Gentamicin serum concentration measurement in children. / Serumkonsentrasjonsmåling av gentamicin hos barn.

BACKGROUND: Gentamicin is often used to treat serious paediatric infections. It has been standard practice in Norway to measure the serum concentration of gentamicin immediately prior to the second or third dose (pre-dose [trough] concentration) to assess the risk of toxicity. The clinical significance of such measurements in children has not previously been evaluated in Norway. MATERIAL AND METHOD: This is a retrospective study of routine pre-dose samples obtained for the measurement of serum gentamicin in paediatric patients aged 1 month to 17 years at four hospitals in Norway. Clinical data were extracted from electronic medical records from two of the hospitals. All children received treatment with intravenous gentamicin at a dose of 7 mg/kg once daily in accordance with Norwegian guidelines. RESULTS: The most common indications for treatment were febrile urinary tract infection, febrile neutropenia, and suspected or confirmed sepsis. The median (interquartile range) duration of treatment in 353 episodes at two of the hospitals was 4 (3-5) days. Serum gentamicin pre-dose samples were analysed for 1,288 treatment episodes across four hospitals. In 1,223 episodes (95 %), the pre-dose sample showed a serum gentamicin concentration of less than 0.6 mg/L. In 7 episodes (0.5 %), the pre-dose sample showed an elevated gentamicin concentration, defined as greater than 1.0 mg/L. INTERPRETATION: An in most cases mildly elevated serum gentamicin concentration was found in the pre-dose sample in 7 of 1,288 treatment episodes. Routine measurement of serum gentamicin via a pre-dose sample should in future be reserved for children receiving long-term gentamicin treatment, those with impaired kidney function, or those who are also receiving nephro- or ototoxic drugs.

[Methicillin-resistant Staphylococcus aureus in wound drainage in children] / Meticillinresistente gule stafylokokker i sårsekret hos barn.

BACKGROUND: Skin and soft tissue infections are common in children. We wished to investigate the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in wound drainage from children in Norway. MATERIAL AND METHOD: We conducted an observational study based on data from the Norwegian Surveillance System for Antimicrobial Drug Resistance (NORM) for the period 2013-21. Resistance data from wound drainage with growth of Staphylococcus aureus from children (0-17 years) and adults were included in the study. RESULTS: A total of 1 416 isolates from wound drainage from children and 7 623 isolates from adults with growth of Staphylococcus aureus were included. MRSA was detected in 33 (2.3 %) of the isolates from children and 95 (1.2 %) of the isolates from adults (p = 0.002). In children, the highest prevalence of MRSA was in those of kindergarten age (1-5 years, 4.4 %), compared to infants (< 1 year, 1.0 %) and children of school age (6-17 years, 1.7 %) (p = 0.011). Kindergarten children had the highest prevalence of erythromycin resistance (9.0 %). INTERPRETATION: The prevalence of methicillin-resistant Staphylococcus aureus in wound drainage from children in Norway was generally low, but somewhat higher in drainage from kindergarten children compared to other age groups. It is not generally necessary to take account of methicillin resistance in the empirical treatment of skin and soft tissue infections in children in Norway.

Corrigendum: Can We Optimize Antibiotic Use in Norwegian Neonates? A Prospective Comparison Between a University Hospital and a District Hospital.

[This corrects the article DOI: 10.3389/fped.2019.00440.].

Antibiotic use in children before, during and after hospitalisation.

PURPOSE: To investigate ambulatory antibiotic use in children during 1 year before and 1 year after in-hospital antibiotic exposure compared to children from the general population that had not received antibiotics in-hospital. METHODS: Explorative data-linkage cohort study from Norway of children aged 3 months to 17 years. One group had received antibiotics in-Hospital (H+), and one group had not received antibiotics in-hospital (H-). The H+ group was recruited during admission in 2017. Using the Norwegian Population Registry, 10 children from the H- group were matched with one child from the H+ group according to county of residence, age and sex. We used the Norwegian Prescription Database to register antibiotic use 1 year before and 1 year after the month of hospitalisation. RESULTS: Of 187 children in the H+ group, 83 (44%) received antibiotics before hospitalisation compared to 288/1870 (15%) in the H- group, relative risk (RR) 2.88 (95% confidence interval 2.38-3.49). After hospitalisation, 86 (46%) received antibiotics in the H+ group compared to 311 (17%) in the H- group, RR 2.77 (2.30-3.33). Comorbidity-adjusted RR was 2.30 (1.84-2.86) before and 2.25 (1.81-2.79) after hospitalisation. RR after hospitalisation was 2.55 (1.99-3.26) in children 3 months-2 years, 4.03 (2.84-5.71) in children 3-12 years and 2.07 (1.33-3.20) in children 13-17 years. CONCLUSIONS: Children exposed to antibiotics in-hospital had two to three times higher risk of receiving antibiotics in ambulatory care both before and after hospitalisation. The link between in-hospital and ambulatory antibiotic exposure should be emphasised in future antibiotic stewardship programs.

Are infants exposed to antimicrobials during the first 3 months of life at increased risk of recurrent use? An explorative data-linkage study.

OBJECTIVES: To investigate whether infants exposed to antimicrobials in hospital during the first 3 months of life had an increased risk of ambulatory antimicrobial use during the following year compared with infants not exposed to antimicrobials during the first 3 months of life. METHODS: Norwegian cohort study of infants less than 3 months consisting of one group exposed to antimicrobials recruited during hospitalization and one group not exposed to antimicrobials. Ten unexposed infants were matched with one exposed infant according to county of residence, birth year and month, and sex. The Norwegian Prescription Database was applied to register antimicrobial use from the month after discharge and 1 year onward. We defined comorbidity based on antimicrobials prescribed as reimbursable prescriptions due to underlying diseases. RESULTS: Of 95 infants exposed to antimicrobials during the first 3 months of life, 23% had recurrent use compared with 14% use in 950 unexposed infants [relative risk (RR) = 1.7 (95% CI = 1.1-2.5) and comorbidity-adjusted RR = 1.4 (95% CI = 0.9-2.2)]. The recurrence use rate in exposed term infants (≥37 weeks, n = 70) was 27% compared with 12% in their unexposed matches [RR 2.3 = (95% CI = 1.4-3.7) and comorbidity-adjusted RR = 1.9 (95% CI = 1.2-3.2). Of 25 exposed preterm infants, 3 (12%) had recurrent use. The total antimicrobial prescription rate was 674/1000 in the exposed group and 244/1000 in the unexposed group [incidence rate ratio = 2.8 (95% CI = 1.6-4.9)]. CONCLUSIONS: Infants exposed to antimicrobials during the first 3 months of life had an increased risk of recurrent use during the following year. This increased risk also appeared in term infants without infection-related comorbidity.

Antibiotic resistance in paediatric UTIs in Norway. / Antibiotikaresistens ved urinveisinfeksjoner hos barn i Norge.

BACKGROUND: Urinary tract infections are common in children. The purpose of this study was to describe national resistance data from urinary isolates from children with a view to informing antibiotic use. METHOD: We conducted an observational study based on culture responses with resistance determination in urine from the Norwegian Surveillance System for Antimicrobial Drug Resistance (NORM). All urinary isolates from children (0-17 years) in the period 2013-17 were included and compared with urinary isolates from adults. For cephalexin resistance, we used data from two Norwegian hospitals covering the period 2015-19. RESULTS: Of 13 211 urinary isolates included in the NORM register, 589 (4.5 %) were from children. Weighted by the number of data collection days, Escherichia coli accounted for 85.2 % of the isolates from children. For E. coli, there was a higher proportion of trimethoprim resistance in urine samples from children (27.0 %) compared to adults (22.9 %), p = 0.02. For ciprofloxacin, we found a lower resistance rate in E. coli in urine samples from children (5.7 %) compared to adults (8.7 %), p = 0.03. For other selected antibiotics, we found the following resistance rates in E. coli in children: nitrofurantoin (0.5 %), mecillinam (4.0 %), cephalexin (4.3 %), amoxicillin-clavulanic acid (7.2 %) and trimethoprim-sulfamethoxazole (24.1 %). INTERPRETATION: Pivmecillinam, cephalexin and amoxicillin-clavulanic acid are relevant choices in the empirical treatment of upper urinary tract infections. Nitrofurantoin and pivmecillinam are relevant for lower urinary tract infections. Trimethoprim and trimethoprim-sulfamethoxazole should only be used after resistance determination.

Half of all hospitalised children treated with antibiotics for pneumonia did not fulfil radiological, microbiological or laboratory criteria.

AIM: Evaluating the management of paediatric pneumonia is important. We aimed to estimate the proportion of children receiving antibiotics for suspected community-acquired pneumonia (CAP) that were likely to have a bacterial infection. Furthermore, we described antibiotic use in relation to guidelines. METHODS: We conducted a prospective observational study from a paediatric department in Norway. During 2017, all admitted children aged 0-17 years receiving antibiotics for CAP were enrolled in the study. We collected relevant data and defined likely CAP as one or more of the following: radiologically confirmed pneumonia, c-reactive protein of at least 100 mg/L, positive bacterial culture from blood or pleura, detection of bacteria from the nasopharynx associated with atypical pneumonia. RESULTS: In total, 70 episodes of suspected CAP were included. Median age was 41.5 months, and 36 (51%) were girls. Of all treatments, 38 (54%) fulfilled our criteria for likely CAP. Median duration of treatment was 10 days. Of empirical treatments, 36 (57%) only involved penicillin. None of the children had neutropenia or complications, and only two needed intensive care. CONCLUSION: Only half of children receiving antibiotics for suspected CAP were likely to have bacterial infection. Despite no obvious reason, antibiotic treatment was longer than currently recommended.

Epidemiology and Antimicrobial Susceptibility of Invasive Bacterial Infections in Children-A Population-Based Study From Norway.

OBJECTIVE: To describe epidemiology and antimicrobial susceptibility testing (AST) data of bacteria causing invasive infections in Norwegian children (0-18 years). METHODS: Population-based observational study using prospectively collected AST data from the Norwegian Surveillance System of Antimicrobial Resistance from 2013 to 2017. We included all clinically relevant bacterial isolates (blood and cerebrospinal fluid), and compared incidence of invasive infections and AST data in isolates from children and adults. RESULTS: We included 1173 isolates from children and 44,561 isolates from adults. Staphylococcus aureus accounted for 220/477 (46.2%, 95% CI: 41.6-50.7) of all isolates in schoolchildren (6-18 years). Compared with Streptococcus pneumonia isolates from adults (N = 2674), we observed higher nonsusceptibility rates to penicillin in isolates from children (N = 151), 11.9% versus 5.8%, P < 0.01; also higher resistance rates to erythromycin (11.3% vs. 4.9%, P < 0.01), clindamycin (9.3% vs. 3.6%, P < 0.001), and trimethoprim/sulfamethoxazole (17.9% vs. 6.4%, P < 0.001). Compared with Escherichia coli isolates in adults (N = 9073), we found lower rates of ESBL in isolates from children (N = 212), 2.4% versus 6.4%, P < 0.05. CONCLUSION: The study indicates the importance of microbiologic surveillance strategies in children and highlights the need for pediatric AST data. The high rates of nonsusceptibility to commonly used antibiotics among S. pneumoniae in children and the high burden of invasive S. aureus infections in schoolchildren calls for modifications of Norwegian guidelines.

Can We Optimize Antibiotic Use in Norwegian Neonates? A Prospective Comparison Between a University Hospital and a District Hospital.

Background: Worldwide, a large proportion of neonates are prescribed antibiotics without having infections leading to increased antimicrobial resistance, disturbance of the evolving microbiota, and increasing the risk of various chronical diseases. Comparing practice between different hospitals/settings is important in order to optimize antibiotic stewardship. Aim: To investigate and compare the potential for improved antibiotic stewardship in neonates in two Norwegian hospitals with different academic culture, with emphasis on antibiotic exposure in unconfirmed infections, treatment length/doses, CRP values and the use of broad-spectrum antibiotics (BSA). All types of infections were investigated, but the main focus was on early-onset sepsis (EOS). Methods: We conducted a prospective observational cohort study of antibiotic use in a Norwegian university hospital (UH) and a district hospital (DH), 2017. Unconfirmed infections were defined as culture negative infections that neither fulfilled the criteria for clinical infection (clinical symptoms, maximum CRP >30 mg/L, and treatment for at least 5 days). Results: Ninety-five neonates at the DH and 89 neonates at the UH treated with systemic antibiotics were included in the study. In total, 685 prescriptions (daily doses) of antibiotics were given at the DH and 903 at the UH. Among term and premature infants (≥ 28 weeks), 82% (75% at the UH and 86% at the DH, p = 0.172) of the treatments for suspected EOS were for unconfirmed infections, and average treatment length in unconfirmed infections was 3.1 days (both hospitals). Median dose for aminoglycoside was higher for term infants at the UH (5.96, 95% CI 5.02-6.89) compared to the DH (4.98, 95% CI 4.82-5.14; p < 0.001). At the UH, all prescriptions with aminoglycosides were gentamicin, while tobramycin accounted for 93% of all prescriptions with aminoglycosides at the DH. Conclusion: There is a potential for reduction in both antibiotic exposure and treatment length in these two neonatal units, and a systematic risk/observational algorithm of sepsis should be considered in both hospitals. We revealed no major differences between the UH and DH, but doses and choice of aminoglycosides varied significantly.

Using a period incidence survey to compare antibiotic use in children between a university hospital and a district hospital in a country with low antimicrobial resistance: a prospective observational study.

OBJECTIVES: To describe and compare antibiotic use in relation to indications, doses, adherence rate to guidelines and rates of broad-spectrum antibiotics (BSA) in two different paediatric departments with different academic cultures, and identify areas with room for improvement. DESIGN: Prospective observational survey of antibiotic use. SETTING: Paediatric departments in a university hospital (UH) and a district hospital (DH) in Norway, 2017. The registration period was 1 year at the DH and 4 months at the UH. PARTICIPANTS: 201 children at the DH (mean age 3.8: SD 5.1) and 137 children at the UH (mean age 2.0: SD 5.9) were treated with systemic antibiotics by a paediatrician in the study period and included in the study. OUTCOME MEASURES: Main outcome variables were prescriptions of antibiotics, treatments with antibiotics, rates of BSA, median doses and adherence rate to national guidelines. RESULTS: In total, 744 prescriptions of antibiotics were given at the UH and 638 at the DH. Total adherence rate to guidelines was 75% at the UH and 69% at the DH (p=0.244). The rate of treatments involving BSA did not differ significantly between the hospitals (p=0.263). Use of BSA was related to treatment of central nervous system (CNS) infections, patients with underlying medical conditions or targeted microbiological treatment in 92% and 86% of the treatments, at the UH and DH, respectively (p=0.217). A larger proportion of the children at the DH were treated for respiratory tract infections (p<0.01) compared with the UH. Children at the UH were treated with higher doses of ampicillin and cefotaxime (p<0.05) compared with the DH. CONCLUSION: Our results indicate that Norwegian paediatricians have a common understanding of main aspects in rational antibiotic use independently of working in a UH or DH. Variations in treatment of respiratory tract infections and in doses of antibiotics should be further studied.

Potential for More Rational Use of Antibiotics in Hospitalized Children in a Country With Low Resistance: Data From eight Point Prevalence Surveys.

BACKGROUND: Antimicrobial resistance is low in Norway, but to prevent an increase, the Norwegian Government has launched a National Strategy including a 30% reduction of broad-spectrum antibiotics (BSA) in hospitals within 2020. BSA are defined as second- and third-generation cephalosporins, carbapenems, piperacillin/tazobactam and quinolones. There are no recent studies of antibiotic use in Norwegian hospitalized children. The aim of this study was to describe the use of antibiotics with emphasis on BSA in Norwegian hospitalized children and neonates to detect possibilities for optimization. METHODS: Data were extracted from 8 national point prevalence surveys of systemic antibiotic prescriptions in Norwegian hospitals between 2015 and 2017. The choices of antibiotics were compared with the empirical recommendations given in available Norwegian guidelines. In total, 1323 prescriptions were issued for 937 patients. RESULTS: Twenty-four percent of pediatric inpatients were given antibiotics. Adherence to guidelines was 48%, and 30% (95% confidence interval: 27%-33%) of all patients on antibiotics received BSA. We identified only small variations in use of BSA between hospitals. One-third of the patients on antibiotic therapy received prophylaxis whereof 13% were given BSA. In 30% of prescriptions with BSA, no microbiologic sample was obtained before treatment. CONCLUSIONS: This study reveals an excess of prescriptions with BSA in relation to the low resistance rate in Norway. Our findings reveal areas for improvement that can be useful in the forthcoming antibiotic stewardship programs in Norwegian pediatric departments.

A comparison between child psychiatric outpatients with AD/HD and anxiety/depression.

BACKGROUND: Studies have shown that children with attention-deficit/hyperactivity disorder (AD/HD) have a lower quality of life (QoL), and lower school and psychosocial functioning than healthy children. AIMS: This is the first study to compare these domains and child competence between children with AD/HD- and anxiety/depression-related problems and healthy children using data from multiple informants. METHOD: Children were matched by age and sex, resulting in two clinical groups consisting of 62 children with AD/HD-related problems, 49 children with anxiety/depression-related problems and a reference group of 65 healthy schoolchildren. The Inventory of Life Quality for Children and Adolescents (parent and child report), the Child Behaviour Checklist (parent report), the Teacher's Report Form and the Children's Global Assessment Scale (therapist evaluation) were used. Differences between group means were analysed by t-tests and analysis of variance. RESULTS: The AD/HD group reported a significantly higher QoL than did the Anxiety/Depression group. However, no significant differences in QoL were found between the two clinical groups by parent proxy report. The AD/HD group reported a significantly higher QoL than shown by parent proxy evaluation. According to parent and teacher reports, both clinical groups showed significantly lower school functioning than the group of healthy children. Further, the AD/HD group showed significantly lower school functioning and total competence than the Anxiety/Depression group. CONCLUSION: To obtain a full clinical picture of subgroups of patients with AD/HD- and anxiety/depression-related problems referred to child mental health outpatient treatment, clinicians should always use multiple informants to evaluate symptoms/problems, functioning and QoL.