Enoxaparin treatment dosing for venous thromboembolism in pediatric patients with obesity.

BACKGROUND: The optimal enoxaparin dosing for treatment of venous thromboembolism (VTE) in pediatric patients with obesity remains uncertain. We described the mean enoxaparin dose required to attain anti-factor Xa (anti-Xa) levels of 0.5-1 unit/mL in pediatric patients with obesity. METHODS: Pediatric patients with obesity (body mass index [BMI] ≥95th percentile) who received treatment dose of enoxaparin from 2013 to 2022 and had at least one appropriately timed anti-Xa level were retrospectively evaluated. Daily enoxaparin dose required to achieve an anti-Xa level of 0.5-1 unit/mL was reviewed and compared by the severity of obesity. The correlation coefficients between enoxaparin dose requirement and BMI, BMI percentile, and weight were measured by Spearman's rank correlation coefficient. RESULTS: Pediatric patients with obesity (n = 89) required a mean enoxaparin dose of 0.8 ± 0.18 mg/kg twice daily to attain a therapeutic anti-Xa level. Children with BMI 95th-99th percentile and weight ≤100 kg achieved the target level on a significantly higher weight-based enoxaparin dose compared to BMI greater than 99th percentile (0.95 ± 0.15 vs. 0.75 ± 0.15 mg/kg twice daily; p < .001) and weight greater than 100 kg (0.95 ± 0.14 vs. 0.7 ± 0.12 mg/kg twice daily; p < .001). BMI, BMI percentile, and weight showed a moderate to strong negative correlation with enoxaparin dose requirement. CONCLUSIONS: Pediatric patients with obesity required a lower weight-based dose of enoxaparin to achieve a therapeutic anti-Xa than the recommended starting dose of 1 mg/kg twice daily for treatment of VTE. Among obesity indices, weight showed the strongest negative correlation with total daily enoxaparin requirement.

Race and Pulse Oximetry in Infants With Single Ventricles Undergoing Stage 1 Palliation.

This cross-sectional study investigates perioperative oxygen saturation differences in Black and White infants with single ventricles undergoing stage 1 palliation.

Enoxaparin thromboprophylaxis in hospitalized obese pediatric patients.

BACKGROUND: Enoxaparin is an anticoagulant used for pharmacologic thromboprophylaxis in pediatrics. Enoxaparin pharmacokinetics can be altered in the setting of obesity. Optimal enoxaparin dosing for thromboprophylaxis in children with obesity remains unclear. PROCEDURE: A retrospective review was conducted of pediatric patients who weighed ≥60 kg with BMI ≥ 95th percentile, received enoxaparin for thromboprophylaxis, and had at least one appropriately drawn anti-factor Xa (anti-Xa) from 2013 to 2022. Anti-Xa levels were reviewed for patients initially treated with enoxaparin 30 mg every 12 h. The average daily enoxaparin dose required to achieve an anti-Xa of 0.2-0.4 unit/mL, which was stratified by BMI percentile and weight, was calculated. RESULTS: Of 116 patients (median age 15.8 years) included for analysis, 106 patients were initially treated with enoxaparin 30 mg every 12 h. Anti-Xa levels were <0.2 unit/mL in 53% of patients with BMI > 99th percentile and 54% of patients >100 kg. Ninety-one patients had at least one anti-Xa 0.2-0.4 unit/mL with an average daily enoxaparin dosing of 66 mg. When stratified by severity of obesity, higher doses were required to attain an anti-Xa 0.2-0.4 unit/mL in patients with BMI > 99th percentile compared with those with 95th-99th percentile (67.8 ± 15.7 vs. 62 ± 5.6 mg/day, p = .01). Patients > 100 kg required significantly higher dose than those ≤100 kg (69.1 ± 15.5 vs 61.2 ± 7.3 mg/day, p = .002). CONCLUSIONS: Increased initial dosing and/or anti-Xa level monitoring should be considered in adolescents with severe obesity receiving enoxaparin thromboprophylaxis.

The Role of Mobile Genetic Elements in the Spread of Antimicrobial-Resistant Escherichia coli From Chickens to Humans in Small-Scale Production Poultry Operations in Rural Ecuador.

Small-scale production poultry operations are increasingly common worldwide. To investigate how these operations influence antimicrobial resistance and mobile genetic elements (MGEs), Escherichia coli isolates were sampled from small-scale production birds (raised in confined spaces with antibiotics in feed), household birds (no movement constraints; fed on scraps), and humans associated with these birds in rural Ecuador (2010-2012). Isolates were screened for genes associated with MGEs as well as phenotypic resistance to 12 antibiotics. Isolates from small-scale production birds had significantly elevated odds of resistance to 7 antibiotics and presence of MGE genes compared with household birds (adjusted odds ratio (OR) range = 2.2-87.9). Isolates from humans associated with small-scale production birds had elevated odds of carrying an integron (adjusted OR = 2.0; 95% confidence interval (CI): 1.06, 3.83) compared with humans associated with household birds, as well as resistance to sulfisoxazole (adjusted OR = 1.9; 95% CI: 1.01, 3.60) and trimethoprim/sulfamethoxazole (adjusted OR = 2.1; 95% CI: 1.13, 3.95). Stratifying by the presence of MGEs revealed antibiotic groups that are explained by biological links to MGEs; in particular, resistance to sulfisoxazole, trimethoprim/sulfamethoxazole, or tetracycline was highest among birds and humans when MGE exposures were present. Small-scale production poultry operations might select for isolates carrying MGEs, contributing to elevated levels of resistance in this setting.

Familiarity with Long-acting Reversible Contraceptives among Obstetrics and Gynecology, Family Medicine, and Pediatrics Residents: Results of a 2015 National Survey and Implications for Contraceptive Provision for Adolescents.

STUDY OBJECTIVE: To assess familiarity with long-acting reversible contraceptives (LARC) among current obstetrics and gynecology (OB/GYN), family medicine (FM), and pediatrics senior residents in the United States. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We selected 156 OB/GYN, FM, and pediatrics residency programs using the American Medical Association Freida database. Senior residents completed a survey addressing any training they had received on LARC, and rated their comfort level counseling about and inserting LARC. Residents rated their likelihood of recommending LARC to an adolescent, nulliparous patient, and indicated whether they would like additional training on LARC. Descriptive and analytic statistics were generated using R statistical software (The R Project for Statistical Computing; https://www.r-project.org). RESULTS: The survey was completed by 326 of 1,583 residents (20.6% response rate); at least 1 resident completed the survey at 105 (67.3%) of the residency programs contacted. Most programs (84.8%) provided some training on LARC. Residents in OB/GYN programs were comfortable counseling about and inserting contraceptive implants (97%, 83%), copper intrauterine devices (IUDs; 100%, 86%), and levonorgestrel (LNG) IUDs (100%, 86%). In FM programs, fewer residents were comfortable counseling about and inserting contraceptive implants (71%, 47%), copper IUDs (68%, 21%), and LNG IUDs (79%, 18%). Residents in pediatrics programs had low comfort levels counseling about contraceptive implants (14%), copper IUDs (14%), and LNG IUDs (25%); no pediatrics residents were comfortable inserting LARC. OB/GYN residents were significantly more likely to recommend a LARC to an adolescent, nulliparous patient (P = .019). Most pediatric and FM residents desired additional training on LARC (82.7% and 60.7%, respectively). CONCLUSION: This study shows that knowledge gaps exist regarding LARC among FM and pediatrics residents.

Variation in Preoperative Testing and Antireflux Surgery in Infants.

BACKGROUND: Despite the availability of objective tests, gastroesophageal reflux disease (GERD) diagnosis and management in infants remains controversial and highly variable. Our purpose was to characterize national variation in diagnostic testing and surgical utilization for infants with GERD. METHODS: Using the Pediatric Health Information System, we identified infants <1 year old diagnosed with GERD between January 2011 and March 2015. Outcomes included progression to antireflux surgery (ARS) and use of relevant diagnostic testing. By using adjusted generalized linear mixed models, we compared facility-level ARS utilization. RESULTS: Of 5 299 943 infants, 149 190 had GERD (2.9%), and 4518 (3.0%) of those patients underwent ARS. Although annual rates of GERD and ARS decreased, there was a wide range of GERD diagnoses (1.8%-6.2%) and utilization of ARS (0.2%-11.2%). Facilities varied in the use of laparoscopic versus open ARS (mean: 66%, range: 23%-97%). Variation in facility-level ARS rates persisted after adjustment. Overall 3.8% of patients underwent diagnostic testing, whereas 22.8% of ARS patients underwent diagnostic testing. The proportion of surgeries done laparoscopically was independently associated with ARS utilization (odds ratio: 1.57; 95% confidence interval: 1.21-2.02). Facility-level utilization of diagnostics (P > .1) and prevalence of GERD (P > .1) were not associated with utilization of ARS. CONCLUSIONS: There is notable variation in the overall utilization of ARS and in the surgical and diagnostic approach in infants with GERD. Fewer than 4% of infants with GERD undergo diagnostic testing. This variation in care merits development of consensus guidelines and further research.

Antibiotic Resistance in Animal and Environmental Samples Associated with Small-Scale Poultry Farming in Northwestern Ecuador.

The effects of animal agriculture on the spread of antibiotic resistance (AR) are cross-cutting and thus require a multidisciplinary perspective. Here we use ecological, epidemiological, and ethnographic methods to examine populations of Escherichia coli circulating in the production poultry farming environment versus the domestic environment in rural Ecuador, where small-scale poultry production employing nontherapeutic antibiotics is increasingly common. We sampled 262 "production birds" (commercially raised broiler chickens and laying hens) and 455 "household birds" (raised for domestic use) and household and coop environmental samples from 17 villages between 2010 and 2013. We analyzed data on zones of inhibition from Kirby-Bauer tests, rather than established clinical breakpoints for AR, to distinguish between populations of organisms. We saw significantly higher levels of AR in bacteria from production versus household birds; resistance to either amoxicillin-clavulanate, cephalothin, cefotaxime, and gentamicin was found in 52.8% of production bird isolates and 16% of household ones. A strain jointly resistant to the 4 drugs was exclusive to a subset of isolates from production birds (7.6%) and coop surfaces (6.5%) and was associated with a particular purchase site. The prevalence of AR in production birds declined with bird age (P < 0.01 for all antibiotics tested except tetracycline, sulfisoxazole, and trimethoprim-sulfamethoxazole). Farming status did not impact AR in domestic environments at the household or village level. Our results suggest that AR associated with small-scale poultry farming is present in the immediate production environment and likely originates from sources outside the study area. These outside sources might be a better place to target control efforts than local management practices. IMPORTANCE In developing countries, small-scale poultry farming employing antibiotics as growth promoters is being advanced as an inexpensive source of protein and income. Here, we present the results of a large ecoepidemiological study examining patterns of antibiotic resistance (AR) in E. coli isolates from small-scale poultry production environments versus domestic environments in rural Ecuador, where such backyard poultry operations have become established over the past decade. Our previous research in the region suggests that introduction of AR bacteria through travel and commerce may be an important source of AR in villages of this region. This report extends the prior analysis by examining small-scale production chicken farming as a potential source of resistant strains. Our results suggest that AR strains associated with poultry production likely originate from sources outside the study area and that these outside sources might be a better place to target control efforts than local management practices.

Indications and Types of Antibiotic Agents Used in 6 Acute Care Hospitals, 2009-2010: A Pragmatic Retrospective Observational Study.

BACKGROUND To design better antimicrobial stewardship programs, detailed data on the primary drivers and patterns of antibiotic use are needed. OBJECTIVE To characterize the indications for antibiotic therapy, agents used, duration, combinations, and microbiological justification in 6 acute-care US facilities with varied location, size, and type of antimicrobial stewardship programs. DESIGN, PARTICIPANTS, AND SETTING Retrospective medical chart review was performed on a random cross-sectional sample of 1,200 adult inpatients, hospitalized (>24 hrs) in 6 hospitals, and receiving at least 1 antibiotic dose on 4 index dates chosen at equal intervals through a 1-year study period (October 1, 2009-September 30, 2010). METHODS Infectious disease specialists recorded patient demographic characteristics, comorbidities, microbiological and radiological testing, and agents used, dose, duration, and indication for antibiotic prescriptions. RESULTS On the index dates 4,119 (60.5%) of 6,812 inpatients were receiving antibiotics. The random sample of 1,200 case patients was receiving 2,527 antibiotics (average: 2.1 per patient); 540 (21.4%) were prophylactic and 1,987 (78.6%) were therapeutic, of which 372 (18.7%) were pathogen-directed at start. Of the 1,615 empirical starts, 382 (23.7%) were subsequently pathogen-directed and 1,231 (76.2%) remained empirical. Use was primarily for respiratory (27.6% of prescriptions) followed by gastrointestinal (13.1%) infections. Fluoroquinolones, vancomycin, and antipseudomonal penicillins together accounted for 47.1% of therapy-days. CONCLUSIONS Use of broad-spectrum empirical therapy was prevalent in 6 US acute care facilities and in most instances was not subsequently pathogen directed. Fluoroquinolones, vancomycin, and antipseudomonal penicillins were the most frequently used antibiotics, particularly for respiratory indications. Infect. Control Hosp. Epidemiol. 2015;37(1):70-79.

Influence of provider and urgent care density across different socioeconomic strata on outpatient antibiotic prescribing in the USA.

OBJECTIVES: Despite a strong link between antibiotic use and resistance, and highly variable antibiotic consumption rates across the USA, drivers of differences in consumption rates are not fully understood. The objective of this study was to examine how provider density affects antibiotic prescribing rates across socioeconomic groups in the USA. METHODS: We aggregated data on all outpatient antibiotic prescriptions filled in retail pharmacies in the USA in 2000 and 2010 from IMS Health into 3436 geographically distinct hospital service areas and combined this with socioeconomic and structural factors that affect antibiotic prescribing from the US Census. We then used fixed-effect models to estimate the interaction between poverty and the number of physician offices per capita (i.e. physician density) and the presence of urgent care and retail clinics on antibiotic prescribing rates. RESULTS: We found large geographical variation in prescribing, driven in part by the number of physician offices per capita. For an increase of one standard deviation in the number of physician offices per capita there was a 25.9% increase in prescriptions per capita. However, the determinants of the prescription rate were dependent on socioeconomic conditions. In poorer areas, clinics substitute for traditional physician offices, reducing the impact of physician density. In wealthier areas, clinics increase the effect of physician density on the prescribing rate. CONCLUSIONS: In areas with higher poverty rates, access to providers drives the prescribing rate. However, in wealthier areas, where access is less of a problem, a higher density of providers and clinics increases the prescribing rate, potentially due to competition.

Assessment of empirical antibiotic therapy optimisation in six hospitals: an observational cohort study.

BACKGROUND: Modification of empirical antimicrobials when warranted by culture results or clinical signs is recommended to control antimicrobial overuse and resistance. We aimed to assess the frequency with which patients were started on empirical antimicrobials, characteristics of the empirical regimen and the clinical characteristics of patients at the time of starting antimicrobials, patterns of changes to empirical therapy at different timepoints, and modifiable factors associated with changes to the initial empirical regimen in the first 5 days of therapy. METHODS: We did a chart review of adult inpatients receiving one or more antimicrobials in six US hospitals on 4 days during 2009 and 2010. Our primary outcome was the modification of antimicrobial regimen on or before the 5th day of empirical therapy, analysed as a three-category variable. Bivariate analyses were used to establish demographic and clinical variables associated with the outcome. Variables with p values below 0·1 were included in a multivariable generalised linear latent and mixed model with multinomial logit link to adjust for clustering within hospitals and accommodate a non-binary outcome variable. FINDINGS: Across the six study sites, 4119 (60%) of 6812 inpatients received antimicrobials. Of 1200 randomly selected patients with active antimicrobials, 730 (61%) met inclusion criteria. At the start of therapy, 220 (30%) patients were afebrile and had normal white blood cell counts. Appropriate cultures were collected from 432 (59%) patients, and 250 (58%) were negative. By the 5th day of therapy, 12·5% of empirical antimicrobials were escalated, 21·5% were narrowed or discontinued, and 66·4% were unchanged. Narrowing or discontinuation was more likely when cultures were collected at the start of therapy (adjusted OR 1·68, 95% CI 1·05-2·70) and no infection was noted on an initial radiological study (1·76, 1·11-2·79). Escalation was associated with multiple infection sites (2·54, 1·34-4·83) and a positive culture (1·99, 1·20-3·29). INTERPRETATION: Broad-spectrum empirical therapy is common, even when clinical signs of infection are absent. Fewer than one in three inpatients have their regimens narrowed within 5 days of starting empirical antimicrobials. Improved diagnostic methods and continued education are needed to guide discontinuation of antimicrobials. FUNDING: US Centers for Disease Control and Prevention, Division of Healthcare Quality Promotion; Robert Wood Johnson Foundation; US Department of Veterans Administration; US Department of Homeland Security.

Extended-Spectrum ß-Lactamase-Producing and Third-Generation Cephalosporin-Resistant Enterobacteriaceae in Children: Trends in the United States, 1999-2011.

BACKGROUND: Enterobacteriaceae infections resistant to extended-spectrum ß-lactams are an emerging problem in children. We used a large database of clinical isolates to describe the national epidemiology of extended-spectrum ß-lactamase (ESBL)-producing and third-generation cephalosporin-resistant (G3CR) Enterobacteriaceae. METHODS: Antimicrobial susceptibilities of Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis reported to ∼300 laboratories participating in The Surveillance Network (TSN) between January 1999 and December 2011 were used to phenotypically identify G3CR and ESBL isolates cultured from patients <18 years. Bi-annual trends in the prevalence of each phenotype were stratified by species, patient location, culture site, age, and region. Children of age 0-1 years were excluded from analysis as data were only available from 2010 onwards. RESULTS: Out of 368,398 pediatric isolates, 1.97% (7255) were identified as G3CR, and 0.47% (1734) as ESBL producers. The prevalence of both phenotypes increased, respectively, from 1.39% and 0.28% in 1999-2001 to 3% and 0.92% in 2010-2011. Trends were significant across all demographic and age groups, including outpatients, with the highest proportion of isolates in the 1-5-year-old age group. The majority of G3CR and ESBL isolates were E. coli (67.8% and 65.2%, respectively). Among ESBLs, resistance to ≥3 antibiotic classes was 74%. The lower regional prevalence of ESBL-producing bacteria in the upper Midwest relative to the rest of the country is consistent with recent local data. CONCLUSIONS: Rates of G3CR and ESBL infections in children are increasing in both inpatient and ambulatory settings nationally. The identification of host factors and exposures leading to infection in children is essential.

Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae Infections in Children: A Two-Center Case-Case-Control Study of Risk Factors and Outcomes in Chicago, Illinois.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae infections are an emerging problem in children. We sought to identify risk factors and describe outcomes associated with pediatric ESBL-producing bacterial infections at 2 hospitals in Chicago, IL from 2008 to 2011. METHODS: A case-case-control study of children aged 0-17 years was conducted. Cases of Escherichia coli, Klebsiella, and Proteus spp. ESBL-producing bacterial infections (n = 30) were compared to uninfected controls and in parallel, cases of non-ESBL-producing bacterial infections (n = 30) were compared to uninfected controls (n = 60). We then qualitatively compared these results. RESULTS: Median age of cases was 1.06 years; 62% of isolates were from urine, and 60% were E. coli. By multivariable analysis, ESBL cases were 5.7 and 3.3 times more likely to have gastrointestinal (P = .001; 95% confidence interval [CI] 1.9-17.0) and neurologic (P = .001; 95% CI 1.1-3.7) comorbidities, respectively, than controls; non-ESBL cases were also more likely to have gastrointestinal comorbidities than controls (P = .014; odds ratio 3.6; 95% CI 1.2-10.1). Study period prevalence remained stable (1.7%). Most (60%) infections occurred in the intensive care unit; however, 30% of children presented in the outpatient setting. Seventy-seven percent of isolates were multidrug resistant (ie, resistant to ≥3 antibiotic classes). Recurrence of infection occurred in 17% of ESBL cases. Crude mortality rates (7%) did not differ between cases and controls. CONCLUSIONS: The incidence of pediatric infection due to ESBL-positive Enterobacteriaceae was stable at 2 large tertiary-care medical centers over a 4-year period. Multidrug resistance in pediatric ESBL isolates is common. Risk factors for infection due to ESBL-producing bacteria include neurologic medical conditions.

Optimizing antimicrobial prescribing: Are clinicians following national trends in methicillin-resistant staphylococcus aureus (MRSA) infections rather than local data when treating MRSA wound infections.

BACKGROUND: Clinicians often prescribe antimicrobials for outpatient wound infections before culture results are known. Local or national MRSA rates may be considered when prescribing antimicrobials. If clinicians prescribe in response to national rather than local MRSA trends, prescribing may be improved by making local data accessible. We aimed to assess the correlation between outpatient trends in antimicrobial prescribing and the prevalence of MRSA wound infections across local and national levels. METHODS: Monthly MRSA positive wound culture counts were obtained from The Surveillance Network, a database of antimicrobial susceptibilities from clinical laboratories across 278 zip codes from 1999-2007. Monthly outpatient retail sales of linezolid, clindamycin, trimethoprim-sulfamethoxazole and cephalexin from 1999-2007 were obtained from the IMS Health XponentTM database. Rates were created using census populations. The proportion of variance in prescribing that could be explained by MRSA rates was assessed by the coefficient of determination (R2), using population weighted linear regression. RESULTS: 107,215 MRSA positive wound cultures and 106,641,604 antimicrobial prescriptions were assessed. The R2 was low when zip code-level antimicrobial prescription rates were compared to MRSA rates at all levels. State-level prescriptions of clindamycin and linezolid were not correlated with state MRSA rates. The variance in state-level prescribing of clindamycin and linezolid was correlated with national MRSA rates (clindamycin R2 = 0.17, linezolid R2 = 0.22). CONCLUSIONS: Clinicians may rely on national, not local MRSA data when prescribing clindamycin and linezolid for wound infections. Providing local resistance data to prescribing clinicians may improve antimicrobial prescribing and would be a possible target for future interventions.

Trends in resistance to carbapenems and third-generation cephalosporins among clinical isolates of Klebsiella pneumoniae in the United States, 1999-2010.

OBJECTIVE: Multidrug-resistant Enterobacteriaceae pose a serious infection control challenge and have emerged as a public health threat. We examined national trends in the proportion of Klebsiella pneumoniae isolates resistant to carbapenems (CRKP) and third-generation cephalosporins (G3CRKP). DESIGN AND SETTING: Retrospective analysis of approximately 500,000 K. pneumoniae isolates cultured between January 1999 and July 2010 at 287 clinical laboratories throughout the United States. METHODS: Isolates were defined as CRKP if they were nonsusceptible to 1 or more carbapenems and were defined as G3CRKP if they were nonsusceptible to ceftazidime, ceftriaxone, or related antibiotics. A multivariable analysis examined trends in the proportion of resistant isolates, adjusting for age, sex, isolate source, patient location, and geographic region. RESULTS: The crude proportion of CRKP increased from less than 0.1% to 4.5% between 2002 and 2010; the frequency of G3CRKP increased from 5.3% to 11.5% between 1999 and 2010. G3CRKP and CRKP were more common among elderly patients (those greater than 65 years of age); the adjusted odds ratio (aOR) relative to pediatric patients (those less than 18 years of age) was 1.2 for G3CRKP (95% confidence interval [CI], 1.2-1.3) and 3.3 for CRKP (95% CI, 2.6-4.2). G3CRKP and CRKP were also more common among patients from the northeastern United States (aOR, 2.9 [95% CI, 2.8-3.0] and 9.0 [95% CI, 7.9-10.4]) than among those from the western United States. The prevalence of outpatient CRKP isolates increased after 2006, reaching 1.9% of isolates in our sample in 2010 (95% CI, 1.6%-2.1%). CONCLUSIONS: The frequency of G3CRKP and CRKP is increasing in all regions of the United States, and resistance is emerging among isolates recovered in the outpatient setting. This underscores the need for enhanced laboratory capacity and coordinated surveillance strategies to contain the further spread of these emerging pathogens.