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Intravenous versus Oral Step-Down for the Treatment of Staphylococcus aureus Bacteremia in a Pediatric Population

Department of Pharmacy, Grandview Medical Center, Birmingham, AL 35243, USA
Department of Antimicrobial Stewardship, University of Mississippi Medical Center, Jackson, MS 39216, USA
Department of Pharmacy Practice, University of Mississippi School of Pharmacy, Jackson, MS 39216, USA
Author to whom correspondence should be addressed.
Pharmacy 2022, 10(1), 16;
Submission received: 13 December 2021 / Revised: 7 January 2022 / Accepted: 12 January 2022 / Published: 15 January 2022
(This article belongs to the Special Issue Improving Antimicrobial Use in Hospitalized Patients)


Limited data are available regarding optimal antimicrobial therapy for Staphylococcus aureus bacteremia (SAB) in pediatric patients. The purpose of this study was to assess clinical characteristics and outcomes associated with intravenous (IV) versus oral step-down treatment of pediatric SAB. This study evaluated patients aged 3 months to 18 years that received at least 72 h of inpatient treatment for SAB. The primary endpoint was 30-day readmission. Secondary endpoints included hospital length of stay and inpatient mortality. One hundred and one patients were included in this study. The median age was 7.9 years. Patients who underwent oral step-down were less likely to be immunocompromised and more likely to have community-acquired SAB from osteomyelitis or skin and soft tissue infection (SSTI). More patients in the IV therapy group had a 30-day readmission (10 (25.6%) vs. 3 (5.3%), p = 0.006). Mortality was low (5 (5%)) and not statistically different between groups. Length of stay was greater in patients receiving IV therapy only (11 vs. 7 days, p = 0.001). In this study, over half of the patients received oral step-down therapy and 30-day readmission was low for this group. Oral therapy appears to be safe and effective for patients with SAB from osteomyelitis or SSTIs.

1. Introduction

Known for its virulence, Staphylococcus aureus can cause significant morbidity and mortality in both pediatric and adult patients. This is particularly true for those with invasive disease, such as bloodstream or endovascular infections [1]. Mortality appears to be lower in the pediatric population than in adults [1,2,3]; however, concern for morbidity, including disease and treatment-related complications, remains [2,4,5].
Extensive research has been conducted on the treatment of adult patients with S. aureus infections [1,6,7,8,9,10,11,12]. In contrast to the abundant literature on adult patients with S. aureus bacteremia (SAB), there is a paucity of evidence to guide practitioners in the treatment of pediatric patients. In the majority of pediatric patients, SAB is associated with bone and joint infections [3,4], whereas adult infections are often related to catheters or other medical devices [1]. These differences in etiology between adults and children make it difficult to know if adult treatment recommendations should be applied in children.
The use of oral antibiotics for SAB has yet to be validated by prospective, randomized controlled trials and has only been evaluated by a select few studies, most of which involved subgroup analyses of larger studies where the predominant number of patients were nonbacteremic [5,13,14,15]. Two retrospective [16,17] and one prospective cohort [18] studies that evaluated oral therapy for adult patients with SAB demonstrated low incidence of complications and similar mortality to patients who received a full course of intravenous therapy. It is important to note that these studies included a majority of patients with low-risk methicillin-susceptible SAB, which limits applicability in settings of higher acuity, more serious infections, or where methicillin resistance may be more prevalent. Only one study has evaluated oral therapy for SAB in children [5]. This study evaluated patients with bacteremic osteoarticular infections and revealed that short-term IV treatment followed by a course of oral therapy may be reasonable in certain pediatric patients.
Possibly as a result of the limited data available, one challenge with SAB in children is the lack of consistency in treatment across institutions. A survey of pediatric infectious diseases (ID) providers revealed wide variability in the treatment of SAB. For patients with osteomyelitis-associated SAB, 50% of providers switched to oral antibiotics for nonpersistent bacteremia and 22% switched after clinical improvement. For nonpersistent, non-osteomyelitis-associated SAB, 54% of providers switched patients to oral antibiotics after receiving empiric vancomycin [14].
The practices at our institution for selecting IV or oral therapy for SAB are heterogeneous in pediatric patients. The goal of this study was to compare the clinical characteristics and outcomes of pediatric patients receiving a full course of IV therapy to those receiving oral step-down treatment for SAB from any source.

2. Materials and Methods

This retrospective cohort was conducted at a tertiary academic medical center and evaluated patients admitted between 1 June 2012 and 19 November 2018. Patients with a positive blood culture were identified using TheraDoc® Clinical Surveillance Software (Premier, Inc., Charlotte, NC, USA) and included if they were between the ages of 3 months and 18 years, had a blood culture positive for S. aureus, and received at least 72 h of inpatient IV treatment. Exclusion criteria were as follows: pregnancy, death within 72 h of initial culture, hospice or palliative care, and polymicrobial bacteremia. For patients with multiple incidences of bacteremia within the study period, only the first qualifying admission was included. Data was collected using Research Electronic Data Capture (REDCap™) (Vanderbilt University, Nashville, TN, USA) [19]. Positive cultures were identified initially using a BD BACTEC FX® instrument (Becton Dickinson, Franklin Lakes, NJ, USA). Prior to 2016, samples demonstrating Gram-positive cocci on Gram stain were identified using biochemical testing and then confirmed using Vitek2 (bioMerieux, Durham, NC, USA). In 2016, this process was changed to include the identification of Gram-positive cocci via a Biofire FilmArray® Blood Culture ID Panel (Salt Lake City, UT, USA), then confirmed using matrix-assisted laser desorption–ionization time-of-flight mass spectrometry with VitekMS and Vitek2 (bioMerieux, Durham, NC, USA).

2.1. Endpoints

The primary endpoint was the rate of 30-day readmissions for patients receiving a full course of IV treatment compared to those who received oral step-down therapy. Secondary endpoints included time to microbiological cure, infection-related length of stay, total hospital length of stay, total duration of therapy, clinical failure at 90 days, 90-day readmission rates, rates of pediatric intensive care unit (PICU) admission, attributable inpatient mortality, all-cause inpatient mortality, and rates of adverse drug reactions (ADRs).

2.2. Definitions

Oral step-down treatment was defined as a transition from IV antistaphylococcal therapy to oral antistaphylococcal therapy after a minimum of 72 h of IV treatment. Community-acquired infection was defined as initial positive blood cultures that were drawn within 48 h of admission, whereas hospital-acquired infection was defined as positive cultures drawn ≥48 h after admission. Healthcare-associated infection was defined as a community-onset infection plus the presence of a medical device in situ.
Microbiological cure was defined as negative blood cultures following the initial positive culture; any further blood cultures within one week of the first negative culture were required to remain negative to confirm microbiological cure (i.e., microbiological cure was not demonstrated if clearance of one blood culture was documented, but a following culture the next day returned positive).
Clinical failure at 90 days was defined as a composite of readmission within 90 days and/or recurrence of bacteremia. Recurrence of bacteremia was defined as a new culture positive for S. aureus that was separated by at least 7 days (but no more than 30 days) from the last positive blood culture for S. aureus with at least one negative blood culture in the interim period. Reinfection was defined as a new culture positive for S. aureus that was separated by at least 30 days from the last positive blood culture for S. aureus with at least one negative blood culture in the interim period.