Case Series: Use of Dalbavancin for Invasive Gram-Positive Infection in Children

Abstract

OBJECTIVE

Dalbavancin, a lipoglycopeptide antibiotic active against Gram-positive bacteria with a prolonged in vivo half-life, was recently approved by the Food and Drug Administration for use in pediatric skin/soft tissue infection. Although use in adult skin/soft tissue infection and off-label use in adult osteoarticular and bloodstream infection are well documented, pediatric data are limited to pharmacokinetic data, 1 clinical trial, and case reports/series. Here, we describe the clinical and microbiologic details of cases in which dalbavancin was used at 2 pediatric hospitals.

METHODS

Chart review of all patients receiving dalbavancin for any indication in 2 pediatric hospitals between August 2020 and July 2025.

RESULTS

Dalbavancin was used in 20 patients (age range 2 weeks to 18 years) in the time period. Fifteen cases had infection with either methicillin-susceptible or -resistant Staphylococcus aureus, 16 had bacteremia, 2 had endocarditis, and 11 cases had isolates available for dalbavancin susceptibility testing; all proved susceptible. Reasons for dalbavancin use included need for intravenous therapy with relative contraindications for alternative oral antibiotics or outpatient parenteral antibiotic therapy, difficulty of intravenous access, and medication nonadherence. Most cases had an uncomplicated recovery. None had microbiologic failure.

CONCLUSIONS

With the limitations of this series and prior published data, dalbavancin may be a safe and efficacious antibiotic for use in certain invasive Gram-positive infections in children. It is a reasonable alternative when faced with relative contraindications to inpatient or outpatient parenteral therapy, especially when bactericidal therapy is needed or preferred. Formal pediatric trials against the standard of care, especially beyond skin/soft tissue infection, are encouraged.

Introduction

Managing invasive staphylococcal and other Gram-positive infections remains challenging. Although conversion to oral therapy is used in select clinical contexts, intravenous (IV) antibiotics for prolonged courses remain the mainstay of treatment in severe infection. Nevertheless, complications with outpatient parenteral antibiotic therapy (OPAT) in children are significant. These include central line-associated bloodstream infection (CLABSI) and thrombosis.^1,2 Additionally, many anti-staphylococcal antibiotics have inherent barriers to care. Nafcillin, oxacillin, cefazolin, vancomycin, and daptomycin require either frequent dosing or blood draws for drug concentration and other laboratory monitoring to surveil for adverse effects. Of the orally bioavailable alternatives, cephalexin and dicloxacillin do not achieve adequate blood concentrations due to short half-lives, linezolid is bacteriostatic and carries substantial contraindications with many psychiatric medications, fluoroquinolones and rifampin have low barriers to resistance for the staphylococci, and clindamycin and trimethoprim/sulfamethoxazole are bacteriostatic and have more limited coverage of Gram-positive pathogens.

One advancement in Gram-positive antibacterial therapy is the development of long-acting lipoglycopeptide antibiotics, dalbavancin and oritavancin. The United States Food and Drug Administration approved dalbavancin for treatment of Gram-positive skin/soft tissue infection (SSTI) in 2014 in adults, and more recently, for pediatric SSTI in 2021.³ The drug is approved for SSTI due to methicillin-susceptible and -resistant Staphylococcus aureus (MSSA/MRSA), Streptococcus pyogenes, S. agalactiae, S. dysgalactiae, S. anginosus group, and vancomycin-susceptible Enterococcus faecalis. Additionally, dalbavancin has demonstrated in vitro activity against pneumococci, coagulase-negative staphylococci, corynebacteria, vancomycin-susceptible E. faecium, and several Gram-positive anaerobic genera (Peptostreptococcus, Peptoniphilus, Anaerococcus, Finegoldia, and Clostridium).^4,5 Dalbavancin’s prolonged in vivo plasma terminal half-life (t_1/2 > 14 days in adults) allows for either weekly and fortnightly (every 2 weeks) dosing, placing this drug, along with oritavancin and benzathine penicillin, as among our few very prolonged half-life antibacterial agents.

Trials suggest the efficacy of dalbavancin in Gram-positive SSTI with or without bacteremia and in CLABSI in adults.^6,7 Off-label use for bloodstream and osteoarticular infection in adults is also described.^8,9

In contrast, pediatric reports on dalbavancin had been mostly limited to pharmacokinetic (PK) and microbiologic studies (Table 1).^10–12 The prolonged half-life of the drug has been confirmed in children: Bradley and co-workers¹⁰ reported a median terminal half-life of 9 days in a small cohort (n = 10) of 12- to 17-year olds, compared with 15.5 days in adults (by noncompartmental PK analysis). Gonzales and colleagues¹² reported median plasma terminal t_1/2’s of 18.1, 16.3, 13.2, and 11.6 days in 12- to 17-year olds, 6- to 11-year-olds, 2- to younger than 6-year olds, and 3 month to younger than 2-year olds, respectively (n = 11 per group except for n = 10 for the 12- to 17-year-old group, calculated by a 3-compartment PK re-analysis of data from the Bradley cohort).

Table 1.

Literature Clinical and Microbiological Characteristics

Reference	Age	Isolate	Isolate Source (Clinical Syndrome)	Rationale for Dalbavancin	Outcome
Gomez de Rueda13	4 yr	MSSA	Not reported (pneumonia)	Failure of prior therapy (cloxacillin, gentamicin, linezolid)	Cure
Giorgobani14	2 wk to 17 yr	MSSA (n = 90) MRSA (n = 6) S. pyogenes (n = 9) other Streptococcus (n = 4) E. faecalis (n = 4)	SSTI site or blood (SSTI)	Clinical trial	97% cure
Deza Leon15	6 mo to 22 yr	MSSA (n = 4) MRSA (n = 9) other (n = 5) none (n = 10)	SSTI site, bone, or blood (osteomyelitis, etc.)	Not reported	73% cure
Caselli16	0.4–18 yr	MSSA (n = 5) MRSA (n = 10) S. pyogenes (n = 2) other (n = 2) none (n = 11)	SSTI site, bone or blood (osteomyelitis or SSTI)	Not reported	4 cases with adverse events 29 cured
Gamell17	0.3–18 yr	MSSA (n = 6) MRSA (n = 2) CONS (n = 7)	Blood, or not reported (osteomyelitis, SSTI, CLABSI)	IV access issues, patient convenience, compliance	2 cases with adverse events 13 cured

CLABSI, central line-associated bloodstream infection; CONS, coagulase-negative Staphylococcus; IV, intravenous; MRSA, methicillin-resistant S. aureus; MSSA, methicillin-susceptible S. aureus; SSTI, skin/soft tissue infection

Before 2023, only a single pediatric case outside of a clinical trial had been reported. A 4-year-old child with an MSSA lobar pneumonia and pleural empyema failed both cloxacillin with gentamicin combination therapy and linezolid salvage treatment, but improved with 4 weeks’ coverage with dalbavancin.¹³

More recently, an industry-sponsored randomized controlled trial in pediatric patients has been reported.¹⁴ In children with SSTI (from birth to <18 years) or sepsis (<3 months only), 191 were partially randomized to receive 2 doses of weekly dalbavancin, a single dose of dalbavancin (lasting 14 days), or non-dalbavancin standard of care. These would be either IV vancomycin with/without transition to oral clindamycin, or IV oxacillin or flucloxacillin with/without transition to oral cefadroxil. The study suggested noninferiority of dalbavancin compared with the comparator antibiotic coverage, with similar favorable 48 to 72 hour clinical responses across the 3 groups (98.6%, 97.4%, and 89.7%, respectively). The study was dominated by patients with MSSA infection (84%), with only 6 patients (5%) with MRSA. Another major limitation of this study was that only 5 infants younger than 3 months were eventually enrolled. They were not randomized; all received a single dose of dalbavancin.

A small case series (n = 26) with ages ranging from 6 months to 22 years from Cincinnati Children’s Hospital was presented at the 2023 IDWeek meeting.¹⁵ This series encompassed children with a more diverse range of pathology, including osteomyelitis, bacteremia, and 2 cases of endocarditis. Of note, this series was concerning, given the high frequency of treatment failure (7 of 26 [27%] patients). In 2024, the pediatric literature on dalbavancin was supplemented by 2 series in Italy and Spain (summarized in Table 1).^16,17

Hesitation to routinely use a new medication, such as dalbavancin, in children is reasonable, given the limited literature and precedence as to when this drug may prove useful, plus unclear expectations for adverse events or risk of treatment failure. The applicability of extant data in adults to younger patients is always an open question. Additionally, high drug costs of dalbavancin are a barrier for routine use, with cost benefits appropriately subject to debate.^18–20 To help address gaps in pediatric knowledge, we report our institutional experience with dalbavancin to add to the collective experience in the field. This report details the rationale for preferring dalbavancin over IV or oral alternatives in 20 children treated in 2 pediatric hospitals over a period of more than 4 years.

Methods

Chart review was conducted retrospectively and prospectively (post April 2022) on case patients treated with dalbavancin in a freestanding tertiary care children’s hospital in the northeastern US through July 2025. On review, the first case for dalbavancin use was in August 2020. An additional case (case 10) is reported from a tertiary care children’s hospital in the midwestern US in the same time period.

There were no other selection criteria for patients beyond receipt of dalbavancin in the study hospitals (i.e., this is an “all comers” study). At the time, dalbavancin was not routinely stocked or used at either children’s hospital.

Routine automated antibiotic susceptibility testing (VITEK 2, bioMerieux, Marcy-l'Étoile, France) was performed by the hospital microbiology laboratory for most isolates. Dalbavancin minimum inhibitory concentrations (MIC) were determined by broth microdilution in a reference laboratory (ARUP, Salt Lake City, Utah). MIC testing for one Lactococcus lactis isolate was done by ARUP.

Results

In 2 children’s hospitals in this study, 20 patients received dalbavancin from August 2020 through July 2025 (Table 2). All cases but 2 represented off-label use at the time. The decision to use dalbavancin was made with pediatric infectious disease consultants. This report additionally discusses patient management details that led the treating clinicians to depart from non-dalbavancin alternatives.

Table 2.

Case Series Clinical and Microbiological Characteristics

Case #	Age/Sex	Isolate	Isolate Source (Clinical Syndrome)	Antibiotic Susceptibility	Antibiotic Resistance	Dalbavancin MIC*, mg/L	Duration of Bacteremia†	Rationale for Dalbavancin	Outcome
1	17 yr/M	MRSA	Blood (PIV-related bacteremia)	CLI, CPT, DAP, ERY, GEN, LVX, LZD, RIF, TET, SXT, VAN	SAM, CFZ, OXA	0.06	1 day	Medication interactions with LZD Difficulty with OPAT	Cure
2	16 yr/M	MSSA	Blood, wound drainage (PIV-related thrombophlebitis)	SAM, CFZ, CLI, GEN, LVX, LZD, OXA, RIF, TET, VAN	ERY, SXT	0.06	4 days	Difficulty with inpatient IV access	Cure
3	8 mo/M	MSSA	Blood (PIV-related bacteremia and SSTI)	SAM, CFZ, CLI, ERY, GEN, LZD, OXA, RIF, TET, VAN	LVX, SXT	0.06	1 day	Difficulty with inpatient IV access	Cure
4	18 yr/M	MSSA	Blood (hardware-associated osteomyelitis)	SAM, CFZ, CLI, ERY, GEN, LVX, LZD, OXA, RIF, TET, SXT, VAN	None	0.12	1 day	Central line contraindicated	Cure
		MSSA	Wound drainage	SAM, CFZ, GEN, LVX, LZD, OXA, RIF, TET, SXT, VAN	CLI, ERY
		CONS, diphtheroids	Wound drainage	Not done	Not done
5	11 yr/F	MRSA	Blood (bacteremic osteomyelitis, arthritis)	CLI, GEN, LZD, RIF, TET, SXT, VAN	SAM, CFZ, ERY, LVX, OXA	0.06	4 days	Failure of prior therapy (CLI) Difficulty with OPAT Medication nonadherence	Microbiologic cure; complicated recovery
			Joint, bone aspirate	CLI, GEN, LZD, RIF, TET, SXT, VAN	SAM, CFZ, ERY, LVX, OXA
			Urine	CLI, ERY, GEN, LZD, RIF, TET, SXT, VAN	SAM, CFZ, LVX, OXA
6	3 yr/F	None	(Necrotizing pneumonia, lung abscess, respiratory syncytial virus)				None	Failure of prior therapy (CLI) Difficulty with OPAT	Cure
7	3 wk/F	MRSA	Wound drainage (SSTI)	GEN, LZD, RIF, TET, VAN	SAM, CFZ, CLI, ERY, LVX, OXA, SXT		None	Lack of oral drug options Difficulty with inpatient IV access	Cure
		Viridans streptococci, anaerobic Gram-negative bacilli	Wound drainage	Not done	Not done
8	3 yr/M	MSSA	Blood (CLABSI, thrombophlebitis)	SAM, CFZ, CLI, ERY, GEN, LVX, LZD, OXA, RIF, TET, SXT, VAN	None	0.06	1 day	Central line contraindicated, IV therapy needed	Cure
9	4 mo/F	S. epidermidis (CONS)	Blood (CLABSI, thrombophlebitis)	DAP, GEN, LVX, LZD, RIF, TET, SXT, VAN; CLI (1 of 7 isolates)	SAM, CFZ, ERY, OXA; CLI (6 of 7 isolates)		5 days	Rapid VAN clearance, need for medical transport, DAP and LZD relatively contraindicated	Cure
10	13 yr/F	Not done	(Abdominal wall abscess, Crohn’s disease)					Lack of oral drug options, OPAT contraindicated	Cure of acute infection; continued chronic disease
11	11 yr/M	MRSA	Blood (osteomyelitis, pyomyositis, arthritis)	CLI, CPT, DAP, ERY, GEN, LVX, LZD, RIF, TET, SXT, VAN	SAM, CFZ, OXA	0.06	5 days	Failure of prior therapy (CLI)	Cure
12	8 wk/M	MSSA	Blood (bacteremia without source)	SAM, CFZ, CLI, ERY, GEN, LVX, LZD, OXA, RIF, TET, VAN	SXT	0.06	1 day	Central line contraindicated	Cure
13	5 mo/M	MSSA	Blood, CSF (endocarditis)	SAM, CFZ, GEN, LVX, LZD, OXA, RIF, TET, SXT, VAN	CLI, ERY	0.06	10 days	Difficulty with OPAT	Microbiologic cure; complicated recovery
14	16 yr/M	MRSA	Blood (CLABSI and endocarditis)	CLI, CPT, DAP, ERY, GEN, LZD, RIF, TET, SXT, VAN	SAM, CFZ, OXA, LVX	0.06	6 days	Medication non-adherence; difficulty with OPAT	Cure
15	2 wk/M	MSSA	Wound drainage (cellulitis)	SAM, CFZ, CLI, GEN, LVX, LZD, OXA, RIF, TET, SXT, VAN	ERY			OPAT relatively contraindicated	Cure
		L. lactis	Blood (bacteremia without source)	penicillin, ceftriaxone, CLI, VAN	None		1 day
16	14 yr/F	MSSA	Blood (SSTI, septic shock, pneumonia with effusion, suspected endovascular infection)	SAM, CFZ, GEN, LVX, LZD, OXA, RIF, TET, SXT, VAN	CLI, ERY		1 day	Intolerance of other medications	Cure. Malignancy diagnosis several months later
17	4 wk/M	S. epidermidis	Blood (fever, rhinovirus bronchiolitis)	Isolate 1: GEN, LVX, LZD, RIF, TET, SXT, VAN Isolate 2: GEN, LVX, LZD, RIF, SXT, VAN Isolate 3: SAM, CFZ, GEN, LVX, LZD, OXA, RIF, TET, SXT, VAN	Isolate 1: SAM, CFZ, CLI, ERY, OXA Isolate 2: SAM, CFZ, CLI, ERY, OXA, TET Isolate 3: CLI, ERY		3 days	LZD relatively contraindicated. Inpatient and OPAT relatively contraindicated	Cure
18	14 yr/M	S. agalactiae (group B streptococcus)	Wound (SSTI)	Not done	Not done			Seizures with β-lactams	Cure
19	20 mo/F	MSSA	Blood	SAM, CFZ, CLI, CPT, DAP, GEN, LVX, LZD, OXA, RIF, TET, SXT, VAN	None		1	Difficult PIV access, need for IV therapy	Cure
		S. hominis	Blood	SAM, CFZ, DAP, GEN, LVX, LZD, OXA, RIF, TET, SXT, VAN	CLI		1
20	16 mo/F	MSSA	Blood	SAM, CFZ, CLI, CPT, DAP, GEN, LZD, OXA, RIF, SXT, VAN	LVX, TET	0.03	2	Need for IV therapy	Cure

CFZ, cefazolin; CLABSI, central line-associated bloodstream infection; CLI, clindamycin; CONS, coagulase-negative Staphylococcus; CPT, ceftaroline; DAP, daptomycin; ERY, erythromycin; F, female; GEN, gentamicin; IV, intravenous; LVX, levofloxacin; LZD, linezolid; M, male; MIC, minimum inhibitory concentration; MRSA, methicillin-resistant S. aureus; MRSA, methicillin-susceptible S. aureus; OPAT, outpatient parenteral antibiotic therapy; OXA, oxacillin; PIV, peripheral intravenous catheter; RIF, rifampin; SAM, ampicillin/sulbactam; SSTI, skin/soft tissue infection; SXT, trimethoprim/sulfamethoxazole; TET, tetracycline; VAN, vancomycin

^* The Clinical and Laboratory Standards Institute dalbavancin MIC susceptibility criterion for S. aureus and certain streptococci is ≤ 0.25 mg/L. There are no approved criteria for other Staphylococcus spp.

^† The duration of bacteremia is estimated by the number of hospital days with laboratory-demonstrated positive blood cultures as a continued duration ending but not including the day of the first negative blood culture without a subsequent positive. For patients with a solitary positive blood culture, this duration is estimated as 1 day.

Most patients received the currently approved dalbavancin dosing appropriate for 14 days of coverage.¹¹ This is a single dose of 1500 mg IV for ages 18 years and older, or 18 mg/kg (maximum 1500 mg) IV for ages 6 years to younger than 18 years, or 22.5 mg/kg IV for ages 3 months to younger than 6 years. Cases 7, 12, 15, and 17 received 22.5 mg/kg, but were younger than 3 months old. Cases 4, 5, 10, and 14 received more extended coverage, as detailed below.

Case 1. A 17-year-old, 101-kg male with bipolar disorder, a history of MRSA-associated sinusitis, and a right ankle fracture repaired with indwelling hardware, was admitted for long QT syndrome. He developed a fever and pain adjacent to an upper extremity peripheral IV line/catheter (PIV) site in association with a left great toe paronychia. MRSA bacteremia was identified. The transthoracic echocardiogram was negative. With orthopedic implants at risk, bactericidal therapy was preferred. Additionally, medication interactions with lithium, aripiprazole, quetiapine, and methylphenidate precluded using linezolid. With the patient’s psychiatric history, both prolonged hospitalization for IV antibiotics and home OPAT by central venous catheter were considered problematic. After 1 week of vancomycin, he subsequently received a single IV dose of dalbavancin (1500 mg) to complete therapy for bacteremia. Follow-up clinical evaluation at 1 week and 2 months posttherapy revealed no symptoms suggestive of microbiologic or clinical relapse.

Case 2. A 16-year-old, 48-kg male with severe autism was admitted for rhabdomyolysis and superior mesenteric artery syndrome. His hospital course had been complicated by tenuous PIV access due to agitation, leading to a PIV-associated basilic vein thrombophlebitis. Blood and PIV site drainage cultures grew MSSA. Self-injurious behavior resulted in repeated PIV loss and treatment interruption. After 9 days of coverage (initially IV vancomycin with ceftriaxone, then narrowed to cefazolin), he was subsequently treated with a single dose of IV dalbavancin (1000 mg, 18 mg/kg) to complete more than 21 days of effective therapy for bacteremic thrombophlebitis. No subsequent MSSA bacteremia complications occurred through discharge 2 months later, though intermittent antibiotic use was needed for episodes of cellulitis and sacral ulcers.

Case 3. An 8-month-old, 6-kg boy with failure to thrive and recurrent vomiting and diarrhea underwent gastrostomy tube placement. He developed an SSTI at a PIV site in his foot, concomitant with MSSA bacteremia. PIV malfunctions and replacements complicate therapy. Given the infant’s history, the feasibility of oral or gastrostomy treatment was uncertain. After 3 days of initial coverage (IV vancomycin, then cefazolin monotherapy), a single dose of IV dalbavancin (135 mg, 22.5 mg/kg) was infused over 30 minutes and tolerated. Follow-up evaluation in the clinic at 2 weeks and 2 months posttherapy revealed no symptoms suggestive of microbiologic or clinical relapse.

Case 4. An 18-year-old, 178-kg male with Blount disease, morbid obesity (body mass index 57 kg/m²), type 2 diabetes mellitus, a recent saddle pulmonary embolism, and a recent tibial osteotomy with external fixation presented with fever and pin site drainage. Delayed healing of the iatrogenic fracture precluded hardware removal. Blood culture grew MSSA; wound drainage grew mixed Gram-positive organisms. Given the history of embolism, central venous catheter placement was contraindicated. After 1 week of coverage (IV vancomycin with cefazolin, followed by cefazolin monotherapy), IV dalbavancin (1500 mg) was given before discharge and again 14 days later, in conjunction with oral trimethoprim/sulfamethoxazole for 4 weeks. Follow-up evaluations at 2 weeks and 2 months posttherapy documented resolution of drainage.

Five months postdischarge, there was a new minor infection associated with pin sites, with the drainage culture growing multiple organisms, including MSSA. This resolved with a brief course of oral cephalexin and external fixator removal. There was no evidence of invasive infection.

Case 5. An 11-year-old, 54-kg girl with a history of eczema and recurrent SSTI experienced a minor injury, then developed MRSA bacteremia with pelvic osteomyelitis, hip septic arthritis, and intramuscular abscesses. She was treated with surgical debridement and antimicrobial coverage (initially IV vancomycin with clindamycin, followed by daptomycin monotherapy). Bactericidal parenteral therapy was preferred, given the extent of disease and slow improvement in clinical examination and on inflammatory markers. However, caregiver education for home OPAT proved inadequate. After 9 sterile days, bacteremia therapy was then completed with IV dalbavancin (1000 mg, 18 mg/kg) administered once, and osteomyelitis/SSTI therapy continued with oral clindamycin, as studies support the lack of antagonism with combination antibiotic therapy.²¹ Interval follow-up revealed continued pain and increased inflammatory markers, as well as worsened imaging, 3 weeks after the dalbavancin dose. This was thought to be indicative of relapsed disease, requiring repeat operative management. Repeat operative and blood cultures were all negative.

With concerns for oral medication nonadherence, repeated dosing of IV dalbavancin (650 mg, 12 mg/kg, once, then 325 mg, 6 mg/kg, outpatient weekly for a total of 6 weeks) was given with oral clindamycin (600 mg 3 times a day, ∼ 33 mg/kg/day). This was followed by an extended course of oral clindamycin (600 mg 3 times a day) with rifampin (600 mg, ∼10 mg/kg/day) for chronic osteomyelitis, for a total of 6 months of therapy. Follow-up evaluations in this period showed no signs of microbiologic or clinical relapse.

Case 6. A 3-year-old, 12-kg unvaccinated girl from a rural religious community was admitted for a febrile illness with respiratory syncytial virus, with concurrent left lower lobe pneumonia that did not respond to home azithromycin therapy. Blood cultures were sterile. Sputum and respiratory cultures were unavailable as the child did not require intubation. Her fever persisted despite IV ceftriaxone monotherapy, followed by ceftriaxone with clindamycin. Computed tomography imaging showed necrotic changes with possible lung abscesses. Finally, broadened coverage with IV vancomycin, ceftriaxone, and metronidazole led to a durable response in the fever curve and inflammatory markers.

Given the child’s clinical course, there was hesitation to narrow coverage. However, owing to the child’s home setting, there was also concern for the feasibility of OPAT, as well as difficulty in transportation back to the hospital if complications occurred. Consequently, on hospital day 10, IV dalbavancin (275 mg, 22.5 mg/kg) was administered to cover potential β-lactam- and clindamycin-resistant Gram-positive organisms. Further coverage of Gram-negatives and anaerobes was completed on an outpatient basis with oral cefdinir (14 mg/kg/day, divided 2 times a day) and metronidazole (30 mg/kg/day, divided 3 times a day) for 14 more days. Follow-up evaluation at 1 and 4 months showed symptom resolution; bloodwork showed a transient, mild elevation of alanine transaminase to 42 U/L, with normal renal function and C-reactive protein. A repeat chest X-ray 4 months later was normal.

Case 7. During her birth hospitalization, a term female infant born small for gestational age (birth weight 2.1 kg) and with exposure to maternal hepatitis C (positive maternal viral antibody testing, negative maternal viral load), methadone, and amphetamines developed fever and facial swelling at 3 weeks of age. Imaging showed a multiloculated fluid collection suggestive of either a cystic malformation or parotitis. Blood cultures were negative. Fluid obtained via computed tomography-assisted drainage grew clindamycin- and trimethoprim/sulfamethoxazole-resistant MRSA.

Improvement on facial swelling was slow on IV vancomycin (60–68 mg/kg/day, divided every 6 hours), followed by vancomycin with oral rifampin (20 mg/kg/day, divided every 12 hours). Percutaneous drainage was repeated twice to help facilitate healing. Treatment was complicated by difficult PIV placement, frequent IV treatment interruption due to access loss, and subtherapeutic vancomycin blood concentrations. Transition to oral therapy was potentially problematic, given the MRSA isolate’s resistance to trimethoprim/sulfamethoxazole and clindamycin, historical hesitancy to use doxycycline in infants, and the patient being at her physiologic hemoglobin nadir at 7.2 g/dL (anemia is a relative contraindication for linezolid). Because dalbavancin dosing for younger infants is not defined, the 3-month dose was used. After 19 days of antibiotic coverage (patient weight increased to 3 kg), a single dose of IV dalbavancin (68 mg, 22.5 mg/kg) was administered to complete therapy, and vancomycin and rifampin were discontinued. Hospitalization was prolonged due to social (home placement) concerns; infection resolved before discharge without signs of infection relapse.

The patient was lost to follow-up until rehospitalization for respiratory syncytial virus bronchiolitis at age 2. There was no sign or history of infection relapse. Follow-up hepatitis C antibody testing was negative.

Case 8. A 3-year-old, 12.7-kg boy was hospitalized due to altered mental status and focal neurologic findings likely due to post-COVID-19 acute disseminated encephalomyelitis (also known as acute demyelinating encephalomyelitis). Response to pulse-dosing methylprednisolone (20 mg/kg/day) proved transient, so a 7-Fr dual-lumen catheter was placed into his right femoral vein for plasmapheresis. Two days later, he developed fevers in the context of catheter clotting. His right thigh later developed swelling and erythema, and a near-occlusive thrombus was found in the external iliac and common femoral veins by Doppler ultrasound. A solitary blood culture bottle grew MSSA, with a delayed time to positivity of 88 hours.

At this point, the child had already received 2 days of empiric oral cephalexin therapy (120 mg/kg/day, divided 4 times a day) for presumptive cellulitis, with the fever resolving and the leg swelling improving. The catheter was removed, and 1 dose of IV dalbavancin (285 mg, 22.5 mg/kg) was administered to complete therapy for presumed septic thrombophlebitis. Rivaroxaban (a factor Xa inhibitor) was started for long-term anti-coagulation/thrombosis therapy. Treatments were tolerated, and the patient was discharged. Follow-up visits through 4 weeks postdischarge revealed no signs of relapse of either cellulitis or bacteremia.

Case 9. A 4-month-old term infant girl, (born at 2.9 kg, later weighing 6.1 kg), with seizures, congenital encephalopathy, antithrombin III deficiency, hypogammaglobulinemia due to protein-losing enteropathy, congenital defect in glycosylation type 1h (defect in α-1,3-glucosyltransferase, gene ALG8), and dependence on total parenteral nutrition previously developed a peripherally inserted central line (PICC)-line-associated left subclavian vein thrombus. She was started on enoxaparin therapy, and had a new right upper extremity PICC placed. She later developed a fever and was found to have a S. epidermidis CLABSI. No new thrombus was demonstrated, although there was no visible vessel lumen by Doppler through much of the PICC line course.

Anti-infective coverage was escalated from empiric IV ceftriaxone (50 mg/kg/day) to IV vancomycin (initially 60 mg/kg/day, divided every 6 hours), and then to IV vancomycin with rifampin (20 mg/kg/day, divided every 12 hours). Bacteremia was eventually cleared on day 6 of treatment, after IV immunoglobulin G (500 mg/kg) was administered. There was difficulty maintaining therapeutic vancomycin concentrations due to rapid clearance of the drug (dosing reached 150 mg/kg/day, divided every 4 hours). There was a need to simplify care, as the patient was to be transferred by plane to an out-of-state hospital to be closer to home. Additionally, suspicion of an infected thrombus would necessitate longer IV therapy, and oral therapy was contraindicated due to poor gut function.

Owing to difficulty with placement, the infected PICC line had to be replaced at the same site. After 6 sterile days (12 days of anti-infective coverage), treatment for presumed thrombophlebitis was completed with a single IV dose of dalbavancin (140 mg, 22.5 mg/kg).

Dalbavancin was considered the least problematic option. The standard of care for S. epidermidis bacteremia (vancomycin) was problematic, given the frequent dosing and laboratory monitoring, her prior need for suprapharmacologic dosing, and the need for air transport. Daptomycin and linezolid were relatively contraindicated, with the patient having transaminase elevation and anemia, respectively. Oral drugs (including linezolid) were also contraindicated due to poor gut function. Although dalbavancin MIC testing was not done specifically for the S. epidermidis isolate due to lack of approved standards, reports of coagulase-negative staphylococci having 90^th percentile MICs of less than 0.12 mg/L^5,22,23 were deemed sufficient to justify use of this nonstandard drug.

Dalbavancin administration was well-tolerated. Communication with the neonatal intensive care unit of the accepting hospital at more than 2 months posttransfer confirmed no relapse of S. epidermidis bacteremia.

Case 10. A 13-year-old, 36.6-kg girl with fistulizing Crohn’s disease, on methotrexate, prednisone, and ustekinumab (interleukin-12/23 blockade) immunosuppression, presented with an abdominal wall abscess from a peristomal infection that proved persistent despite drainage. She had failed outpatient oral ciprofloxacin (26.3 mg/kg/day) with metronidazole (40 mg/kg/day) and was admitted to the hospital for further management. Cultures of the drainage fluid showed only skin flora.

On readmission, physical examination was additionally concerning for pyoderma gangrenosum. She then underwent an incision and drainage of the persistent abscess. No cultures were sent. She was started on IV vancomycin and piperacillin/tazobactam for empiric coverage, and had a satisfactory clinical response. With her clinical course, there were concerns for fluoroquinolone-resistant Gram-positives contributing to her presentation. OPAT was considered unsafe due to patient and home issues. Because of her use of high-dose sertraline for anxiety/depression, linezolid was likewise considered contraindicated for oral step-down therapy for Gram-positive coverage.

After 1 week of inpatient therapy, a dose of IV dalbavancin (660 mg, 18 mg/kg) was given, and she was discharged on oral ciprofloxacin (26.3 mg/kg/day) and metronidazole (40 mg/kg/day) for additional Gram-negative and anaerobic coverage. A second dose of dalbavancin (18 mg/kg) was given as an outpatient at 8 days postdose due to concern for slow improvement. Dalbavancin doses were tolerated without issue. Ciprofloxacin and metronidazole were stopped 3 weeks postdischarge, with apparent improvement. She has been continually followed by the gastroenterology and surgery services for ongoing Crohn’s disease-related issues.

Case 11. An 11-year-old, 41-kg boy presented with left leg pain and fever, with an antecedent history of a minor injury involving the knee 6 weeks before presentation. He was diagnosed by magnetic resonance imaging with a left proximal femur osteomyelitis, hip arthritis, and pyomyositis in association with clindamycin-susceptible MRSA bacteremia. His fever had quickly resolved with initial empiric IV cefazolin (6 g/day, ∼150 mg/kg/day divided every 6 hours) and clindamycin (1600 mg/day; 40 mg/kg/day divided every 6 hours). However, bacteremia did not resolve until 1 day after therapy was switched to IV daptomycin (9 mg/kg/day) after identification of the MRSA. A transthoracic echocardiogram was negative.

With the child’s prolonged bacteremia (5 days), there was hesitation to continue the patient on clindamycin alone, due to the nominal inferiority of this drug, due to lack of bactericidal activity, limited experience, and prior failures with bacteremia, and older guidelines²⁴ going against this. After 4 daily doses of daptomycin, the patient was discharged on 8 weeks of oral clindamycin (1800 mg/day, 30 mg/kg/day divided 3 times a day) for osteomyelitis and SSTI, with 1 dose of IV dalbavancin (750 mg, 18 mg/kg) given before discharge, for nominal additional coverage for the bacteremia. Follow-up at 1 and 5 weeks postdischarge documented recovery.

Case 12. An 8-week-old, 4.2-kg term infant male was admitted for fever, rhinorrhea, cough, and posttussive vomiting. This was preceded by the gradual development of a palpable, eczematous rash starting from the scalp and then involving the torso and all extremities. Owing to an elevated procalcitonin concentration, leukocytosis, and eosinophilia (2000 cells/mm³), a septic workup was done, and he was started on IV ceftriaxone (50 mg/kg/day). MSSA was isolated in a single blood culture. With bacteremia, parenteral bactericidal therapy was preferred, but this would necessitate in-hospital care due to the young age. PICC line placement in a patient with an ongoing whole-body rash may also have proven problematic. After 48 hours of cefazolin (100 mg/kg/day, divided every 8 hours) and confirmation of sterile blood cultures, IV dalbavancin (95 mg, 22.5 mg/kg) was given, and the infant was discharged. Follow-up visits at 1 week, 2 months, and 5 months postdischarge showed no signs of invasive infection, but continued eczema with intermittent eosinophilia. He has had intermittent illnesses, including gastroenteritis and upper respiratory infections, but no further invasive infection. He was also seen in the emergency department at 6 months of age (4 months postdischarge) for 3 days of fever, when he was sent home for a presumed viral infection.

Case 13. A 5-month-old, 6-kg boy with fever, cough, rash, lethargy, and seizure was admitted for sepsis. A brain magnetic resonance image was suggestive of thromboembolic disease. Serial blood cultures grew MSSA; cerebrospinal fluid grew a single colony of MSSA. A transthoracic echocardiogram revealed mitral valve endocarditis. He was initially on empiric IV vancomycin (90 mg/kg/day, divided every 6 hours), ceftriaxone (100 mg/kg/day, divided every 12 hours) and doxycycline (4.4 mg/kg/day, divided every 12 hours). Upon identification of MSSA, coverage was switched to IV oxacillin (200 mg/kg/day, divided every 6 hours) plus gentamicin (6 mg/kg/day, divided every 8 hours). Bacteremia was persistent until escalation to oxacillin (200 mg/kg/day, divided every 6 hours) with ertapenem (30 mg/kg/day, divided every 12 hours) salvage therapy. He later developed PICC site ulceration with peripheral eosinophilia, suggestive of Sweet syndrome, as well as neutropenia requiring filgrastim (granulocyte colony-stimulating factor) and antibiotic change to vancomycin for continued treatment. To facilitate completion of 8 weeks of effective parenteral therapy, after 6 sterile weeks, he received a single dose of IV dalbavancin (143 mg, 22.5 mg/kg) and was discharged.

The patient was readmitted 2 weeks postdischarge with acute cardiac failure secondary to severe mitral valve regurgitation, with myxomatous degeneration of the posterior leaflet noted on echocardiogram. This was thought to be a mechanical sequela of the endocarditis. Blood cultures were negative; no signs of relapsed infection were observed. The defect was repaired with a partial annuloplasty and removal of the mitral filament. There remains no sign of microbiologic relapse at 5 months postoperation.

Case 14. A 16-year-old, 57-kg male with hemoglobin SS sickle cell disease who received an allogeneic stem cell transplant the year prior was admitted for fatigue and fevers. He was on tacrolimus immunosuppression, had lichenoid skin graft versus host disease, and a prior history of MSSA bacteremia. Blood cultures taken from his Broviac catheter repeatedly grew MRSA, and a transthoracic echocardiogram revealed a vegetation or thrombus on the tricuspid valve. Empiric coverage with IV vancomycin and oxacillin was switched to IV daptomycin (8 mg/kg/day). Bacteremia rapidly cleared after catheter removal.

Given a history of patient medication nonadherence, OPAT with vancomycin, ceftaroline, or daptomycin was deemed problematic. Consequently, on treatment day 7, a loading dose of IV dalbavancin (1000 mg) was given, and he was discharged on weekly IV dalbavancin (500 mg) in the outpatient hematology clinic to complete 6 weeks of therapy for MRSA endocarditis.

The patient was readmitted 2 weeks postdischarge for back pain. Blood cultures were negative. A repeat echocardiogram was unchanged. He was diagnosed with mild COVID-19, given remdesivir preemptive therapy, and discharged with the previous plan to complete endocarditis therapy. A follow-up echocardiogram 9 months later demonstrated resolution of the lesion.

Case 15. A 2-week-old, 3.5-kg term infant male with a history of a brief hospitalization for neonatal hypoglycemia was seen in the emergency department for a 1-week history of a pustular groin rash. The patient had an antecedent conjunctivitis treated with ocular antibiotics, as well as cough and congestion. There were family contacts with upper respiratory infections, and a prior family history of MRSA cellulitis. There was an unclear history of fever in the infant; none were noted while in medical observation. The patient was initially placed on IV clindamycin (30 mg/kg/day, divided every 8 hours). Groin lesion cultures grew MSSA. An MRSA nasal swab culture, spinal fluid culture, and herpes simplex virus testing of the lesion and spinal fluid were negative. A blood culture grew Lactococcus lactis at 16 hours, and therapy was shifted to IV ampicillin/sulbactam (200 mg amoxicillin component/kg/day, divided every 6 hours). There was symptomatic improvement. A repeat blood culture was negative.

Given the patient’s young age, there was hesitation to discount the positive blood culture, but further parenteral coverage would necessitate PICC line placement and lengthen the hospital stay (OPAT is of potentially higher risk in neonates). Hence, on treatment day 4, the infant was given a single IV dose of dalbavancin (80 mg, 22.5 mg/kg), after which he was discharged on oral amoxicillin/clavulanate (100 mg amoxicillin component/kg/day, divided every 12 hours) for a further 10 days. Outpatient follow-up at 1 week postdischarge was unremarkable. There were no signs or history of invasive infection in an emergency room visit for a head trauma injury at age 9 months.

Although dalbavancin susceptibility in Lactococcus has not been reported in the literature, favorable dalbavancin MICs in multiple aerobic and anaerobic Gram-positive genera were considered sufficient to support its use in this case.⁴ The β-lactam was added to the infant’s coverage, given limited pharmacokinetic data for dalbavancin at this age, and as ancillary coverage if this isolate proved glycopeptide-resistant. Susceptibility testing of the Lactococcus isolate was only available post-discharge. The isolate was penicillin- and vancomycin-susceptible.

Case 16. A 14-year-old, 54-kg girl with a history of anxiety presented with fever, nausea, vomiting, dry cough, right facial swelling, right leg and flank pain, and inability to walk, with concern for foot drop. She was admitted to the intensive care unit for septic shock. Initial laboratory investigation showed pancytopenia with a white blood cell count of 800/mm³, a differential count of 25% neutrophils, 58% lymphocytes, and 12% atypical lymphocytes, hemoglobin of 9.4 g/dL, and platelets at 130,000/mm³. C-reactive protein was elevated at 82 mg/L. Computed tomography of the chest showed multiple bilateral pulmonary nodules with a halo sign. Initial blood cultures grew MSSA and subsequent cultures after starting broad-spectrum coverage were negative. Testing for Legionella, Mycoplasma, respiratory viruses, cytomegalovirus, Epstein-Barr virus, and blood fungal antigens (galactomannan and 1,3-beta-d-glucan) was negative. Parvovirus IgG was borderline, with IgM negative. The patient’s empiric anti-infective coverage initially comprised of IV cefepime (adult dosing at 2 g every 8 hours) and vancomycin (45 mg/kg/day, divided every 8 hours), was escalated to meropenem (1 g every 8 hours), vancomycin (45 mg/kg/day, divided every 8 hours) and liposomal amphotericin B (5 mg/kg/day), and then narrowed to oxacillin (2 g every 6 hours) with ampicillin/sulbactam (3 g every 6 hours).

There was initial concern for a hematologic malignancy with possible fungal infection. However, a bone marrow aspirate was reassuring, and she began to improve. Metagenomic sequencing of plasma microbial cell-free DNA (Karius, Redwood City, California) was only notable for MSSA (10,952 molecules/μL; SCCmec not detected). This was eventually considered the sole cause of her presentation. The severity of her presenting symptoms and chest radiology findings (suspected to be from septic emboli) were concerning for endovascular involvement. However, a transthoracic echocardiogram and Doppler imaging of the great vessels were normal.

Owing to suspicion of endovascular infection, therapy was narrowed to IV cefazolin (2 g every 8 hours; ∼100 mg/kg/day) by PICC line, and she was discharged on the same drug for OPAT. Within a week, she developed increased work of breathing, nausea and vomiting with IV administration, and inability to walk due to malaise and fatigue. She was readmitted and found to have a right pleural effusion; this required thoracocentesis. Her condition was hypothesized to be secondary to her previous septic emboli and possible immune reconstitution, given her resolving pancytopenia. Blood and pleural fluid cultures were negative, and she continued on IV cefazolin with ongoing issues with nausea and inability to tolerate orals.

With the patient’s significant anxiety limiting oral treatment options (including antiemetics) and difficulty with previous home care, a decision was made to treat with a single dose of IV dalbavancin (1000 mg, ∼18 mg/kg) to complete the final 2 weeks of her 6-week antibiotic course. Her nausea resolved with cessation of IV cefazolin, and she was discharged home. Outpatient follow-up at 2 weeks postdischarge showed sustained improvement without signs of infectious relapse. Eight months later, the patient was readmitted due to fever and nausea, when she was found to be pancytopenic again (white blood cell count 400/mm³, hemoglobin 5 g/dL, platelets 12,000/mm³). She was subsequently diagnosed with B-cell acute lymphoblastic leukemia.

Case 17. A 4-week-old, 4.6-kg male with neonatal abstinence syndrome and prenatal exposure to maternal gonorrhea, Chlamydia, Trichomonas, and untreated hepatitis C (maternal viral load of 1.1 million units/mL) was admitted for progressive coughing fits with apnea and dyspnea requiring oxygen support. Oropharyngeal swab testing for gonorrhea and Chlamydia by nucleic acid detection was negative, and nasopharyngeal swab viral panel polymerase chain reaction testing was positive for rhinovirus. Laboratory data were notable for leukocytosis with relative lymphopenia and macrocytic anemia. With his young age, blood cultures were drawn on admission. These returned positive at 31 hours with methicillin-resistant S. epidermidis. A repeat blood culture drawn prior to antibiotics grew methicillin-resistant S. epidermidis at 23 hours. There was a fever coincident with the second culture; he was not febrile before this. IV vancomycin (60 mg/kg/day, divided every 6 hours) was initiated. A third blood culture grew at 22 hours after 1 day of vancomycin administration, now with methicillin-susceptible S. epidermidis. Fevers resolved by day 3 of antibiotics. Subsequent blood cultures were negative. Lumbar puncture revealed negative cultures and panel polymerase chain reaction, and a urine culture was negative.

The bacteremia was deemed bona fide due to growth in 3 cultures, with minor differences in antibiotic susceptibility potentially due to isolate heteroresistance. In terms of management, prolonged inpatient IV therapy was deemed problematic due to the patient living at some distance from the hospital, whereas OPAT would be of higher risk in a newborn. Additionally, linezolid was deemed relatively contraindicated due to the infant’s anemia. Hence, at day 7 of vancomycin, the infant was treated with a single dose of dalbavancin (95 mg, 22.5 mg/kg) to complete therapy for bacteremia. The infant was discharged thereafter. He was well until rehospitalization 7 weeks later with respiratory syncytial virus and rhinovirus infection, requiring admission to the pediatric intensive care unit and noninvasive ventilation. At age 6 months, he has not required readmission but is under budesonide therapy for presumed reactive airway disease. An immunologic workup is negative to date; hepatitis C infection has been excluded.

Case 18. A 14-year-old, 81-kg male with cerebral palsy and complex partial epilepsy secondary to prematurity and periventricular leukomalacia, inferior vena cava calcification and thrombosis (from infancy) with decreased circulation to lower extremities, and a solitary kidney (with normal function) and obesity, was admitted for a right foot/ankle cellulitis associated with a right ankle superficial abscess and fever. He had previously received oral cephalexin without improvement (this was later determined to be potentially underdosed at 500 mg twice daily). On admission, he was started on empiric IV clindamycin (600 mg every 8 hours). The abscess was drained operatively; fluid later grew rare S. agalactiae (group B streptococcus). No blood cultures were obtained. A magnetic resonance image of the foot and ankle did not show osteomyelitis or a deeper abscess. IV cefazolin (2 g every 6 hours) was started, and the patient improved on dual coverage.

On hospital day 2, the patient developed a rash that was suspicious for an allergy. Antibiotics were switched to oral linezolid (600 mg every 12 hours) to cover both S. agalactiae and Gram-positives that may have been pretreated with clindamycin. He developed breakthrough seizures on linezolid, prompting a switch to oral trimethoprim-sulfamethoxazole (320 mg trimethoprim component per day, divided twice a day) and cephalexin (500 mg 4 times a day), and he was discharged home.

He developed recurrent symptoms with the development of erythema, warmth, and swelling of the dorsum of his right foot on day 13 of his planned 14-day course of antibiotics, prompting readmission. There was concern that his poor peripheral circulation at baseline led to the recurrence of cellulitis during oral therapy. The blood culture was negative. He was started on IV ampicillin (2 g every 6 hours), with improvement. However, the family was not comfortable transitioning back to oral treatment, given 2 prior failures on oral coverage. He was then switched to IV ceftriaxone (1 g daily) with a plan for outpatient intramuscular ceftriaxone to complete therapy. However, he developed worsening seizures on ceftriaxone. Penicillin G was also considered for OPAT; however, concerns were raised about a potential decrease in seizure threshold with penicillin. Vancomycin was ruled out due to the patient’s solitary kidney and the complexity of administration at home.

Options of PICC line placement for OPAT daptomycin versus using single-dose dalbavancin were discussed with the family. They felt more comfortable with the latter. A single dose of IV dalbavancin (1500 mg) was given, and the child was discharged. There was subsequent improvement in erythema and swelling.

The child developed a right external iliac deep vein thrombosis 1 week after discharge, requiring readmission and anticoagulation (the patient has a personal and family history of thrombosis). There was no recurrence of cellulitis. He was discharged after the workup and was started on oral anticoagulation outpatient.

Case 19. A 20-month-old, 8.6-kg female with a history of extreme prematurity at 23 weeks, bronchopulmonary dysplasia, pulmonary hypertension, home oxygen dependence, and receiving feeds through a gastrojejunal tube was admitted to the pediatric floor for vomiting and diarrhea due to rotavirus infection. Abdominal X-rays at the time showed air-fluid levels suggestive of enterocolitis. She was briefly placed in the intensive care unit for refractory hypotension, hypernatremia, and increasing oxygen requirement. After recovery, she was returned to the floor. Of note, PIV access was repeatedly difficult to establish for this patient.

On hospital day 4, the patient had a fever at 40°C, rigors, and worsening hypoxia, prompting a return to the intensive care unit. Chest X-rays showed chronic findings of basilar opacities (suspected to be regional scarring from chronic lung disease). Two blood cultures on separate days grew MSSA and S. hominis with prolonged times to positivity at 34 and 27 hours, respectively. Transthoracic echocardiogram and great vessel Doppler studies did not reveal an endovascular source of infection.

Antibiotic coverage initially consisted of IV vancomycin (60 mg/kg/day, divided every 6 hours), followed by IV cefazolin (100 mg/kg/day, divided every 8 hours) upon report of antibiotic susceptibilities. By day 6, the patient had recovered to her preillness baseline, and options for completing therapy for bacteremia by PIV (in hospital), versus the use of dalbavancin, were discussed with the child’s parents. Given difficulties keeping PIV access in this patient, and to help facilitate discharge, a single dose of dalbavancin was given (202 mg, 22.5 mg/kg) to complete therapy. This was tolerated, and the child was sent home. Outpatient follow-up in various clinics participating in the patient’s care through 6 months postdischarge revealed no further signs of invasive infection.

Case 20. A 16-month-old, 11.9-kg male with severe eczema, peanut allergy (history of anaphylaxis), and intermittent constipation was seen in the emergency department for refusal to ambulate, irritability, and rigors. He was initially afebrile, but spiked a fever of 39.8°C in the emergency room. Complete blood counts, sedimentation rate, and C-reactive protein levels were normal, but creatine kinase was noted to be minimally elevated at 207 unit/L (normal < 170 unit/L). Influenza, respiratory syncytial virus, and COVID-19 polymerase chain reaction testing were negative. After improvement with ibuprofen, the child was sent home with a presumed diagnosis of viral myositis.

The patient was recalled to the emergency room the next day after the blood culture drawn on the day prior grew Gram-positive cocci in clusters at 22 hours. The patient appeared well but still had some refusal to ambulate. He had been on alternating ibuprofen and acetaminophen for fevers. On examination, a right-sided otitis media was noted. Blood cultures were redrawn, and he was given a dose of ceftriaxone (50 mg/kg) and sent home.

The patient was recalled again the next day, once the first blood culture was confirmed to grow S. aureus, and the second blood culture turned positive at 27 hours. On admission, the patient’s symptoms were improved, though he still seemed to favor his right leg over his left. He was placed on IV cefazolin (150 mg/kg/day, divided every 6 hours) for therapy for MSSA bacteremia. Investigations to find a source of infection, including a transthoracic echocardiogram, X-rays of the legs, ultrasound of the hips, liver, spleen, and kidneys, and a nuclear medicine bone/joint scan (Technetium-99m methylene diphosphonate) were all negative.

The patient was mostly asymptomatic throughout his hospital course. His blood cultures were negative after the first dose of antibiotic was received. With his workup being negative, it was decided that the patient warranted parenteral therapy for uncomplicated bacteremia without a source (apart from potentially his eczema). With the child’s rather well appearance, as well as eagerness on the family’s part to go home, therapy was completed with a single dose of dalbavancin (260 mg, 22.5 mg/kg). This was tolerated, and the patient was discharged. A clinic follow-up 2 weeks later was unrevealing for any signs of invasive infection.

Discussion

This report documents dalbavancin use in 20 children, including 11 children younger than 3 years and 4 younger than 3 months.

With its prolonged in vivo plasma half-life, dalbavancin is an appealing parenteral antibiotic that may decrease hospital length of stay and avoid complications of OPAT or continued inpatient IV therapy. There is potential for this drug to also decrease overall hospital costs, though cost/benefit analyses have only been done in the adult setting.^8,18–20 With extant adult clinical data and pediatric pharmacokinetic studies, the treating physicians in the current report judged the nuance and treatment restraints of each case sufficient to outweigh the risks of using therapy with a paucity of published pediatric experience. Many of the cases here occurred before the recent references14^–17 were published and before Food and Drug Administration approval for pediatric use. Reasons for dalbavancin use in these cases were varied, and included problematic PIV access, contraindications for central catheters (current or prior thrombosis, skin lesions, etc.), poor home situation for OPAT, medication nonadherence, and the lack of oral antibiotic options due to either isolate resistance or medication interactions.

Although the bulk of published experience with dalbavancin is in adults with SSTI, osteomyelitis, and bacteremia, both a published pediatric case¹³ and case 6 dealt with complicated pneumonia that failed first- and second-line therapy. Dalbavancin concentrations in intrapulmonary epithelial lining fluid are more than 10 times the MIC of susceptible bacteria through more than 168 hours postdose.²⁵ Together with in vitro data showing broad coverage for both aerobic and anaerobic Gram-positive bacteria, including pneumococci and other streptococci,^4,5 we suggest the potential utility of dalbavancin in complex lung infection, such as lung abscesses or necrotizing pneumonia. This application is particularly timely, considering recent data reporting increasing β-lactam and fluoroquinolone resistance among S. pneumoniae pediatric isolates.²⁶

Just as with the current published pediatric data, this report has limitations. Our sample size is small, and this study is not controlled. Case 5, as well as one case in the Cincinnati series,¹⁵ had protracted recovery for osteomyelitis, despite reports of excellent bone penetration of the drug.²⁷

Additionally, endocarditis remains rarely reported in pediatric experience with dalbavancin. There were 2 cases of endocarditis in the Cincinnati series, one of which had treatment failure.¹⁵ Neither the Italian nor the Spanish pediatric dalbavancin reports reported endocarditis cases.^16,17 Our report adds 2 cases. Case 13 had the drug only used as the last dose of therapy, and had a problematic recovery without evidence of microbiologic relapse. Case 14 received dalbavancin for most of his therapy and had an uncomplicated recovery. This sparse pediatric data stands in contrast to adult medicine, where, in addition to substantial published case experience, a randomized trial, including endocarditis, is pending a formal report.²⁸

In this series, all tested isolates were susceptible to vancomycin (MIC ≤ 0.5, 1, or 2 mg/L) and, when available (for S. aureus only), to dalbavancin (MIC 0.06 or 0.12 mg/L), so the utility of dalbavancin against glycopeptide-nonsusceptible Gram-positives remains uninterrogated, both in this series and in the literature. Most importantly, risks of dalbavancin here were likely minimal, as all patients had normal renal function and no history of glycopeptide intolerance/allergy. Of note, dalbavancin has been recently reported to be safely administered to vancomycin-intolerant adults in a small series.²⁹

Lastly, for all our cases, bacteremia, when present, resolved before the antibiotic switch to dalbavancin. Many of our cases have also used dalbavancin for the later portion of therapy, after initial treatment with standard-of-care antibiotics. Additionally, excluding our 2 endocarditis cases, the duration of bacteremia in our patients was relatively brief at 5 days or less. Both of these conditions may explain our lower apparent treatment failure rate, especially compared with the Cincinnati pediatric series.¹⁵

An additional note of caution on dalbavancin use would be the current limits of approved dosing, versus what would be “off-label” use of the drug in the real world. As of the time of this report, the latter would still include any indication beyond SSTIs and any use beyond 1 or 2 doses (to cover for 14 days). The PK data to date suggest that dalbavancin in vivo exposure is lower in younger children (<6 years) than in adults and older children. The higher mg/kg dosing for children older than 3 months through younger than 6 years of age is meant to compensate for this; however, we note that even within the published data,¹² there is a suggestion that within this age cohort, there is evidence for lower drug exposure in infants and toddlers younger than 2 years compared with those 2 to younger than 6.

Reports of clinical use in infants younger than 3 months old remain rare. Giorgobani and colleagues¹⁴ have 5 such infants in their study. Our cohort here includes 4, where we have extrapolated dosing from the published reports in older infants. Despite this, we remain without formal PK data to support use in our youngest patients.

We encourage continued publication of pediatric clinical experience with the long-acting lipoglycopeptides. Head-to-head comparisons of dalbavancin or oritavancin versus standard of care, especially for non-SSTI disease, including bacteremia/CLABSI, endocarditis, and pneumonia, remain needed to clarify the safety and efficacy of these newer antibiotics in infants and children. The lack of PK data for younger infants remains a gap that also needs to be addressed.

ABBREVIATIONS

CLABSI

central line-associated bloodstream infection;

IV

intravenous;

MIC

minimum inhibitory concentration;

MRSA

methicillin-resistant Staphylococcus aureus;

MSSA

methicillin-susceptible Staphylococcus aureus;

OPAT

outpatient parenteral antibiotic therapy;

PICC

peripherally-inserted central catheter;

PIV

peripheral intravenous line/catheter;

PK

pharmacokinetic;

SSTI

skin/soft tissue infection