Correction to: Implementation and impact of pediatric antimicrobial stewardship programs: a systematic scoping review.

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

Implementation and impact of pediatric antimicrobial stewardship programs: a systematic scoping review.

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.

Antibiotic treatment and antimicrobial resistance in children with urinary tract infections.

OBJECTIVES: The aim of this study was to describe antibiotic prescribing patterns and antimicrobial resistance rates in hospitalised children with febrile and afebrile urinary tract infections (UTIs). METHODS: Antibiotic prescriptions and antibiograms for neonates, infants and older children with UTI admitted to a general district hospital in Central Greece were evaluated. Data covering a 5-year period were collected retrospectively from the Paediatric Department's Electronic Clinical Archive. Patients were included based on clinical and microbiological criteria. Antimicrobial susceptibility was determined by the Kirby-Bauer disk diffusion method. RESULTS: A total of 230 patients were included in the study. Among 459 prescriptions identified, amikacin (31.2%) was the most common antibiotic prescribed in this population, followed by amoxicillin/clavulanic acid (17.4%) and ampicillin (13.5%). Children received prolonged intravenous (i.v.) treatments for febrile (mean ± S.D., 5.4 ± 1.45 days) and afebrile UTIs (mean ± S.D., 4.4 ± 1.64 days). A total of 236 pathogens were isolated. The main causative organism was Escherichia coli (79.2%) with high reported resistance rates to ampicillin (42.0%), trimethoprim/sulfamethoxazole (26.5%) and amoxicillin/clavulanic acid (12.2%); lower resistance rates were identified for third-generation cephalosporins (1.7%), nitrofurantoin (2.3%), ciprofloxacin (1.4%) and amikacin (0.9%). Klebsiella spp. isolates were highly resistant to cefaclor (27.3%). CONCLUSION: High prescribing rates for amikacin and penicillins (± ß-lactamase inhibitors) and prolonged i.v. treatments were observed. Escherichia coli was highly resistant to ampicillin, whilst third-generation cephalosporins exhibited greater in vitro efficacy. Establishment of antimicrobial stewardship programmes and regular monitoring of antimicrobial resistance could help to minimise inappropriate prescribing for UTIs.

Influence of national culture and context on healthcare workers' perceptions of infection prevention in Greek neonatal intensive care units.

BACKGROUND: Healthcare-associated infections (HAIs) in neonatal intensive care units (NICUs) result in increased morbidity, mortality and healthcare costs. HAI rates in Greek NICUs are among the highest in Europe. There is a need to identify the factors that influence the transmission of HAIs and implementation of prevention interventions in this setting. AIM: To understand healthcare workers' perceptions about HAI prevention in Greek NICUs. METHODS: Qualitative interviews were conducted with NICU staff (physicians and nurses) and infection prevention stakeholders (infectious diseases physicians and infection control nurses) working in three hospitals in Athens. Interviews were conducted in Greek, transcribed and translated into English, and analysed using a modified grounded theory approach. FINDINGS: Interviews were conducted with 37 respondents (20 physicians and 17 nurses). Four main barriers to HAI prevention were identified: (1) resource limitations leading to understaffing and cramped space; (2) poor knowledge about HAI prevention; (3) Greek-specific cultural norms, including hierarchy-driven decisions, a reluctance for public workers to do more than they are paid for, a belief that personal experience trumps evidence-based knowledge, and reactive rather than proactive approaches to societal challenges; and (4) lack of a national infection prevention infrastructure. Respondents believed that these barriers could be overcome through organized initiatives, high-quality HAI performance data, interpersonal interactions to build engagement around HAI prevention, and leveraging the hierarchy to promote change from the 'top down'. CONCLUSION: Implementing HAI prevention interventions in Greek NICUs will require consideration of contextual features surrounding the delivery of care, with particular attention paid to national culture.

Factors associated with persistent colonisation with methicillin-resistant Staphylococcus aureus.

We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38-17·40), prior MRSA infection (OR 3·59; 95% CI 1·05-12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7-159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08-0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.

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.

Surgical site infections in a longitudinal cohort of neonatal intensive care unit patients.

OBJECTIVE: To estimate the incidence and identify risk factors for surgical site infections (SSIs) among infants in the neonatal intensive care unit (NICU). STUDY DESIGN: A prospective cohort study of infants undergoing surgical procedures from May 2009 to April 2012 in three NICUs was performed. SSI was identified if documented by an attending neonatologist and treated with intravenous antibiotics. Independent risk factors were identified using logistic regression, adjusting for NICU. RESULT: A total of 902 infants underwent 1346 procedures and experienced 60 SSIs (incidence: 4.46/100 surgeries). Risk factors for SSIs included younger chronological age (odds ratio (OR) 1.03 per day decrease, 95% confidence interval (CI) 1.01, 1.04), lower gestational age (OR 1.09 per week decrease, CI 1.02, 1.18), male sex (OR 1.17, CI 1.04, 1.34) and use of central venous catheter (OR 4.40, CI 1.19, 9.62). Only 43% had surgical site cultures obtained and Staphylococcus aureus was most commonly isolated. CONCLUSION: SSIs complicated 4.46% of procedures performed in the NICU. Although few modifiable risk factors for SSIs were identified, future efforts should focus on evaluating the impact of current prevention strategies on the incidence of neonatal SSI.

A prospective, cohort, multicentre study of candidaemia in hospitalized adult patients with haematological malignancies.

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.

Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation

To develop an evidence-based guideline for the empiric management of pediatric fever and neutropenia (FN). The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group composed of experts in pediatric oncology and infectious disease as well as a patient advocate. The Panel was convened for the purpose of creating this guideline. We followed previously validated procedures for creating evidence-based guidelines. Working groups focused on initial presentation, ongoing management, and empiric antifungal therapy. Each working group developed key clinical questions, conducted systematic reviews of the published literature, and compiled evidence summaries. The Grades of Recommendation Assessment, Development, and Evaluation approach was used to generate summaries, and evidence was classified as high, moderate, low, or very low based on methodologic considerations. Recommendations were made related to initial presentation (risk stratification, initial evaluation, and treatment), ongoing management (modification and cessation of empiric antibiotics), and empiric antifungal treatment (risk stratification, evaluation, and treatment) of pediatric FN. For each recommendation, the strength of the recommendation and level of evidence are presented. This guideline represents an evidence-based approach to FN specific to children with cancer. Although some recommendations are similar to adult-based guidelines, there are key distinctions in multiple areas. Implementation will require adaptation to the local context.

Potential for pet animals to harbour methicillin-resistant Staphylococcus aureus when residing with human MRSA patients.

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.

The impact of household transmission on duration of outpatient colonization with methicillin-resistant Staphylococcus aureus.

We identified eight consecutive patients who presented with a skin or soft tissue infection due to MRSA. Of seven household members of these cases, three were colonized with MRSA. The mean duration of MRSA colonization in index cases was 33 days (range 14-104), while mean duration of colonization in household cases was 54 days (range 12-95). There was a borderline significant association between having a concurrent colonized household member and a longer duration of colonization (mean 44 days vs. 26 days, P=0.08).

Invasive zygomycosis in neonates and children.

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 (< or =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.

Invasive fungal infections in the paediatric and neonatal population: diagnostics and management issues.

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.

The role of group C and group G streptococci in acute pharyngitis in children.

Group C streptococci (GCS) and group G beta-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 beta-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.

Performance of a predictive model for streptococcal pharyngitis in children.

CONTEXT: Group A beta-hemolytic streptococcus (GABHS) pharyngitis is a common childhood illness. The clinical diagnosis is difficult to determine and laboratory tests have limitations; hence, the condition is generally overdiagnosed and overtreated. Several clinical pediatric-specific predictive models have been published but none have been prospectively studied. OBJECTIVE: To test the performance of a previously published predictive model for GABHS pharyngitis in children in different clinical settings and during different seasons. DESIGN: Prospective cohort study. SETTINGS: Pediatric emergency department and 2 pediatric outpatient clinics. PATIENTS: Children aged between 1 and 18 years with pharyngitis on initial examination at study sites between April 1, 1999, and March 31, 2000. INTERVENTIONS: Recording of clinical features during initial evaluation using a standardized form and recovery of GABHS from patients' throats using reference standard methods. MAIN OUTCOME MEASURES: Posttest probability for GABHS positive throat culture associated with the model's positive predictors (moderate to severe tonsillar swelling, cervical lymphadenopathy [moderate to severe tenderness and enlargement of cervical lymph nodes], scarletiniform rash, and the absence of coryza) and the models' negative predictors (absence of the above signs and the presence of coryza). RESULTS: Of 587 patients analyzed, 218 (37%) had a positive throat culture for GABHS. Forty-nine percent were boys. Mean +/- SD age was 6.7 +/- 3.9 years. There was no difference between the subsets within the sample. The posttest probability values for a positive throat culture associated with positive and negative predictors of the model were 79% and 12%, respectively. CONCLUSIONS: A pediatric predictive model for GABHS pharyngitis performed better than physicians' subjective estimates for a positive throat culture and was comparable with a rapid antigen detection test. The model performed consistently well in different populations and across seasons. It can be useful if reliable microbiological testing and/or follow-up are not attainable.

In vitro activities of linezolid, meropenem, and quinupristin-dalfopristin against group C and G streptococci, including vancomycin-tolerant isolates.

The in vitro activities of meropenem, linezolid, quinupristin-dalfopristin, vancomycin, and penicillin against 130 clinical isolates of group C and G streptococci, including vancomycin-tolerant isolates, were evaluated. Meropenem, linezolid, quinupristin-dalfopristin, vancomycin, and penicillin MICs at which 90% of the isolates were inhibited were 0.06, 2.0, 0.25, 0.5, and < or = 0.016 microg/ml, respectively. Meropenem, linezolid, quinupristin-dalfopristin, and penicillin were active against group C and G streptococci, including vancomycin-resistant strains.

Antibiotic susceptibilities of group C and group G streptococci isolated from patients with invasive infections: evidence of vancomycin tolerance among group G serotypes.

A retrospective review of medical records for 32 patients with invasive group C streptococcus (GCS) or group G streptococcus (GGS) infections was performed. MICs and minimum bactericidal concentrations (MBCs) of penicillin, erythromycin, and vancomycin for all isolates were obtained. Tolerance of vancomycin, defined as an MBC 32 or more times higher than the MIC, was exhibited by 18 GGS isolates (54%). The identification of tolerance in clinical isolates of GGS and GCS may have clinical implications in treating these seriously ill patients.

Multivariate predictive models for group A beta-hemolytic streptococcal pharyngitis in children.

OBJECTIVES: To create predictive models for the clinical diagnosis of group A beta-hemolytic streptococcal (GABHS) pharyngitis in children. METHODS: Patients aged 6 months to 18 years presenting to a pediatric ED with suspected GABHS pharyngitis were prospectively enrolled in the study. Clinicians recorded pertinent clinical information using a standardized form and obtained a throat swab to culture GABHS using a reference standard method. Twelve demographic and clinical features of patients with positive throat cultures were compared with the features of patients with negative throat cultures. Significantly different features were entered in a stepwise logistic regression analysis to create predictive models for the diagnosis. RESULTS: Eighty-five patients (29%) were culture-positive and 212 (71%) were culture-negative for GABHS. Respective mean ages were 6.2 years and 6.1 years in the two groups. Univariate chi-square analysis of the 12 features identified six variables that were significantly associated with GABHS. All significant features were initially included in a stepwise logistic regression analysis. In model I, four independent variables were identified: moderate to severe presentation of tonsillar swelling, moderate to severe tenderness and enlargement of cervical lymph nodes, the presence of scarlatiniform rash, and the absence of moderate to severe coryza, yielding a 95% probability for GABHS. Excluding the rare scarlatiniform rash, the remaining variables were used in the second regression analysis. In model II, three independent variables were identified: moderate to severe tonsillar swelling, moderate to severe tenderness and enlargement of cervical lymph nodes, and absence of moderate to severe coryza, yielding a probability of 65% for the diagnosis. A probability of <15% was observed in the absence of scarlatiniform rash, the absence of moderate to severe tenderness and enlargement of cervical lymph nodes, and the presence of moderate to severe coryza. CONCLUSIONS: In children with moderate to severe presentation of tonsillar swelling, tenderness and enlargement of cervical lymph nodes, and the absence of coryza, the probability of a positive throat culture is >65%. Conversely, in the absence of a moderate to severe presentation of tonsillar swelling, enlargement of cervical nodes, and the presence of coryza, the probability of a positive throat culture is <15%. If prospectively validated, these models could be integrated into a consistent treat, test, and no treatment/no testing approach to the clinical management of childhood pharyngitis.