Mitigating Risk of Acute Kidney Injury Among Children With Methicillin-resistant Staphylococcus aureus Osteomyelitis.

OBJECTIVE: Children with acute hematogenous osteomyelitis (AHO) from methicillin-resistant Staphylococcus aureus (MRSA) are treated with vancomycin despite the risk of acute kidney injury (AKI). This study evaluates the rate of AKI and resource utilization for children with or without AKI when vancomycin is used in this setting. METHODS: Children with MRSA AHO treated with vancomycin were retrospectively studied. AKI was assessed by clinical diagnosis and Kidney Disease Improving Global Outcomes (KDIGO) criteria. Cohorts of children with or without AKI were compared for differences in treatment, resource utilization, and outcomes. Multivariate logistic regression analysis assessed factors associated with risk for AKI. Cost analysis was performed using the Pediatric Health Information System and Healthcare Cost and Utilization Project databases. RESULTS: Among 85 children studied, 14 (16.5%) had chart-diagnosed AKI and 24 (28.2%) met KDIGO criteria. Children with AKI had more febrile days and higher thrombosis rates. They had longer vancomycin treatment (8 vs 5 d), higher troughs (27.8 vs 17.5 mg/L), and prolonged hospitalization (19.9 vs 11.1 d). Multivariate analysis found a maximum vancomycin trough level (odds ratio: 1.05, P = 0.003) with a cutoff of 21.7 mg/L predicted AKI.Only 2 of 20 (10%) children who had MRSA isolates with a minimum inhibitory concentration of 2 achieved therapeutic vancomycin levels. Pediatric Health Information System data of 3133 children with AHO treated with vancomycin identified 75 (2.4%) with AKI who had significantly longer lengths of stay (13 vs 7 d) and higher billed charges ($117K vs $51K) than children without AKI. CONCLUSIONS: Chart documentation of AKI (16.5%) grossly underestimated KDIGO-defined occurrence (28.2%). This study showed that vancomycin-associated AKI required substantially greater resource utilization and higher health care costs. Lowering the targeted trough range, shortening the duration of vancomycin therapy, and considering alternative antibiotics when minimum inhibitory concentration ≥2 will reduce the risk and cost of AKI among children with MRSA AHO. LEVEL OF EVIDENCE: Level III-retrospective comparative therapeutic study.

Cutaneous Leishmania mexicana infections in the United States: defining strains through endemic human pediatric cases in northern Texas.

Over a 6-month span, three patients under 5 years old with cutaneous leishmaniasis presented to the Pediatric Infectious Diseases Clinic at the University of Texas Southwestern Medical Center/Children's Health Dallas. None had traveled outside of northern Texas/southern Oklahoma; all had Leishmania mexicana infections confirmed by PCR. We provide case descriptions and images to increase the awareness of this disease among United States (US) physicians and scientists. Two patients responded to fluconazole, but the youngest required topical paromomycin. Combining these cases with guidelines and our literature review, we suggest that (i) higher doses (10-12 mg/kg/day) of fluconazole should be considered in young children to maximize likelihood and rapidity of response and (ii) patients should transition to alternate agents if they do not respond to high-dose fluconazole within 6 weeks. Furthermore, and of particular interest to the broad microbiology community, we used samples from these cases as a proof of concept to propose a mechanism to strain-type US-endemic L. mexicana. For our analysis, we sequenced three housekeeping genes and the internal transcribed sequence 2 of the ribosomal RNA gene. We identified genetic changes that not only allow us to distinguish US-based L. mexicana strains from strains found in other areas of the Americas but also establish polymorphisms that differ between US isolates. These techniques will allow documentation of genetic changes in this parasite as its range expands. Hence, our cases of cutaneous leishmaniasis provide significant evolutionary, treatment, and public health implications as climate change increases exposure to formerly tropical diseases in previously non-endemic areas. IMPORTANCE: Leishmaniasis is a parasitic disease that typically affects tropical regions worldwide. However, the vector that carries Leishmania is spreading northward into the United States (US). Within a 6-month period, three young cutaneous leishmaniasis patients were seen at the Pediatric Infectious Diseases Clinic at the University of Texas Southwestern Medical Center/Children's Health Dallas. None had traveled outside of northern Texas and southern Oklahoma. We document their presentations, treatments, and outcomes and compare their management to clinical practice guidelines for leishmaniasis. We also analyzed the sequences of three critical genes in Leishmania mexicana isolated from these patients. We found changes that not only distinguish US-based strains from strains found elsewhere but also differ between US isolates. Monitoring these sequences will allow tracking of genetic changes in parasites over time. Our findings have significant US public health implications as people are increasingly likely to be exposed to what were once tropical diseases.

Cutaneous Leishmania mexicana Infections in the United States: Defining Strains Through Endemic Human Pediatric Cases in Northern Texas.

Over a six-month span, three patients under five years old with cutaneous leishmaniasis presented to the Pediatric Infectious Diseases Clinic at the University of Texas Southwestern Medical Center/Children's Health Dallas. None had traveled outside of the United States (US); all had confirmed L. mexicana infections by PCR. We provide case descriptions and images to increase the awareness of this disease among US physicians and scientists. Two patients responded to fluconazole, but one required topical paromomycin. Combining these cases with guidelines and our literature review, we suggest that: 1) higher doses (ten-twelve mg/kg/day) of fluconazole should be considered in young children to maximize likelihood and rapidity of response and 2) patients should transition to alternate agents if they do not respond to high-dose fluconazole within six weeks. Furthermore, and of particular interest to the broad microbiology community, we used samples from these cases as a proof-of-concept to propose a mechanism to strain-type US-endemic L. mexicana. For our analysis, we sequenced three housekeeping genes and the internal transcribed sequence 2 of the ribosomal RNA gene. We identified genetic changes that not only allow us to distinguish US-based L. mexicana strains from strains found in other areas of the Americas, but also establish polymorphisms that differ between US isolates. These techniques will allow documentation of genetic changes in this parasite as its range expands. Hence, our cases of cutaneous leishmaniasis provide significant evolutionary, treatment and public health implications as climate change increases exposure to formerly tropical diseases in previously non-endemic areas.

Monoclonal Antibody Use for Coronavirus Disease 2019 in Pediatric Patients: A Multicenter Retrospective Study.

Monoclonal antibodies for COVID-19 are authorized in high-risk patients aged ≥12 years, but evidence in pediatric patients is limited. In our cohort of 142 patients treated at seven pediatric hospitals between 12/1/20 and 7/31/21, 9% developed adverse events, 6% were admitted for COVID-19 within 30 days, and none received ventilatory support or died.

Early Transition to Oral Antimicrobial Therapy Among Children With Staphylococcus aureus Bacteremia and Acute Hematogenous Osteomyelitis.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) is a frequent complication of acute hematogenous osteomyelitis (AHO) in children, but data on the optimal duration of parenteral antibiotics prior to transition to oral antibiotics remains sparse. We examined clinical outcomes associated with early transition to oral antimicrobial therapy among children admitted to our institution with AHO and SAB, and evaluated the utility of a severity of illness score (SIS) to guide treatment decisions in this setting. METHODS: Children with AHO and SAB admitted to our institution between January 1, 2009, and December 31, 2018, were retrospectively reviewed and stratified according to a previously validated SIS into mild (0-3), moderate (4-7) and severe (8-10) cohorts. Groups were assessed for differences in treatment (eg, parenteral and oral antibiotic durations, surgeries) and clinical response (eg, bacteremia duration, acute kidney injury, length of stay and treatment failure). RESULTS: Among 246 children identified with AHO and SAB, median parenteral antibiotic duration differed significantly between mild (n = 80), moderate (n = 98) and severe (n = 68) cohorts (3.6 vs. 6.5 vs. 14.3 days; P ≤ 0.001). SIS cohorts also differed with regard to number of surgeries (0.4 vs. 1.0 vs. 2.1; P ≤ 0.001), duration of bacteremia (1.0 vs. 2.0 vs. 4.0 days; P ≤ 0.001), acute kidney injury (0.0% vs. 3.0% vs. 20.5%; P ≤ 0.001), hospital length of stay (4.8 vs. 7.4 vs. 16.4 days; P ≤ 0.001) and total duration of antibiotics (34.5 vs. 44.7 vs. 60.7 days; P ≤ 0.001). Early transition to oral antimicrobial therapy among mild or moderate SIS cohorts was not associated with treatment failure despite SAB. CONCLUSIONS: SAB is associated with a wide range of illness among children with AHO, and classification of severity may be useful for guiding treatment decisions. Early transition to oral antimicrobial therapy appears safe in children with mild or moderate AHO despite the presence of SAB.

Team Approach: Pediatric Musculoskeletal Infection.

A team approach is optimal in the evaluation and treatment of musculoskeletal infection in pediatric patients given the complexity and uncertainty with which such infections manifest and progress, particularly among severely ill children. The team approach includes emergency medicine, pediatric intensive care, pediatric hospitalist medicine, infectious disease service, orthopaedic surgery, radiology, anesthesiology, pharmacology, and hematology. These services follow evidence-based clinical practice guidelines with integrated processes of care so that children and their families may benefit from data-driven continuous process improvement. Important principles based on our experience in the successful treatment of pediatric musculoskeletal infection include relevant information gathering, pattern recognition, determination of the severity of illness, institutional workflow management, closed-loop communication, patient and family-centered care, ongoing dialogue among key stakeholders within and outside the context of direct patient care, and periodic data review for programmatic improvement over time. Such principles may be useful in almost any setting, including rural communities and developing countries, with the understanding that the team composition, institutional capabilities or limitations, and specific approaches to treatment may differ substantially from one setting or team to another.

Safety Concerns Surrounding Quinolone Use in Children.

Fluoroquinolones are highly effective antibiotics with many desirable pharmacokinetic and pharmacodynamic properties including high bioavailability, large volume of distribution, and a broad spectrum of antimicrobial activity. Despite their attractive profile as anti-infective agents, their use in children is limited, primarily due to safety concerns. In this review we highlight the pharmacological properties of fluoroquinolones and describe their current use in pediatrics. In addition, we provide a comprehensive assessment of the safety data associated with fluoroquinolone use in children. Although permanent or destructive arthropathy remains a significant concern, currently available data demonstrate that arthralgia and arthropathy are relatively uncommon in children and resolve following cessation of fluoroquinolone exposure without resulting in long-term sequelae. The concern for safety and risk of adverse events associated with pediatric fluoroquinolone use is likely driving the limited prescribing of this drug class in pediatrics. However, in adults, fluoroquinolones are the most commonly prescribed broad-spectrum antibiotics, resulting in the development of drug-resistant bacteria that can be challenging to treat effectively. The consequence of misuse and overuse of fluoroquinolones leading to drug resistance is a greater, but frequently overlooked, safety concern that applies to both children and adults and one that should be considered at the point of prescribing.

Recent Developments in Pediatric Community-Acquired Pneumonia.

Community-acquired pneumonia (CAP) is the most common acute infectious cause of death in children worldwide. Consequently, research into the epidemiology, diagnosis, treatment, and prevention of pediatric CAP spans the translational research spectrum. Herein, we aim to review the most significant findings reported by investigators focused on pediatric CAP research that has been reported in 2014 and 2015. Our review focuses on several key areas relevant to the clinical management of CAP. First, we will review recent advances in the understanding of CAP epidemiology worldwide, including the role of vaccination in the prevention of pediatric CAP. We also report on the expanding role of existing and emerging diagnostic technologies in CAP classification and management, as well as advances in optimizing antimicrobial use. Finally, we will review CAP management from the policy and future endeavors standpoint, including the influence of clinical practice guidelines on clinician management and patient outcomes, and future potential research directions that are in the early stages of investigation.

Balancing vancomycin efficacy and nephrotoxicity: should we be aiming for trough or AUC/MIC?

Sixty years later, the question that still remains is how to appropriately utilize vancomycin in the pediatric population. The Infectious Diseases Society of America published guidelines in 2011 that provide guidance for dosing and monitoring of vancomycin in adults and pediatrics. However, goal vancomycin trough concentrations of 15-20 µg/mL for invasive infections caused by methicillin-resistant Staphylococcus aureus were based primarily on adult pharmacokinetic and pharmacodynamic data that achieved an area under the curve to minimum inhibitory concentration ratio (AUC/MIC) of ≥400. Recent pediatric literature shows that vancomycin trough concentrations needed to achieve the target AUC/MIC are different than the adult goal troughs cited in the guidelines. This paper addresses several thoughts, including the role of vancomycin AUC/MIC in dosing strategies and safety monitoring, consistency in laboratory reporting, and future directions for calculating AUC/MIC in pediatrics.