Impact of outpatient SARS-CoV-2 infections in minority children.

ABSTRACT: Data regarding COVID-19 in the adult population and hospitalized children is rapidly evolving, but little is known about children infected with severe acute respiratory syndrome coronavirus 2 who do not require hospitalization.In an observational, retrospective study we analyzed risk factors, demographics and clinical course of non-hospitalized patients ≤ 21 years of age with COVID-19 infection.Of the 1,796 patients evaluated, 170 were infected, and 40 participated in a telephone survey. Children older >10 years of age (OR: 2.19), Hispanic ethnicity (OR: 3) and residing in counties with higher rates of poverty (OR: 1.5) were associated with higher risk of infection, while older girls were more likely to experience prolonged duration of symptoms (median: 32 days). Consistent with prior reports, fever and cough were present in most of our patients. Shortness of breath, diarrhea, anosmia, and ageusia were more common in our outpatient population than previously reported.Larger studies addressing the clinical and psychosocial impact of CoVID-19 infection in children living in high-risk environments are warranted.

Impact of a Rapid Diagnostic Meningitis/Encephalitis Panel on Antimicrobial Use and Clinical Outcomes in Children.

Rapid molecular diagnostic assays are increasingly used to guide effective antimicrobial therapy. Data on their effectiveness to decrease antimicrobial use in children have been limited and varied. We aimed to assess the impact of the implementation of the FilmArray Meningitis Encephalitis Panel (MEP) on antimicrobial use and outcomes in children. In an observational retrospective study performed at Atlantic Health System (NJ), we sought to evaluate the duration of intravenous antibiotic treatment (days of therapy (DoT)) for patients <21 years of age hospitalized and evaluated for presumptive meningitis or encephalitis before and after the introduction of the MEP. A secondary analysis was performed to determine if recovery of a respiratory pathogen influenced DoT. The median duration of antibiotic therapy prior to the implementation of the MEP was 5 DoT (interquartile range (IQR): 3-6) versus 3 DoT (IQR: 1-5) (p < 0.001) when MEP was performed. The impact was greatest on intravenous third-generation cephalosporin and ampicillin use. We found a reduction in the number of inpatient days associated with the MEP. In the regression analysis, a positive respiratory pathogen panel (RPP) was not a significant predictor of DoT (p = 0.08). Furthermore, we found no significant difference between DoT among patients with negative and positive RPP (p = 0.12). Our study supports the implementation of rapid diagnostics to decrease the utilization of antibiotic therapy among pediatric patients admitted with concerns related to meningitis or encephalitis.

Improvements in Antimicrobial Prescribing and Outcomes in Pediatric Complicated Appendicitis.

BACKGROUND: Complicated appendicitis, characterized by perforation and/or peritonitis, is common in children, and late infectious complications are frequent. The best antibiotic treatment approach is unknown, resulting in substantial variation in care. We evaluated the effects of 2 successive interventions, an antimicrobial stewardship program (ASP) and a condition-specific clinical practice guideline (CPG), on antimicrobial utilization and patient outcomes in these patients. METHODS: The ASP at our institution was begun in March 2012. The CPG, a standardized antibiotic treatment, was implemented in July 2013. We reviewed every case of complicated appendicitis managed with early appendectomy between January 2011 and October 2014. Patients were thus divided into 3 eras based on their exposure to the following: (1) neither intervention, (2) ASP only or (3) both ASP and CPG. We compared measures of antibiotic utilization and clinical outcomes among the 3 eras. RESULTS: A total of 313 patients were included in the study: 91 exposed to neither intervention; 100 exposed to only the ASP; and 122 exposed to both interventions. With ASP implementation, there were declines in the use of unnecessarily broad or toxic antibiotic regimens. With CPG implementation, there was a decrease in total antibiotic utilization and discharges with intravenous antibiotics. Compliance with CPG-recommended antibiotics exceeded 90%. There was no significant change in overall adverse events; there was a decline in the incidence of surgical-site infections in patients exposed to both interventions. CONCLUSIONS: Complicated appendicitis is an important target for antimicrobial stewardship and quality improvement efforts. A condition-specific CPG can improve both antimicrobial utilization and clinical outcomes.

Reducing Antimicrobial Use in an Academic Pediatric Institution: Evaluation of the Effectiveness of a Prospective Audit With Real-Time Feedback.

INTRODUCTION: Antimicrobial use is decreasing across freestanding children's hospitals, predominantly in institutions with antimicrobial stewardship programs (ASPs) in place. A highly effective ASP should effect a greater decrease in use than predicted by existing trends. Antimicrobial stewardship programs depend on clinician adherence to program recommendations, but little is known about factors associated with adherence. METHODS: Parenteral antimicrobial-use data for our institution and 43 additional freestanding children's hospitals were obtained and normalized for patient census. Segmental linear regression was used to compare rates of change of parenteral antimicrobial use before and after ASP implementation. Time-series models were developed to predict use in the absence of intervention. The odds of adherence to ASP recommendations were determined based on provider characteristics and recommendation type. RESULTS: In the 38 months before ASP implementation, parenteral antimicrobial use was decreasing at our hospital by 3.7%/year, similar to the 3.4%/year found across children's hospitals. The rate of change after implementation of the ASP at our hospital was 11.1%/year, compared to 5.6%/year for other hospitals over the same period. Of 643 interventions, teams adhered with recommendations in 495 cases (77.0%). According to adjusted analysis, primary service was not associated with adherence (P = .356). There was an association between adherence and the role of the clinician receiving a recommendation (P = .009) and the recommendation type (P = .009). CONCLUSIONS: Understanding factors associated with adherence to ASP recommendations can help those who administer such programs to strategize interventions for maximizing efficacy. Our findings reveal the value of a formal ASP in reducing use when controlling for secular trends.

The Use of a Computerized Provider Order Entry Alert to Decrease Rates of Clostridium difficile Testing in Young Pediatric Patients.

BACKGROUND Infants and young children are frequently colonized with C. difficile but rarely have symptomatic disease. However, C. difficile testing remains prevalent in this age group. OBJECTIVE To design a computerized provider order entry (CPOE) alert to decrease testing for C. difficile in young children and infants. DESIGN An interventional age-targeted before-after trial with comparison group SETTING Monroe Carell Jr. Children's Hospital at Vanderbilt University, Nashville, Tennessee. PATIENTS All children seen in the inpatient or emergency room settings from July 2012 through July 2013 (pre-CPOE alert) and September 2013 through September 2014 (post-CPOE alert) INTERVENTION In August of 2013, we implemented a CPOE alert advising against testing in infants and young children based on the American Academy of Pediatrics recommendations with an optional override. We further offered healthcare providers educational seminars regarding recommended C. difficile testing. RESULTS The average monthly testing rate significantly decreased after the CPOE alert for children 0-11 months old (11.5 pre-alert vs 0 post-alert per 10,000 patient days; P<.001) and 12-35 months old (61.6 pre-alert vs 30.1 post-alert per 10,000 patients days; P<.001), but not for those children ≥36 months old (50.9 pre-alert vs 46.4 post-alert per 10,000 patient days; P=.3) who were not targeted with a CPOE alert. There were no complications in those children who testing positive for C. difficile. CONCLUSIONS The average monthly testing rate for C. difficile for children <35 months old decreased without complication after the use of a CPOE alert in those who tested positive for C. difficile. Infect Control Hosp Epidemiol 2017;38:542-546.

Vancomycin Use: Room for Improvement Among Hospitalized Children.

INTRODUCTION: The use of vancomycin is common among hospitalized children. We sought to evaluate the impact of prospective audit with real-time feedback on vancomycin use and pharmacy costs. METHODS: Vancomycin use was evaluated at Monroe Carell Jr Children's Hospital at Vanderbilt (MCJCHV) before and after the implementation of prospective audit with intervention and feedback to providers in 2012. Antibiotic use was compared to academic children's hospitals with established antimicrobial stewardship programs (ASPs). Two similar pediatric academic institutions without an ASP were used as nonintervention controls. Analysis of monthly days of antibiotic therapy (DoT) per 1000 patient-days was performed by interrupted time series analysis. RESULTS: Monthly vancomycin use decreased from 114 DoTs/1000 patient-days to 89 DoTs/1000 patient-days ( P < .0001). We did not find significant differences in the slope of change in vancomycin use between MCJCHV and institutions with ASPs either before or after the intervention ( P = .86 and P = .71, respectively). When compared to children's hospitals without ASPs, the use of vancomycin was significantly lower at MCJCHV ( P < .001). CONCLUSION: The use of vancomycin at academic children's hospitals with an ASP is declining. In our experience, prospective audit with real-time intervention and feedback to providers significantly reduced the use and costs associated with vancomycin.

Effect of a Clinical Practice Guideline for Pediatric Complicated Appendicitis.

IMPORTANCE: Complicated appendicitis is a common condition in children that causes substantial morbidity. Significant variation in practice exists within and between centers. We observed highly variable practices within our hospital and hypothesized that a clinical practice guideline (CPG) would standardize care and be associated with improved patient outcomes. OBJECTIVE: To determine whether a CPG for complicated appendicitis could be associated with improved clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: A comprehensive CPG was developed for all children with complicated appendicitis at Monroe Carell Jr Children's Hospital at Vanderbilt, a freestanding children's hospital in Nashville, Tennessee, and was implemented in July 2013. All patients with complicated appendicitis who were treated with early appendectomy during the study period were included in the study. Patients were divided into 2 cohorts, based on whether they were treated before or after CPG implementation. Clinical characteristics and outcomes were recorded for 30 months prior to and 16 months following CPG implementation. EXPOSURE: Clinical practice guideline developed for all children with complicated appendicitis at Monroe Carell Jr Children's Hospital at Vanderbilt. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the occurrence of any adverse event such as readmission or surgical site infection. In addition, resource use, practice variation, and CPG adherence were assessed. RESULTS: Of the 313 patients included in the study, 183 were boys (58.5%) and 234 were white (74.8%). Complete CPG adherence occurred in 78.7% of cases (n = 96). The pre-CPG group included 191 patients with a mean (SD) age of 8.8 (4.0) years, and the post-CPG group included 122 patients with a mean (SD) age of 8.7 (4.1) years. Compared with the pre-CPG group, patients in the post-CPG group were less likely to receive a peripherally inserted central catheter (2.5%, n = 3 vs 30.4%, n = 58; P < .001) or require a postoperative computed tomographic scan (13.1%, n = 16 vs 29.3%, n = 56; P = .001), and length of hospital stay was significantly reduced (4.6 days post-CPG vs 5.1 days pre-CPG, P < .05). Patients in the post-CPG group were less likely to have a surgical site infection (relative risk [RR], 0.41; 95% CI, 0.27-0.74) or require a second operation (RR, 0.35; 95% CI, 0.12-1.00). In the pre-CPG group, 30.9% of patients (n = 59) experienced any adverse event, while 22.1% of post-CPG patients (n = 27) experienced any adverse event (RR, 0.72; 95% CI, 0.48-1.06). CONCLUSIONS AND RELEVANCE: Significant practice variation exists among surgeons in the management of pediatric complicated appendicitis. In our institution, a CPG that standardized practice patterns was associated with reduced resource use and improved patient outcomes. Most surgeons had very high compliance with the CPG.

Subcutaneous Colletotrichum truncatum Infection in a Child.

Human infection with Colletotrichum species is typically limited to ophthalmologic manifestations. We present the first reported pediatric case of subcutaneous Colletotrichum truncatum infection. This case highlights the potential importance of C. truncatum as an agent of subcutaneous or disseminated disease in immunocompromised children.

Phototoxicity, Pseudoporphyria, and Photo-onycholysis Due to Voriconazole in a Pediatric Patient With Leukemia and Invasive Aspergillosis.

Voriconazole is a triazole antifungal agent superior to amphotericin B in the treatment of invasive aspergillosis. It is generally well tolerated and has excellent oral bioavailability, providing significant benefit in the treatment of invasive fungal infections. There have been numerous reports of dermatologic reactions to this agent, including erythroderma, cheilitis, Stevens-Johnson syndrome, discoid lupus erythematosus, pseudoporphyria, squamous cell carcinoma, and photosensitivity reactions. Pseudoporphyria, a dermatologic condition mimicking porphyria cutanea tarda, has been described as an adverse effect of voriconazole use. Clinical findings include photosensitivity, vesicles, bullae, milia, and scarring in sun-exposed areas. Photo-onycholysis is a phenomenon of nail discoloration and onycholysis that has been described in the setting of a phototoxic drug reaction and pseudoporphyria. Implicated drugs have most commonly been tetracyclines, fluoroquinolones, and psoralens; others have been reported as well. We report a case of a pediatric patient with leukemia who developed symptoms consistent with pseudoporphyria and later photo-onycholysis while being treated with voriconazole. To our knowledge, this is the first reported case of pseudoporphyria due to voriconazole in a pediatric patient and the first reported case of photo-onycholysis as a consequence of voriconazole use.

Trends of fluoroquinolone-resistant Escherichia coli amongst urinary isolates in children: a 10 year surveillance study.

We evaluated 3122 children with E. coli urinary isolates over a 10 year period in order to assess the emergence of fluoroquinolone resistance. Susceptibilities remained stable; however, hospitalized children had a statistically higher risk of developing fluoroquinolone-resistant isolates when compared with outpatients. Stewardship monitoring of fluoroquinolone use amongst hospitalized children is warranted.

Candida species bloodstream infections in hospitalised children: A 10-year experience.

In a 10-year retrospective study we assessed the epidemiology of candidemia and the association between the presence and removal of indwelling central venous catheters, antifungal use and clinical outcomes among hospitalised children. Demographic and clinical information were retrieved from the electronic medical records. One hundred six episodes of candidemia were identified in 83 unique patients. Candida parapsilosis was the most prevalent (52%) species, followed by C. albicans (25%). Non-oncologic children receiving fluconazole within 30 days of developing candidemia were most likely to develop C. parapsilosis infection (40%, P = 0.006), independent of total parenteral nutrition (odds ratio (OR) 2.5, 95% confidence interval (CI): 0.6-11, P = 0.3). Crude mortality rate was 12% and significantly higher for children less than 2 years (OR: 6.7, 95% CI: 1.9-23, P = 0.003), and those infected with C. lusitaniae (OR: 9, 95% CI: 1.6-51, P = 0.02). The aggregate use of antifungal agents decreased overtime (χ(2) : 16.7, P < 0.0001). Fluconazole remained the most common antifungal agent used during the study.

Implications and impact of prior authorization policy on vancomycin use at a tertiary pediatric teaching hospital.

BACKGROUND: We evaluated the performance of two consecutive antimicrobial stewardship interventions on vancomycin use. METHODS: Prospective audit with intervention and real time feedback to providers were implemented in April 2004. In February 2009, the institutional vancomycin policy was modified requiring preauthorization by the pediatric infectious diseases clinician on-call. Monthly vancomycin use was calculated as doses administered per 1000 patient-days. RESULTS: After 5 years of prospective-audit vancomycin use declined from 378 doses administered/1000 patient-days to 208 doses administered/1000 patient-days (45%). Following the implementation of preauthorization, vancomycin use decreased by an additional 16% in the subsequent 4 years. When compared with the trend of vancomycin use with prospective-audit, the trend of vancomycin use after the implementation of the restriction policy increased by 3.9 doses per month (SE: 1.51, P=0.012) during the subsequent 51 months. CONCLUSIONS: Implementation of preauthorization didn't significantly reduce the use of vancomycin beyond the accomplishments by prospective-audit and feedback by a team of an infectious disease pharmacist and physician.

The quest for the best metric of antibiotic use and its correlation with the emergence of fluoroquinolone resistance in children.

We evaluated the correlation between fluoroquinolone use, measured by doses administered and days of therapy, with the emergence of ciprofloxacin and levofloxacin resistance among Gram-negative bacilli infections in children hospitalized at one pediatric center between April 2001 and March 2009. Both metrics and drug resistance were highly correlated.

Chronic primary central nervous system histoplasmosis in a healthy child with intermittent neurological manifestations.

Meningitis is an unusual clinical manifestation of Histoplasma capsulatum infection in nonimmunosuppressed children. We report a previously healthy 6-year-old boy with primary, chronic histoplasma meningitis and magnetic resonance imaging findings consistent with demyelinating disease presenting with brief, intermittent neurological manifestations for 7 months before diagnosis.

Effects of aggregate and individual antibiotic exposure on vancomycin MICs for Staphylococcus aureus isolates recovered from pediatric patients.

We evaluated the evolution of vancomycin MICs for Staphylococcus aureus and their relationship with vancomycin use among hospitalized children. S. aureus isolates recovered from sterile sites were prospectively tested for vancomycin susceptibility using the Etest between 1 April 2000 and 31 March 2008. Vancomycin MICs were grouped into three categories: ≤ 1, 1.5, and 2 µg/ml. The association between vancomycin MICs and aggregate vancomycin use and individual patient vancomycin exposure 6 months prior to the documented infection was assessed. The geometric mean values for vancomycin MICs for S. aureus fluctuated over time without a significant trend (P = 0.146). Of the 436 patients included in the study, 363 (83%) had methicillin-susceptible S. aureus (MSSA) and 73 (17%) had methicillin-resistant S. aureus (MRSA) infections. The rate of isolates with a vancomycin MIC of 2 µg/ml increased from 4% (2 of 46) in 2000 to 2001 to 24% (11 of 46) in 2007 to 2008, despite a decrease in vancomycin use (r = -0.11; P = 0.825). The percentage of isolates with a vancomycin MIC of 2 µg/ml was higher for MRSA (15%; 11 of 73) than for MSSA strains (5.2%; 19 of 363) (χ(2) = 9.2; P = 0.01). Individual patient vancomycin exposure was not associated with a higher vancomycin MIC. In the unadjusted model, in which we compared patients with S. aureus infections with MICs of ≤ 1 µg/ml, the odds ratios of exposure rates for patients with isolates with MICs of 1.5 µg/ml and 2 µg/ml were 1.02 (P = 0.929) and 1.13 (P = 0.767), respectively. In our experience, the geometric means of vancomycin MICs from S. aureus isolates recovered from hospitalized children oscillated over time and were not associated with previous individual patient vancomycin exposure or aggregate vancomycin use.

Influence of body mass index and antibiotic dose on the risk of surgical site infections in pediatric clean orthopedic surgery.

OBJECTIVE: To evaluate body mass index (BMI) and antimicrobial dose as risk factors for surgical site infections in pediatric patients. PATIENTS AND METHODS: Children between 2 and 19 years of age undergoing clean orthopedic procedures and receiving at least one dose of perioperative antibiotics (cefazolin, vancomycin, or clindamycin) were studied. The retrospective case-controlled study was conducted at the Alfred I. duPont Hospital for Children, a 180-bed tertiary-care academic pediatric hospital in Wilmington, DE. Data were collected from January 1, 2002, to December 31, 2005. RESULTS: Underweight children had a higher risk for SSIs than overweight and normal-weight children. American Society of Anesthesiologists classes II and greater were associated with a greater risk of SSI. Longer procedures were also associated with a higher risk of SSI, specifically, duration of surgery >2 h. Children weighing ≥70 kg who received a standard dose of cefazolin (maximum of 1 g) had a higher risk of SSI caused by methicillin-sensitive Staphylococcus aureus (MSSA). CONCLUSIONS: Being underweight and undergoing an operation lasting >2 h created significant risks for SSI. Children weighing ≥70 kg receiving a standard 1-g dose of cefazolin had a greater risk of MSSA SSIs than children weighing <70 kg who received an appropriate weight-based dose of this antibiotic.

Benefits of a pediatric antimicrobial stewardship program at a children's hospital.

OBJECTIVE: To prospectively evaluate the effect of a comprehensive antimicrobial stewardship program on antimicrobial use, physician interventions, patient outcomes, and rates of antimicrobial resistance. METHODS: Active surveillance of antimicrobial use with intervention and real-time feedback to providers and reinforcement of prior authorization for selected antimicrobials were introduced at a pediatric teaching hospital. Antimicrobial-use indications were incorporated as a mandatory field in the computerized information system. An automated report of antimicrobials prescribed, doses, patient demographics, and microbiology data was generated and reviewed by an infectious-disease pharmacist and a pediatric infectious-disease physician. Antimicrobial use, expressed as the number of doses administered per 1000 patient-days, was measured 3 years before and after the implementation of the program. RESULTS: Total antimicrobial use peaked at 3089 doses administered per 1000 patient-days per year in 2003-2004 before implementation of the program and steadily decreased to 1904 doses administered per 1000 patient-days per year during the postintervention period. Targeted-antimicrobial use declined from 1250 to 988 doses administered per 1000 patient-days per year. Nontargeted-antimicrobial use declined from 1839 to 916 doses administered per 1000 patient-days per year. Rates of antimicrobial resistance to broad-spectrum antimicrobials among the most common Gram-negative bacilli remained low and stable over time. CONCLUSIONS: The successful implementation of antimicrobial stewardship strategies had a significant impact on reducing targeted- and nontargeted-antimicrobial use, improving quality of care of hospitalized children and preventing emergence of resistance.

Impact of antimicrobial stewardship program on vancomycin use in a pediatric teaching hospital.

BACKGROUND: Increasing rates of resistant gram-positive coccal infections led to an increased use of vancomycin. We evaluated the impact of implementing an Antimicrobial Stewardship Program on density of vancomycin use at a pediatric tertiary-care teaching hospital. METHODS: An Antimicrobial Stewardship Program was implemented April 1, 2004. Indications for vancomycin use were incorporated as mandatory fields using the integrated computerized information system. An automated report of vancomycin prescriptions, doses, patient demographics, and microbiology data was reviewed by an infectious disease pharmacist Monday through Friday. Interventions were discussed with a pediatric infectious disease physician and real-time feedback provided to clinicians. Density of vancomycin use was evaluated by measuring the number of doses administered/1000 patient-days. RESULTS: Density of vancomycin use declined overtime from 378 doses administered/1000 patient-days to 255 doses administered/1000 patient-days despite increasing rates of Staphylococcus aureus infected patients, and was not associated with increased use of other antibiotics with similar antimicrobial activity. Nonapproved vancomycin indications were selected in 28% of vancomycin doses administered. Of the 317 Antimicrobial Stewardship Program interventions performed, 190 qualified as vancomycin prescription errors, most commonly, vancomycin dosing and premature stop. After the implementation of the program, the rate of vancomycin prescription errors decreased. CONCLUSIONS: Implementation of an integrated Antimicrobial Stewardship Program using real-time evaluation and feedback to physicians, and optimization of the clinical informatics system, reduced vancomycin utilization and vancomycin prescribing errors, improving the quality of care and safety of hospitalized children in our institution.

Antimicrobial prescription errors in hospitalized children: role of antimicrobial stewardship program in detection and intervention.

BACKGROUND: Antimicrobial stewardship programs (ASP) are an effective strategy to ensure that antibiotics are used in accordance with scientific evidence to improve patient outcome, minimize antimicrobial (AM) resistance, and reduce hospital costs. The article describes the impact of the implementation of an ASP on AM prescription errors. METHODS: Prospective, single-center study performed at a tertiary pediatric teaching hospital that actively monitored 13 targeted AMs (amikacin, amphotericin B, cefepime, ceftriaxone, ciprofloxacin, fluconazole, levofloxacin, linezolid, meropenem, piperacillin-tazobactam, tobramycin, vancomycin, and voriconazole) and microbiology data. The ASP was implemented using CareNet and PharmNet. An infectious disease physician and pharmacist determined the need for intervention. RESULTS: The authors screened 5564 dispensed prescriptions of the 13 targeted AMs. The rate of AM errors associated with these was 0.09/1000 doses administered and 5 errors/1000 patient days. CONCLUSIONS: Active surveillance and optimization of computerized physician order entry system allows early detection and intervention of AMs prescriptions errors in hospitalized children.