
==== Front
Turk Arch Pediatr
Turk Arch Pediatr
Turkish Archives of Pediatrics
2757-6256
Turkish Pediatrics Association

10.5152/TurkArchPediatr.2024.24108
tap-59-5-469
Original Article
Clinical Outcomes of Oral Antibiotic Switch in Children with Staphylococcus aureus Bacteremia
Demirhan Salih 12http://orcid.org/0000-0001-5476-0353

Anosike Brenda I. 12http://orcid.org/0000-0002-5172-3036

1 Albert Einstein College of Medicine, Bronx, New York
2 Children’s Hospital at Montefiore, Bronx, New York
Corresponding author:Brenda I. Anosike ક banosike@montefiore.org
Cite this article as: Demirhan S, Anosike BI. Clinical outcomes of oral antibiotic switch in children with Staphylococcus aureus bacteremia. Turk Arch Pediatr. 2024;59(5):469-475 .

9 2024
01 9 2024
59 5 469475
15 5 2024
11 7 2024
2024 authors
2024
authors
https://creativecommons.org/licenses/by-nc/4.0/ Content of this journal is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Objective:

Staphylococcus aureus is one of the leading causes of bacteremia in children. In this study, we aimed to evaluate our center’s experience on the etiology, management, and outcomes of pediatric Staphylococcus aureus bacteremia (SAB) with particular focus on transitioning to oral antibiotic therapy.

Materials and Methods:

This retrospective cohort study included children aged ≤ 19 years diagnosed with SAB over a 5-year period. The main outcome was poor clinical outcome related to SAB defined as (1) recurrence of SAB within 30 days after discontinuation of SAB treatment and (2) any-cause mortality within 30 days after detection of SAB.

Results:

Over a 5-year period, 88 SAB episodes of 76 unique patients were included. The most common source of SAB attributed to central line (n = 34), followed by osteoarticular (n = 24), infections. All patients received at least one day of intravenous (IV) antibiotics and treatment was switched to an oral agent in 45.5% of SAB episodes. Sources of SAB in the oral switch group were osteoarticular (n = 21), skin and soft tissue (n = 7), central line (n = 3), thrombophlebitis (n = 2), head and neck infection (n = 1), and unknown (n = 6). 30-day mortality and SAB recurrence within 30 days after initial treatment completion occurred in 3 and 5 SAB episodes, respectively. None of the patients in oral switch group had poor clinical outcomes.

Conclusion:

Our study results indicate that 30-day any-cause mortality and SAB-related mortality is low in children. Similar to growing adult literature, oral switch in SAB treatment was not associated with poor SAB outcomes in selected patients.

Keywords

Staphylococcus aureus bacteremia
oral switch
step-down
This study received no funding.
==== Body
pmcWhat is already known on this topic?

Recent clinical trials demonstrated the safety and efficacy of oral switch in adult patients with uncomplicated Staphylococcus aureus bacteremia. However, the pediatric literature is limited.

What this study adds on this topic?

Our findings indicate that 30-day any-cause mortality and SAB-related mortality is low in children.

Our results add to the growing, albeit limited, body of infectious disease and pediatric literature, demonstrating oral switch for SAB maybe a reasonable and safe approach in a selected group of patients, particularly in uncomplicated SAB.

Introduction

Staphylococcus aureus is one of the major causative pathogens of invasive diseases in children and adults presenting with a wide clinical spectrum that ranges from skin and soft tissue infections, pneumonia, and osteoarticular conditions to more serious, life- threatening infections such as bacteremia and septicemia.1 Management of Staphylococcus aureus bacteremia (SAB) can often be challenging due to several factors. As a defense mechanism, S. aureus biofilm production evades the host’s innate immune system, rendering it impenetrable to various antibiotics, and makes S. aureus prone to re-colonization while increasing the risk of metastatic infections such as septic emboli and vertebral abscess.2,3

The burden of SAB significantly differs between adults and children with SAB-associated complications and mortality occurring at much lower rates in children compared to adults.1,4,5 A recent systematic review reported a 30-day mortality rate of 18.1% in adult patients with SAB6 whereas pediatric studies have reported a mortality rate of ~3%.1,4,5 Accordingly, treatment guidelines for SAB differ between adult and children with longer parenteral therapy often recommended/utilized for adults with uncomplicated SAB compared to children.7 However, this paradigm has been shifting with several recent studies examining the efficacy and safety of shorter intravenous (IV) and total antibiotic treatment in adults with (uncomplicated) SAB.8,9 Pediatric data. however, remains limited.

In this retrospective study, we aimed to evaluate our center’s 5-year experience on the etiology, management, and outcomes of pediatric SAB with particular focus on transitioning to oral antibiotic therapy.

Materials and Methods

Study Design and Patient Population

This retrospective cohort study included children aged ≤ 19 years diagnosed with SAB over a 5-year period between January 2019 and December 2023 at the Children’s Hospital at Montefiore in the Bronx, NY, USA. Patients admitted to the neonatal intensive care unit and those who did not complete their SAB treatment course at our hospital were excluded from the study.

Patients with SAB were identified using microbiology database of an electronic medical record (EMR) system. All charts were then reviewed by the authors. Demographic, clinical, and laboratory data were collected and recorded. Each SAB episode was counted separately. A unique patient may have more than one SAB episode if a subsequent episode was identified at any time after discontinuation of prior SAB treatment.

Definitions and Outcome Measures

The main outcome of this study was poor clinical outcome related to SAB defined as (1) recurrence of SAB within 30 days after discontinuation of SAB treatment, (2) any-cause mortality within 30 days after initial detection of SAB. Any deaths that occurred within 30 days were also included as a poor clinical outcome. The cause of death was assessed by the study author upon review of available documentation by the primary treating clinicians in the EMR. The rates of SAB-associated poor clinical outcomes were evaluated between two different group comparisons: (1) methicillin-sensitive Staphylococcus aureus (MSSA) infections versus methicillin-resistant Staphylococcus aureus (MRSA) and (2) IV to oral antibiotic switch versus non-oral antibiotic switch.

As a secondary outcome, we evaluated treatment outcomes of oral switch in SAB. Patients who started and completed SAB treatment with intravenous (IV) antibiotics were classified as the “non-oral switch” group whereas patients who received an active oral S. aureus antibiotic after an IV course were classified as the “oral switch” group.

The duration of SAB was defined as the time difference between the first and the last positive blood culture with S. aureus growth. In cases where there was only one positive blood culture, the duration of SAB was recorded as one day. Complicated SAB was defined as SAB with metastatic foci or persistent SAB. Persistent bacteremia was defined as SAB lasting > 3 consecutive days. For the purposes of this study, targeted antibiotic treatments after antimicrobial susceptibility results were recorded. Empiric antibiotics were not recorded. Dual antibiotic treatment was defined as utilization of two S. aureus (SA)-active antibiotics administered concomitantly. Outpatient parenteral antibiotic therapy (OPAT) was defined as continuation of parenteral antibiotics after hospital discharge through an established central venous catheter or similar either at home or nursing facility. Detection of SAB ≥ 48 hours after hospital admission was accepted as a nosocomial infection.

Microbiological Process

Blood cultures were collected in pediatric bottles under sterile conditions and incubated in automated machines. Bacterial identification was done using MALDI-TOF (Bruker, Billerica, Md, USA). Assessment of methicillin resistance was done by rapid polymerase chain reaction (PCR) test, The Xpert® MRSA/SA blood culture assay (Cepheid, Sunnyvale, California, USA) and confirmed with classical antimicrobial susceptibility testing. Antimicrobial susceptibility testing was performed using BD Phoenix™ (Becton Dickinson, Franklin Lakes, NJ, USA) automated identification and susceptibility testing system in conjunction with The Clinical and Laboratory Standards Institute (CLSI) guidelines. Routinely reported antibiotic panel for blood culture antimicrobial susceptibility testing for MSSA were oxacillin, clindamycin, trimethoprimsulfamethoxazole (TMP-SMX), tetracycline, and additionally vancomycin for MRSA. Additional antibiotic susceptibility tests were performed and reported upon clinicians’ requests.

Ethical Considerations

This study was approved by Albert Einstein College of Medicine Institutional Review Board with a waiver of informed consent (No. 2022-13796, Amendment approval date: March 21, 2024).

Statistical Analysis

Categorical variables were presented as count and percentages. Distribution of continuous variables were assessed by histograms, skewness, and kurtosis tests. Continuous variables with non-normal distribution were presented as median and interquartile range (IQR). Demographic and clinical data were compared between groups (MSSA vs. MRSA and oral antibiotic switch vs. no oral antibiotics switch). Comparisons were made using chi-square or Fisher exact test for categorical variables and Mann-Whitney U for continuous variables. Multivariable regression analysis was not done due to low event (poor outcome) number. A P-value <.05 was considered statistically significant. All statistical analyses were performed using Stata 17.0 (StataCorp, College Station, Texas, USA). Figure 1 was created with GraphPad Prism 10 (GraphPad Software Inc., San Diego, California, USA).

Results

Demographics and Clinical Features of SAB

Over a 5-year period, 90 SAB episodes of 78 unique patients were identified. Two patients were transferred out to an outside hospital and were therefore excluded from the analysis/dataset. A total of 88 SAB episodes of 76 patients were included in the final analysis. The median age was 7.0 (1.3-12.9) years, and 51 patients (67.1%) were male; 40.8% were Hispanic and 34.2% were black. The median duration of SAB was 2 (1-3) days, with the most common source attributed to central line (n = 34), followed by osteoarticular (n = 24), skin and soft tissue (n = 9), and head and neck infections (n = 5). Of those with central-lined-associated SAB, line removal was performedin 58.8% of episodes (20/ 34), while salvage therapy with line retention occurred in 41.1% (14/34) SAB episodes. As a part of salvage therapy, vancomycin and ethanol lock were applied in 9 and 1 SAB episodes, respectively. A pediatric infectious diseases consultation was requested and involved in all SAB cases. Transthoracic and transesophageal echocardiogram were performed in 64.8% of all SAB episodes, and infective endocarditis was detected in 2 cases. Eighteen SAB episodes were complicated by metastatic foci with pulmonary septic emboli as the most common site (n = 8) followed by endovascular (n = 7). Nearly one-third of SAB episodes (30.6%) were MRSA. There was no statistically significant difference in demographics and basic clinical findings between patients with MSSA and MRSA. However, metastatic foci were significantly more common in the MRSA compared to the MSSA group (33.3% vs, 15.33%, P = .04). (Table 1)

Antimicrobial Susceptibility and Treatment of SAB

MSSA isolates were susceptible to TMP-SMX in 95.1% of SAB episodes, tetracycline in 83.6% of SAB episodes, and clindamycin in 70.5% of SAB episodes. Antibiotic resistance to at least one of the aforementioned antibiotics was detected in 42.6% of MSSA isolates. All 27 MRSA isolates were susceptible to vancomycin and all of those tested were also susceptible to daptomycin and linezolid. Susceptibility of MRSA isolates to TMP-SMX, clindamycin, and tetracycline were 92.6%, 88.9%, and 85.2%, respectively (Figure 1). Cefazolin (n = 25) and oxacillin (n = 16) were the most commonly prescribed antibiotics in the MSSA group while vancomycin (n = 14) and daptomycin (n = 12) were utilized more in the MRSA group. The median total duration and IV SAB treatment were 26 (14-37) days and 15 (7-28) days, respectively. Nearly 40% of the patients received a total of ≤14 days of antibiotics after clearance of the bacteremia. All patients received at least 1 day of IV antibiotics and treatment was switched to an oral agent in 45.5% (40/88) of SAB episodes. The most prescribed oral antibiotics were cephalexin (n = 22) in the MSSA group and clindamycin (n = 8) in the MRSA group. Eight (9.1%) of the SAB episodes were treated with dual SA active antibiotics, more commonly in the MRSA group compared to the MSSA group (22.2% vs. 3.3%, P = .004). In 27 (30.7%) SAB episodes, patients were discharged from hospital on OPAT (Table 2).

Outcomes of SAB

The median hospital length of stay (LOS) was 16 (9-34) days; intensive care unit and mechanical ventilatory support were required in 25 (28.4%) and 14 (15.9%) SAB episodes, respectively. The main study outcomes, 30-day mortality and SAB recurrence within 30 days after initial treatment completion occurred in 3 (3.4%) and 5 (5.7%) SAB episodes, respectively. Intensive care, need for ventilatory support, and 30-day mortality was more common in the MRSA group compared to the MSSA group (44.4% vs. 21.3% P = .02, 37.0% vs. 6.6% P = .001, 11.1% vs. 0% P = .03, respectively) (Table 1). All 5 patients with SAB recurrence had a retained central line. Thirty-day mortality was observed in 3 patients with one associated with SAB and the other 2 due to an underlying chronic disease. Patients with SAB-related mortality presented with MRSA sinusitis associated with intracranial extension and multiple metastatic foci. Details of SAB episodes with poor clinical outcomes are presented in Supplementary Table 1.

Oral Antibiotic Switch in SAB Treatment

The proportion of patients with a central line at SAB detection was lower in the oral switch group compared to non-oral switch group (7.5% vs. 64.6%, P < .001). The source of the SAB significantly differed between the oral switch and non-oral switch groups (p < .001): with the majority of SAB episodes associated with an osteoarticular source (52.5%) for the oral switch group, and the central line as the most common source in the non-oral switch group (64.6%). Duration of IV antibiotics was significantly shorter in oral switch group (7 vs. 19 days, P < .001). None of the patients in the oral switch group had poor clinical outcomes (Table 3).

Discussion

The incidence of invasive bacterial infections in children has decreased significantly after introduction of Streptococcus pneumoniae and Haemophilus influenzae vaccines.10 In the absence of an effective vaccine against S. aureus, it currently is one of the leading causes of bacteremia in both adults and children.11,12 SAB causes significant mortality and morbidity albeit less in the pediatric population.4 In this 5-year retrospective study, we described 88 SAB episodes of 76 unique patients and with a 30-day all-cause mortality rate of 3.4%. This mortality rate was similar to previously published pediatric studies from developed countries.4,13,14 Despite a low mortality rate, ~20% of the cohort had metastatic foci with the presence of metastatic foci and mortality more commonly observed in patients with MRSA bacteremia. A higher proportion of complications and poor clinical outcomes associated with MRSA compared to MSSA has been well-described in the literature and is thought to be related to several MRSA virulence factors.4,15

Traditionally, SAB has been treated with a prolonged IV antibiotic course due to concerns for significant complications and higher risk of treatment failure. For uncomplicated SAB, at least 2 weeks of IV treatment is often utilized while complicated SAB is often treated with 4-6 weeks of antibiotics. However, there is growing interest in the role of oral treatment in adults and children16 due to socioeconomic barriers and adverse events related to prolonged IV access. Recent clinical trials have demonstrated non-inferiority with partial oral treatment compared to all IV treatment for uncomplicated SAB in adults.17 The use of an oral antibiotic group has been commonly utilized in children with SAB of osteoarticular origin, particularly with a known IV to peroralbioequivalent agents and known antimicrobial susceptibilities where applicable. This practice has increasingly gained popularity in the setting of challenges including establishing long-term IV access in young children, heightened risk of line-associated complications such discomfort, potential acquisition of a secondary infection, bleeding, and psychological distress for the patient and/or families. The Infectious Diseases Society of America (IDSA) and Pediatric Infectious Diseases Society (PIDS) published hematogenous osteomyelitis and bacterial arthritis guidelines in 2021 and 2023, respectively where oral switch after initial good response to IV treatment is recommended for most osteoarticular infections in the setting of uncomplicated SAB.18,19 In our study, we show successful utilization of oral switch in 40 SAB episodes with various sources (~half osteoarticular) and none had poor outcomes. Although current guidelines, suggest oral switch for uncomplicated SAB, oral switch was achieved in 10 SAB episodes that did not meet uncomplicated SAB criteria (5 metastatic focus and 5 persistent SAB) without poor clinical outcomes at 30 days. A growing body of adult data appear to suggest successful use of oral switch treatment even in patients with complicated SAB who could not complete IV treatment.20

Another challenge in SAB management is continued emergence of antimicrobial resistance (AMR) which limits oral antibiotic options. In this study, rates of clindamycin resistance were found in 28% of MSSA isolates; 42.6% were resistant to at least one of three oral antibiotics, (clindamycin, TMP-SMX, or tetracycline). These results are representing concerning AMR trends for these commonly prescribed oral therapies indicated for osteoarticular infections due to their ability to achieve excellent tissue distribution and used as alternative therapeutic agent penicillin allergic patients. Another large US based pediatric study showed comparable high rates of clindamycin resistance reporting 21.5% of clindamycin-resistant MSSA isolates from blood cultures. Though, the authors purported much higher rates of clindamycin-resistant MRSA isolates compared to our study (39.9% vs. 11.1%).21 However, a single-center study from Türkiye reported very low rates of Clindamycin resistance for both MSSA and MRSA healthcare-associated infections (1.8% and 3.5%, respectively).22 Differing resistance rates across the globe shows the importance of local antibiograms in selecting empiric antibiotics as well as the need for antimicrobial stewardship programs in regions with high resistance rates.

Source control is the mainstay of any successful bacteremia treatment along with antibiotics. This principle is particularly important for SAB because of the tendency to cause persistent bacteremia and distant metastasis. In central line-associated bacteremia, source control should be achieved by central line removal. IDSA guidelines recommend catheter removal in all SAB; however, salvage therapy, in some instances, has been e attempted in cases where there is ongoing need for central access and/or inability to obtain alternative venous access.23 In our cohort, all recurrent SAB episodes were in patients with central line-associated SAB with line retention. Recurrence rates was observed in 35.7% (5/14) of SAB episodes managed as catheter salvage therapy. In keeping with our finding, other pediatric studies showed 21.5% failure rates for those managed with salvage therapy for SAB.24 Considering relatively high rates of SAB recurrence, central line removal, where feasible and can be safely done, remains the preferred first line approach in SAB management per IDSA guidelines.

Our study had several limitations that should be considered. First, the retrospective design restricts our ability to establish causal relationships between variables. Second, the small sample size limits the statistical power of our study, potentially affecting the reliability of our findings. Furthermore, the poorer clinical outcomes observed in the non-switch group may reflect greater disease severity at initial presentation. Since the study groups were not randomized, this imbalance in disease severity could have influenced the observed outcomes. Additionally, due to the relatively low number of SAB episodes and poor clinical outcomes, we were unable to perform multivariable regression analysis to adjust for multiple independent variables. Moreover, nearly half of the patients in the oral switch group had an osteoarticular infection related to SAB. Therefore, it is important to recognize that the outcomes observed in our cohort may not generalize to cohorts with different distributions of SAB etiologies. Lastly, our study was conducted at a single center, which may limit the generalizability of our findings to other settings or patient populations.

Conclusion

In conclusion, our study results indicate that 30-day any-cause mortality and SAB-related mortality is low in children. Our study results add to the growing, albeit limited, body of infectious disease and pediatric literature, demonstrating oral switch for SAB maybe a reasonable and safe approach in a select group of patients, particularly in uncomplicated SAB. Larger prospective pediatric studies are needed to further investigate the safety of oral switch in complicated and uncomplicated SAB of various sources.

Figure 1. Antibiotic susceptibility pattern of Methicillin sensitive Staphylococcus aureus (MSSA) and Methicillin resistant Staphylococcus aureus (MRSA) blood culture isolates. All MSSA (n = 61) and MRSA (n = 27) isolates were tested for oxacillin, clindamycin, trimethoprim-sulfamethoxazole and tetracycline susceptibility. All MRSA isolates were tested for vancomycin susceptibility. Additionally, a subset of isolates was tested for daptomycin (n = 12) and ceftaroline (n = 6) susceptibility.

Table 1. Demographic and Clinical Characteristics of Patients and Staphylococcus aureus Bacteremia Episodes

Patients	Overall, n = 76	MSSA, n = 50	MRSA, n = 26	P	
Age, years, median (IQR)	7 (1.3-12.9)	6.0 (1-10.1)	10 (1.5-15)	.09a	
Sex, male, n (%)	51 (67.1)	30 (60.0)	21 (80.8)	.07b	
Race, n (%)1				.7c	
 Asian	1 (1.5)	1 (2.3)	0		
 Black	26 (38.8)	16 (37.2)	10 (41.7)		
 White	5 (7.5)	3 (7.0)	2 (8.3)		
 Other	35 (52.2)	23 (53.5)	12 (50.0)		
Ethnicity, n (%)1				.9b	
 Hispanic	31 (46.3)	20 (46.5)	11 (45.8)		
 Non-Hispanic	36 (53.7)	23 (53.5)	13 (54.2)		
SAB Episodes	Overall, n = 88	MSSA, n = 61	MRSA, n = 27	P	
Source, n (%)				.1c	
 Central line	34 (38.6)	25 (41.0)	9 (33.3)		
  Osteoarticular	24 (27.3)	17 (27.9)	7 (25.9)		
 Skin and soft tissue	9 (10.2)	6 (9.8)	3 (11.1)		
 Head and neck	5 (5.7)	1 (1.6)	4 (14.8)		
 Thrombophlebitis	3 (3.4)	2 (3.3)	1 (3.7)		
 Pneumonia	2 (2.3)	1 (1.6)	1 (3.7)		
 Pericarditis	1 (1.1)	0	1 (3.7)		
 Unknown	10 (11.4)	9 (14.8)	1 (3.7)		
Duration of SAB, median (IQR)	2 (1-3)	2 (1-3)	2 (1-4)	.3a	
Persistent SAB (>3 days), n (%)	16 (18.2)	9 (14.8)	7 (25.9)	.2b	
Nosocomial, n (%)	21 (23.9)	13 (21.3)	8 (29.6)	.4b	
Central line at SAB detection, n (%)	34 (38.6)	25 (41.0)	9 (33.3)	.5b	
 Central line removal	20/34 (60.6)	14/25 (58.3)	6/9 (66.7)	.7b	
Echocardiogram, n (%)					
 Transthoracic	57 (64.8)	36 (59.0)	21 (77.8)	.09b	
 Transesophageal	2 (2.3)	2 (3.3)	0	.9c	
Echocardiogram result, n (%)					
 Infective endocarditis	2/57 (3.5)	2 (5.6)	0		
 Septic thrombus	2/57 (3.5)	2 (5.6)	0		
 Pericarditis	1/57 (1.8)	0	1 (4.8)		
Metastatic focus*, n (%)	18 (20.5)	9 (14.8)	9 (33.3)	.04 b	
 Pulmonary emboli	8	6	2		
 Endovascular	7	3	4		
 Intracranial	2	1	1		
 Endocarditis	2	0	2		
 Pericarditis	1	1	0		
 Spinal abscess	1	1	0		
Outcomes					
Length of stay, day, median (IQR)	16 (9-34)	16 (9-33)	17 (10-39)	.4a	
Intensive care, n (%)	25 (28.4)	13 (21.3)	12 (44.4)	.02 b	
Ventilatory support, n (%)	14 (15.9)	4 (6.6)	10 (37.0)	.001 c	
30-day mortality, n (%)	3 (3.4)	0	3 (11.1)	0.03 c	
SAB recurrence in 30 days, n (%)	4 (4.6)	4 (6.6)	1 (3.7)	.9c	
*Three patients had more than one focus.

aMann–Whitney U-test.

bChi-square test.

cFisher’s exact test.

1Race and ethnicity were not reported in 9 patients.

Table 2. Treatment of Staphylococcus aureus Bacteremia

	Overall, n = 88	MSSA, n = 61	MRSA, n = 27	P	
Intravenous antibiotics*, n					
 Cefazolin	25	25	0		
 Oxacillin	16	16	0		
 Vancomycin	14	0	14		
 Daptomycin	12	0	12		
 Nafcillin	10	10	0		
 Ceftaroline	6	0	6		
 Others	19	17	2		
Oral antibiotics,* n					
 Cephalexin	22	22	0		
 Clindamycin	10	2	8		
 Linezolid	6	3	3		
 Others	4	3	1		
Total treatment duration, days, median (IQR)	26 (14-37)	25 (14-31)	28 (15-42)	.3 a	
 Intravenous duration	15 (7-28)	15 (7-27)	16 (8-37)	.2 a	
 Oral duration	21 (10-27)	21 (7-26)	23 (10-34)	.3 a	
Dual antibiotic treatment, n (%)	8 (9.1)	2 (3.3)	6 (22.2)	.009 c	
OPAT, n (%)	27 (30.7)	20 (32.8)	7 (25.9)	.5 b	
Oral switch, n (%)	40 (45.5)	29 (47.5)	11 (40.7)	.6 b	
Antibiotic course ≤14 days, n (%)	35 (39.8)	27 (44.3)	8 (29.6)	.2 b	
OPAT, outpatient parenteral antibiotic therapy.

*Some patients received more than one antibiotic.

aMann-Whitney U-test.

bChi-square test.

cFisher’s exact test.

Table 3. Comparison of Demographic and Clinical Findings Between Oral Switch Versus Non-oral Switch Groups

SAB Episodes	Oral Switch, n = 40	Non-oral Switch, n = 48	P	
Age in years, median (IQR)	7.1 (1.4-10.2)	7.6 (1.1-13.4)	.7a	
Central line, n (%)	3 (7.5)	31 (64.6)	<.001 c	
Methicillin, n (%)			.6b	
 Sensitive	29 (72.5)	32 (66.7)		
 Resistant	11 (27.5)	16 (33.3)		
Duration of SAB, days, median (IQR)	2 (1-3)	2 (1-3)	.9a	
Source, n (%)			<.001 c	
 Central line	3 (7.5)	31 (64.6)		
 Osteoarticular	21 (52.5)	3 (6.25)		
 Skin and soft tissue	7 (17.5)	2 (4.2)		
 Head and neck	1 (2.5)	4 (8.3)		
 Thrombophlebitis	2 (5.0)	1 (2.1)		
 Pneumonia	0	2 (4.2)		
 Pericarditis	0	1 (2.1)		
 Unknown	6 (15.0)	4 (8.3)		
Metastatic focus, n (%)	5 (12.5)	13 (27.1)	.1b	
Persistent SAB (>3 days), n (%)	5 (12.5)	11 (22.9)	.2b	
Total treatment duration, days, median (IQR)	29 (14-42)	19 (15-31)	.5a	
 Intravenous duration	7 (4-14)	19 (15-31)	<.001 a	
Oral switch, n (%)				
Antibiotic course ≤14 days, n (%)	15 (37.5)	20 (41.7)	.7b	
Recurrence in 30 days, n (%)	0	5 (10.4)	.06c	
30-day mortality, n (%)	0	3 (6.3)	.2c	
aMann–Whitney U-test.

bChi-square test.

cFisher’s exact test.

Supplementary Table 1. Clinical and Demographics Characteristics of Patients with Poor Staphylococcus aureus Bacteremia Outcomes

N	Failure	Age	Sex	Race	Ethnicity	Methicillin	Source	CL Removal	MF	SAB Duration	Treatment Duration	Oral Switch	Cause of Death	
1	Recurrence 20 days after stopping antibiotics	12.7	Female	Black	Hispanic	Sensitive	Central line	No	No	1	14	No	.	
2	Recurrence 18 days after stopping antibiotics	0.4	Male	Other	Hispanic	Sensitive	Central line	No	No	1	30	No	.	
3	Recurrence 5 days after stopping antibiotics	0.4	Male	Other	Hispanic	Sensitive	Central line	No	No	1	14	No	.	
4	Recurrence 5 days after stopping antibiotics	4.8	Male	Other	Hispanic	Resistant	Central line	No	No	2	19	No	.	
5	Recurrence 25 days after stopping antibiotics	8.9	Female	Other	Hispanic	Sensitive	Central line	No	No	1	14	No	-	
6	Mortality 7 days after detection of SAB	5.6	Male	Black	Not Hispanic	Resistant	Head and neck	.	Yes**	6	7*	No	SAB	
7	Mortality 17 days after detection of SAB	13.3	Male	White	Not Hispanic	Resistant	Central line	No	No	1	17*	No	1	
8	Mortality 25 days after detection of SAB	0.4	Male	Other	Hispanic	Resistant	Central line	Yes	No	4	14	No	2	
*Died during treatment; **Intracranial extension and pulmonary septic emboli; CL, central line; MF, metastatic focus; SAB, Staphylococcus aureus bacteremia.

1, ECMO complication, lung transplant candidate; 2, cessation of comfort care.

Ethics Committee Approval: This study was approved by Albert Einstein College of Medicine Institutional Review Board (approval number: 2022-13796; date: March 21, 2024).

Informed Consent: Informed consent was waived due to retrospective nature of the study.

Peer-review: Externally peer-reviewed.

Author Contributions: Concept – S.D., B.I.A.; Design – S.D., B.I.A.; Supervision – B.I.A.; Resources – S.D., B.I.A.; Materials – S.D., B.I.A.; Data Collection and/or Processing – S.D.; Analysis and/or Interpretation – S.D., B.I.A.; Literature Search – S.D., B.I.A.; Writing – S.D., B.I.A.; Critical Review – B.I.A.

Declaration of Interests: The authors have no conflicts of interest to declare.
==== Refs
References

1. Gordon O Cohen MJ Gross I , et al. Staphylococcus aureus bacteremia in children: antibiotic resistance and mortality. Pediatr Infect Dis J. 2019;38 (5 ):459 463. (10.1097/INF.0000000000002202)30239476
2. Peng Q Tang X Dong W Sun N Yuan W . A review of biofilm formation of Staphylococcus aureus and its regulation mechanism. Antibiotics (Basel). 2022;12 (1 ). (10.3390/antibiotics12010012)
3. Clerc Berestein MÁ Salerno MC Giralda RN Ferrer ML Gil MF Fasano MV . Metastatic infections in pediatric patients with Staphylococcus aureus bacteremia assisted at a Children's Hospital in La Plata, Argentina. Arch Argent Pediatr. 2021;119 (6 ):408 413. Metástasis infecciosas en pacientes pediátricos con bacteriemia por Staphylococcus aureus asistidos en el Hospital de Niños de La Plata. (10.5546/aap.2021.eng.408)34813234
4. Campbell AJ Al Yazidi LS Phuong LK , et al. Pediatric Staphylococcus aureus Bacteremia: Clinical Spectrum and Predictors of Poor Outcome. Clin Infect Dis. 2022;74 (4 ):604 613. (10.1093/cid/ciab510)34089594
5. Hamdy RF Dona D Jacobs MB Gerber JS . Risk factors for complications in children with Staphylococcus aureus bacteremia. J Pediatr. 2019;208 :214 220.e2. (10.1016/j.jpeds.2018.12.002)30879729
6. Bai AD Lo CKL Komorowski AS , et al. Staphylococcus aureus bacteraemia mortality: a systematic review and meta-analysis. Clin Microbiol Infect. 2022;28 (8 ):1076 1084. (10.1016/j.cmi.2022.03.015)35339678
7. Sanchez MJ Patel K Lindsay EA , et al. Early transition to oral Antimicrobial Therapy among children with Staphylococcus aureus bacteremia and acute hematogenous osteomyelitis. Pediatr Infect Dis J. 2022;41 (9 ):690 695. (10.1097/INF.0000000000003594)35703303
8. Wildenthal JA Atkinson A Lewis S , et al. Outcomes of partial oral antibiotic treatment for complicated Staphylococcus aureus bacteremia in people who inject drugs. Clin Infect Dis. 2023;76 (3 ):487 496. (10.1093/cid/ciac714)36052413
9. Grillo Perez S Diaz-Brochero C Garzon Herazo JR Muñoz Velandia OM . Short-term versus usual-term antibiotic treatment for uncomplicated Staphylococcus aureus bacteremia: a systematic review and meta-analysis. Ther Adv Infect Dis. 2024;11 :20499361241237615. (10.1177/20499361241237615)38476737
10. Herz AM Greenhow TL Alcantara J , et al. Changing epidemiology of outpatient bacteremia in 3- to 36-month-old children after the introduction of the heptavalent-conjugated pneumococcal vaccine. Pediatr Infect Dis J. 2006;25 (4 ):293 300. (10.1097/01.inf.0000207485.39112.bf)16567979
11. de Kraker ME Jarlier V Monen JC Heuer OE van de Sande N Grundmann H . The changing epidemiology of bacteraemias in Europe: trends from the European Antimicrobial Resistance Surveillance System. Clin Microbiol Infect. 2013;19 (9 ):860 868. (10.1111/1469-0691.12028)23039210
12. Schöneweck F Schmitz RPH Rißner F , et al. The epidemiology of bloodstream infections and antimicrobial susceptibility patterns in Thuringia, Germany: a five-year prospective, state-wide surveillance study (AlertsNet). Antimicrob Resist Infect Control. 2021;10 (1 ):132. (10.1186/s13756-021-00997-6)34493334
13. Klieger SB Vendetti ND Fisher BT Gerber JS . Staphylococcus aureus bacteremia in hospitalized children: incidence and outcomes. Infect Control Hosp Epidemiol. 2015;36 (5 ):603 605. (10.1017/ice.2014.91)25880680
14. Inagaki K Ansari MAY Hobbs CV . Readmission after hospitalization with Staphylococcus aureus bacteremia in children. Am J Infect Control. 2021;49 (11 ):1402 1407. (10.1016/j.ajic.2021.04.088)33989724
15. Cheung GYC Bae JS Otto M . Pathogenicity and virulence of Staphylococcus aureus. Virulence. 2021;12 (1 ):547 569. (10.1080/21505594.2021.1878688)33522395
16. Minter DJ Appa A Chambers HF Doernberg SB . Executive summary: state-of-the-art review: contemporary management of Staphylococcus aureus bacteremia: controversies in clinical practice. Clin Infect Dis. 2023;77 (11 ):1489 1491. (10.1093/cid/ciad525)38031168
17. Kaasch AJ López-Cortés LE Rodríguez-Baño J , et al. Efficacy and safety of an early oral switch in low-risk Staphylococcus aureus bloodstream infection (SABATO): an international, open-label, parallel-group, randomised, controlled, non-inferiority trial. Lancet Infect Dis. 2024;24 (5 ):523 534. (10.1016/S1473-3099(23)00756-9)38244557
18. Woods CR Bradley JS Chatterjee A , et al. Clinical practice guideline by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA): 2023 guideline on diagnosis and management of acute bacterial arthritis in pediatrics. J Pediatr Infect Dis Soc. 2024;13 (1 ):1 59. (10.1093/jpids/piad089)
19. Woods CR Bradley JS Chatterjee A , et al. Clinical practice guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: 2021 guideline on diagnosis and management of acute hematogenous osteomyelitis in pediatrics. J Pediatr Infect Dis Soc. 2021;10 (8 ):801 844. (10.1093/jpids/piab027)
20. Kouijzer IJE van Leerdam EJ Gompelman M , et al. Intravenous to oral switch in complicated Staphylococcus aureus bacteremia without endovascular infection: a retrospective single-center cohort study. Clin Infect Dis. 2021;73 (5 ):895 898. (10.1093/cid/ciab156)33606007
21. Vicetti Miguel CP Mejias A Leber A Sanchez PJ . A decade of antimicrobial resistance in Staphylococcus aureus: a single center experience. PLoS One. 2019;14 (2 ):e0212029. (10.1371/journal.pone.0212029)30753206
22. Yakut N Ergenc Z Tuncay SA , et al. Healthcare-associated Staphylococcus aureus infections in children in Turkey: a six-year retrospective, single-center study. Asian Pac J Trop Med. 2023;16 (8 ):354 362. (10.4103/1995-7645.380721)
23. Mermel LA Allon M Bouza E , et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;49 (1 ):1 45. (10.1086/599376)19489710
24. Corkum KS Jones RE Reuter CH Kociolek LK Morgan E Lautz TB . Central venous catheter salvage in children with Staphylococcus aureus central line-associated bloodstream infection. Pediatr Surg Int. 2017;33 (11 ):1201 1207. (10.1007/s00383-017-4165-5)28948347
