Coverage gaps in empiric antibiotic regimens used to treat serious bacterial infections in neonates and children in Southeast Asia and the Pacific

Background: High levels of antimicrobial resistance (AMR) are propagating deaths due to neonatal and paediatric infections globally. This is of particular concern in Southeast Asia and the Pacific, where healthcare resources are constrained and access to newer agents to treat multidrug-resistant pathogens is limited. Methods: To assess the coverage provided by commonly prescribed empiric antibiotic regimens for children in low- and middle-income countries in Southeast Asia and the Pacific, we built a weighted incidence syndromic combination antibiogram (WISCA), parameterised using data obtained from a systematic review of published literature incorporating WHO-defined SEARO and WPRO regions in Ovid MEDLINE, EMBASE, Global Health and PubMed. Susceptibility data for bacterial pathogens were extracted to provide coverage estimates for pre-specified antibiotics (aminopenicillins, gentamicin, third-generation cephalosporins and carbapenems), reported at the regional level. Findings: 6648 bacterial isolates from 11 countries across 86 papers were included in the Bayesian WISCA model, which weighted bacterial incidence and antimicrobial susceptibility of relevant isolates. Coverage provided by aminopenicillins in neonatal sepsis/meningitis was 26% (80% credible interval: 16–49) whilst gentamicin coverage was 45% (29–62). Third-generation cephalosporin coverage was only 29% (16–49) in neonatal sepsis/meningitis, 51% (38–64) in paediatric sepsis and 65% (51–77) in paediatric meningitis. Carbapenems were estimated to provide the highest coverage: 81% (65–90) in neonatal sepsis/meningitis, 83% (72–90) in paediatric sepsis and 79% (62–91) in paediatric meningitis. Interpretation: These findings reveal alarmingly high rates of resistance to commonly prescribed empirical therapies for neonatal and paediatric sepsis and meningitis in the Asia–Pacific region

Stress in nurses : stress-related affect and its determinants examined over the nursing day

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Guidelines for the treatment of dysentery (shigellosis): a systematic review of the evidence

Background: Shigella remains the primary cause of diarrhoea in paediatric patients worldwide and accounts for up to 40,000 deaths per year. Current guidelines for the treatment of shigellosis are based on data which are over a decade old. In an era of increasing antimicrobial resistance, an updated review of the appropriate empirical therapy for shigellosis in children is necessary, taking into account susceptibility patterns, cost and the risk of adverse events. Methods: A systematic review of the current published literature on the treatment of shigella dysentery was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: The initial search produced 131 results, of which nine studies met the inclusion criteria. The quality of the studies was assessed as per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. International guidelines were also reviewed. There is a lack of current research regarding the clinical treatment of shigellosis in paediatric and adult patients, despite rising antimicrobial resistance worldwide. In particular, there is a lack of studies assessing the non-susceptibility of community-acquired strains, with almost all published research pertaining to microbiological data from hospital-based settings. Discussion: Current WHO guidelines support the use of fluoroquinolones (first-line), β-lactams (second-line) and cephalosporins (second-line) which accords with currently available evidence and other international guidelines, and there is no strong evidence for changing this guidance. Azithromycin is appropriate as a second-line therapy in regions where the rate of non-susceptibility of ciprofloxacin is known to be high, and research suggests that, from a cardiac point of view, azithromycin is safer than other macrolide antibiotics. Cefixime is also a reasonable alternative, although its use must be weighed against the risk of dissemination of extended-spectrum β-lactamase-producing organisms

Grading antimicrobial susceptibility data quality: room for improvement – Authors' reply

We concur with Elizabeth Ashley and colleagues' pertinent point identifying the shortage of robust scientific schemes for assessing the quality of microbiology data, and the failure of Grading of Recommendations Assessment, Development, and Evaluation (GRADE) analysis to necessarily concur with the quality of other important analyses within a scientific paper (or, as in the case of our Review,1 the quality of microbiology results)

Guidelines for the management of paediatric cholera infection: a systematic review of the evidence

Background: Vibrio cholerae is a highly motile Gram-negative bacterium which is responsible for 3 million cases of diarrhoeal illness and up to 100,000 deaths per year, with an increasing burden documented over the past decade. Current WHO guidelines for the treatment of paediatric cholera infection (tetracycline 12.5 mg/kg four times daily for 3 days) are based on data which are over a decade old. In an era of increasing antimicrobial resistance, updated review of the appropriate empirical therapy for cholera infection in children (taking account of susceptibility patterns, cost and the risk of adverse events) is necessary. Methods: A systematic review of the current published literature on the treatment of cholera infection in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was undertaken. International clinical guidelines and studies pertaining to adverse effects associated with treatments available for cholera infection were also reviewed. Results: The initial search produced 256 results, of which eight studies met the inclusion criteria. Quality assessment of the studies was performed as per the Grading of Recommendations Assessment, Development and Evaluation guidelines. Conclusions In view of the changing non-susceptibility rates worldwide, empirical therapy for cholera infection in paediatric patients should be changed to single-dose azithromycin (20 mg/kg), a safe and effective medication with ease of administration. Erythromycin (12.5 mg/kg four times daily for 3 days) exhibits similar bacteriological and clinical success and should be listed as a second-line therapy. Fluid resuscitation remains the cornerstone of management of paediatric cholera infection, and prevention of infection by promoting access to clean water and sanitation is paramount.

Guidelines for the treatment of severe acute malnutrition: a systematic review of the evidence for antimicrobial therapy

Abstract: Severe acute malnutrition (SAM) affects nearly twenty million children and is responsible for up to one million deaths per year in children under the age of five years. The current WHO guidelines recommend oral amoxicillin for children with uncomplicated malnutrition and parenteral benzylpenicillin and gentamicin for children with complicated malnutrition, although the administration of empirical antibiotics for children with SAM has recently been debated in the literature in light of cost pressures and increasing antimicrobial resistance (AMR) worldwide. METHODS: We conducted a systematic review of the current published literature assessing the efficacy, safety, cost effectiveness and pharmacokinetics of antimicrobial treatment of children with SAM, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: The initial search produced 712 papers, of which eight met the inclusion criteria. Quality assessment of the studies was performed as per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines.34 International guidelines and clinical data registries were also reviewed, revealing inconsistencies in current first- and second-line therapies and dosing regimens. INTERPRETATION: The current evidence supports the continued use of broad-spectrum oral amoxicillin for treating children as outpatients with uncomplicated SAM. There is no strong evidence base to change the current parenteral therapy guidelines for children admitted with complicated SAM, although they should be clarified to harmonise the dosage regiment of amoxicillin for the treatment of SAM to 40mg/kg twice daily, and to continue parenteral antimicrobials beyond 2 days if indicated by the clinical condition

Grading antimicrobial susceptibility data quality: room for improvement – Authors' reply

We concur with Elizabeth Ashley and colleagues' pertinent point identifying the shortage of robust scientific schemes for assessing the quality of microbiology data, and the failure of Grading of Recommendations Assessment, Development, and Evaluation (GRADE) analysis to necessarily concur with the quality of other important analyses within a scientific paper (or, as in the case of our Review,1 the quality of microbiology results)

Antimicrobial resistance among children in sub-Saharan Africa

Antimicrobial resistance is an important threat to international health. Therapeutic guidelines for empirical treatment of common life-threatening infections depend on available information regarding microbial aetiology and antimicrobial susceptibility, but sub-Saharan Africa lacks diagnostic capacity and antimicrobial resistance surveillance. We systematically reviewed studies of antimicrobial resistance among children in sub-Saharan Africa since 2005. 18 of 1075 articles reviewed met inclusion criteria, providing data from 67 451 invasive bacterial isolates from inconsistently defined populations in predominantly urban tertiary settings. Among neonates, Gram-negative organisms were the predominant cause of early-onset neonatal sepsis, with a high prevalence of extended-spectrum β-lactamase-producing organisms. Gram-positive bacteria were responsible for a high proportion of infections among children beyond the neon atal period, with high reported prevalence of non-susceptibility to treatment advocated by the WHO therapeutic guidelines. There are few up-to-date or representative studies given the magnitude of the problem of antimicrobial resistance, especially regarding community-acquired infections. Research should focus on differentiating resistance in community-acquired versus hospital-acquired infections, implementation of standardised reporting systems, and pragmatic clinical trials to assess the efficacy of alternative treatment regimens