

Cryptococcus gattii in an Immunocompetent Patient in the Southeastern United States.

Cryptococcal infections are seen throughout the United States in both immunocompromised and immunocompetent patients. The most common form is C. neoformans. In the Northwestern United States, C. gattii has received considerable attention secondary to increased virulence resulting in significant morbidity and mortality. There are no cases in the extant literature describing a patient with C. gattii requiring neurosurgical intervention in Alabama. A middle-aged immunocompetent male with no recent travel or identifiable exposure presented with meningitis secondary to C. gattii. The patient underwent 12 lumbar punctures and a ventriculoperitoneal shunt and required 83 days of inpatient therapy with 5-flucytosine and amphotericin B. The patient was found to have multiple intracranial lesions and a large intramedullary spinal cryptococcoma within his conus. Following an almost 3-month hospitalization the patient required treatment with oral voriconazole for one year. In the United States meningitis caused by C. gattii infection is not isolated to the Northwestern region.

Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: Prospective randomized comparison with parenteral therapy

To compare the efficacy and safety of inpatient oral antibiotic treatment (oral) versus standard parenteral antibiotic treatment (intravenous) for right-sided staphylococcal endocarditis in injection drug users. In a prospective, randomized, non-blinded trial, febrile injection drug users were assigned to begin oral or intravenous (IV) treatment on admission, before blood culture results were available. Oral therapy consisted of ciprofloxacin and rifampin. Parenteral therapy was oxacillin or vancomycin, plus gentamicin for the first 5 days. Antibiotic dosing was adjusted for renal dysfunction. Administration of other antibacterial drugs was not permitted during the treatment or follow-up periods. Bacteremic subjects having right-sided staphylococcal endocarditis received 28 days of inpatient therapy with the assigned antibiotics. Test-of-cure blood cultures were obtained during inpatient observation 6 and 7 days after the completion of antibiotic therapy, and again at outpatient follow-up 1 month later. Criteria for treatment failure and for drug toxicity were prospectively defined. Of 573 injection drug users who were hospitalized because of a febrile illness and suspected right-sided staphylococcal endocarditis, 93 subjects (16.2%) had two or more sets of blood cultures positive for staphylococci; 85 of these bacteremic subjects (14.8%) satisfied diagnostic criteria for at least possible right-sided staphylococcal endocarditis (no other source of bacteremia was apparent) and entered the trial. Forty-four (oral, 19; IV, 25) of these 85 subjects completed inpatient treatment and evaluation including test-of-cure blood cultures. There were four treatment failures (oral, 1 [5.2%]; IV, 3 [12.0%]; not significant, Fisher's exact test). Drug toxicity was significantly more common in the parenterally treated group (oral, 3%; IV, 62%; P < 0.0001), consisting largely of oxacillin-associated increases in liver enzymes. For selected patients with right-sided staphylococcal endocarditis, oral ciprofloxacin plus rifampin is effective and is associated with less drug toxicity than is intravenous therapy.

Effect of Octreotide on Refractory AIDS-associated Diarrhea

To determine the efficacy and safety of octreotide for treatment of refractory, profuse diarrhea in patients with the acquired immunodeficiency syndrome (AIDS). A prospective, open-label study. Inpatient metabolic units of four university medical centers. Fifty-one patients infected with human immunodeficiency virus (HIV) who had uncontrolled diarrhea (greater than or equal to 500-mL liquid stool per day) despite treatment with maximally tolerable doses of antidiarrheal medications. After initial baseline studies, patients received octreotide, 50 micrograms every 8 hours for 48 hours. If stool volume was not reduced to less than 250 mL/d, the dose of octreotide was increased stepwise to 100, 250, and 500 micrograms. Fifty men and one woman (mean age, 36.3 +/- 1.1 years) entered and completed the 28-day protocol (14 days of inpatient therapy and 14 days of outpatient therapy). Stool frequency and volume decreased significantly (6.5 +/- 0.5 stools per day on day 0 compared with 3.8 +/- 0.3 stools per day on day 21 [P less than 0.001] and 1604 +/- 180 mL/d on day 0 compared with 1084 +/- 162 mL/d on day 14 [P less than 0.001], respectively). Twenty-one patients (41.2%) were considered to be partial or complete responders (reduction in daily stool volume by greater than or equal to 50% of initial collections or reduction to less than or equal to 250 mL/d). Of the 21 responders, 14 (67%) had no identifiable pathogens at initial screening compared with 9 of 30 (30%) nonresponders (P less than 0.01). Patients with AIDS-associated refractory watery diarrhea, especially those without identifiable pathogens, may respond favorably to subcutaneously administered octreotide. This drug deserves further study in a randomized, placebo-controlled trial.