Nikos Spyridis

Changes in clinical indications for community antibiotic prescribing for children in the UK from 1996 to 2006: will the new NICE prescribing guidance on upper respiratory tract infections just be ignored?

Objective: To analyse changes in clinical indications for community antibiotic prescribing for children in the UK between 1996 and 2006 and relate these findings to the new NICE guidelines for the treatment of upper respiratory tract infections in children. Study design: Retrospective cohort study. Method: The IMS Health Mediplus database was used to obtain annual antibiotic prescribing rates and associated clinical indications in 0–18-year-old patients between 1 January 1996 and 31 December 2006 in the UK. Results: Antibiotic prescribing declined by 24% between 1996 and 2000 but increased again by 10% during 2003–2006. Respiratory tract infection was the most common indication for which an antibiotic was prescribed, followed by “abnormal signs and symptoms”, ear and skin infections. Antibiotic prescriptions for respiratory tract infections have decreased by 31% (p<0.01) mainly because of reduced prescribing for lower respiratory tract infections (56% decline, p<0.001) and specific upper respiratory tract infections including tonsillitis/pharyngitis (48% decline, p<0.001) and otitis (46% decline, p<0.001). Prescribing for non-specific upper respiratory tract infection increased fourfold (p<0.001). Prescribing for “abnormal signs and symptoms” increased significantly since 2001 (40% increase, p<0.001). Conclusion: There has been a marked decrease in community antibiotic prescribing linked to lower respiratory tract infection, tonsillitis, pharyngitis and otitis. Overall prescribing is now increasing again but is associated with non-specific upper respiratory tract infection diagnoses. General practitioners may be avoiding using diagnoses where formal guidance suggests antibiotic prescribing is not indicated. The new NICE guidance on upper respiratory tract infections is at risk of being ignored.

The effect of age on whole blood interferon-gamma release assay response among children investigated for latent tuberculosis infection.

OBJECTIVE To evaluate the effect of age upon QuantiFERON-TB Gold-In-Tube (QFT-IT) assay outcome among children examined for latent tuberculosis infection (LTBI). STUDY DESIGN A cross-sectional study was conducted among 761 children (mean age ± SD: 7.84 ± 4.68 years) evaluated for LTBI. Participants were examined with both tuberculin skin test and QFT-IT (Cellestis, Australia) and categorized into 4 age groups. Multivariate logistic and linear regressions were used to evaluate the association between selected demographic and patient characteristics upon the qualitative and quantitative QFT-IT outcomes. Agreement between the tuberculin skin test and QFT-IT within groups was evaluated with the κ statistic. RESULTS QFT-IT indeterminate results occurred more frequently among young children (8.1%; P < .0001) and children (2.7%; P = .025) than adolescents (0.7%). Among QFT-IT positive patients, infants had higher mean (± SD) interferon-gamma (IFNγ) concentration than adolescents. QFT-IT positive (vs negative) outcome was associated with origin from a high tuberculosis endemicity setting (AOR = 4.54; 95% CI, 3.22-6.25) and lack of previous Bacille Calmette Guerin immunization (AOR = 2.70; 95% CI, 1.89-3.85), but not patient age (AOR = 0.96; 95% CI, 0.92-0.99). However, among QFT-IT positive patients, the IFNγ concentration was inversely associated with patient age (P = .009) and positively with mitogen response (P = .0002). Agreement between tests was not significantly different between younger and older children in the different risk groups. CONCLUSIONS Qualitative QFT-IT assay results are not affected by patient age. However, indeterminate results occur more frequently among younger children. Among patients with LTBI the quantitative QFT-IT result (ie, IFNγ) is inversely associated with patient age.

Off-label antibiotic use in children in three European countries

ObjectiveAntibiotics are the drugs most frequently prescribed for children, and most of them lack patent protection. The aim of this study was to evaluate off-label antibiotic use in three European countries.MethodsData relating to all patients admitted to the neonatal intensive care units (NICUs) and paediatric wards of the participating centres were collected by the same investigator over a 2-week survey period between February and May 2009. The data included age, date of birth, weight, relevant medical history and diagnosis, together with details of all of the antibiotics prescribed (compound, route of administration, dose, and indication for use).ResultsThe study involved 616 children (110 admitted to NICUs: 62 in the UK, 38 in Italy and 10 in Greece; 506 admitted to general paediatric wards: 265 in the UK, 94 in Italy and 147 in Greece). A total of 1244 antibiotic prescriptions were issued (290 in NICUs and 954 in paediatric wards). The results showed that off-label antibiotic use is very common among European paediatric patients, with generally only slight, but sometimes significant differences between countries. However, this use relates almost exclusively to doses and indications, and rarely to age. The only antibiotics found to be used off-label in an age-related manner in paediatric clinical practice are meropenem for neonates and quinolones or linezolid for older children, which represent priorities for future studies.ConclusionEuropean-wide educational programmes are urgently needed to meet the objectives of improving paediatricians’ working knowledge of the recommendations surrounding licensed antibiotics-use in children, and of reducing uncontrolled patterns of prescribing.

The European Union Antibiotic Awareness Day: the paediatric perspective

The European Centre for Disease Prevention and Control (ECDC) has marked 18 November 2008 as the first of the proposed annual European Union (EU) Antibiotic Awareness Days in an attempt to improve the use of antibiotics by families and professionals. Antibiotics are the most common medicines given to children. In the UK, there are around 6 million antibiotic prescriptions for children each year, the majority given unnecessarily for viral upper respiratory tract infections.1 There is clear evidence linking antibiotic resistance to prescribing, with a possible threshold effect beyond which high prescribing can select resistant isolates.2 Factors such as duration of treatment, dose and class of selected antibiotic3 are important in the resistance chain, along with host susceptibility and pathogen transmissibility.4 Children are an excellent environment for the selection of resistant bacterial pathogens after recent antibiotic use, particularly in day care. As recent studies have suggested, the individual child can host resistant pathogens after antibiotic use for up to 3 months, which is sufficient to sustain a high level of antibiotic resistance in the general population.5 If the amount of antibiotics prescribed in children could be reduced, selection and transmission of resistant strains should occur less often, with an effect on the general population. Is Europe responding to this challenge? Surveillance of antimicrobial consumption in European children is currently surprisingly poor and not systematic. European organisations such as ESAC (European Surveillance of Antimicrobial Consumption) and EARSS (European Antimicrobial Resistance Surveillance System) collect some excellent data on antibiotic consumption and resistance in the adult population of Europe, but provide very limited paediatric country-specific and age-specific data. In adults, there is very significant variation in antibiotic use across Europe. In a study recently published by ESAC, total outpatient antibiotic use in 2003 varied by a factor of 3 …

Comparing neonatal and paediatric antibiotic prescribing between hospitals: a new algorithm to help international benchmarking

OBJECTIVES The WHO anatomical therapeutic chemical (ATC)/defined daily dose (DDD) methodology is a standardized method of comparing antimicrobial use. The ATC/DDD is defined as the average maintenance daily dose of a drug used in a 70 kg adult, ignoring the considerable differences in body weight of neonates and children. The aim of this study was to develop a new standardized way of comparing rates of antimicrobial prescribing between European childrens hospitals. METHODS This pilot study at four European childrens hospitals (in the UK, Greece and Italy) collected data including demographics, antibiotic use, dosing and indication in children and neonates over a 14 day period. RESULTS A total of 1217 antibiotic prescriptions were issued with 47 different antibiotics used. Approximately half of all children and a third of all neonates received antibiotics, with wide variation between centres in the type and dose of antibiotic used. We propose a new pragmatic three-step algorithm. The first step includes a simple comparison of the proportion of hospitalized children on antibiotics by weight bands and the number of antimicrobials that account for 90% of total DDD drug usage (DU90%). The second step is a comparison of the dosing used (mg/kg/day). The third step is to compare overall drug exposure using DDD/100 bed days for standardized weight bands between centres. CONCLUSIONS This novel method has the potential to be a useful tool to provide antibiotic use comparator data and requires validation in a large prospective point prevalence study.

MenACWY-TT vaccine for active immunization against invasive meningococcal disease

Meningococcal disease remains a significant global cause of morbidity and mortality despite the availability of polysaccharide and conjugate vaccines. The implementation of monovalent meningococcal serogroup C vaccine in developed countries has significantly decreased the incidence of meningococcal disease, while the recent introduction of monovalent serogroup A conjugate vaccine in the African meningitis belt aims to reduce the incidence of high endemic disease in this area. Three quadrivalent meningococcal vaccines have already been licensed; a polysaccharide (MenACWY-PS) and two conjugated (MenACWY-DT and MenACWY-CRM) vaccines. An investigational MenACWY-TT vaccine is described in this article. Clinical trials in infants older than 9 months of age, toddlers, children, adolescents and adults have indicated that this vaccine is well tolerated and immunogenic. The inclusion of a spacer molecule coupled with the polysaccharide (for serogroups A and C) and tetanus toxoid as the carrier protein aims to elicit robust immune responses. The tolerability of this vaccine is comparable to that of polysaccharide quadrivalent vaccines and monovalent meningococcal serogroup C vaccines. More importantly, the immunogenicity, antibody persistence and induction of immune memory aim to provide protection to a wide range of susceptible subjects.

Variation in paediatric hospital antibiotic guidelines in Europe

Objective To assess the availability and source of guidelines for common infections in European paediatric hospitals and determine their content and characteristics. Design Participating hospitals completed an online questionnaire on the availability and characteristics of antibiotic prescribing guidelines and on empirical antibiotic treatment including duration of therapy for 5 common infection syndromes: respiratory tract, urinary tract, skin and soft tissue, osteoarticular and sepsis in neonates and children. Results 84 hospitals from 19 European countries participated in the survey of which 74 confirmed the existence of guidelines. Complete guidelines (existing guidelines for all requested infection syndromes) were reported by 20% of hospitals and the majority (71%) used a range of different sources. Guidelines most commonly available were those for urinary tract infection (UTI) (74%), neonatal sepsis (71%) and sepsis in children (65%). Penicillin and amoxicillin were the antibiotics most commonly recommended for respiratory tract infections (RTIs) (up to 76%), cephalosporin for UTI (up to 50%) and for skin and soft tissue infection (SSTI) and bone infection (20% and 30%, respectively). Antistaphylococcal penicillins were recommended for SSTIs and bone infections in 43% and 36%, respectively. Recommendations for neonatal sepsis included 20 different antibiotic combinations. Duration of therapy guidelines was mostly available for RTI and UTI (82%). A third of hospitals with guidelines for sepsis provided recommendations for length of therapy. Conclusions Comprehensive antibiotic guideline recommendations are generally lacking from European paediatric hospitals. We documented multiple antibiotics and combinations for most infections. Considerable improvement in the quality of guidelines and their evidence base is required, linking empirical therapy to resistance rates.

Trends in the epidemiology of childhood tuberculosis in Greece

SETTING A hospital referral center for childhood tuberculosis (TB). OBJECTIVE To evaluate the epidemiological and clinical features of childhood TB in the Greater Athens area in the last decade. DESIGN We retrospectively reviewed the medical records of patients aged <14 years treated for active TB between January 2000 and December 2009 at our pediatric TB clinic and compared the results with the patient turnover during the previous decade (1990-1999). Data concerning demographic and clinical characteristics were analyzed. RESULTS A total of 321 children (median age 5.57 years, 157 males) with active TB were identified. About one third originated from areas where TB was previously recognized to be highly endemic. Twenty-three children (7%) had extra-pulmonary TB, and 61% of them originated from TB-endemic areas. Bacteriological confirmation was obtained in 40% of patients from whom specimens were obtained: 1 of 26 (3.8%) strains was multidrug-resistant. Most cases with drug-resistant Mycobacterium tuberculosis were noted among immigrant children. The average annual TB incidence was estimated at 5.37 per 100 000 for children aged <14 years in the Greater Athens area. Time trend analysis for the 20-year period revealed a significant reduction in the total number of TB cases (P = 0.002) and in TB among children from low-incidence countries (P < 0.0001). CONCLUSIONS In our settings, active TB is decreasing among children of Greek origin; disease epidemiology and drug resistance is influenced by the increasing influx of immigrants from areas where the disease is highly prevalent.

Increasing skin infections and Staphylococcus aureus complications in children, England, 1997-2006.

During 1997–2006, general practitioner consultations for skin conditions for children <18 years of age in England increased 19%, from 128.5 to 152.9/1,000 child-years, and antistaphylococcal drug prescription rates increased 64%, from 17.8 to 29.1/1,000 child-years. During the same time period, hospital admissions for Staphylococcus aureus infections rose 49% from 53.4 to 79.3/100,000 child-years.

Impact of the Gen-Probe Amplified MTD® Test on tuberculosis diagnosis in children.

OBJECTIVE To evaluate the performance of the Gen-Probe Amplified MTD® Test (AMTD) for childhood tuberculosis (TB) diagnosis compared to conventional culture. DESIGN We retrospectively studied 121 childhood cases (73 males; median age 7 years, range 1-16). Pulmonary samples (104/152, 68%) included gastric aspirates (n = 53), induced sputum samples (n = 43), bronchial aspirates and bronchoalveolar lavage (n = 8). Extra-pulmonary samples (48/152, 32%) included lymph nodes (n = 34) and other sterile fluids (n = 14). Specimens were examined using acid-fast bacilli (AFB) microscopy, AMTD and bacterial culture using BACTEC™ MGIT™ 960 and Löwenstein-Jensen (LJ) media. RESULTS A clinical diagnosis of TB was made in 50/121 (41%) children (43/50 pulmonary disease). AFB microscopy was positive in 6%; Mycobacterium tuberculosis was recovered by culture from 16/50 (32%) and AMTD was positive in 29/50 (58%). AMTD sensitivity, specificity, positive predictive value and negative predictive value compared to culture were respectively 100%, 85%, 50% and 100%. For pulmonary vs. extra-pulmonary disease, the performance of AMTD compared to culture was respectively 100%, 77%, 46% and 100% vs. 100%, 97.5%, 75% and 100%. CONCLUSIONS Nucleic acid amplification tests are more sensitive and very specific methods for the rapid detection of M. tuberculosis. The AMTD technique increases TB detection in children compared to conventional culture.