Lactococcus Species Central Line-Associated Bloodstream Infection in Pediatrics: A Case Series.

Lactococcus spp. is typically thought to be of low virulence and seldom considered pathogenic. Few cases of significant infections in children have been reported, all outside of the United States. There is also limited data on antimicrobial susceptibility testing for Lactococcus spp. We present three pediatric patients with central line bloodstream infections due to Lactococcus spp. between 2018 and 2020, along with a review of the pediatric literature.

Therapeutic Monitoring of Vancomycin for Serious Methicillin-resistant Staphylococcus aureus Infections: A Revised Consensus Guideline and Review by the American Society of Health-system Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists.

Recent clinical data on vancomycin pharmacokinetics and pharmacodynamics suggest a reevaluation of current dosing and monitoring recommendations. The previous 2009 vancomycin consensus guidelines recommend trough monitoring as a surrogate marker for the target area under the curve over 24 hours to minimum inhibitory concentration (AUC/MIC). However, recent data suggest that trough monitoring is associated with higher nephrotoxicity. This document is an executive summary of the new vancomycin consensus guidelines for vancomycin dosing and monitoring. It was developed by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists vancomycin consensus guidelines committee. These consensus guidelines recommend an AUC/MIC ratio of 400-600 mg*hour/L (assuming a broth microdilution MIC of 1 mg/L) to achieve clinical efficacy and ensure safety for patients being treated for serious methicillin-resistant Staphylococcus aureus infections.

Executive Summary: Therapeutic Monitoring of Vancomycin for Serious Methicillin-Resistant Staphylococcus aureus Infections: A Revised Consensus Guideline and Review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists.

BACKGROUND: Recent vancomycin PK/PD and toxicodynamic studies enable a reassessment of the current dosing and monitoring guideline in an attempt to further optimize the efficacy and safety of vancomycin therapy. The area-under-the-curve to minimum inhibitory concentration (AUC/MIC) has been identified as the most appropriate pharmacokinetic/pharmacodynamic (PK/PD) target for vancomycin. The 2009 vancomycin consenus guidelines recommended specific trough concentrations as a surrogate marker for AUC/MIC. However, more recent toxicodynamic studies have reported an increase in nephrotoxicity associated with trough monitoring. METHODS AND RESULTS: This is the executive summary of the new vancomycin consensus guidelines for dosing and monitoring vancomycin therapy and was developed by the American Society of Health-Systems Pharmacists, Infectious Diseases Society of America, Pediatric Infectious Diseases Society and the Society of Infectious Diseases Pharmacists vancomycin consensus guidelines committee. CONCLUSIONS: The recommendations provided in this document are intended to assist the clinician in optimizing vancomycin for the treatment of invasive MRSA infections in adult and pediatric patients. An AUC/MIC by broth microdilution (BMD) ratio of 400 to 600 (assuming MICBMD of 1 mg/L) should be advocated as the target to achieve clinical efficacy while improving patient safety for patients with serious MRSA infections. In such cases, AUC-guided dosing and monitoring is the most accurate and optimal way to manage vancomycin therapy.

Description of Respiratory Microbiology of Children With Long-Term Tracheostomies.

BACKGROUND: There is little evidence in the medical literature to guide empiric treatment of pediatric patients with long-term tracheostomies who present with signs and symptoms of a bacterial respiratory infection. The overall goal of this study was to describe the respiratory microbiology in this study population at our institution. METHODS: This study was a retrospective chart review of all subjects with tracheostomies currently receiving care at the Arkansas Center for Respiratory Technology Dependent Children. Descriptive statistics were used to describe the respiratory microbiology of the full study group. Several subgroup analyses were conducted, including description of microbiology according to time with tracheostomy, mean time to isolation of specific organisms after the tracheostomy tube was placed, association between Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus isolation and prescribed antibiotic courses, and description of microbiology according to level of chronic respiratory support. Available respiratory culture results up to July 2011 were collected for all eligible subjects. Descriptive statistics were used to describe subject characteristics, and chi-square analysis was used to analyze associations between categorical data. P < .05 was considered statistically significant. RESULTS: A total of 93 subjects met inclusion criteria for the study. The median (interquartile range) age at time of tracheotomy was 0.84 (0.36-3.25) y, and the median (interquartile range) time with tracheostomy was 4.29 (2.77-9.49) y. The most common organism isolated was P. aeruginosa (90.3%), with Gram-negative organisms predominating. However, 55.9% of the study population had a respiratory culture positive for methicillin-resistant S. aureus. The first organism isolated after tracheostomy placement was Methiciliin-sensitive S. aureus was isolated the soonest after tracheostomy placement. Specific organisms were not related to level of chronic respiratory support or likelihood of receiving antibiotics. CONCLUSIONS: This study provides an updated overview of the variety of potential pathogens isolated from respiratory cultures of pediatric subjects with long-term tracheostomies.

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.

Antimicrobial stewardship in pediatrics: how every pediatrician can be a steward.

Antimicrobial stewardship (AS) programs are effective in improving clinical outcomes associated with antimicrobial therapies while improving patient safety by reducing adverse events and development of bacterial resistance. Understanding the basic principles of AS is essential to the successful development and implementation of AS strategies. Identifying and developing strategies to address barriers and challenges to AS can facilitate the establishment of financial, administrative, and organizational support, and agreement and participation by individual prescribers. Review of published outcomes of AS demonstrates the effectiveness in reducing unnecessary antimicrobial use and adverse events such as Clostridium difficile infections. We also illustrate the need for further research and expansion of AS activities to office-based practices and communities by using novel and innovative AS strategies and by influencing regional and national policies.

Intravenous voriconazole therapy in a preterm infant.

A preterm infant younger than 3 months developed a disseminated fluconazole-resistant Candida albicans infection that was treated with liposomal amphotericin B for 52 days, followed by the combination of intravenous voriconazole and liposomal amphotericin B for an additional 19 days. The infant received concomitant phenobarbital throughout the hospital stay. The infection resolved after addition of voriconazole to the treatment regimen. Intravenous voriconazole was begun at a high dosage, 6 mg/kg every 12 hours, for anticipated developmental and drug-induced changes in volume of distribution and clearance. On day 4 of therapy, serum concentrations of voriconazole were 3.27 microg/ml immediately after infusion and 0.33 microg/ml 6 hours after infusion. These levels were significantly lower than those achieved in adult pharmacokinetic and safety studies. After the infant's dosage was increased to 6 mg/kg every 8 hours, serum concentrations were 5.33 microg/ml 30 minutes after infusion and 2.67 microg/ml 6 hours after infusion. These levels were similar to those observed in adults. Intravenous voriconazole 6 mg/kg every 8 hours was administered safely, with concomitant phenobarbital therapy, in this preterm infant with developmentally diminished renal function.

Pharmacokinetics of intravenously administered azithromycin in pediatric patients.

BACKGROUND: The objective of this study was to characterize the pharmacokinetics and tolerance of a single intravenous (IV) azithromycin dose in children. METHODS: Subjects were stratified into 4 age groups: 0.5-2 years; >2-<6 years; 6-<12 years; and 12-<16 years. Each subject received a single 10 mg/kg dose (500 mg maximum) infused in 1 hour. Serial venous blood samples were obtained for a 168-hour period, and laboratory safety evaluations were performed immediately preceding azithromycin administration and at the conclusion of the study. Serum azithromycin concentrations were quantified with a validated high performance liquid chromatography method with mass spectrometric detection. Pharmacokinetic indices were calculated for each subject by noncompartmental techniques. RESULTS: Thirty-two subjects (6.7 +/- 5.0 years, 11 boys) participated. Mean serum concentration-time data were comparable for the 4 age groups. For all subjects with evaluable data, the mean area under the curve from 0 to 72 hours (AUC0-72) was 8.2 microg . h/mL (n = 26), the maximum concentration (Cmax) was 2.4 microg/mL and the elimination half-life (t1/2) was 65.2 hours (n = 25). The AUC0-72 and Cmax were not associated with age. The dose was well-tolerated with no serious adverse events. CONCLUSION: The disposition of azithromycin after a single 10-mg/kg IV dose (maximum labeled adult dose of 500 mg) is comparable in pediatric patients between 0.5 and 16 years of age. These pharmacokinetic data can be used to guide dose selection for future therapeutic trials of IV azithromycin in pediatric patients.

Nonadherence with pediatric human immunodeficiency virus therapy as medical neglect.

OBJECTIVE: To examine the results of an interventionist approach applied to human immunodeficiency virus (HIV)-infected children for whom caregiver nonadherence was suspected as the cause of treatment failure. METHODS: The medical records of a cohort of 16 perinatally HIV-infected children whose care was managed at the Arkansas Children's Hospital Pediatric HIV Clinic for an uninterrupted period of >or=3 years were reviewed through July 2003. Data collected included date of birth, dates of and explanations for clinic visits and hospitalizations, dates of laboratory evaluations, CD4(+) T cell percentages, plasma HIV-1 RNA levels, antiretroviral medications, viral resistance tests (eg, phenotype and genotype), and physician-initiated interventions to enhance adherence to the medication regimen. A stepwise interventionist approach was undertaken when patients continued to demonstrate high viral loads, despite documented viral sensitivity to the medication regimen and caregivers' insistence that medications were being administered regularly. Step 1 was prescribing a home health nurse referral, step 2 was administering directly observed therapy (DOT) while the patient was hospitalized for 4 days, and step 3 was submitting a physician-initiated medical neglect report to the Arkansas Department of Human Services. RESULTS: The results for 6 patients for whom this stepwise approach was initiated are reported. Home health nurse referrals failed to result in sustained improvements in adherence in all 6 cases. Viral load assays performed before and after DOT provided an objective measure of the effect of adherence, with 12 hospitalizations resulting in a mean +/- SD decrease in HIV RNA levels of 1.09 +/- 0.5 log(10) copies per mL, with a range of 0.6 to 2.1 log(10) copies per mL. Four families responded to DOT hospitalization, and sustained decreases in the respective patients' viral loads were noted. In 2 cases, medical neglect reports were submitted when DOT did not result in improved adherence. These patients were eventually placed in foster care, with subsequent improvements in their viral loads and CD4(+) T cell percentages. CONCLUSIONS: Nonadherence with antiretroviral therapy can be established on the basis of persistently elevated HIV RNA levels that decrease with DOT. Nonadherence poses a danger to the child that is grave and potentially irreversible. Caregivers should be offered all available resources to help them adhere to a sound treatment plan. In cases of demonstrated inability to provide needed care, it is necessary to consider seeking child protection, even for apparently healthy children.

Famotidine disposition in children and adolescents with chronic renal insufficiency.

The pharmacokinetics of intravenous famotidine (0.5 mg/kg, maximum 20 mg) were evaluated in 18 pediatric patients (ages 1-18 years) with stable, chronic renal insufficiency. Subjects were stratified by calculated creatinine clearance (Clcr) into mild (Clcr > or = 50 to < 90 mL/min/1.73 m2), moderate (Clcr > or = 25 to < 50 mL/min/1.73 m2), and severe (Clcr < or = 10 mL/min/1.73 m2) renal insufficiency groups. Significant differences between the mild, moderate, and severe groups were found for elimination rate (Kel), apparent elimination half-life (t1/2), area under the curve (AUC), and total plasma clearance (Clp) (p < 0.01). Famotidine renal clearance (Clr) was found to be significantly different between the mild and severe groups (p < 0.05). A linear relationship was observed between Clcr and Clp (p < 0.0001; R2 = 0.70). No significant differences in nonrenal clearance (Clnr) were found between groups; however, Clnr as a percentage of Clp was significantly different in the severe group (92.9% +/- 7.3% Clnr) compared to the combined mild and moderate groups (21.9% +/- 45.6% Clnr) (p < 0.05). It was concluded that the pharmacokinetics of famotidine are significantly altered in children with chronic renal insufficiency; accordingly, dosing should be based on glomerular filtration rate (i.e., Clcr).