Empiric Vancomycin Therapy Research Articles

Significance of colonization by antibiotic-resistant organisms prior to congenital heart disease surgery in children from low- to middle-income countries sent by non-governmental organizations to Switzerland.

Children with congenital heart disease (CHD) from low- to middle-income countries (LMIC) are suspected to have a high prevalence of antibiotic-resistant microorganisms (ARMOs) carriage, but data are currently lacking. Carriage of ARMOs could impact the post-operative course in pediatric intensive care unit (PICU). The aim of the study was to assess the prevalence of ARMOs carriage in children with CHD from LMIC and its impact on post-operative outcomes. This was a retrospective monocentric study from 01/2019 to 12/2022. Included patients were children (0-18 years) from a LMIC admitted after CHD surgery and with AMRO screening performed the week before. Infections and post-operative evolution were compared based on ARMOs carriage status. Among 224 surgeries (median age 38.5 months (IQR 22-85.5)), ARMOs carriage was evidenced in 95 cases (42.4%). Main organisms isolated were Extended Spectrum Beta-Lactamase (ESBL) producing E. coli (75/224) 33.5%)) and ESBL-K. pneumoniae (30/224) 13.4%)). Median mechanical ventilation duration was 1 day (IQR 0-1), PICU stay 3 days (IQR 2-4) and hospital stay 6.5 days (IQR 5-10). A total of 17 infectious episodes occurred in 15 patients, mostly consisting in hospital-acquired pneumonia (HAP) (12/17). Only two infections were caused by a colonizing ARMO. Occurrence of infections and patients' outcome were similar between ARMO carriers and non-carriers. Higher use of carbapenems (6 (6.3%) vs 1 (0.8%), p = 0.04) and a trend to a higher use of vancomycin (14 (13.7%) vs 9 (6.9%), p = 0.04) in case of ARMOs carriage. Applying current guidelines, negative swab screening could have led to sparing most of empirical vancomycin therapy (11/12) for HAP based on current guidelines. Prevalence of AMROs carriage is high in children from LMIC and has a limited impact on patients' outcome. However, ARMOs carriage leads to higher consumption of antibiotics. Screening may help saving use of broad-spectrum antibiotic in non-carrier patients.

SAT214 A Rare Case Of Biopsy-proven Non-uremic Calciphylaxis In A Patient With Secondary Hyperparathyroidism

Abstract Disclosure: U.A. Ogar: None. A.G. Olafimihan: None. I. Asemota: None. E. Krishnaraju: None. A. Okafor: None. Introduction: Calciphylaxis, also known as calcific uremic arteriolopathy, is a rare, lethal, metastatic calcification involving cutaneous microvasculature that presents as painful necrotic skin lesions. It typically occurs in patients with end-stage kidney disease (ESKD), renal transplant, or acute kidney injury requiring renal replacement therapy. Calciphylaxis occurring without these comorbidities is termed non-uremic calciphylaxis (NUC), which is rarer. NUC’s etiology is unclear but it has been associated with hyperparathyroidism, malignancies, alcohol liver disease, and connective tissue disorders. There are only a few reported cases of biopsy-proven NUC in patients with secondary hyperparathyroidism, as in our patient. Clinical Case: A 63-year-old female with a history of COPD on home oxygen therapy, smoking, and alcohol use disorder presented with a four-day history of severe, painful, purplish left thigh rash. She had no recent trauma or insect bite. Her physical exam showed a large (6x10 cm), tender, distal anterior left thigh bruise. Laboratory findings were significant for elevated creatine of 4.3 mg/dL from a normal baseline creatinine (0.6 mg/dL), normal serum corrected calcium (10.1 mg/dL) and elevated phosphate (4.7mg/dL). Three days following her admission, the skin lesion had progressed into multiple brown coalescing bullae with central ulceration, collarette, surrounding erythema, warmth, and induration. Due to concern for possible skin and soft tissue infection, empiric vancomycin therapy was started. However, the overall clinical picture was not convincing of an infection, necessitating consultation with the Dermatology team. A skin biopsy was recommended, and this was diagnostic of calciphylaxis. Further testing revealed hyperparathyroidism (202pg/ml), low 25 hydroxy Vitamin D (12ng/ml), and negative autoimmune and thrombophilia workup. Her treatment plan included wound care with debridement, analgesia, and interdisciplinary clinic follow-up. During outpatient follow-up, her wound was seen to be slowly healing with daily wound dressing, and her elevated serum creatinine had resolved. Conclusion: NUC has a high mortality rate (52%) and requires a high index of clinical suspicion to ensure prompt diagnosis and initiation of treatment. Differential diagnoses include atherosclerotic vascular disease, vasculitis, hypercoagulable disorders, and cellulitis as in our patient. Skin biopsy is diagnostic. Aggressive wound care and analgesia are pivotal to treatment, in addition to addressing underlying precipitating conditions. Other treatment options like sodium thiosulphate exist but with uncertain outcomes. Efforts geared at definitive therapeutic modalities are needed. Presentation: Saturday, June 17, 2023

1287: METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS NARES SCREEN LEADS TO VANCOMYCIN DE-ESCALATION IN TRAUMA

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) nares swab is a proven screening tool to de-escalate vancomycin therapy due to its high negative predictive value in pneumonia and other infections. However, data are lacking on the utility of this test in the critically ill trauma population, which is at high risk for hospital-acquired infections. This study evaluated the impact of empiric MRSA PCR nares screening on de-escalation of vancomycin therapy in critically ill trauma patients. Methods: This is a single center, pre-post observational cohort study conducted at an academic, level I trauma center. Adult patients who were admitted for trauma and received empiric vancomycin therapy for suspected infection in the trauma intensive care unit were included. Patients were grouped by whether they were included 6 months before (pre-cohort) and 6 months after (post-cohort) the implementation of empiric rapid MRSA PCR nares screening in September 2021. The primary outcome was duration of vancomycin therapy. Secondary outcomes included rate of acute kidney injury (AKI), positive MRSA screen or cultures, ICU length of stay (LOS), hospital LOS, and mortality. Results: One-hundred fifty-eight patients were included: 82 in the pre-cohort group and 76 in the post-cohort group. Ninety vancomycin initiation orders were observed in the pre-cohort versus 80 orders in the post-cohort. Baseline demographics were similar between groups. There was a significantly higher rate of MRSA PCR orders in the post-cohort group (75%) compared to (21%) in the pre-cohort (p< 0.001). The pre-cohort group had higher rates of positive MRSA screens (26 vs. 13%, p=0.18) and MRSA positive cultures (17 vs. 9%, p=0.22) compared to post-cohort. There were no reported instances of positive MRSA cultures with a negative PCR. Vancomycin duration was significantly shorter in the post-cohort group (2.55 days vs. 3.5, p=0.02). Hospital and ICU LOS, rates of AKI, and mortality were not different between groups. Conclusions: Implementation of empiric rapid MRSA nares screening led to a shorter overall duration of vancomycin therapy by nearly one day in critically ill trauma patients. Further study is required to evaluate the potential cost savings of empiric MRSA screening in critically ill trauma patients.

Augmented Renal Clearance of Vancomycin in Suspected Sepsis: Single-Center, Retrospective Pediatric Cohort.

To identify associations between augmented renal clearance (ARC) in pediatric patients treated for suspected sepsis and vancomycin pharmacokinetics. ARC has been associated with lower serum drug levels in both adult and pediatric cohorts for multiple drugs. We hypothesize that presence of ARC is associated with subtherapeutic initial vancomycin trough level (VTL). Retrospective study, with patients divided into two groups based on the presence of ARC (estimated glomerular filtration rate [eGFR] above 130 mL/min/1.73 m2) in comparison with VTL. Multivariable logistic regression analysis was performed to evaluate the association between eGFR and subtherapeutic VTL. Tertiary children's hospital. Hospitalized children (0-18 yr) initiated on empiric vancomycin therapy for suspected sepsis. Retrospective measurement of VTL, eGFR, and clinical variables. Seventy-three patients were treated with empiric vancomycin for sepsis. ARC was present in 32 patients (44%). Subtherapeutic first VTL was present in 40 patients (55%). Higher eGFR was independently associated with subtherapeutic VTL in the multivariable logistic regression analysis. Subtherapeutic VTL is associated with ARC in our single-center retrospective cohort of children with suspected sepsis. This problem may present a potential risk of treatment failure in Gram-positive sepsis or longer time to clinical response. Prospective studies to investigate the clinical significance and effect of optimizing vancomycin dose in patients with ARC are recommended.

Detection of vancomycin variable enterococci (VVE) among clinical isolates of Enterococcus faecium collected across India-first report from the subcontinent

PurposeEmergence of vancomycin variable enterococci (VVE) poses a challenge to empiric vancomycin therapy. Vancomycin-variable enterococci (VVE) are vanA-positive, yet phenotypically vancomycin-susceptible enterococci that can switch to a vancomycin-resistant phenotype when exposed to vancomycin. The aim of the present study was to determine the prevalence of VVE in India. MethodsIsolates of phenotypically vancomycin susceptible Enterococcus faecium from 20 tertiary care hospitals across India were collected and tested for the presence of vanA, vanR, vanS, vanB and vanC genes by conventional PCR using previously published primers. Isolates positive for vanA gene were considered as VVE. ResultsThe prevalence of VVE was 1.5% (5/340). Only one VVE isolate was positive for vanR and vanS, and all the isolates were negative for vanB and vanC. ConclusionsAlthough the prevalence is low, our finding emphasizes the importance of routinely screening for van genes in enterococci that are phenotypically susceptible. Silenced vanA able to escape detection and revert to resistance during vancomycin therapy represents a new challenge in clinical settings.

Optimizing Empiric Vancomycin Use in Febrile Neutropenia Patients

Introduction: National guidelines do not support routine empiric vancomycin use in the initial management of febrile neutropenia (FN) and only recommend it in patients with specific clinical indications. This bi-phasic quality improvement project aimed to evaluate current vancomycin use in FN and improve compliance with a guideline-driven algorithm (GDA) to ensure appropriate prescribing and therapy duration in a community hospital. Methods: Phase I was a retrospective review of charts of adults receiving empiric vancomycin therapy for FN at a community hospital. Phase II was a prospective review of charts of patients with FN, who received pharmacist-led interventions, to improve de-escalation of vancomycin as warranted. Results: A total of 48 and 32 patients were included in phase I and phase II, respectively. While initiation of vancomycin therapy according to guideline-recommended clinical indications was comparable among phases, appropriate de-escalation of vancomycin increased from 23% in phase I to 78% in phase II. Overall compliance with the GDA increased from 15% in phase I to 38% in phase II. Average duration of therapy in phase I was 4.77 days versus 2.69 days in phase II and there were less patients who continued vancomycin beyond 48 hours in phase II. The pharmacy intervention rate was 56% (18 of 32) and the health-care practitioner acceptance rate was 100%. Discussion: Pharmacist interventions had an impact in increasing compliance with national guideline recommendations and decreasing the duration of empiric vancomycin therapy in patients with FN.

Effect of rapid methicillin-resistant Staphylococcus aureus nasal polymerase chain reaction screening on vancomycin use in the intensive care unit.

PurposeTo determine the impact of a pharmacist-driven methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) screen on vancomycin duration in critically ill patients with suspected pneumonia.MethodsThis was a retrospective, quasi-experimental study at a 613-bed academic medical center with 67 intensive care beds. Adult patients admitted to the intensive care unit (ICU) between 2017 and 2019 for 24 hours or longer and empirically started on intravenous vancomycin for pneumonia were included. The primary intervention was the implementation of a MRSA nasal PCR screen protocol. The primary outcome was duration of empiric vancomycin therapy. Secondary outcomes included the rate of acute kidney injury (AKI), the number of vancomycin levels obtained, the rate of resumption of vancomycin for treatment of pneumonia, ICU length of stay, hospital length of stay, the rate of ICU readmission, and the rate of in-hospital mortality.ResultsA total of 418 patients were included in the final analysis. The median vancomycin duration was 2.59 days in the preprotocol group and 1.44 days in the postprotocol group, a reduction of approximately 1.00 day (P < 0.01). There were significantly fewer vancomycin levels measured in the postprotocol group than in the preprotocol group. Secondary outcomes were similar between the 2 groups, except that there was a lower rate of AKI and fewer vancomycin levels obtained in the postprotocol group (despite implementation of area under the curve–based vancomycin dosing) as compared to the preprotocol group.ConclusionThe implementation of a pharmacist-driven MRSA nasal PCR screen was associated with a decrease in vancomycin duration and the number of vancomycin levels obtained in critically ill patients with suspected pneumonia.

227. Evaluation of Empiric Vancomycin Utilization at 72 Hours Post Admission: is De-escalation of Vancomycin Appropriate?

BackgroundAt both of our institutions in 2018, the average vancomycin days of therapy per 1,000 patient days was 112. The purpose of this study was to examine a 72-hour time-out as an effective de-escalation tool by evaluating the indication and clinical appropriateness of the continuation of empiric vancomycin therapy.MethodsA retrospective chart review was performed from January 2018 to October 2018 at two community hospitals. Patients > 18 years who received at least 3 days of empiric vancomycin therapy were included. Patients were excluded if immunocompromised, pregnant, on hemodialysis, received vancomycin for surgical prophylaxis, or expired within 72 hours of vancomycin initiation. Criteria for appropriate continuation of vancomycin at 3 days: positive culture for methicillin-resistant Staphylococcus aureus (MRSA), presence of infection with or without defined sources with systemic signs of infection (i.e. white blood cells >12,000 cells/L or < 5,000 cells/L and/or elevated temperature ≥ 37.5°C), or pending wound/sputum cultures after vancomycin initiation.ResultsA total of 160 adult patients initiated on vancomycin were analyzed; 118 of 160 (74%) met appropriate criteria. The most common indications for vancomycin were: skin and soft tissue infections (SSTI) 82 patients (51%); pneumonia 37 patients (23%); and positive blood culture 20 patients (13%). Risk factors for MRSA were similar between both groups. Forty-four (28%) patients had cultures pending and 23 patients (14%) had a known non-MRSA pathogen at time of assessment. American Indian race (OR 3.01 (1.21, 7.53) p-value= 0.0174) and SSTI indication (OR 2.87 (1.24, 6.80) p-value= 0.0147) were associated with not meeting appropriate criteria. ConclusionApproximately 25% of patients receiving empiric vancomycin therapy did not meet clinical criteria for continuation beyond 72 hours. The indication most commonly associated with continued vancomycin utilization was SSTI. These results identified indications in which empiric vancomycin prescribing can be optimized, and a 72-hour antibiotic time-out may be warranted as a stewardship intervention. Timely culture obtainment and intervention when another pathogen is identified are possible strategies to ensure success of 72-hour time-out.Disclosures All Authors: No reported disclosures

Appropriateness of Anti-MRSA Therapy in Hospitalized Patients With Suspected Community-Onset Infections

Background: Inappropriate use of MRSA-spectrum antibiotics is an important antimicrobial stewardship target. Contributors to inappropriate use include empiric treatment of patients who are determined to not be infected or who are infected but lack MRSA risk factors, and by excessive treatment duration when suspected MRSA infection is disproven. To characterize opportunities for improvement, we conducted a medical use evaluation (MUE) in 27 VA medical centers. The primary objectives were to assess the following proportions: (1) courses of unjustified empiric vancomycin therapy (patients in whom all antibacterials were halted within 2 days or without a principal or secondary discharge infection diagnosis); (2) courses of unjustified continuation of anti-MRSA therapy beyond day 4 (no MRSA risk factors or proven MRSA infection); and (3) excess anti-MRSA days of therapy (DOT), that is, DOT in unjustified empiric courses plus DOT after day 4 in unjustified continued courses. Methods: Clinical pharmacists performed retrospective, structured, manual record reviews of patients started on intravenous vancomycin on day 1 or 2 of hospitalization from June 2017 to May 2018. Exclusion criteria included surgical prophylaxis, recent MRSA infection, β-lactam allergy, renal insufficiency, severe immunosuppression, or infection that warranted anti-MRSA therapy other than vancomycin. Results: Of 2,493 evaluated patients, 1,320 met the inclusion criteria. Among them, 44% of courses were initiated in the emergency department, 37% of patients had ≥1 risk factor for healthcare-associated infections, and 50% of patients had ≥2 SIRS criteria or required vasopressor support. The most common admission diagnoses were skin and soft-tissue infection (SSTI, 40%; 68% nonpurulent) and pneumonia (27%; 46% without healthcare risk factors). Clinical cultures recovered MRSA from 8% of patients. Empiric therapy was not justified in 342 patients (26%; 57% were clinically stable). Continued therapy was unjustified in 46% of the 320 patients who received &gt;4 days of anti-MRSA therapy. Of all days of anti-MRSA therapy, 23% were unjustified; 65% of these were due to unjustified empiric therapy. Site-specific variations in unjustified empiric therapy better correlated with the proportion of unjustified DOT than did unjustified continuation of therapy (Pearson correlation coefficients [PCC], 0.75 and 0.54, respectively) (Fig. 1). Facility-specific proportions of unjustified DOT modestly correlated with anti-MRSA DOT (PCC, 0.45; n = 27) (Fig. 2) but not the anti-MRSA standardized antimicrobial administration ratio (PCC, 0.15; n = 21). Conclusions: In this multicenter MUE, 26% of all days of anti-MRSA therapy lacked justification; this rate correlated with total facility-specific anti-MRSA DOT. Unnecessary empiric therapy, largely in the ED and for nonpurulent SSTIs and pneumonia without risk factors, was the principal contributor to unjustified DOT.Funding: NoneDisclosures: None

Pharmacist-Driven MRSA Nasal PCR Screening and the Duration of Empirical Vancomycin Therapy for Suspected MRSA Respiratory Tract Infections.

ObjectiveTo assess the effect of a pharmacist-driven, polymerase chain reaction (PCR)−based nasal screening protocol for methicillin-resistant Staphylococcus aureus (MRSA) on vancomycin therapy duration and on rates of adverse drug events and 30-day hospital readmission.Patients and MethodsFrom July 8, 2017, through January 31, 2019, we performed a retrospective, multicenter, preimplementation-postimplementation study. Patients with a vancomycin order to treat lower respiratory tract infection (LRTI) underwent MRSA PCR screening; tests were ordered by health care providers, including physicians, physician assistants, and advanced practice registered nurses. During the preimplementation period (July 8, 2017, through September 30, 2018), pharmacists could order MRSA PCR screening only after receiving a verbal order from a health care provider. During the postimplementation period (October 1, 2018, through January 31, 2019), a collaborative practice agreement allowed pharmacists to order MRSA PCR screening tests.ResultsThe preimplementation group included 241 patients, and the postimplementation group included 74 patients. Of these patients, 124 in the preimplementation group and 62 in the postimplementation group received MRSA PCR screening. Twenty patients (16.1%) in the preimplementation group and 9 (14.5%) in the postimplementation group had a positive MRSA PCR screening test result (between-group difference, 1.6%; P=.80). Duration of therapy was significantly shorter in the postimplementation group (median [interquartile range], 14.3 [5.0-28.6] hours vs 24.0 [12.4-47.0] hours; P<.001).ConclusionVancomycin therapy carries a risk of adverse events and may increase health care costs. A pharmacist-driven protocol for MRSA nasal swab PCR screening effectively reduces the duration of vancomycin therapy for patients with lower respiratory tract infection.

Expediting Discharge in Hospitalized, Adult Patients with Skin and Soft Tissue Infections Who Received Empiric Vancomycin Therapy with Oritavancin: Description of Findings from an Institutional Pathway.

BackgroundAn internal quality assurance review at AtlantiCare Regional Medical Center (ARMC) revealed that patients admitted with skin and soft tissue infections (SSTIs) remained in hospital post-resolution of acute symptoms and demonstrated a delayed transition to step-down oral antibiotic therapy. A non-mandatory institutional pathway was developed and implemented in 2016 to expedite hospital discharge in hemodynamically stable SSTI patients by utilizing oritavancin.ObjectiveTo describe the outcomes associated with use of single-dose oritavancin therapy to expedite hospital discharge in hemodynamically stable inpatients with SSTIs.MethodsA retrospective, descriptive cohort was evaluated for outcomes of patients with SSTIs who received either oritavancin to expedite discharge or were discharged on oral step-down antibiotics. Patients were included in this analysis if they were: ≥ 18 years old; hospitalized; received empiric vancomycin; not pregnant or nursing; hemodynamically stable at the time of assessment; and received either oritavancin or oral step-down antibiotics to facilitate discharge. The primary outcomes were index hospital length of stay (LOS), 30-day SSTI-related readmissions, and 30-day SSTI progression.ResultsOverall, 199 patients met the study criteria (oritavancin = 99 and oral step-down antibiotics = 100). Groups were well matched at baseline. Patients who received oritavancin had a shorter mean index hospital LOS than those in the oral step-down antibiotic group (3.5 days vs. 5.6 days). Patients receiving oritavancin also had lower SSTI 30-day readmission and SSTI-progression rates.ConclusionsAn institutional pathway that used oritavancin to expedite hospital discharge of hemodynamically stable SSTI patients resulted in shorter hospital LOS, less 30-day SSTI-related hospital readmissions, and decreased SSTI progression relative to those discharged on conventional oral step-down therapy.

Effect of Pharmacists’ Interventions on the Appropriateness of Empiric Vancomycin Therapy in Oncology Patients with Febrile Neutropenia

The purpose of this observational study is to evaluate the effect of an active pharmacy intervention to facilitate timely discontinuation of empiric vancomycin therapy in oncology patients with febrile neutropenia who lack objective evidence of a Gram-positive infection. This was a two-phase study. Vancomycin use was evaluated retrospectively on all oncology patients with febrile neutropenia over four weeks (phase I). In a parallel four weeks a year later, vancomycin use in this patient population was evaluated prospectively (phase II). In the absence of evidence of Gram-positive infection after 72 hours of treatment initiation, the team was contacted by a pharmacist to encourage discontinuation. Usage was compared between both phases. Forty-three patients in phase I and 25 patients in phase II were treated with vancomycin with no evidence for Gram-positive infections. Pharmacists’ interventions were documented on 18 patients in phase II. Of these, 56% of interventions to discontinue vancomycin were accepted, but only 33.3% of patients had treatment stopped within 72 hours of initiation. Although not significant, a trend in more appropriate use of vancomycin in oncology patients with febrile neutropenia was observed. Pharmacist’s interventions might have played a role in this observation.

Impact of a Pharmacist-driven Methicillin-resistant Staphylococcus aureus Polymerase Chain Reaction Nasal Swab Protocol on the De-escalation of Empiric Vancomycin in Patients with Pneumonia in a Rural Healthcare Setting.

IntroductionPneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) carries a high rate of morbidity and mortality. Many clinicians empirically treat those at risk of developing MRSA pneumonia with vancomycin. Several studies have identified a high negative predictive value of the MRSA polymerase chain reaction (PCR) nasal swab test in lower respiratory tract infections, suggesting it can be used to guide the de-escalation of empiric anti-MRSA therapy.ObjectiveTo evaluate the impact of a pharmacist-driven MRSA PCR nasal swab protocol on the de-escalation of empiric vancomycin in patients with pneumonia in a rural healthcare setting. Secondarily, to assess the rate of hospital length of stay, the rate of vancomycin-associated acute kidney injury, and in-hospital mortality after pharmacist-driven de-escalation of empiric vancomycin in patients with pneumonia. MethodsA retrospective, single-center, pre-post cohort study was conducted in patients after the implementation of a pharmacist-driven protocol allowing pharmacists to obtain nasal swabs and PCR testing for MRSA in those on empiric vancomycin therapy for suspected MRSA pneumonia. Based on negative test results, pharmacists recommended a de-escalation of empiric vancomycin to the physician. Patients were included if they were adults at least 18 years of age, had a physician diagnosis of suspected or confirmed pneumonia, and initiated on at least one dose of intravenous vancomycin within 48 hours of admission.ResultsA total of 79 patients were identified for inclusion in the pre-protocol group (n=32) or post-protocol group (n= 47). The mean duration of vancomycin therapy in the pre-protocol group was 3.1 days as compared to 1.7 days in the post-protocol group for a 1.4 days reduction (p=0.044). There was no significant impact on the number of vancomycin cases de-escalated within 24 hours (p=0.14) but there was a significant reduction at 48 hours (p=0.01). Protocol implementation was associated with a reduction in the average length of hospitalization (8 versus 5.20 days, p=0.006). Neither group had a vancomycin-associated acute kidney injury or in-hospital mortality.ConclusionAmong patients with suspected MRSA pneumonia, a pharmacist-driven MRSA PCR nasal swab protocol resulted in a significant reduction of empiric vancomycin duration of therapy without an adverse impact on clinical outcomes in a rural healthcare setting.

1564. Target Attainment of Empiric Vancomycin Therapy to Achieve Safe and Effective Exposure When it Matters Most: How Much of the Drug Do We Really Need in the First 48 Hours?

BackgroundEmpiric dosing of vancomycin (VAN) to reach targets is a daunting task due to the large variability observed in the pharmacokinetics of this agent. With the change to AUC driven dosing on the horizon, the goal of this study was to establish empiric dosing requirements of vancomycin that effectively achieve the desired AUC of 400 to 600 mg hours/L targets in the first 48 hours of therapy.MethodsVAN TDM data were used in this analysis. A two-compartment model was fitted with Bayesian routines to establish the AUCs. Then, the AUC achieved was used to identify the desired total daily dose (TDD, capped at 4,500 mg) needed to attain an AUC in the target range for days 1 and 2, per patient. Next, multivariable regression was undertaken to predict this desired dose with frequently calculated weight and renal function indices. Last, model validation in a test data set based on calculated ME, RMSE and their 95% CI took place, and then the best model was used to simulate TDDs at 24 h intervals. To evaluate the agreement between the 2 pharmacists selecting the final TDDs by screening the simulated regimens, a weighted Kappa was calculated.Results1450 concentrations from 268 patients (60.9% male) with mean (IQR) age of 62.8 (52.7, 75) years, weight of 79.1 (63.2, 90.9) kg and CrCl of 76.7 (36.8, 110.6) mL/minute were analyzed. Fit of the model to data was excellent with R2 = 0.98 (Figure 1). AUC attainment with actual dose vs. the AUCs based on the desired dose was poor (Figure 2). Final regression model [ME (95% CI) 31.58 (−160.38, 217.34) mgs; RMSE (95% CI) 761.98 (628.19, 895.93) mgs] identified adjusted body weight (ABW) (P = 0.02), CrCl (P < 0.001), age (P = 0.05) and sex (P = 0.01) on day 1, vs. CrCl (P < 0.001), age (P = 0.02) and sex (P = 0.002) on day 2 as predictors of TDD. Kappas showed near perfect agreement for day 1 (0.992, P < 0.01) and day 2 (0.883, P < 0.01) between the raters resulting in the selection of the final dosing regimens (Figures 3 and 4).ConclusionOur model accurately identified the 4 major variables most likely to explain VAN variability in predicting AUC in the first 48 hours. These detailed dosing recommendations—strengthened by rigorous external validation and near perfect between rater agreements—allow for the design of safe and effective AUC driven empiric dosing regimens. Disclosures All authors: No reported disclosures.

Clinical Outcomes of Hospital-Acquired and Healthcare-Associated Pneumonia With and Without Empiric Vancomycin in a Noncritically Ill Population

Background Recent evidence suggests that not all patients diagnosed with hospital-acquired pneumonia (HAP) and healthcare-associated pneumonia (HCAP) are at risk for methicillin-resistant Staphylococcus aureus. The objective of the study was to examine outcomes of noncritically ill HAP/HCAP patients who received empiric vancomycin compared with those who did not. Methods This was a multicenter retrospective cohort study. Chart review was used to identify HAP/HCAP patients for study inclusion. Treatment groups were patients who received empiric vancomycin versus those who did not. Primary outcome was clinical success at the time of antibiotic completion or discharge for pneumonia treatment. Secondary outcomes included c, time to clinical stability, all-cause mortality, time to antibiotic de-escalation, and 30-day readmission rates for pneumonia. Safety was examined by rates of nephrotoxicity. Results A total of 279 patients met study criteria (105 vancomycin vs. 174 nonvancomycin). There was no significant difference in clinical success (vancomycin 93.3% vs. nonvancomycin 96.6%; P = 0.124). The vancomycin group had longer length of stay (P &lt; 0.001) and time to therapy deescalation (P &lt; 0.001). No significant difference was observed in hospital all-cause mortality and 30-day readmission for pneumonia. Patients who did not receive vancomycin reached clinical stability faster. Rate of nephrotoxicity was similar between both groups (vancomycin 33.3% vs nonvancomycin 28.7%; P = 0.437). Conclusions No difference in clinical success was observed for empiric vancomycin therapy. This study supports the updated HAP guideline that empiric vancomycin therapy may not be necessary in this population.

MRSA colonization status as a predictor of clinical infection: A systematic review and meta-analysis

Vancomycin is often used as empiric therapy for methicillin-resistant Staphylococcus aureus (MRSA), but can be associated with clinically important adverse events including renal failure. MRSA colonization swabs are primarily used for infection control; their use as a diagnostic test to inform the decision to add empiric vancomycin therapy has not been well elucidated. We performed a Medline and Embase systematic review for peer-reviewed studies reporting the diagnostic accuracy of using MRSA colonization status to predict MRSA infections. Meta-analysis was performed using Cochrane guidelines. Grey literature was excluded. 29 studies were included involving 24225 patients. In cases where the pathogen is not known to be S. aureus, specificities were greater than 85% for bacteremia, lower respiratory tract infections, skin and soft tissue infections (SSTI), and all infections pooled together. Sensitivities ranged between 54.0% and 77.5%. In cases where the pathogen is known to be S. aureus, we found studies on bacteremia and SSTI and arrived at pooled estimates of sensitivities ranging between 56.6% and 56.9%, and of specificities greater than 91%. Most importantly, for most infections in settings where the prevalence of MRSA as a causative organism is below 15%, the negative predictive value of a negative MRSA colonization swab exceeds 90%. In settings of low-moderate MRSA prevalence, negative MRSA screening swabs may prevent unnecessary vancomycin use. More research is needed to assess if this strategy can mitigate the cost of screening in areas with a low MRSA colonization rate.

Rate of positive cultures necessitating definitive treatment in patients receiving empiric vancomycin therapy.

Vancomycin is a commonly prescribed empiric antibiotic used when methicillin-resistant Staphylococcus aureus (MRSA) infection is suspected. In this study, we aimed to determine the rate of culture-positive infection requiring vancomycin therapy.

The Role of Negative Methicillin-Resistant Staphylococcus aureus Nasal Surveillance Swabs in Predicting the Need for Empiric Vancomycin Therapy in Intensive Care Unit Patients.

OBJECTIVES The role of methicillin-resistant Staphylococcus aureus (MRSA) nasal surveillance swabs (nasal swabs) in guiding decisions about prescribing vancomycin is unclear. We aimed to determine the likelihood that patients with negative MRSA nasal swabs develop subsequent MRSA infections; to assess avoidable vancomycin days for patients with negative nasal swabs; and to identify risk factors for having a negative nasal swab and developing a MRSA infection during the intensive care unit (ICU) stay. METHODS This retrospective cohort study was conducted in 6 ICUs at a tertiary-care hospital from December 2013 through June 2015. The negative predictive value (NPV), defined as the ability of a negative nasal swab to predict no subsequent MRSA infection, was calculated. Days of vancomycin continued or restarted after 3 days from the collection time of the first negative nasal swab were determined. A matched case-control study identified risk factors for having a negative nasal swab and developing MRSA infection. RESULTS Of 11,441 patients with MRSA-negative nasal swabs, the rate of subsequent MRSA infection was 0.22%. A negative nasal swab had a NPV of 99.4% (95% confidence interval [CI], 99.1%-99.6%). Vancomycin was continued or started after nasal swab results were available in 1,431 patients, translating to 7,364 vancomycin days. No risk factors associated with MRSA infection were identified. CONCLUSIONS In our hospital with a low prevalence of MRSA transmission, a negative MRSA nasal swab was helpful in identifying patients with low risk of MRSA infection in whom empiric vancomycin therapy could be stopped and in whom the subsequent initiation of vancomycin therapy during an ICU admission could be avoided. Infect Control Hosp Epidemiol 2018;39:290-296.

Empirical Vancomycin Dosing in Pediatric Patients with Congenital Heart Disease and the Impact of Cardiopulmonary Bypass on Trough Concentrations.

To determine the optimal vancomycin dosing regimen to achieve empirical goal trough concentrations in pediatric patients with congenital heart disease and to examine the impact of cardiopulmonary bypass on vancomycin dosing requirements. Patients younger than 18 years admitted to the pediatric cardiovascular intensive care unit (CVICU) at our institution from October 1, 2012-December 31, 2014, who received at least one dose of vancomycin, were reviewed retrospectively. Included patients had a steady-state vancomycin trough concentration drawn during the study period. The first steady-state vancomycin trough drawn after being initiated on empirical vancomycin therapy was analyzed for each patient. Excluded patients were those who received mechanical circulatory support, any form of renal replacement therapy, or had a serum creatinine result greater than 1.0 mg/dl on the day of vancomycin initiation. Overall, 77 patients met inclusion criteria, of which 57.1% had undergone cardiopulmonary bypass (CPB) before CVICU admission. Median age was 62 days (interquartile range [IQR] 8.3-176 days). Median daily vancomycin dose was 36.25 mg/kg/day (IQR 29-40 mg/kg/day), resulting in a median steady-state trough of 10.0 μg/ml (IQR 6.3-12.9 μg/ml). Therapeutic troughs occurred in 50.6% of patients; supratherapeutic and subtherapeutic concentrations were attained in 18.2% and 31.2% of patients, respectively. A subgroup analysis of patients who were post-CPB revealed that the only additional variable to affect vancomycin trough concentrations was aortic cross-clamp time (median 56 min, IQR 0-123.3 min, p=0.02). Empirical vancomycin dosing to achieve troughs of 8-15 μg/dl in patients with congenital heart disease without evidence of significant acute kidney injury should be 30 mg/kg/day for neonates, 35-40 mg/kg/day for infants, and 45 mg/kg/day in children, with adjustments required for patients with elevated creatinine or significant aortic cross-clamp time. The receipt and duration of CPB did not affect total daily vancomycin dose requirements.

Effect of the Methicillin-Resistant Staphylococcus aureus Nasal Polymerase Chain Reaction on Vancomycin Days and Clinical Outcomes in Pneumonia

BackgroundPrevious studies have demonstrated that the methicillin-resistant Staphylococcus aureus(MRSA) nasal polymerase chain reaction (PCR) assay has a high negative predictive value for MRSA pneumonia, and that a negative result may be used to guide antibiotic de-escalation. Despite increasing use in clinical practice, limited data exist regarding the impact of nasal MRSA testing on the duration of MRSA-directed therapy and patient outcomes. This study evaluated the effect of the MRSA nasal PCR result on vancomycin days and clinical outcomes in patients treated for pneumonia with empiric vancomycin therapy.MethodsA retrospective study of adult inpatients with an MRSA nasal PCR assay ordered between January 2015 and September 2015 was conducted. Patients with confirmed or presumed pneumonia and who were treated with empiric vancomycin therapy were included. Outcomes were compared for patients with a negative vs. a positive MRSA nasal PCR result. The primary outcome was the number of days of vancomycin therapy. Secondary outcomes included restart of vancomycin within 7 days, length of hospitalization, 30-day readmission, 30-day mortality, and predictive value of the MRSA PCR assay. Analyses were performed for the overall cohort and a propensity score-matched cohort.Results324 patients were included. In the overall cohort, the median duration of vancomycin therapy was 3 (interquartile range [IQR] 2–6) days in the negative MRSA nasal PCR group (n = 282) and 6 (IQR 4–9) days in the positive nasal PCR group (n = 42), P < 0.01. In the propensity score-matched cohort, the median number of vancomycin days was 3 (IQR 2–5) and 5 (IQR 4–8.5) in the negative (n = 137) and positive (n = 39) nasal PCR groups, respectively, P < 0.01. This difference persisted in an additional analysis of only patients with no positive respiratory cultures. No significant differences were observed in any secondary outcomes. The MRSA PCR assay demonstrated a positive predictive value of 45% and a negative predictive value of 98%.ConclusionA negative MRSA nasal PCR correlated with fewer days of vancomycin therapy without negatively impacting other clinical outcomes. The use of the MRSA nasal PCR assay may reduce the duration of MRSA-active therapy in PCR-negative patients.Disclosures All authors: No reported disclosures.