CAHQL: A patient reported outcome instrument to assess health-related quality of life in congenital adrenal hyperplasia.

CONTEXT: Measuring health-related quality of life (HRQoL) is a crucial aspect of evaluating health care outcomes. Patients with congenital adrenal hyperplasia (CAH) often self-report deficiencies in HRQoL. OBJECTIVE: The aim of our study was to develop a disease-specific patient reported outcome (PRO) instrument to evaluate the HRQoL of patients >16 years old with classic congenital adrenal hyperplasia (CAH). DESIGN, SETTING AND OUTCOMES: Following the FDA guidelines for developing PRO instruments, we developed a conceptual framework for the instrument. A preliminary instrument was created after interviewing a representative sample of 12 patients with CAH between 16 to 68 years old and 3 parents, and obtaining expert feedback from 4 endocrinologists. The instrument was edited after cognitive interviews with 6 patients. Internal consistency of the instrument was evaluated using Cronbach's alpha. Validity was assessed by comparing the scores of our instrument with scores from widely used validated instruments for HRQoL and PRO not specific to CAH. RESULTS: Sixty-nine patients 16 to 75 years old participated in validating our preliminary instrument. The final questionnaire consists of 44 questions within 7 domains: General Health, Adrenal Insufficiency, Glucocorticoid Excess, Physical Functioning, Mental Health and Cognition, Social Functioning, and Sexual Functioning, with acceptable internal consistency (Chronbach's alpha≥0.6) and validity (r = -0.350 to 0.866). CONCLUSION: CAHQL is the first validated PRO instrument to capture disease specific HRQoL outcomes in CAH. In addition to its anticipated use in the clinical setting, the instrument could be used to assess the efficacy of novel treatments in development.

Gonadotropin-Releasing Hormone Agonist Therapy and Longitudinal Bone Mineral Density in Congenital Adrenal Hyperplasia.

CONTEXT: Children with congenital adrenal hyperplasia (CAH) are at risk for early puberty. Gonadotropin-releasing hormone analog (GnRHa) is frequently used and can decrease bone mineral density (BMD). OBJECTIVE: Our aim was to investigate the effect of GnRHa therapy on BMD in a longitudinal study of patients with CAH spanning both childhood and adulthood. DESIGN AND SETTING: Sixty-one patients with classic CAH due to 21-hydroxylase deficiency (20 treated with GnRHa) were followed with dual-energy X-ray absorptiometry (DXA) scans at puberty onset, attainment of adult height, and during early adulthood. MAIN OUTCOME MEASURES: Whole body, lumbar spine, femoral neck, total hip, and distal radius BMD z-score at adult height. Longitudinal BMD and adult height were also assessed. RESULTS: Twenty patients received GnRHa for an average of 4.5 ± 2 years. There were no differences in BMD between GnRHa-treated and -untreated groups at adult height for all sites. Overall, the follow-up DXA during early adulthood showed decreases in BMD z-scores for whole body (P = .01), lumbar spine (P < .0001), femoral neck (P = .06), total hip (P = .009), and distal radius (P = .05). GnRHa treatment correlated with improved height outcomes compared to predicted height at puberty onset after adjusting for midparental height (P = .02). Patients in both groups achieved similar adult height. CONCLUSION: In children with CAH, GnRHa does not compromise BMD. However, BMD decreases with time and during the second and third decades of life is a possible effect of chronic supraphysiologic glucocorticoids. Children with CAH who experience early puberty benefit from GnRHa treatment as evidenced by the positive effect on height.

New-Onset Primary Adrenal Insufficiency and Autoimmune Hypothyroidism in a Pediatric Patient Presenting with MIS-C.

INTRODUCTION: There is emerging speculation that the inflammatory state associated with SARS-CoV-2 infection may trigger autoimmune conditions, but no causal link is established. There are reports of autoimmune thyroiditis and adrenal insufficiency in adults post-COVID-19. We describe the first pediatric report of adrenal insufficiency and autoimmune hypothyroidism after COVID-19. CASE PRESENTATION: A 14-year-old previously healthy girl, with vitiligo, presented in shock following 1 week of fever, lethargy, diarrhea, and vomiting. Three weeks prior, she had congestion and fatigue and known familial exposure for COVID-19. Labs were remarkable for sodium 129 mmol/L, K 4.3 mmol/L, creatinine 2.9 mg/dL, hemoglobin 8.3 g/dL, and positive COVID-19 PCR and SARS-CoV-2 IgG. She was resuscitated with normal saline and required pressor support. EKG showed abnormal repolarization presumed secondary to myocarditis. She met the criteria for multisystem inflammatory syndrome in children (MIS-C), received intravenous immune globulin and IL-1R antagonist and was admitted for intensive care. Persistent hypotension despite improved inflammatory markers and undetectable cortisol led to initiation of hydrocortisone. She was then able to rapidly wean off pressors and hydrocortisone within 48 h. Thereafter, tests undertaken for persistent bradycardia confirmed autoimmune hypothyroidism with TSH 131 µU/mL, free T4 0.85 ng/dL, and positive thyroid autoantibodies. Basal and stimulated cortisol were <1 µg/dL on a standard 250 µg cosyntropin stimulation test, with baseline ACTH >1,250 pg/mL confirming primary adrenal insufficiency. Treatment was initiated with hydrocortisone, levothyroxine, and fludrocortisone. Adrenal sonogram did not reveal any hemorrhage and anti-adrenal antibody titers were positive. The family retrospectively reported oligomenorrhea, increased salt craving in the months prior, and a family history of autoimmune thyroiditis. The cytokine panel was notably different from other cases of MIS-C. CONCLUSION: This is the first pediatric report, to our knowledge, of primary adrenal insufficiency and hypothyroidism following COVID-19, leading to a unique presentation of autoimmune polyglandular syndrome type 2. The initial presentation was attributed to MIS-C, but the subsequent clinical course suggests the possibility of adrenal crisis. It remains unknown if COVID-19 had a causal relationship in triggering the autoimmune adrenal insufficiency and hypothyroidism.

Ectopic Parathyroid Adenoma in an 11-Year-Old Girl: Case Report and Literature Review.

OBJECTIVE: Primary hyperparathyroidism secondary to an ectopic parathyroid adenoma is rare among children and adolescents. METHODS: We describe the case of an 11-year-old girl with incidentally diagnosed primary hyperparathyroidism secondary to an intrathymic parathyroid adenoma and performed a review of the related literature. RESULTS: 99mTechnetium sestamibi single-photon emission computerized tomography/computed tomography and 4-dimensional computed tomography confirmed the ectopic location of the adenoma. The patient underwent thoracoscopic thymectomy and remained normocalcemic with elevated parathyroid hormone showing a downward trend. Parathyroid hormone normalized 18 months after successful parathyroidectomy. CONCLUSION: We review the case of a rare mediastinal parathyroid adenoma in a pediatric patient and summarize the epidemiologic profile, diagnosis, and management of similar pediatric cases.

Overweight and obese children with optimal control in the T1D Exchange Registry: How are they different from lean children with optimal control?

AIMS: Increased adiposity is a risk factor for suboptimal diabetes control and cardiovascular disease (CVD) complications. Our goal was to identify modifiable behavioral characteristics of overweight and obese pediatric patients with type 1 diabetes mellitus (T1DM) who achieve optimal glycemic control and to evaluate their CVD risk compared to lean patients. Our hypothesis was that optimally controlled obese and overweight participants require more total daily insulin and are at higher CVD risk compared to optimally controlled lean participants. METHODS: We analyzed a cohort of 9263 participants with T1DM aged <21 years in the T1D Exchange Registry. Optimal diabetes control was defined as HbA1c ≤ 7.5% (58 mmol/mol). We compared factors that influence glycemic control in lean, overweight and obese participants with optimal vs. suboptimal control, using logistic regression. RESULTS: Age, race, overweight status, continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) use were important variables influencing glycemic control. In the optimally controlled cohort, 27% of participants were overweight or obese versus 30% in the suboptimally controlled cohort (P < 0.001). Overweight and obese participants with optimal control were not significantly different from lean participants in terms of CSII use, total daily insulin dosage per kg of bodyweight, glucose checks per day, boluses with bedtime snack, use of CGM, but had higher LDL cholesterol and triglycerides, and lower HDL cholesterol (P < 0.05). CONCLUSIONS: There were no differences in modifiable behavioral characteristics between the obese, overweight and lean optimally controlled participants. However, predictors of cardiovascular disease were higher in the overweight and obese group.

Triple A syndrome (Allgrove syndrome): improving outcomes with a multidisciplinary approach.

Allgrove syndrome or triple A (3A) syndrome is a multisystem disorder which classically involves the triad of esophageal achalasia, alacrima, and adrenal insufficiency due to adrenocorticotropin hormone insensitivity. It follows an autosomal recessive pattern of inheritance and is associated with mutations in the AAAS (achalasia-addisonianism-alacrima syndrome) gene. Since its first description in 1978, the knowledge on clinical and genetic characteristics has been expanding; however, the current literature is limited to case reports and case reviews. Early recognition of the syndrome is challenging, given the rarity of the condition and high phenotypic heterogeneity even among members of kin. The coordination of care for these patients requires a multidisciplinary team of specialists, including endocrinologists, neurologists, gastroenterologists, ophthalmologists, developmental specialists, dentists, geneticists, and surgeons. In this review, we aim to summarize the current recommendations for the diagnosis, management, and follow-up of patients with 3A syndrome.

Correlation of Opioid Mortality with Prescriptions and Social Determinants: A Cross-sectional Study of Medicare Enrollees.

BACKGROUND: The opioid epidemic is an escalating health crisis. We evaluated the impact of opioid prescription rates and socioeconomic determinants on opioid mortality rates, and identified potential differences in prescription patterns by categories of practitioners. METHODS: We combined the 2013 and 2014 Medicare Part D data and quantified the opioid prescription rate in a county level cross-sectional study with data from 2710 counties, 468,614 unique prescribers and 46,665,037 beneficiaries. We used the CDC WONDER database to obtain opioid-related mortality data. Socioeconomic characteristics for each county were acquired from the US Census Bureau. RESULTS: The average national opioid prescription rate was 3.86 claims per beneficiary that received a prescription for opioids (95% CI 3.86-3.86). At a county level, overall opioid prescription rates (p < 0.001, Coeff = 0.27) and especially those provided by emergency medicine (p < 0.001, Coeff = 0.21), family medicine physicians (p = 0.11, Coeff = 0.008), internal medicine (p = 0.018, Coeff = 0.1) and physician assistants (p = 0.021, Coeff = 0.08) were associated with opioid-related mortality. Demographic factors, such as proportion of white (p white < 0.001, Coeff = 0.22), black (p black < 0.001, Coeff = - 0.19) and male population (p male < 0.001, Coeff = 0.13) were associated with opioid prescription rates, while poverty (p < 0.001, Coeff = 0.41) and proportion of white population (p white < 0.001, Coeff = 0.27) were risk factors for opioid-related mortality (p model < 0.001, R 2 = 0.35). Notably, the impact of prescribers in the upper quartile was associated with opioid mortality (p < 0.001, Coeff = 0.14) and was twice that of the remaining 75% of prescribers together (p < 0.001, Coeff = 0.07) (p model = 0.03, R 2 = 0.03). CONCLUSIONS: The prescription opioid rate, and especially that by certain categories of prescribers, correlated with opioid-related mortality. Interventions should prioritize providers that have a disproportionate impact and those that care for populations with socioeconomic factors that place them at higher risk.

Inappropriate Management of Asymptomatic Patients With Positive Urine Cultures: A Systematic Review and Meta-analysis.

BACKGROUND: Mismanagement of asymptomatic patients with positive urine cultures (referred to as asymptomatic bacteriuria [ASB] in the literature) promotes antimicrobial resistance and results in unnecessary antimicrobial-related adverse events and increased health care costs. METHODS: We conducted a systematic review and meta-analysis of studies that reported on the rate of inappropriate ASB treatment published from 2004 to August 2016. The appropriateness of antimicrobial administration was based on guidelines published by the Infectious Diseases Society of America. RESULTS: A total of 2142 nonduplicate articles were identified, and among them 30 fulfilled our inclusion criteria. The pooled prevalence of antimicrobial treatment among 4129 cases who did not require treatment was 45% (95% CI, 39-50). Isolation of gram-negative pathogens (odds ratio [OR], 3.58; 95% CI, 2.12-6.06), pyuria (OR, 2.83; 95% CI, 1.9-4.22), nitrite positivity (OR, 3.83; 95% CI, 2.24-6.54), and female sex (OR, 2.11; 95% CI, 1.46-3.06) increased the odds of receiving treatment. The rates of treatment were higher in studies with ≥100 000 cfu/mL cutoff values compared with <10 000 cfu/mL for bacterial growth (P, .011). The implementation of educational and organizational interventions designed to eliminate the overtreatment of ASB resulted in a median absolute risk reduction of 33% (rangeARR, 16-36%, medianRRR, 53%; rangeRRR, 25-80%). CONCLUSION: The mismanagement of ASB remains extremely frequent. Female sex and the overinterpretation of certain laboratory data (positive nitrites, pyuria, isolation of gram-negative bacteria and cultures with higher microbial count) are associated with overtreatment. Even simple stewardship interventions can be particularly effective, and antimicrobial stewardship programs should focus on the challenge of differentiating true urinary tract infection from ASB.

The impact of HIV infection and socioeconomic factors on the incidence of gonorrhea: A county-level, US-wide analysis.

BACKGROUND: Gonorrhea is the second most commonly reported identifiable disease in the United States (U.S.). Importantly, more than 25% of gonorrheal infections demonstrate antibiotic resistance, leading the Centers for Disease Control and Prevention (CDC) to classify gonorrhea as an "urgent threat". METHODS: We examined the association of gonorrhea infection rates with the incidence of HIV and socioeconomic factors. A county-level multivariable model was then constructed. RESULTS: Multivariable analysis demonstrated that HIV incidence [Coefficient (Coeff): 1.26, 95% Confidence Interval (CI): 0.86, 1.66, P<0.001] exhibited the most powerful independent association with the incidence of gonorrhea and predicted 40% of the observed variation in gonorrhea infection rates. Sociodemographic factors like county urban ranking (Coeff: 0.12, 95% CI: 0.03, 0.20, P = 0.005), percentage of women (Coeff: 0.41, 95% CI: 0.28, 0.53, P<0.001) and percentage of individuals under the poverty line (Coeff: 0.45, 95% CI: 0.32, 0.57, P<0.001) exerted a secondary impact. A regression model that incorporated these variables predicted 56% of the observed variation in gonorrhea incidence (Pmodel<0.001, R2 model = 0.56). CONCLUSIONS: Gonorrhea and HIV infection exhibited a powerful correlation thus emphasizing the benefits of comprehensive screening for sexually transmitted infections (STIs) and the value of pre-exposure prophylaxis for HIV among patients visiting an STI clinic. Furthermore, sociodemographic factors also impacted gonorrhea incidence, thus suggesting another possible focus for public health initiatives.

Extended-spectrum ß-lactamase-producing Enterobacteriaceae colonisation in long-term care facilities: a systematic review and meta-analysis.

The objectives of this study were to estimate the colonisation rate by extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) among residents of long-term care facilities (LTCFs) and to identify pertinent risk factors. A systematic search of PubMed and EMBASE databases for studies published up to May 2016 that provided raw data for gastrointestinal colonisation by ESBL-PE among LTCF residents was performed. Twenty-three studies reporting data on 9775 screened subjects met the inclusion criteria. The pooled prevalence of ESBL-PE among LTCF residents was 18% [95% confidence interval (CI) 12-24%]. Risk factors for colonisation included recent antibiotic use (within 6 months) [odds ratio (OR) = 2.06, 95% CI 1.78-2.38], previous hospitalisation (within 2.5 years) (OR = 1.50, 95% CI 1.04-2.15), history of invasive procedures (within 2 years) (OR = 2.79, 95% CI 1.66-4.70), previous ESBL-PE colonisation or infection (OR = 6.77, 95% CI 1.33-34.62), history of urinary tract infection (OR = 2.66, 95% CI 1.76-4.01) and urinary catheter use (OR = 2.55, 95% CI 1.29-5.04). In conclusion, almost one in five LTCF residents is colonised with ESBL-PE, and colonised residents are more likely to have a history of recent antibiotic use or healthcare facility utilisation. Strict adherence to antimicrobial stewardship in LTCFs is needed to address these high resistance rates.

The Dose-Dependent Efficacy of Cefepime in the Empiric Management of Febrile Neutropenia: A Systematic Review and Meta-Analysis.

BACKGROUND: Despite reports questioning its efficacy, cefepime remains a first-line option in febrile neutropenia. We aimed to re-evaluate the role of cefepime in this setting. METHODS: We searched the PubMed and EMBASE databases to identify randomized comparisons of (1) cefepime vs alternative monotherapy or (2) cefepime plus aminoglycoside vs alternative monotherapy plus aminoglycoside, published until November 28, 2016. RESULTS: Thirty-two trials, reporting on 5724 patients, were included. Clinical efficacy was similar between study arms (P = .698), but overall mortality was greater among cefepime-treated patients (risk ratio [RR] = 1.321; 95% confidence interval [CI], 1.035-1.686; P = .025). Also of note, this effect seemed to stem from trials using low-dose (2 grams/12 hours, 100 mg/kg per day) cefepime monotherapy (RR = 1.682; 95% CI, 1.038-2.727; P = .035). Cefepime was also associated with increased mortality compared with carbapenems (RR = 1.668; 95% CI, 1.089-2.555; P = .019), a finding possibly influenced by cefepime dose, because carbapenems were compared with low-dose cefepime monotherapy in 5 of 9 trials. Treatment failure in clinically documented infections was also more frequent with cefepime (RR = 1.143; 95% CI, 1.004-1.300; P = .043). Toxicity-related treatment discontinuation was more common among patients that received high-dose cefepime (P = .026), whereas low-dose cefepime monotherapy resulted in fewer adverse events, compared with alternative monotherapy (P = .009). CONCLUSIONS: Cefepime demonstrated increased mortality compared with carbapenems, reduced efficacy in clinically documented infections, and higher rates of toxicity-related treatment discontinuation. The impact of cefepime dosing on these outcomes is important, because low-dose regimens were associated with lower toxicity at the expense of higher mortality.

Comparison Between Carbapenems and ß-Lactam/ß-Lactamase Inhibitors in the Treatment for Bloodstream Infections Caused by Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae: A Systematic Review and Meta-Analysis.

BACKGROUND: Carbapenems are widely used for the management of bloodstream infections (BSIs) caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE). However, the wide use of carbapenems has been associated with carbapenem-resistant Enterobacteriaceae development. METHODS: We searched the PubMed and Scopus databases (last search date was on June 1, 2016) looking for studies that reported mortality in adult patients with ESBL-PE BSIs that were treated with carbapenems or ß-lactam/ß-lactamase inhibitors (BL/BLIs). RESULTS: Fourteen studies reported mortality data in adult patients with ESBL-PE BSI that were treated with carbapenems or BL/BLIs. Among them, 13 studies reported extractable data on empiric therapy, with no statistically significant difference in mortality of patients with ESBL-PE BSI that were treated empirically with carbapenems (22.1%; 121 of 547), compared with those that received empiric BL/BLIs (20.5%; 109 of 531; relative risk [RR], 1.05; 95% confidence interval [CI], 0.83-1.37; I2 = 20.7%; P = .241). In addition, 7 studies reported data on definitive therapy. In total, 767 patients (79.3%) received carbapenems and 199 patients (20.6%) received BL/BLIs as definitive therapy, and there was again no statistically significant difference (RR, 0.62; 95% CI, 0.25-1.52; I2 = 84.6%; P < .001). Regarding specific pathogens, the use of empiric BL/BLIs in patients with BSI due to ESBL-Escherichia coli was not associated with a statistically significant difference in mortality (RR, 1.014; 95% CI, 0.491-2.095; I2 = 62.5%; P = .046), compared with the use of empiric carbapenems. CONCLUSIONS: These data do not support the wide use of carbapenems as empiric therapy, and BL/BLIs might be effective agents for initial/empiric therapy for patients with BSI caused by likely ESBL-PE, and especially ESBL-E coli.

Bloodstream infections due to extended-spectrum ß-lactamase-producing Enterobacteriaceae among patients with malignancy: a systematic review and meta-analysis.

Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) are an increasing cause of resistant infections among patients with malignancy. This study sought to estimate the prevalence of bloodstream infections (BSIs) caused by ESBL-PE in this population and to examine regional and temporal differences. The PubMed and EMBASE databases (to 30 April 2016) were searched to identify studies reporting ESBL-PE BSI rates among patients with malignancies. Of 593 non-duplicate reports, 22 studies providing data on 5650 BSI cases satisfied the inclusion criteria. Among all BSIs the pooled prevalence of ESBL-PE was 11% (95% CI 8-15%) and among Gram-negative BSIs it was 21% (95% CI 16-27%). Among patients with haematological malignancies, the pooled ESBL-PE prevalence was 11% (95% CI 8-15%), whereas no studies providing specific data on patients with solid tumours were identified. Stratifying per geographic region, the pooled prevalence was 7% each in Europe (95% CI 5-11%), the Eastern Mediterranean region (95% CI 4-11%) and South America (95% CI 2-14%), 10% in the Western Pacific region (95% CI 4-19%) and 30% in Southeast Asia (95% CI 18-44%). Importantly, there was a 7.1% annual increase in the ESBL-PE incidence (P = 0.004). Overall, ca. 1 in 10 BSIs in patients with malignancy is caused by ESBL-PE and in some areas this rate can be as high as 1 in 3 cases. Additionally, the incidence of these resistant infections is rising. These findings should be considered when selecting empirical antimicrobial therapy and should prompt strict adherence to antimicrobial stewardship.

Colonization With Vancomycin-Resistant Enterococci and Risk for Bloodstream Infection Among Patients With Malignancy: A Systematic Review and Meta-Analysis.

BACKGROUND: Vancomycin-resistant enterococci (VRE) cause severe infections among patients with malignancy, and these infections are usually preceded by gastrointestinal colonization. METHODS: We searched the PubMed and EMBASE databases (up to May 26, 2016) to identify studies that reported data on VRE gastrointestinal colonization among patients with solid or hematologic malignancy. RESULTS: Thirty-four studies, reporting data on 8391 patients with malignancy, were included in our analysis. The pooled prevalence of VRE colonization in this population was 20% (95% confidence interval [CI], 14%-26%). Among patients with hematologic malignancy, 24% (95% CI, 16%-34%) were colonized with VRE, whereas no studies reported data solely on patients with solid malignancy. Patients with acute leukemia were at higher risk for VRE colonization (risk ratio [RR] = 1.95; 95% CI, 1.17-3.26). Vancomycin use or hospitalization within 3 months were associated with increased colonization risk (RR = 1.92, 95% CI = 1.06-3.45 and RR = 4.68, 95% CI = 1.66-13.21, respectively). Among the different geographic regions, VRE colonization rate was 21% in North America (95% CI, 13%-31%), 20% in Europe (95% CI, 9%-34%), 23% in Asia (95% CI, 13%-38%), and 4% in Oceania (95% CI, 2%-6%). More importantly, colonized patients were 24.15 (95% CI, 10.27-56.79) times more likely to develop a bloodstream infection due to VRE than noncolonized patients. CONCLUSIONS: A substantial VRE colonization burden exists among patients with malignancy, and colonization greatly increases the risk for subsequent VRE bloodstream infection. Adherence to antimicrobial stewardship is needed, and a re-evaluation of the use of vancomycin as empiric therapy in this patient population may be warranted.

Colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae in solid organ transplantation: A meta-analysis and review.

BACKGROUND: Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) may cause severe infections, often preceded by ESBL-E gastrointestinal (GI) colonization. METHODS: We conducted a review of the literature, investigating the prevalence of ESBL-E GI colonization in solid organ transplant (SOT) patients and the risk for subsequent ESBL-E infection. We searched the PubMed and EMBASE databases (to April 1, 2016) looking for studies that contained data on ESBL-E colonization among transplant patients. RESULTS: Of 341 non-duplicate citations, four studies reporting data on 1089 patients fulfilled our inclusion criteria. Among them, the pooled prevalence for ESBL-E colonization was 18% (95% confidence interval [CI] 5%-36%). Stratifying by transplant type, we identified an ESBL-E colonization rate of 17% (95% CI 3%-39%) among liver transplant recipients and 24% (single report) among kidney transplant recipients. CONCLUSIONS: Among SOT patients, approximately one in five patients is colonized with ESBL-E, although this finding may be skewed by reporting bias from centers with high ESBL-E prevalence. ESBL-E screening in SOT patients should be considered and evaluated in future studies.

Vancomycin-resistant enterococci colonisation, risk factors and risk for infection among hospitalised paediatric patients: a systematic review and meta-analysis.

The objective of this study was to estimate the rate and significance of colonisation with vancomycin-resistant enterococci (VRE) among hospitalised children. The PubMed and EMBASE databases were systematically searched (last accessed on 29 May 2016) to identify studies evaluating VRE colonisation of the gastrointestinal tract of hospitalised children in non-outbreak periods. Of 945 non-duplicate citations, 19 studies enrolling 20 234 children were included. The overall and paediatric intensive care unit (PICU) rate of VRE colonisation were both 5% [95% confidence interval (CI) 3-8% overall and 95% CI 2-9% in the PICU] but was 23% in haematology/oncology units (95% CI 18-29%). Studies that were exclusively performed in haematology/oncology units reported significantly higher rates compared with all other studies in the univariate and multivariate analyses (P = 0.001). Previous vancomycin [risk ratio (RR) = 4.34, 95% CI 2.77-6.82] or ceftazidime (RR = 4.15, 95% CI 2.69-6.40) use was a risk factor for VRE colonisation. Importantly, VRE colonisation increased the risk of subsequent VRE infection (RR = 8.75, 95% CI 3.19-23.97). In conclusion, a high rate of VRE colonisation was found among hospitalised children in institutions that performed targeted screening. Importantly, colonised children were almost 9 times more likely to develop subsequent VRE infection. Judicious use of specific antibiotics along with intensification of infection control measures should be considered in high-prevalence institutions. Also, the high incidence of VRE colonisation among children with haematological/oncological diseases identifies a high-risk population.

Prevalence of ESBL-Producing Enterobacteriaceae in Pediatric Bloodstream Infections: A Systematic Review and Meta-Analysis.

BACKGROUND: Pediatric bloodstream infections (BSIs) with Extended-Spectrum Beta-Lactamase- producing Enterobacteriaceae (ESBL-PE) are associated with worse clinical outcomes. We aimed to estimate the prevalence of and the mortality associated with ESBL-PE in this patient population. METHODS: A systematic review and meta-analysis using PubMed and EMBASE and included studies reporting the prevalence of ESBL-PE among confirmed BSIs in patients <19 years old. RESULTS: Twenty three (out of 1,718 non-duplicate reports) studies that provided data on 3,381 pediatric BSIs from 1996 to 2013 were included. The prevalence of ESBL-PE was 9% [95%CI (6, 13)] with an annual increase of 3.2% (P = 0.04). The prevalence was 11% [95%CI (6, 17)] among neonates, compared to 5% [95%CI (0, 14)] among children older than 28 days. The pooled prevalence was 15% in Africa [95%CI (8, 23)], 12% in South America [95%CI (5, 23)], 11% in India [95%CI (7, 17)], 7% in the rest of Asia [95%CI (0, 22)], 4% in Europe [95%CI (1, 7)] and 0% in Oceania [95%CI (0, 3)]. Importantly, the mortality in neonates with BSI due to ESBL-PE was 36% [95%CI (22, 51)], compared to 18% [95%CI (15, 22)] among all other neonates with BSI and this difference was statistically significant (P = 0.01). CONCLUSIONS: In the pediatric population, the prevalence of BSI due to ESBL-PE is significant and is associated with increased mortality in neonates. Further studies are warranted to establish a high-risk group and the evaluation of preventive measures, such as antibiotic stewardship programs and infection control measures, in this population is urgently needed.

Prevalence of ESBL-producing Enterobacteriaceae in paediatric urinary tract infections: A systematic review and meta-analysis.

OBJECTIVES: We aimed to evaluate the prevalence of paediatric urinary tract infections (UTIs) caused by extended spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE), identify predisposing factors and examine their effect on the length of hospital stay (LOS). METHODS: For this systematic review and meta-analysis, we searched the PubMed and EMBASE databases for studies that provide data on the rate of ESBL-PE among paediatric UTIs. RESULTS: Out of 1828 non-duplicate citations, 16 studies reporting a total of 7374 cases of UTI were included. The prevalence of ESBL-PE was 14% [(95%CI 8, 21)]. Vesicoureteral reflux (VUR) [OR = 2.79, (95%CI 1.39, 5.58)], history of UTI [OR = 2.89 (95%CI 1.78, 4.68)] and recent antibiotic use [OR = 3.92, (95%CI 1.76, 8.7)] were identified as risk factors. The LOS was significantly longer among children infected with ESBL-PE, compared to those infected with other uropathogens. [SMD = 0.88, (95%CI 0.40, 1.35)]. CONCLUSIONS: In the paediatric population, 1 out of 7 UTIs are caused by ESBL-PE. Patients with VUR, previous UTI or recent antibiotic use constitute a high risk group and these pathogens are associated with increased LOS. The significant incidence of ESBL-PE in this population should be taken into consideration in the development of empiric treatment protocols and antibiotic stewardship programmes, especially in high-prevalence areas.