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OBJECTIVE: The aim of this study was to evaluate the impact of previous antimicrobial exposure on the development of antimicrobial resistance in children with their first urinary tract infection (UTI). METHODS: We conducted a retrospective cohort study of children aged 6 months to 6 years and received their first diagnosis of UTI in a network of 27 outpatient pediatric practices between July 1, 2001, and May 31, 2006. We examined the relationship between antimicrobial resistance in UTI isolates and exposure to specific antimicrobial agents (amoxicillin, amoxicillin-clavulanate, cefdinir, trimethoprim-sulfamethoxazole, and azithromycin) in the previous 120 days. We developed multivariable logistic regression models for resistance to ampicillin, amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, and first-generation and third-generation cephalosporins, adjusting for potential confounders such as age, number of siblings, recent hospitalizations, and child care exposure. RESULTS: Of the 533 children who had a first UTI, 8%, 14%, and 21% were exposed to antimicrobial agents within 30, 60, and 120 days before the UTI, respectively. Amoxicillin exposure within 30 days (odds ratio [OR]: 3.6 [95% confidence interval (CI): 1.6-8.2]) and 31 to 60 days (OR: 2.8 [95% CI: 1.0-7.5]) before UTI both were associated with ampicillin resistance. Exposure to amoxicillin >60 days before the UTI was not associated with ampicillin resistance. Amoxicillin exposure within 30 days of UTI was also associated with amoxicillin-clavulanate resistance (OR: 3.9 [95% CI: 1.8-8.7]). No association between exposure to other antimicrobial agents and resistance to any of the antimicrobial agents was seen. CONCLUSIONS: Recent antimicrobial exposure is associated with antimicrobial-resistant UTIs among pediatric outpatients, and the magnitude of this association decreases with time since exposure. Judicious antimicrobial prescribers should consider this association when selecting empiric antimicrobial agents for a new UTI and should use strategies to reduce unnecessary antimicrobial use to avoid development of resistant bacteria. [ABSTRACT FROM AUTHOR]

Invasive zygomycosis in neonates and children has both similarities to and differences from that in adults. We searched PubMed and individual references for English-language reports of single cases or case series of neonatal (<1 month) and paediatric (≤18 years) zygomycosis and compared the results with published results in adults. Cases were included if they fulfilled pre-specified criteria. A total of 59 cases of neonatal zygomycosis were reported to July 2007; 157 paediatric cases were published up to 2004 and an additional 30 paediatric cases were reported more recently. Prematurity was a major underlying factor among neonatal cases. The most common manifestations of zygomycosis were gastrointestinal (54%) and cutaneous (36%). This pattern differs from the sinopulmonary and rhinocerebral patterns typical in older children and adults. Overall mortality was 64% in neonates, 56% in children and 53% in adults. A tendency for dissemination was higher in neonates than adults. Dissemination and young age (<1 year) were independent risk factors for death in children. Most patients who survived received antifungal therapy. Surgery combined with antifungal therapy was a protective factor against death. Most neonates and children who survived had received an amphotericin B formulation. Zygomycosis is a life-threatening infection in children and neonates with differing patterns of involvement in individuals of different ages. The most common management strategy in survivors involved a combination of amphotericin B and surgery. [ABSTRACT FROM AUTHOR]

Group C streptococci (GCS) and group G β-haemolytic streptococci (GGS) have caused well-documented epidemics of acute pharyngitis in children, but the importance of these organisms in causing endemic or sporadic pharyngitis is uncertain. The heterogeneity of GCS and GGS may obscure the role of certain subtypes, such as the large-colony-forming strains of group C ( Streptococcus dysgalactiae subsp. equisimilis) or group G, in endemic pharyngitis. For a 1-year period, children (aged 6 months to 18 years) ( n = 2085) who presented with pharyngitis to the children's hospital emergency department and two outpatient offices were enrolled in a cross-sectional study to ascertain the role of large-colony-forming GCS and GGS in acute pharyngitis. Control patients ( n = 194) were children who presented to the same locations during the same time period with non-respiratory tract symptoms or to the orthopaedic cast clinic. Throat cultures were obtained by a standard reference method, and swabs were plated on Strep-Selective Agar. Lancefield grouping and species identification was performed on all β-haemolytic isolates. In total, 65 (3%) large-colony-forming GCS and GGS strains were obtained from pharyngitis patients, and three (1.5%) were obtained from the control group (odds ratio 2.0; 95% confidence interval 0.6–6.1). The low isolation rate of large-colony-forming strains of GCS and GGS indicates that even if these organisms are associated with acute, sporadic pharyngitis in paediatric patients, they represent an unusual pathogen. [ABSTRACT FROM AUTHOR]

Invasive candidiasis is a life-threatening infection in patients with haematological malignancies. The objective of our study was to determine the incidence, microbiological characteristics and clinical outcome of candidaemia among hospitalized adult patients with haematological malignancies. This is a population-based, prospective, multicentre study of patients ≥18 years admitted to haematology and/or haematopoietic stem cell transplantation units of nine tertiary care Greek hospitals from January 2009 through to February 2012. Within this cohort, we conducted a nested case-control study to determine the risk factors for candidaemia. Stepwise logistic regression was used to identify independent predictors of 28-day mortality. Candidaemia was detected in 40 of 27 864 patients with haematological malignancies vs. 967 of 1 158 018 non-haematology patients for an incidence of 1.4 cases/1000 admissions vs. 0.83/1000 respectively (p <0.001). Candidaemia was caused predominantly (35/40, 87.5%) by non- Candida albicans species, particularly Candida parapsilosis (20/40, 50%). In vitro resistance to at least one antifungal agent was observed in 27% of Candida isolates. Twenty-one patients (53%) developed breakthrough candidaemia while receiving antifungal agents. Central venous catheters, hypogammaglobulinaemia and a high APACHE II score were independent risk factors for the development of candidaemia. Crude mortality at day 28 was greater in those with candidaemia than in control cases (18/40 (45%) vs. 9/80 (11%); p <0.0001). In conclusion, despite antifungal prophylaxis, candidaemia is a relatively frequent infection associated with high mortality caused by non- C. albicans spp., especially C. parapsilosis. Central venous catheters and hypogammaglobulinaemia are independent risk factors for candidaemia that provide potential targets for improving the outcome. [ABSTRACT FROM AUTHOR]

Colonization by methicillin-resistant Staphylococcus aureus (MRSA) may be persistent in people and is horizontally transmissible. The scientific literature suggests that domestic pets may also participate in cross-transmission of MRSA within households. The objectives of this study were to evaluate the prevalence of and risk factors for MRSA carriage by pets residing in households with an MRSA-infected person. From 66 households in which an MRSA-infected patient resided, we screened 47 dogs and 52 cats using a swab protocol. Isolates from pets and humans were genotyped using two techniques and compared for concordance. Human participants completed a 22-question survey of demographic and epidemiologic data relevant to staphylococcal transmission. Eleven of 99 pets (11.5%) representing 9 (13.6%) of households were MRSA-positive, but in only six of these households were the human and animal-source strains genetically concordant. Human infection by strain USA 100 was significantly associated with pet carriage [OR = 11.4 (95% CI 1.7, 76.9); P = 0.013]. Yet, for each day of delay in sampling the pet after the person's MRSA diagnosis, the odds of isolating any type of MRSA from the pet decreased by 13.9% [(95% CI 2.6, 23.8); P = 0.017)]. It may be concluded that pets can harbour pandemic strains of MRSA while residing in a household with an infected person. However, the source of MRSA to the pet cannot always be attributed to the human patient. Moreover, the rapid attrition of the odds of obtaining a positive culture from pets over time suggests that MRSA carriage may be fleeting. [ABSTRACT FROM AUTHOR]

Invasive fungal infections in children appear to have increased over the past few decades. Especially neonates and children with primary and secondary immunodeficiencies are at risk. Candida and Aspergillus spp. are the most commonly isolated organisms. In addition, Malassezia may cause systemic infections in newborns and zygomycosis is important because of its rising incidence and high case fatality rate. Timely diagnosis and initiation of appropriate antifungal therapy is imperative for improving outcomes. However, traditional techniques are time-consuming and representative sample material, using invasive procedures, may be difficult to obtain in the paediatric setting. This review provides an overview of the advances in detection and rapid species identification, with a focus on issues relevant in these settings. Subsequently, the current antifungal treatment options for neonates and children are discussed in light of the antifungal spectrum of the available agents and the specific pharmacokinetic properties in different age groups. Although a multitude of newer antifungal compounds have become available within the last decade, further studies are necessary to clearly establish the role for each of these agents among neonates and children. [ABSTRACT FROM AUTHOR]

Context: The evidence regarding risk factors for recurrent urinary tract infection (UTI) and the risks and benefits of antimicrobial prophylaxis in children is scant.Objectives: To identify risk factors for recurrent UTI in a pediatric primary care cohort, to determine the association between antimicrobial prophylaxis and recurrent UTI, and to identify the risk factors for resistance among recurrent UTIs.Design, Patients, and Setting: From a network of 27 primary care pediatric practices in urban, suburban, and semirural areas spanning 3 states, a cohort of children aged 6 years or younger who were diagnosed with first UTI between July 1, 2001, and May 31, 2006, was assembled. Time-to-event analysis was used to determine risk factors for recurrent UTI and the association between antimicrobial prophylaxis and recurrent UTI, and a nested case-control study was performed among children with recurrent UTI to identify risk factors for resistant infections.Main Outcome Measures: Time to recurrent UTI and antimicrobial resistance of recurrent UTI pathogens.Results: Among 74 974 children in the network, 611 (0.007 per person-year) had a first UTI and 83 (0.12 per person-year after first UTI) had a recurrent UTI. In multivariable Cox time-to-event models, factors associated with increased risk of recurrent UTI included white race (0.17 per person-year; hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.22-3.16), age 3 to 4 years (0.22 per person-year; HR, 2.75; 95% CI, 1.37-5.51), age 4 to 5 years (0.19 per person-year; HR, 2.47; 95% CI, 1.19-5.12), and grade 4 to 5 vesicoureteral reflux (0.60 per person-year; HR, 4.38; 95% CI, 1.26-15.29). Sex and grade 1 to 3 vesicoureteral reflux were not associated with risk of recurrence. Antimicrobial prophylaxis was not associated with decreased risk of recurrent UTI (HR, 1.01; 95% CI, 0.50-2.02), even after adjusting for propensity to receive prophylaxis, but was a risk factor for antibimicrobial resistance among children with recurrent UTI (HR, 7.50; 95% CI, 1.60-35.17).Conclusion: Among the children in this study, antimicrobial prophylaxis was not associated with decreased risk of recurrent UTI, but was associated with increased risk of resistant infections. [ABSTRACT FROM AUTHOR]

Background: Antibiotics are the most common medicines prescribed to children in hospitals and the community, with a high proportion of potentially inappropriate use. Antibiotic misuse increases the risk of toxicity, raises healthcare costs, and selection of resistance. The primary aim of this systematic review is to summarize the current state of evidence of the implementation and outcomes of pediatric antimicrobial stewardship programs (ASPs) globally. Methods: MEDLINE, Embase and Cochrane Library databases were systematically searched to identify studies reporting on ASP in children aged 0–18 years and conducted in outpatient or in-hospital settings. Three investigators independently reviewed identified articles for inclusion and extracted relevant data. Results: Of the 41,916 studies screened, 113 were eligible for inclusion in this study. Most of the studies originated in the USA (52.2%), while a minority were conducted in Europe (24.7%) or Asia (17.7%). Seventy-four (65.5%) studies used a before-and-after design, and sixteen (14.1%) were randomized trials. The majority (81.4%) described in-hospital ASPs with half of interventions in mixed pediatric wards and ten (8.8%) in emergency departments. Only sixteen (14.1%) studies focused on the costs of ASPs. Almost all the studies (79.6%) showed a significant reduction in inappropriate prescriptions. Compliance after ASP implementation increased. Sixteen of the included studies quantified cost savings related to the intervention with most of the decreases due to lower rates of drug administration. Seven studies showed an increased susceptibility of the bacteria analysed with a decrease in extended spectrum beta-lactamase producers E. coli and K. pneumoniae; a reduction in the rate of P. aeruginosa carbapenem resistance subsequent to an observed reduction in the rate of antimicrobial days of therapy; and, in two studies set in outpatient setting, an increase in erythromycin-sensitive S. pyogenes following a reduction in the use of macrolides. Conclusions: Pediatric ASPs have a significant impact on the reduction of targeted and empiric antibiotic use, healthcare costs, and antimicrobial resistance in both inpatient and outpatient settings. Pediatric ASPs are now widely implemented in the USA, but considerable further adaptation is required to facilitate their uptake in Europe, Asia, Latin America and Africa. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Clostridium difficile is the main cause of nosocomial and antibiotic-associated diarrhea in adults. Recently, the incidence and severity of C difficile-associated disease in adults have been increasing. Whether similar phenomena are occurring among children remains unknown. Our study describes the epidemiological features of C difficile-associated disease in hospitalized children. METHODS: We conducted a retrospective cohort study of hospitalized children with C difficile-associated disease at 22 freestanding children's hospitals in the United States, from 2001 to 2006. Cases of C difficile-associated disease were defined as a hospitalized child with a discharge code for C difficile infection, a laboratory billing charge for a C difficile toxin assay, and receipt of antimicrobial therapy for C difficile-associated disease. RESULTS: We identified 4895 patients with C difficile-associated disease. Over the study period, the annual incidence of C difficile-associated disease increased from 2.6 to 4.0 cases per 1000 admissions and from 4.4 to 6.5 cases per 10 000 patient-days. The median age of children with C difficile-associated disease was 4 years. Twenty-six percent of patients were <1 year of age. The majority of patients (67%) had underlying chronic medical conditions. The colectomy and all-cause mortality rates among children with C difficile-associated disease did not increase during the study period. CONCLUSIONS: The annual incidence of C difficile-associated disease in hospitalized children increased significantly from 2001 to 2006. However, the rates of colectomy and in-hospital death have not increased in children with C difficile-associated disease as they have among adults. The risk factors and outcomes for children with C difficile-associated disease remain to be defined in future studies. [ABSTRACT FROM AUTHOR]

The original article [1] contains an error in Fig. 1 whereby the number of selected articles of the first box is incorrect. [ABSTRACT FROM AUTHOR]