Renal fungus balls in neonates and very young infants treated with local amphotericin B deoxycholate: Two case reports and review of the literature.

INTRODUCTION: Fungal urinary tract infections predominantly affect the critically ill premature infant and those with urogenital tract abnormalities. Fungal balls are an uncommon complication which require prompt detection and treatment to prevent morbidity and mortality. The evidence on the management of fungus balls in young infants with Candida urinary tract infections is very scarce. METHODS: Case reports and review of the literature. RESULTS: We report two immunocompetent young infants with urogenital abnormalities that received local amphotericin B deoxycholate, and systemic therapy, for the treatment and prevention of Candida urinary tract infection-associated fungus balls. We identified 21 similar cases in the literature, with very limited data about drug compounding, optimal dosages, dwell times and length of treatment. Different management strategies are discussed. CONCLUSIONS: Amphotericin B deoxycholate local irrigations were safe and effective for the therapeutic management and prophylaxis of Candida fungus balls in young infants, in combination with systemic antifungal therapy.

Renal Function Impairment in Children With Congenital Cytomegalovirus Infection: A Cross-sectional Study.

BACKGROUND: We aimed to determine the prevalence and severity of glomerular and tubular renal dysfunction by means of urinalysis in infants and toddlers with congenital cytomegalovirus infection (cCMV) and their association with cCMV disease, viruria and antiviral treatment. METHODS: This cross-sectional study was done using the Spanish Registry of Congenital Cytomegalovirus Infection. First-morning urine samples were collected from January 2016 to December 2018 from patients <5 years old enrolled in Spanish Registry of Congenital Cytomegalovirus Infection. Samples were excluded in case of fever or other signs or symptoms consistent with acute infection, bacteriuria or bacterial growth in urine culture. Urinary protein/creatinine and albumin/creatinine ratios, urinary beta-2-microglobulin levels, hematuria and CMV viruria were determined. A 0.4 cutoff in the urinary albumin/protein ratio was used to define tubular (<0.4) or glomerular (>0.4) proteinuria. Signs and symptoms of cCMV at birth, the use of antivirals and cCMV-associated sequelae at last available follow-up were obtained from Spanish Registry of Congenital Cytomegalovirus Infection. RESULTS: Seventy-seven patients (37 females, 48.1%; median [interquartile range] age: 14.0 [4.4-36.2] months) were included. Symptom-free elevated urinary protein/creatinine and albumin/creatinine ratios were observed in 37.5% and 41.9% of patients, respectively, with tubular proteinuria prevailing (88.3%) over glomerular proteinuria (11.6%). Proteinuria in the nephrotic range was not observed in any patients. In multivariate analysis, female gender was the only risk factor for tubular proteinuria (adjusted odds ratio = 3.339, 95% confidence interval: 1.086-10.268; P = 0.035). cCMV disease at birth, long-term sequelae, viruria or the use of antivirals were not associated with urinalysis findings. CONCLUSIONS: Mild nonsymptomatic tubular proteinuria affects approximately 40% of infants and toddlers with mostly symptomatic cCMV in the first 5 years of life.

Assessment of the Plans to Optimize Antimicrobial Use in the Pediatric Population in Catalan Hospitals: The VINCat Pediatric PROA SHARP Survey.

In Spain, many programs have been introduced in recent years to optimize antimicrobial stewardship in pediatric care (known as pediatric PROA). However, information on the current situation of these programs is scarce. The present study assesses current antimicrobial use in pediatric care in the hospitals of Catalonia affiliated with the VINCat pediatric PROA group. Between December 2020 and January 2021, an electronic survey related to the design and use of PROA was administered to members of PROA teams in our hospital network. The survey was conducted at 26 hospitals. Twelve percent of the hospitals had pediatric PROA in operation, 42% were included in adult PROA, and 46% carried out pediatric PROA activities but not as part of an established program. At 81%, the pediatric PROA team included a pediatrician, in 58% a pharmacist, and in 54% a microbiologist. The main activities were monitoring the use of antimicrobials and bacterial resistance. Twenty-seven percent measured indicators regularly. The VINCat Pediatric PROA group's hospitals have implemented measures for optimizing antimicrobial stewardship, but few have a pediatric PROA program in place. Specific measures and indicators must be defined, and the resources available should be increased. The development of pediatric PROA should be monitored in the coming years.

Adequacy of the 10 mg/kg Daily Dose of Antituberculosis Drug Isoniazid in Infants under 6 Months of Age.

In 2010, the WHO recommended an increase in the daily doses of first-line anti-tuberculosis medicines in children. We aim to characterize the pharmacokinetics of the once-daily isoniazid (INH) dose at 10 mg/kg of body weight in infants <6 months of age. We performed a multicenter pharmacokinetic study in Spain. The N-acetyltransferase 2 gene was analyzed to determine the acetylation status. Samples were analyzed using a validated UPLC-UV assay. A non-compartmental pharmacokinetic analysis was performed. Twenty-three pharmacokinetic profiles were performed in 20 infants (8 females) at a median (IQR) age of 19.0 (12.6-23.3) weeks. The acetylator statuses were homozygous fast (n = 1), heterozygous intermediate (n = 12), and homozygous slow (n = 7). INH median (IQR) Cmax and AUC0-24h values were 4.8 (3.7-6.7) mg/L and 23.5 (13.4-36.7) h*mg/L and the adult targets (>3 mg/L and 11.6-26.3 h*mg/L) were not reached in three and five cases, respectively. The age at assessment or acetylator status had no impact on Cmax values, but a larger INH AUC0-24h (p = 0.025) and trends towards a longer half-life (p = 0.055) and slower clearance (p = 0.070) were observed in homozygous slow acetylators. Treatment was well tolerated; mildly elevated alanine aminotransferase levels were observed in three cases. In our series of young infants receiving isoniazid, no major safety concerns were raised, and the target adult levels were reached in most patients.

Host, technical, and environmental factors affecting QuantiFERON-TB Gold In-Tube performance in children below 5 years of age.

Interferon-gamma release assays performance can be impaired by host-related, technical and environmental factors, but data in young children are limited. We performed a cross-sectional study of children < 5 years-of-age at risk of tuberculosis (TB), using QuantiFERON-TB Gold In-Tube (QFT-GIT) assays. The impact of the following was evaluated: (i) host-related [age; hematological parameters; erythrocyte sedimentation rate (ESR); C-reactive protein (CRP); and tobacco smoke exposure (TSE) based on serum cotinine concentrations], (ii) technical (pre-analytical delay) and (iii) environmental factors (annual season; monthly temperatures). Of 204 children, 35 (17.2%) were diagnosed with latent TB infection or TB disease. QFT-GIT results were indeterminate in 14 (6.9%) patients. In multivariate analysis, younger age and higher ESR were associated with lower positive control responses (beta: 0.247, p = 0.002 and - 0.204, p = 0.007, respectively), and increasing age was associated with lower rates of indeterminate QFT-GIT results [OR (95% CI) 0.948 (0.903-0.996) per month, p = 0.035]. In children with positive QFT-GIT results, average monthly temperatures correlated with antigen responses (r = 0.453, p = 0.020); also, antigen responses were lower in winter than in other seasons (p = 0.027). Serum cotinine concentrations determined in a subgroup of patients (n = 41) indicated TSE in 36 (88%), positive control responses being lower in children with TSE (p = 0.034). In children < 5 years-of-age, young age, elevated ESR, temperature, annual season and TSE can affect the performance of QFT-GIT assays.

Impact and quality of antimicrobial use in a referral pediatric intensive care unit.

INTRODUCTION: We aimed to describe antimicrobial use (AU) and quality of prescriptions (QP) in a 28-bed medical-surgical PICU of a European referral children's hospital during 2019. METHODS: AU data were expressed as days-of-therapy (DOT) over 100 days-present (DP) and as length-of-treatment (LOT). QP was based on monthly cross-sectional point-prevalence surveys. Length-of-stay (LOS), readmission rates (RR), and mortality rates (MR) were also collected. RESULTS: PICU AU accounted for 13.5% of the global hospital AU; the median PICU density of AU was 1.4 (IQR 1.3-1.5) times higher than that of the rest of the hospital areas. Antibacterials represented 88.5% of the overall AU, cefazolin and amoxicillin-clavulanate being the most used drugs. A high QP rate was observed (149/168 optimal, 88.9%), with room for improvement in prophylactic regimens and de-escalation of broad-spectrum regimens. LOT, LOS, RR, and MR remained stable. CONCLUSIONS: PICU AU represented a major portion of the global hospital AU. Despite high QP rates, prophylactic and broad-spectrum antibiotic regimens were optimizable.

Impact and quality of antimicrobial use in a referral pediatric intensive care unit.

INTRODUCTION: We aimed to describe antimicrobial use (AU) and quality of prescriptions (QP) in a 28-bed medical-surgical PICU of a European referral children's hospital during 2019. METHODS: AU data were expressed as days-of-therapy (DOT) over 100 days-present (DP) and as length-of-treatment (LOT). QP was based on monthly cross-sectional point-prevalence surveys. Length-of-stay (LOS), readmission rates (RR), and mortality rates (MR) were also collected. RESULTS: PICU AU accounted for 13.5% of the global hospital AU; the median PICU density of AU was 1.4 (IQR 1.3-1.5) times higher than that of the rest of the hospital areas. Antibacterials represented 88.5% of the overall AU, cefazolin and amoxicillin-clavulanate being the most used drugs. A high QP rate was observed (149/168 optimal, 88.9%), with room for improvement in prophylactic regimens and de-escalation of broad-spectrum regimens. LOT, LOS, RR, and MR remained stable. CONCLUSIONS: PICU AU represented a major portion of the global hospital AU. Despite high QP rates, prophylactic and broad-spectrum antibiotic regimens were optimizable.

Effects of a Paediatric Antimicrobial Stewardship Program on Antimicrobial Use and Quality of Prescriptions in Patients with Appendix-Related Intraabdominal Infections.

The effectiveness of antimicrobial stewardship programs (ASP) in reducing antimicrobial use (AU) in children has been proved. Many interventions have been described suitable for different institution sizes, priorities, and patients, with surgical wards being one of the areas that may benefit the most. We aimed to describe the results on AU and length of stay (LOS) in a pre-post study during the three years before (2014-2016) and the three years after (2017-2019) implementation of an ASP based on postprescription review with feedback in children and adolescents admitted for appendix-related intraabdominal infections (AR-IAI) in a European Referral Paediatric University Hospital. In the postintervention period, the quality of prescriptions (QP) was also evaluated. Overall, 2021 AR-IAIs admissions were included. Global AU, measured both as days of therapy/100 patient days (DOT/100PD) and length of therapy (LOT), and global LOS remained unchanged in the postintervention period. Phlegmonous appendicitis LOS (p = 0.003) and LOT (p < 0.001) significantly decreased, but not those of other AR-IAI diagnoses. The use of piperacillin-tazobactam decreased by 96% (p = 0.044), with no rebound in the use of other Gram-negative broad-spectrum antimicrobials. A quasisignificant (p = 0.052) increase in QP was observed upon ASP implementation. Readmission and case fatality rates remained stable. ASP interventions were safe, and they reduced LOS and LOT of phlegmonous appendicitis and the use of selected broad-spectrum antimicrobials, while increasing QP in children with AR-IAI.

Benefits of a Pediatric Antimicrobial Stewardship Program in Antimicrobial Use and Quality of Prescriptions in a Referral Children's Hospital.

OBJECTIVES: To evaluate the results of the first 24 months of a postprescription review with feedback-based antimicrobial stewardship program in a European referral children's hospital. STUDY DESIGN: We performed a pre-post study comparing antimicrobial use between the control (2015-2016) and the intervention periods (2017-2018) expressed in days of therapy/100 days present. Quality of prescriptions was evaluated by quarterly cross-sectional point-prevalence surveys. Length of stay, readmission rates, in-hospital mortality rates, cost of systemic antimicrobial agents, and antimicrobial resistance rates were included as complementary outcomes. RESULTS: Total antimicrobial use and antibacterial use significantly decreased during the intervention period (P = .002 and P = .001 respectively), and total antifungal use remained stable. A significant decline in parenteral antimicrobial use was also observed (P < .001). In 8 quarterly point-prevalence surveys (938 prescriptions evaluated), the mean prevalence of use of any antimicrobial among inpatients was 39%. An increasing trend in the rate of optimal prescriptions was observed after the first point-prevalence survey (P = .0898). Nonoptimal prescriptions were more common in surgical than in medical departments, in antibacterial prescriptions with prophylactic intention, and in empirical more than in targeted treatments. No significant differences were observed in terms of mortality or readmission rates. Only minor changes in antimicrobial resistance rates were noted. CONCLUSIONS: Our antimicrobial stewardship program safely decreased antimicrobial use and expenditure, and a trend toward improvement in quality of prescription was also observed.

Impact of Baseline Tuberculin Skin Test and Isoniazid Chemoprophylaxis on Subsequent Quantiferon-TB Gold In-Tube Performance in Young Children Assessed After Tuberculosis Contact in Catalonia.

We investigated the impact of baseline tuberculin skin tests (TSTs) and preventive isoniazid chemoprophylaxis on subsequent QuantiFERON-TB Gold In-Tube (QFT-GIT) assays performed after a 10- to 12-week window period in 114 children <5 years of age. Previous TSTs and chemoprophylaxis had no impact on the magnitude of subsequent antigen-induced responses in QFT-GIT. Furthermore, previous TSTs did not induce conversion from a negative to a positive QFT-GIT result.

Performance of Tuberculin Skin Tests and Interferon-γ Release Assays in Children Younger Than 5 Years.

BACKGROUND: Available data to assess the optimal diagnostic approach in infants and preschool children at risk of tuberculosis (TB) are limited. METHODS: We conducted a prospective observational study in children younger than 5 years undergoing assessment with both tuberculin skin tests (TST) and QuantiFERON-TB Gold In-Tube (QFT-GIT) assays at 2 tertiary TB units in Barcelona, Spain. RESULTS: A total of 383 children were included. One of 304 participants considered uninfected developed active TB during follow-up {median [interquartile range (IQR)]: 47 [30; 48] months}, compared with none of 40 participants with latent TB infection [follow-up since completion of anti-TB treatment: 42 (32; 45) months]. Overall test agreement between TST and QFT-GIT was moderate (κ = 0.551), but very good in children screened after TB contact (κ = 0.801) and in Bacillus Calmette-Guérin (BCG)-unvaccinated children (κ = 0.816). Discordant results (16.8%, all TST+/QFT-GIT-) were mainly observed in new-entrant screening and in BCG-vaccinated children. Children with indeterminate QFT-GIT results were on average younger than those with determinate results (median age: 12 vs. 30 months; P < 0.001). The sensitivity of TSTs and QFT-GIT assays in children with confirmed active TB was 100% (95% confidence interval: 79.4%-100%) and 93.7% (95% confidence interval: 69.8%-99.8%), respectively. In patients with latent TB infection or active TB, there was no correlation between age and antigen-stimulated interferon-γ responses (r = -0.044; P = 0.714). CONCLUSIONS: In young BCG-unvaccinated children with recent TB contact, a dual testing strategy using TST and QFT-GIT in parallel may not be necessary. However, TST+/QFT-GIT- discordance is common, and it remains uncertain if this constellation indicates TB infection or not. In active TB, QFT-GIT assays do not perform better than TSTs.

Impact of nursing interventions on adherence to treatment with antituberculosis drugs in children and young people: A nonrandomized controlled trial.

AIM: To evaluate the association of a new nursing intervention on the adherence to antituberculosis treatment in a paediatric cohort (<18 years). BACKGROUND: Tuberculosis remains a public health problem worldwide. The risk of developing tuberculosis after primary infection and its severity are higher in children. Proper adherence to antituberculosis treatment is critical for disease control. DESIGN: Nonrandomized controlled trial; Phase 1, retrospective (2011-2013), compared with Phase 2, prospective with intervention (2015-2016), in a referral centre for paediatric tuberculosis in Spain (NCT03230409). METHODS: A total of 359 patients who received antituberculosis drugs after close contact with a smear-positive patient (primary chemoprophylaxis) or were treated for latent tuberculosis infection or tuberculosis disease were included, 261 in Phase 1 and 98 in Phase 2. In Phase 2, a new nurse-led intervention was implemented in all patients and included two educational steps (written information in the child's native language and follow-up telephone calls) and two monitoring steps (Eidus-Hamilton test and follow-up questionnaire) that were exclusively carried out by nurses. RESULTS: Adherence to antituberculosis treatment increased from 74.7% in Phase 1% to 87.8% in Phase 2 (p = 0.014; Chi-square test), after the implementation of the nurse-led intervention. In Phase 2, nonadherence was only associated with being born abroad (28.6% vs. 7.8%; p = 0.019; Chi-square test) and with foreign origin families (27.3% vs. 0%; p < 0.0001; Chi-square test). CONCLUSION: The nurse-led intervention was associated to an increase in adherence to antituberculosis treatment. Immigrant-related variables remained major risk factors for sub-optimal adherence in a low-endemic setting.

Use of procalcitonin in the diagnosis of tuberculosis in infants and preschool children.

Normal procalcitonin (PCT) levels have been reported in adult pulmonary tuberculosis (TB) but have not been previously investigated in children. We aimed to assess PCT levels at diagnosis of TB in young children in a low-burden setting. In a cross-sectional observational study in a referral pediatric center in Barcelona (Spain), we assessed the value of PCT and other inflammatory markers (leucocyte counts, C-reactive protein, and erythrocyte sedimentation rate) in the diagnosis of TB in pre-school children (< 6 years at diagnosis, n = 45), as compared with two control groups (pneumococcal pneumonia, n = 25; and healthy controls, n = 49). Normal PCT levels were observed at diagnosis of TB in most cases, while C-reactive protein values and leucocyte counts were slightly elevated when compared to healthy controls. All three inflammatory biomarkers were significantly higher in children with pneumococcal pneumonia. CONCLUSIONS: In our study, PCT was not a useful diagnostic test for TB in young children. In a low-burden TB setting, PCT may be of some value in distinguishing pulmonary TB from pneumococcal pneumonia. What is Known: • Diagnosis of pediatric tuberculosis on clinical evidence is difficult, particularly in infants and small children. • Studies in adults with tuberculosis have mostly reported normal procalcitonin levels at diagnosis. What is New: • In pre-scholars with tuberculosis, erythrocyte sedimentation rate and white blood cell counts were higher than in healthy controls, but procalcitonin was not. • Procalcitonin may be useful in the differential diagnosis of intrathoracic tuberculosis and pneumococcal pneumonia.

Adherence to Antituberculosis Drugs in Children and Adolescents in A Low-Endemic Setting: A Retrospective Series.

Adherence to antituberculosis drug regimens is critical for the prevention and treatment of tuberculosis in pediatrics. In a large retrospective series of children and adolescents in Barcelona, Spain, completion of treatment was worse among patients treated for latent infection, compared with those treated for active tuberculosis or receiving primary chemoprophylaxis. Toxicity and cultural and language barriers were identified as predictors of nonadherence.

Is a nasopharyngeal tube effective as interface to provide bi-level noninvasive ventilation?

BACKGROUND: The nasopharyngeal tube (NT) is a potential interface for noninvasive ventilation (NIV) available in all health care centers. The aim of the study was to describe our experience in the use of the NT for bi-level NIV in infants and its effectiveness. METHODS: Prospective observational study from January 2007 to December 2010, including all patients ≤ 6 months old admitted to the pediatric ICU (PICU) and treated with NIV with two levels of pressure using the NT. Clinical data collected before starting NIV, and at 2, 8, 12 and 24 h, were analyzed following NIV initiation: first-line or initial NIV (i-NIV), elective postextubation NIV (e-NIV), and rescue postextubation NIV (r-NIV). The need for intubation was considered to be NIV failure. RESULTS: One hundred fifty-one episodes of NIV were included in the study, with 65% of patients having bronchiolitis. e-NIV was most frequently used (48%) (i-NIV 44%, r-NIV 8%), and the failure rate, 27% in total, was highest in the i-NIV group (37%) (e-NIV 18%, r-NIV 25%). Case patients with successful outcomes had shorter PICU stays (8.5 vs. 13 d, P = .001) and hospital stays (17 vs. 23 d, P = .03) stays. The NT needed to be changed for another interface in only 5 case patients, few complications (4 of 151 patients) were observed, and mortality (2 of 151 patients) was unrelated to NIV. CONCLUSIONS: Use of the NT showed 73% effectiveness, with few complications. The effectiveness was higher in e-NIV than i-NIV.