Current and Emerging Antiviral Agents in the Prevention and Treatment of Cytomegalovirus in Pediatric Transplant Recipients.

Despite current prophylaxis regimens, cytomegalovirus (CMV) is common in hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT) and remains a significant cause of morbidity and mortality. Newer antiviral medications are reshaping the landscape for prevention and treatment of CMV DNAemia, infection, and disease. Letermovir is approved for CMV prevention in adult HCT patients and is attractive due to the absence of marrow suppression seen with ganciclovir/valganciclovir. Letermovir should not be routinely used for CMV treatment due to its low threshold for resistance. Maribavir is approved for the treatment of refractory or resistant CMV disease in HCT and SOT recipients ≥12 years of age, though it has no current role in CMV prevention. More research is needed to fully elucidate the roles, efficacy, and safety of these newer agents in prevention and treatment of CMV in pediatric transplant recipients.

International consensus recommendations for the use of prolonged-infusion beta-lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists: An executive summary.

Intravenous ß-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. ß-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PI) can be applied during the administration of intravenous ß-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of ß-lactam PI developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug monitoring considerations, and the use of PI ß-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of ß-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

International consensus recommendations for the use of prolonged-infusion beta-lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists.

Intravenous ß-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. ß-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PIs) can be applied during the administration of intravenous ß-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of PI ß-lactams developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug-monitoring considerations, and the use of PI ß-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of ß-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

Optimizing Vancomycin Therapy in Critically Ill Children: A Population Pharmacokinetics Study to Inform Vancomycin Area under the Curve Estimation Using Novel Biomarkers.

Area under the curve (AUC)-directed vancomycin therapy is recommended, but Bayesian AUC estimation in critically ill children is difficult due to inadequate methods for estimating kidney function. We prospectively enrolled 50 critically ill children receiving IV vancomycin for suspected infection and divided them into model training (n = 30) and testing (n = 20) groups. We performed nonparametric population PK modeling in the training group using Pmetrics, evaluating novel urinary and plasma kidney biomarkers as covariates on vancomycin clearance. In this group, a two-compartment model best described the data. During covariate testing, cystatin C-based estimated glomerular filtration rate (eGFR) and urinary neutrophil gelatinase-associated lipocalin (NGAL; full model) improved model likelihood when included as covariates on clearance. We then used multiple-model optimization to define the optimal sampling times to estimate AUC24 for each subject in the model testing group and compared the Bayesian posterior AUC24 to AUC24 calculated using noncompartmental analysis from all measured concentrations for each subject. Our full model provided accurate and precise estimates of vancomycin AUC (bias 2.3%, imprecision 6.2%). However, AUC prediction was similar when using reduced models with only cystatin C-based eGFR (bias 1.8%, imprecision 7.0%) or creatinine-based eGFR (bias -2.4%, imprecision 6.2%) as covariates on clearance. All three model(s) facilitated accurate and precise estimation of vancomycin AUC in critically ill children.

A Pharmacokinetic Analysis of Tobramycin in Patients Less than Five Years of Age with Cystic Fibrosis: Assessment of Target Attainment with Extended-Interval Dosing through Simulation.

Extended interval dosing of tobramycin is recommended for treatment of pulmonary exacerbations in adults and older children with cystic fibrosis (CF), but data are limited in patients less than 5 years of age. We performed a retrospective population pharmacokinetic (PK) analysis of hospitalized children with CF <5 years of age prescribed intravenous tobramycin for a pulmonary exacerbation from March 2011 to September 2018 at our hospital. Children with normal renal function who had ≥1 tobramycin concentration available were included. Nonlinear mixed effects population PK modeling was performed using NONMEM using data from the first 48 h of tobramycin treatment. Monte Carlo simulations were implemented to determine the fraction of simulated patients that met published therapeutic targets with regimens of 10-15 mg/kg/day once-daily dosing. Fifty-eight patients received 111 tobramycin courses (range 1-9/patient). A two-compartment model best described the data. Age, glomerular filtration rate, and vancomycin coadministration were significant covariates on tobramycin clearance. The typical values of clearance and central volume of distribution were 0.252 L/hr/kg^0.75 and 0.308 L/kg, respectively. No once-daily regimens achieved all pre-specified targets simultaneously in >75% of simulated subjects. A dosage of 13 mg/kg/dose best met the predefined targets of Cmax >25 mg/L and AUC24 of 80-120 mg·h/L. Based on our population PK analysis and simulations, once-daily dosing of tobramycin would not achieve all therapeutic goals in young patients with CF. However, extended-interval dosing regimens may attain therapeutic targets in the majority of young patients.

Multicenter Interim Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing agents with potential antiviral activity continue to expand such that updated guidance is needed regarding use of these agents in children. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion. RESULTS: Given the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or noninvasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir.

Effect of Cystatin C on Vancomycin Clearance Estimation in Critically Ill Children Using a Population Pharmacokinetic Modeling Approach.

BACKGROUND: Vancomycin is eliminated by glomerular filtration, but current approaches to estimate kidney function in children are unreliable. The authors sought to compare the suitability of cystatin C (CysC)-based glomerular filtration rate equations with the most commonly used creatinine-based equation, bedside Schwartz, to estimate vancomycin clearance (CL). METHODS: This prospective observational study enrolled critically ill patients (2-18 years) receiving intravenous vancomycin at the Children's Hospital of Philadelphia during December 2015-November 2017. Vancomycin levels were collected during clinical care and at 3 times during a single dosing interval. Plasma CysC was measured within 24 hours before intravenous vancomycin (baseline) initiation or immediately after enrollment and along with the third pharmacokinetic sample. Nonlinear mixed effects modeling was performed using NONMEM software. Covariate selection was used to test model fit with inclusion of the estimated glomerular filtration rate (eGFR) on CL using bedside Schwartz versus various published CysC-based equations. RESULTS: In total, 83 vancomycin levels were obtained from 20 children. The median age was 12.7 years; 6 patients were women. A 1-compartment model best described the data; CL was allometrically scaled to 0.75. During covariate selection, inclusion of the eGFR calculated using a CysC-based equation significantly improved model fit [reduction in objective function value (OFV) range: -17.191 to -18.704] than bedside Schwartz ([INCREMENT]OFV -12.820). Including the full age spectrum equation, an eGFR equation based on both creatinine and CysC, led to the largest OFV reduction (-22.913); female sex was also a significant covariate of CL in the model. Final model pharmacokinetic indices were CL = 0.29 L/h/kg and volume of distribution = 0.48 L/kg. CONCLUSIONS: CysC-based equations help better estimate vancomycin CL than bedside Schwartz in critically ill children.

Utility of Procalcitonin as a Biomarker for Sepsis in Children.

Sepsis is a complex process defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. It is associated with significant morbidity and mortality rates in both adults and children, and emphasis has been placed on its early recognition and prompt provision of antimicrobials. Owing to limitations of current diagnostic tests (i.e., poor sensitivity and delayed results), significant research has been conducted to identify sepsis biomarkers. Ideally, a biomarker could reliably and rapidly distinguish bacterial infection from other, noninfectious causes of systemic inflammatory illness. In doing so, a sepsis biomarker could be used for earlier identification of sepsis, risk stratification/prognostication, and/or guidance of antibiotic decision-making. In this minireview, we review one of the most common clinically used sepsis biomarkers, procalcitonin, and its roles in sepsis management in these three areas. We highlight key findings in the adult literature but focus the bulk of this review on pediatric sepsis. The challenges and limitations of procalcitonin measurement in sepsis are also discussed.

Implementation of a Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: the Optimizing Antibiotic Strategies in Sepsis (OASIS) II Study.

BACKGROUND: Biomarkers can facilitate safe antibiotic discontinuation in critically ill patients without bacterial infection. METHODS: We tested the ability of a biomarker-based algorithm to reduce excess antibiotic administration in patients with systemic inflammatory response syndrome (SIRS) without bacterial infections (uninfected) in our pediatric intensive care unit (PICU). The algorithm suggested that PICU clinicians stop antibiotics if (1) C-reactive protein <4 mg/dL and procalcitonin <1 ng/mL at SIRS onset and (2) no evidence of bacterial infection by exam/testing by 48 hours. We evaluated excess broad-spectrum antibiotic use, defined as administration on days 3-9 after SIRS onset in uninfected children. Incidence rate ratios (IRRs) compared unadjusted excess length of therapy (LOT) in the 34 months before (Period 1) and 12 months after (Period 2) implementation of this algorithm, stratified by biomarker values. Segmented linear regression evaluated excess LOT among all uninfected episodes over time and between the periods. RESULTS: We identified 457 eligible SIRS episodes without bacterial infection, 333 in Period 1 and 124 in Period 2. When both biomarkers were below the algorithm's cut-points (n = 48 Period 1, n = 31 Period 2), unadjusted excess LOT was lower in Period 2 (IRR, 0.53; 95% confidence interval, 0.30-0.93). Among all 457 uninfected episodes, there were no significant differences in LOT (coefficient 0.9, P = .99) between the periods on segmented regression. CONCLUSIONS: Implementation of a biomarker-based algorithm did not decrease overall antibiotic exposure among all uninfected patients in our PICU, although exposures were reduced in the subset of SIRS episodes where biomarkers were low.

Comparative Performance of Urinary Biomarkers for Vancomycin-Induced Kidney Injury According to Timeline of Injury.

Urinary biomarkers are superior to serum creatinine for defining onset and extent of kidney injury. This study classifies the temporal predictive ability of biomarkers for vancomycin-induced kidney injury (VIKI) as defined by histopathologic damage. Male Sprague-Dawley rats (n = 125) were randomized to receive 150 to 400 mg/kg of body weight/day vancomycin via once or twice daily intraperitoneal injection over 1, 3, or 6 days. Urine was collected once during the 24 h prior to euthanasia or twice for rats treated for 6 days. Receiver operating characteristic (ROC) curves were employed to assess the urinary biomarker performances of kidney injury molecule 1 (KIM-1), clusterin, osteopontin (OPN), cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) to predict histopathologically defined VIKI (using a national standard pathological assessment scheme from hematoxylin and eosin stained kidneys). Urinary KIM-1, clusterin, and OPN outperformed cystatin C and NGAL with regard to sensitivity and specificity. For the earliest injury, urinary KIM-1 (area under the receiver operating characteristic curve [AUC], 0.662; P < 0.001) and clusterin (AUC, 0.706; P < 0.001) were the most sensitive for predicting even low-level histopathologic damage at 24 h compared to NGAL. KIM-1 and clusterin are the earliest and most sensitive predictors of VIKI. As injury progresses, KIM-1, clusterin, and OPN best define the extent of damage.

Vancomycin Prescribing and Therapeutic Drug Monitoring in Children With and Without Acute Kidney Injury After Cardiac Arrest.

BACKGROUND: Acute kidney injury (AKI) commonly occurs after cardiac arrest. Those subsequently treated with vancomycin are at additional risk for drug-induced kidney injury. OBJECTIVE: We aimed to determine whether opportunities exist for improved drug monitoring after cardiac arrest. METHODS: This was a retrospective cohort study of children aged 30 days-17 years treated after cardiac arrest in an intensive care unit from January 2010 to September 2014 who received vancomycin within 24 h of arrest. Vancomycin dosing and monitoring were compared between those with and without AKI, with AKI defined as pRIFLE (pediatric risk, injury, failure, loss, end-stage renal disease) stage 2-3 AKI at day 5 using Schwartz formula-calculated estimated glomerular filtration rate (eGFR). RESULTS: Of 43 children, 16 (37%) had AKI at day 5. Age, arrest duration, median time to first vancomycin dose, and the number of doses before and time to first vancomycin concentration measurement were similar between groups. Children with AKI had higher initial vancomycin concentrations than those without AKI (median 16 vs. 7 mg/L; p = 0.003). A concentration was not measured before the second dose in 44% of children with AKI. Initial eGFR predicted day 5 AKI. In children with AKI, the initial eGFR was lower in those with than those without a concentration measurement before the second dose (29 mL/min/1.73 m2 [interquartile range (IQR) 23-47] vs. 52 [IQR 50-57]; p = 0.03) but well below normal in both. CONCLUSIONS: In children with AKI after cardiac arrest, decreased vancomycin clearance was evident early, and early monitoring was not performed universally in those with low initial eGFR. Earlier vancomycin therapeutic drug monitoring is indicated in this high-risk population.

Clinical Features and Outcomes of Children with Culture-Negative Septic Arthritis.

BACKGROUND: Septic arthritis is a serious infection, but the results of blood and joint fluid cultures are often negative in children. We describe here the clinical features and management of culture-negative septic arthritis in children at our hospital and their outcomes. METHODS: We performed a retrospective review of a cohort of children with septic arthritis who were hospitalized at Children's Hospital of Philadelphia between January 2002 and December 2014. Culture-negative septic arthritis was defined as a joint white blood cell count of >50000/µL with associated symptoms, a clinical diagnosis of septic arthritis, and a negative culture result. Children with pretreatment, an intensive case unit admission, Lyme arthritis, immunodeficiency, or surgical hardware were excluded. Treatment failure included a change in antibiotics, surgery, and/or reevaluation because of a lack of improvement/worsening. RESULTS: We identified 157 children with septic arthritis. The patients with concurrent osteomyelitis (n = 28) had higher inflammatory marker levels at presentation, had a longer duration of symptoms (median, 4.5 vs 3 days, respectively; P < .001), and more often had bacteremia (46.4% vs 6.2%, respectively; P < .001). Among children with septic arthritis without associated osteomyelitis, 69% (89 of 129) had negative culture results. These children had lower C-reactive protein levels (median, 4.0 vs 7.3 mg/dL, respectively; P = .001) and erythrocyte sedimentation rates (median, 39 vs 51 mm/hour, respectively; P = .01) at admission and less often had foot/ankle involvement (P = .02). Among the children with culture-negative septic arthritis, the inpatient treatment failure rate was 9.1%, and treatment failure was more common in boys than in girls (17.1% vs 3.8%, respectively; P = .03). We found no association between treatment failure and empiric antibiotics or patient age. No outpatient treatment failures occurred during the 6-month follow-up period, although 17% of the children discharged with a peripherally inserted central catheter line experienced complications, including 3 with bacteremia. CONCLUSIONS: The majority of septic arthritis infections at our institution were culture negative. Among patients with culture-negative infection, empiric antibiotics failed for 9% and necessitated a change in therapy. More sensitive diagnostic testing should be implemented to elucidate the causes of culture-negative septic arthritis in children.

Urinary kidney injury biomarkers and tobramycin clearance among children and young adults with cystic fibrosis: a population pharmacokinetic analysis.

BACKGROUND: Tobramycin is frequently used for treatment of bronchopneumonia in patients with cystic fibrosis (CF). Variability in tobramycin clearance (CL) is high in this population with few reliable approaches to guide dosing. OBJECTIVES: We sought to evaluate the pharmacokinetics of once-daily intravenous tobramycin in patients with CF and test the influence of covariates on tobramycin CL, including serum creatinine (SCr) and urinary biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), retinol-binding protein (RBP) and kidney injury molecule-1 (KIM-1). METHODS: This was a prospective, observational cohort study of children/young adults with CF receiving once-daily intravenous tobramycin from October 2012 to May 2014 at Cincinnati Children's Hospital Medical Center. Therapeutic drug monitoring data were prospectively obtained. Population pharmacokinetic analyses were performed using non-linear mixed-effects modelling. RESULTS: Thirty-seven patients (median age 15.3 years, IQR 12.7-19.5) received 62 tobramycin courses. A one-compartment model with allometrically scaled weight for tobramycin CL and volume of distribution (V) best described the data. Urinary NGAL was associated with tobramycin CL (P < 0.001), as was urinary RBP (P < 0.001). SCr, estimated glomerular filtration rate and urinary KIM-1 were not significant covariates. The population pharmacokinetic parameter estimates were CL = 8.60 L/h/70 kg (relative standard error 4.3%) and V = 31.3 L/70 kg (relative standard error 4.7%). CONCLUSIONS: We describe urinary biomarkers as predictors of tobramycin CL using a population pharmacokinetic modelling approach. Our findings suggest that patient weight and urinary NGAL or RBP could be used to individualize tobramycin therapy in patients with CF.

Non-typeable Haemophilus influenzae purulent pericarditis in a child with cystic fibrosis.

Early airway colonization and infection with Haemophilus influenzae in children with cystic fibrosis (CF) is common. Although the pathogenicity of non-typeable H. influenzae (NTHi) in patients with CF is controversial, this organism can cause both upper and lower respiratory tract infections. Extra-pulmonary disease, however, is rare. Purulent pericarditis is a suppurative complication of bacterial infection of the pericardial space that can arise as a result of direct extension from an adjacent infection. We describe a case of purulent pericarditis due to NTHi in a young child with CF that developed as a complication of inadequately treated bronchopneumonia.

Risk factors for acute kidney injury during aminoglycoside therapy in patients with cystic fibrosis.

BACKGROUND: Aminoglycoside (AG) therapy is a common cause of acute kidney injury (AKI) in cystic fibrosis (CF) patients. The aim of this study was to identify factors associated with AKI during intravenous AG courses in this population. METHODS: This was a matched case-control study utilizing two independent cohorts of hospitalized CF patients receiving ≥ 3 days of intravenous AG at Cincinnati Children's Hospital Medical Center and Children's of Alabama. All admissions with AKI (cases, N = 82) were matched to two randomly selected admissions without AKI (controls, N = 164) by center, gender, and age ±3 years of the case. AKI was defined as a 1.5-fold increase in the baseline serum creatinine (SCr) level or by an increase in SCr level of 0.3 mg/dL within 48 h. Admissions with AKI before day 4 or without at least weekly SCr monitoring were excluded from the analysis. Factors were compared between cases and controls using simple and multiple conditional logistic regression. RESULTS: Multivariable analysis identified receipt of an AG within 90 days prior to admission, longer duration of AG therapy, low serum albumin, and receipt of trimethoprim/sulfamethoxazole as independent risk factors for developing AKI. Infection with Staphylococcus aureus diminished the odds of developing AKI. CONCLUSIONS: This study identifies risk factors contributing to AG-associated AKI in CF patients. These findings can be used to anticipate high-risk scenarios and limit AKI in CF patients under clinical care.

Daily serum creatinine monitoring promotes earlier detection of acute kidney injury in children and adolescents with cystic fibrosis.

BACKGROUND: The epidemiology of aminoglycoside-associated acute kidney injury (AG-AKI) has not been well described in pediatric patients with cystic fibrosis (CF). We aimed to assess the impact of daily serum creatinine (SCr) measurement on detection of AG-AKI at our institution. METHODS: We examined a cohort of hospitalized patients with CF who received an intravenous (IV) aminoglycoside for ≥ 3 days. We compared the rate, timing, and medical management surrounding detection of AG-AKI during 2 periods: January 2010-May 2011 (Era 1, SCr measured at the discretion of the medical team, N=124) and June 2011-June 2012 (Era 2, SCr measured daily, N=103). Our primary outcome was detection of AG-AKI defined as ≥ 50% increase in SCr from baseline (lowest value in prior 6 months), or ≥ 0.3mg/dL rise within 48 h, occurring after day 2. RESULTS: The use of once daily tobramycin (p=0.02) and IV fluids (p<0.001) was higher during Era 2, while AG courses were shorter (p=0.04), and fewer concomitant nephrotoxins (p=0.04) were given; higher daily tobramycin doses (p<0.001) were administered. Although the rate of AG-AKI was not significantly different (12% during Era 1 vs. 20% during Era 2, p=0.09), the number of AG-AKI days detected increased (5.5 vs. 2.9 per 100 AG days, p=0.003), and detection occurred earlier (median 6 vs. 9 days, log rank test p=0.02) during the daily SCr period. CONCLUSIONS: Daily SCr measurement promoted earlier and increased detection of AG-AKI in patients with CF at our institution. We suggest systematic evaluation for AKI during aminoglycoside administration in patients with CF.

Practice variation in screening for sexually transmitted infections with nucleic acid amplification tests during prepubertal sexual abuse evaluations.

BACKGROUND: Although recent recommendations for children after suspected sexual abuse incorporate nucleic acid amplification tests (NAATs) in algorithms that detect sexually transmitted infections (STIs), screening practices in the community remain uncertain. STUDY OBJECTIVE: We examined screening practices over time and across a variety of pediatric settings for the evaluation of STIs in sexually abused children. METHODS: A consecutive cohort of prepubertal children younger than 11 years of age who were suspected to have been sexually abused were identified between May 2002 and April 2005 at a large tertiary children's hospital and its supporting primary care network. Detailed histories and examinations based on chart abstraction were linked to hospital laboratory records to identify those who were screened for Chlamydia trachomatis and Neisseria gonorrhoeae by means of cultures, NAATs, or both. Chi-square and logistic regression analyses identified factors associated with screening, including the effects of screening location and year of study on the likelihood that particular tests were obtained. RESULTS: Among the initial visits of 1068 children, 32% occurred in the specialty child abuse clinic (CARE Clinic), 62% in the emergency department, and 6% in the primary care setting. Follow-up visits occurred in only 7% of children. The performance of at least one screening test increased each year, from 12% in year 1 to 18% in year 3 (P = 0.01). Among the 162 children in whom tests were obtained, there was a significant decrease in the use of culture techniques over time, from 100% in year 1 to 75% in year 3 (P < 0.001). At the same time, there was a steady increase in the use of NAATs in total (from 2% in year 1 to 41% in year 3, P < 0.001), and in the absence of culture techniques (from 0% in year 1 to 26% in year 3, P < 0.001). This growth in the use of NAATs alone was particularly seen in the emergency department setting, where 33% of children were screened only by NAAT by year 3 (P = 0.001). CONCLUSIONS: Screening rates for STIs increased over time, a trend that is explained primarily by the use of NAATs in the absence of other tests. The increasing use of NAATs will have to be addressed more fully in creating future guidelines for this population.

Polymicrobial bloodstream infections among children and adolescents with central venous catheters evaluated in ambulatory care.

BACKGROUND: Bloodstream infections (BSIs) are an ever-present concern for clinicians evaluating ill-appearing pediatric patients with central venous catheters (CVCs) in the ambulatory care setting. METHODS: We performed a case-control study of a cohort of 200 pediatric patients who were evaluated in the ambulatory care setting and who were found to have laboratory-confirmed BSI in the context of a CVC. This study sought to compare patients with polymicrobial versus monomicrobial BSIs to identify potential risk factors for polymicrobial BSI. RESULTS: Of the 200 patients enrolled in the study, 73 (37%) had a polymicrobial BSI. Patients with polymicrobial BSI were more likely than those with monomicrobial BSI to be younger (P=.002) and less likely to have been recently discharged from the hospital (P=.01). The odds of a polymicrobial BSI were >4 times greater for patients aged <3 years than for those aged >or=3 years (odds ratio, 4.54; 95% confidence interval, 1.68-12.29), and the odds were 50% lower for those discharged from the hospital in the prior 7 days than for those without recent hospitalization (odds ratio, 0.46; 95% confidence interval, 0.22-0.95) after controlling for an underlying cancer diagnosis and the time of year during which a patient presented. Recent antibiotic use, recent BSI, duration that the CVC had been in place, and underlying gastrointestinal dysfunction were not associated with a risk of polymicrobial BSI. CONCLUSIONS: Younger children and those who had not recently been discharged from the hospital had an increased risk of developing catheter-related polymicrobial BSI. Special consideration should be given to the increased likelihood of polymicrobial BSIs in these pediatric patients when initiating empirical antimicrobial therapy.