Economic analysis of rapid and sensitive polymerase chain reaction testing in the emergency department for influenza infections in children.

BACKGROUND: Rapid multiplex polymerase chain reaction (PCR) assays simultaneously detect several respiratory viral pathogens with high sensitivity. Maximizing detection of influenza at the point of care has the potential to reduce unnecessary antibiotic use, laboratory tests and hospitalizations. However, the cost-effectiveness of rapid multiplex PCR assays for influenza has not been compared with other diagnostic methods in children. METHODS: For children presenting to the emergency department with influenza-like illness, we compared costs and outcomes using 4 different testing strategies for detection of influenza: (1) a rapid multiplex PCR platform (FilmArray); (2) traditional PCR; (3) direct-fluorescent antibody and (4) rapid antigen tests. Costs were assessed from the hospital perspective, and effectiveness was defined as quality-adjusted life years (QALYs). Input parameters were obtained from previous studies, and the model was run separately for children aged 3-36 months and 3-18 years. RESULTS: Rapid multiplex PCR testing was the most effective testing strategy for children in both age groups. The incremental cost-effectiveness when compared with rapid antigen tests was $115,556 per QALY for children aged 3-36 months and from $228,000 per QALY for children aged 3-18 years. The cost-effectiveness of rapid multiplex PCR was sensitive to estimates for influenza prevalence, the proportion of patients treated with antivirals and the cost per test. CONCLUSIONS: Our model identifies scenarios in which identification of influenza in the emergency department using rapid multiplex PCR testing is a cost-effective strategy for infants and children 3 months through 18 years. Including detection of other respiratory viruses in the analysis would further improve cost-effectiveness.

Pharmacokinetics and pharmacodynamics of antifungals in children and their clinical implications.

Invasive fungal infections are a significant cause of morbidity and mortality in children. Successful management of these systemic infections requires identification of the causative pathogen, appropriate antifungal selection, and optimisation of its pharmacokinetic and pharmacodynamic properties to maximise its antifungal activity and minimise toxicity and the emergence of resistance. This review highlights salient scientific advancements in paediatric antifungal pharmacotherapies and focuses on pharmacokinetic and pharmacodynamic studies that underpin current clinical decision making. Four classes of drugs are widely used in the treatment of invasive fungal infections in children, including the polyenes, triazoles, pyrimidine analogues and echinocandins. Several lipidic formulations of the polyene amphotericin B have substantially reduced the toxicity associated with the traditional amphotericin B formulation. Monotherapy with the pyrimidine analogue flucytosine rapidly promotes the emergence of resistance and cannot be recommended. However, when used in combination with other antifungal agents, therapeutic drug monitoring of flucytosine has been shown to reduce high peak flucytosine concentrations, which are strongly associated with toxicity. The triazoles feature large inter-individual pharmacokinetic variability, although this pattern is less pronounced with fluconazole. In clinical trials, posaconazole was associated with fewer adverse effects than other members of the triazole family, though both posaconazole and itraconazole display erratic absorption that is influenced by gastric pH and the gastric emptying rate. Limited data suggest that the clinical response to therapy may be improved with higher plasma posaconazole and itraconazole concentrations. For voriconazole, pharmacokinetic studies among children have revealed that children require twice the recommended adult dose to achieve comparable blood concentrations. Voriconazole clearance is also affected by the cytochrome P450 (CYP) 2C19 genotype and hepatic impairment. Therapeutic drug monitoring is recommended as voriconazole pharmacokinetics are highly variable and small dose increases can result in marked changes in plasma concentrations. For the echinocandins, the primary source of pharmacokinetic variability stems from an age-dependent decrease in clearance with increasing age. Consequently, young children require larger doses per kilogram of body weight than older children and adults. Routine therapeutic drug monitoring for the echinocandins is not recommended. The effectiveness of many systemic antifungal agents has been correlated with pharmacodynamic targets in in vitro and in murine models of invasive candidiasis and aspergillosis. Further study is needed to translate these findings into optimal dosing regimens for children and to understand how these agents interact when multiple antifungal agents are used in combination.

Outpatient Parenteral Antimicrobial Therapy Practices Among Pediatric Infectious Diseases Consultants: Results of an Emerging Infections Network Survey.

We conducted a survey of pediatric members of the Emerging Infections Network regarding outpatient parenteral antimicrobial therapy (OPAT) practices and clinical decision making about OPAT initiation. We identified substantial variation in characteristics and resources of pediatric OPAT practices. Opportunities to improve oversight of OPAT in children should be explored.

Cerebrospinal fluid pleocytosis in febrile infants 1-90 days with urinary tract infection.

Sterile cerebrospinal fluid pleocytosis occurs in febrile infants with urinary tract infection. Coinfection with enterovirus is a possible cause. We evaluated 57 infants with urinary tract infection and cerebrospinal fluid pleocytosis. All had enterovirus testing by polymerase chain reaction. An explanation for pleocytosis was determined for 24 infants (42%). Enterovirus infection was detected in 4 and is an uncommon cause of cerebrospinal fluid pleocytosis in infants with urinary tract infection.

Therapeutic monitoring of voriconazole in children less than three years of age: a case report and summary of voriconazole concentrations for ten children.

Voriconazole is the treatment of choice for invasive aspergillosis and its use is increasing in pediatrics. Minimal pharmacokinetic data exist in young children. We report voriconazole concentrations for 10 children <3 years of age and pharmacokinetic parameters for 1 infant who had therapeutic drug monitoring performed. Trough concentrations were unpredictable based on dose, highlighting the need to follow values during therapy.

Molecular analysis improves pathogen identification and epidemiologic study of pediatric parapneumonic empyema.

BACKGROUND: Parapneumonic empyema (PPE) is an increasingly common complication of bacterial pneumonia. Epidemiologic study is complicated by the low frequency of positive cultures. We sought to describe the epidemiology of PPE in children using molecular analysis of pleural fluid. METHODS: We performed molecular testing for bacterial pathogens using archived pleural fluid from children hospitalized in 2009 with PPE. Real-time polymerase chain reaction (PCR) to detect Streptococcus pneumoniae, Staphylococcus aureus (including methicillin-resistant), Streptococcus pyogenes, Haemophilus influenzae, and Mycoplasma pneumoniae as well as PCR-based serotyping of S. pneumoniae was performed. Demographic, laboratory, and microbiologic data were abstracted. RESULTS: Pleural fluid specimens from 63 children were available for PCR. By culture, a pathogen was isolated from blood and/or pleural fluid in 22 (35%) patients, with S. pneumoniae in 15 (24%), S. pyogenes in 3 (5%), and methicillin-resistant Staphylococcus aureus in 4 (6%). By PCR, a pathogen was detected in 53 (84%), including S. pneumoniae in 45 (71%). Compared with culture, PCR testing significantly increased detection of any pathogen (35% vs. 84%; P < 0.001) and of S. pneumoniae (24% vs. 71%; P < 0.001). Serotype 7F was the most common pneumococcal serotype detected. Comparison of culture-negative to culture-positive disease showed differences in both the pathogen profile and clinical outcomes. CONCLUSIONS: Molecular analysis of pleural fluid more than doubled the detection of pathogens causing PPE. S. pneumoniae was the most common cause of both culture-positive and culture-negative PPE, although serotype distribution and outcomes differed.