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BACKGROUND: In mid-2018, the Australian childhood 13-valent pneumococcal conjugate vaccine schedule changed from 3+0 to 2+1, moving the third dose to 12 months of age, to address increasing breakthrough cases of invasive pneumococcal disease (IPD), predominantly in children aged >12 months. This study assessed the impact of this change using national IPD surveillance data. METHODS: Pre- and postschedule change 3-dose 13-valent pneumococcal conjugate vaccine breakthrough cases were compared by age group, serotype, and clinical syndrome. Annual rates of breakthrough cases were calculated (per 100 000) using respective birth cohort sizes and 3-dose vaccine coverage. Using time-series modelling, observed IPD rates in children aged <12 years were compared to that expected if the 3+0 schedule were continued. FINDINGS: Over 2012-2022, rate of 3-dose breakthrough cases in children aged >12 months was 2.8 per 100 000 (n = 557; 11 birth cohorts). Serotype 3 replaced 19A as predominant breakthrough serotype (respectively, 24% and 65% in 2013 to 60% and 20% in 2022) followed by 19F. In breakthrough cases, the most frequent clinical phenotype was bacteremic pneumonia (69%), with meningitis accounting for 3%-4%. In cohorts eligible for 2+1 versus 3+0 schedules, rate of breakthrough cases was lower for all vaccine serotypes, except type 3 (incidence rate ratio, 0.50 [95% confidence interval, .28-.84] and 1.12 [0.71-1.76], respectively). Observed compared to expected IPD was 51.7% lower (95% confidence interval, -60.9 to -40.7%) for vaccine serotypes, but the change for nonvaccine types was not significant 12% (-9.6 to 39.7). INTERPRETATIONS: The 2+1 schedule is likely superior to 3+0 for overall IPD control, a finding that may be worth consideration for other countries considering or using 3+0 PCV schedules.
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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. Funding: This research was funded in whole, or in part, by the Wellcome Trust [220211]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. PCMW is supported by a National Health and Medical Research Council (NHMRC) Investigator Grant. NHMRC had no involvement in the design or conduct of the research.
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OBJECTIVES: The 2022 seasonal respiratory syncytial virus (RSV) epidemic in Sydney, Australia saw an unprecedented number of RSV detections. We aimed to characterize genomic and immunologic factors associated with the surge in RSV cases. METHODS: Whole genome sequences of RSV were generated from 264 RSV-infected infants and linked to case-matched clinical data from the 2022 southern hemisphere RSV season. We then performed an immunologic analysis of baseline RSV-specific humoral immunity in women of childbearing age before and throughout the coronavirus disease 2019 pandemic. RESULTS: Clinical analysis revealed a high burden of disease across patients of all health backgrounds. More than one-half of RSV-related health care visits by infants resulted in hospitalization, and one-quarter required high-flow respiratory support or a higher level of care. Viral phylogenetic analyses revealed that 2022 Sydney RSV sequences were closely related to viruses that had been circulating globally since 2017, including those detected in recent US outbreaks. Nonsynonymous mutations within the palivizumab and nirsevimab binding sites were detected at low frequencies. There was no difference in baseline RSV-neutralizing antibody titers between 2020 and 2022. CONCLUSIONS: Collectively, these findings suggest that neither the emergence of a novel RSV genotype nor hypothesized immune debt was associated with the surge of RSV cases and hospitalizations in 2022. Continued genomic and immunologic surveillance is required to further understand the factors driving outbreaks of RSV globally, and to inform guidelines for the rollout and ongoing use of recently developed immunotherapeutics and vaccines.
Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Syncytial Viruses , Infant , Humans , Female , Antiviral Agents/therapeutic use , Respiratory Syncytial Virus Infections/drug therapy , Phylogeny , Palivizumab , GenomicsABSTRACT
BACKGROUND: Ventilator-associated pneumonia (VAP) caries a morbidity and mortality risk in the preterm neonate, particularly in the context of rising global antimicrobial resistance driving infections due to multidrug-resistant Gram-negative bacteria. Cefiderocol, a siderophilic cephalosporin, has broad Gram-negative antimicrobial activity and central nervous system penetration and is used for the treatment of hospital-acquired pneumonia or VAP in adults. Scarce data exists on its use in neonates. CASE: A female neonate born at 26 + 6 weeks developed VAP at 21 days of life. She was commenced on corticosteroids, vancomycin and ceftazidime but continued to deteriorate. Sputum cultures yielded Stenotrophomonas maltophilia resistant to trimethoprim/sulfamethoxazole, ciprofloxacin and ceftazidime, with potential susceptibility to cefiderocol. Cerebrospinal fluid showed an elevated white cell count. In view of worsening respiratory and hemodynamic status, antibiotic treatment was changed to cefiderocol monotherapy at 30 mg/kg/dose every 8 hours. Within 72 hours of commencing cefiderocol, the neonate was successfully extubated to variable-flow continuous positive airway pressure and showed ongoing clinical improvement. CONCLUSIONS: Cefiderocol was integral for the care of our neonate without any immediate adverse safety consequences. We relied on dosing data from a conference abstract, due to the paucity of evidence on the use of novel antimicrobials. This lack of evidence is particularly concerning given preterm neonates are particularly vulnerable to infections with multidrug-resistant Gram-negative organisms due to their immature immune systems, prolonged hospital stay, repeated interventions and antimicrobial exposure.
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A global resurgence of invasive pneumococcal disease (IPD) has been noted in children. We provide a detailed clinical and epidemiological analysis of IPD in Australian children following relaxation of nonpharmaceutical interventions against coronavirus disease 2019, revealing significant morbidity and mortality-even in vaccinated children without known predisposing risk factors. Almost half of the IPD cases were caused by serotypes not covered by the 13-valent pneumococcal conjugate vaccine.
Subject(s)
COVID-19 , Pneumococcal Infections , Child , Humans , Infant , Streptococcus pneumoniae , SARS-CoV-2 , Australia/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/complications , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Infections/etiology , Pneumococcal Vaccines , Serogroup , Incidence , Vaccines, ConjugateABSTRACT
BACKGROUND: Pneumonia remains a leading cause of hospitalization and death among young children worldwide, and the diagnostic challenge of differentiating bacterial from non-bacterial pneumonia is the main driver of antibiotic use for treating pneumonia in children. Causal Bayesian networks (BNs) serve as powerful tools for this problem as they provide clear maps of probabilistic relationships between variables and produce results in an explainable way by incorporating both domain expert knowledge and numerical data. METHODS: We used domain expert knowledge and data in combination and iteratively, to construct, parameterise and validate a causal BN to predict causative pathogens for childhood pneumonia. Expert knowledge elicitation occurred through a series of group workshops, surveys and one-on-one meetings involving 6-8 experts from diverse domain areas. The model performance was evaluated based on both quantitative metrics and qualitative expert validation. Sensitivity analyses were conducted to investigate how the target output is influenced by varying key assumptions of a particularly high degree of uncertainty around data or domain expert knowledge. RESULTS: Designed to apply to a cohort of children with X-ray confirmed pneumonia who presented to a tertiary paediatric hospital in Australia, the resulting BN offers explainable and quantitative predictions on a range of variables of interest, including the diagnosis of bacterial pneumonia, detection of respiratory pathogens in the nasopharynx, and the clinical phenotype of a pneumonia episode. Satisfactory numeric performance has been achieved including an area under the receiver operating characteristic curve of 0.8 in predicting clinically-confirmed bacterial pneumonia with sensitivity 88% and specificity 66% given certain input scenarios (i.e., information that is available and entered into the model) and trade-off preferences (i.e., relative weightings of the consequences of false positive versus false negative predictions). We specifically highlight that a desirable model output threshold for practical use is very dependent upon different input scenarios and trade-off preferences. Three commonly encountered scenarios were presented to demonstrate the potential usefulness of the BN outputs in various clinical pictures. CONCLUSIONS: To our knowledge, this is the first causal model developed to help determine the causative pathogen for paediatric pneumonia. We have shown how the method works and how it would help decision making on the use of antibiotics, providing insight into how computational model predictions may be translated to actionable decisions in practice. We discussed key next steps including external validation, adaptation and implementation. Our model framework and the methodological approach can be adapted beyond our context to broad respiratory infections and geographical and healthcare settings.
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Anti-Bacterial Agents , Pneumonia , Humans , Bayes Theorem , Surveys and Questionnaires , AustraliaABSTRACT
BACKGROUND: Diagnosing urinary tract infections (UTIs) in children in the emergency department (ED) is challenging due to the variable clinical presentations and difficulties in obtaining a urine sample free from contamination. Clinicians need to weigh a range of observations to make timely diagnostic and management decisions, a difficult task to achieve without support due to the complex interactions among relevant factors. Directed acyclic graphs (DAG) and causal Bayesian networks (BN) offer a way to explicitly outline the underlying disease, contamination and diagnostic processes, and to further make quantitative inference on the event of interest thus serving as a tool for decision support. METHODS: We prospectively collected data on children present to ED with suspected UTIs. Through knowledge elicitation workshops and one-on-one meetings, a DAG was co-developed with clinical domain experts (the Expert DAG) to describe the causal relationships among variables relevant to paediatric UTIs. The Expert DAG was combined with prospective data and further domain knowledge to inform the development of an application-oriented BN (the Applied BN), designed to support the diagnosis of UTI. We assessed the performance of the Applied BN using quantitative and qualitative methods. RESULTS: We summarised patient background, clinical and laboratory characteristics of 431 episodes of suspected UTIs enrolled from May 2019 to November 2020. The Expert DAG was presented with a narrative description, elucidating how infection, specimen contamination and management pathways causally interact to form the complex picture of paediatric UTIs. Parameterised using prospective data and expert-elicited parameters, the Applied BN achieved an excellent and stable performance in predicting Escherichia coli culture results, with a mean area under the receiver operating characteristic curve of 0.86 and a mean log loss of 0.48 based on 10-fold cross-validation. The BN predictions were reviewed via a validation workshop, and we illustrate how they can be presented for decision support using three hypothetical clinical scenarios. CONCLUSION: Causal BNs created from both expert knowledge and data can integrate case-specific information to provide individual decision support during the diagnosis of paediatric UTIs in ED. The model aids the interpretation of culture results and the diagnosis of UTIs, promising the prospect of improved patient care and judicious use of antibiotics.
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Urinary Tract Infections , Anti-Bacterial Agents/therapeutic use , Bayes Theorem , Child , Humans , Prospective Studies , ROC Curve , Urinary Tract Infections/diagnosis , Urinary Tract Infections/drug therapyABSTRACT
The reality of human induced climate change is no longer in doubt, but the concerted global action required to address this existential crisis remains inexcusably inert. Together with climate change, biodiversity collapse is increasingly driving the emergence and spread of infectious diseases, the consequences of which are inequitable globally. Climate change is regressive in its nature, with those least responsible for destroying planetary health at greatest risk of suffering the direct and indirect health consequences. Over half a billion of the world's children live in areas vulnerable to extreme weather events. Without immediate action, the health of today's children and future generations will be compromised. We consider the impact of biodiversity collapse on the spread of infectious diseases and outline a duty of care along a continuum of three dimensions of medical ethics. From a medical perspective, the first dimension requires doctors to serve the best interests of their individual patients. The second dimension considers the public health dimension with a focus on disease control and cost-effectiveness. The neglected third dimension considers our mutual obligation to the future health and wellbeing of children and generations to come. Given the adverse impact of our ecological footprint on current and future human health, we have a collective moral obligation to act.
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Climate Change , Communicable Diseases , Humans , Child , Biodiversity , Public HealthABSTRACT
Human immunodeficiency virus (HIV) is a neurotropic virus that has a detrimental impact on the developing central nervous system (CNS) of children growing up with perinatal HIV (PHIV) due to a combination of pathophysiological processes related to direct viral cytopathic effects and immune activation. This leads to a spectrum of neurocognitive impairment ranging from severe encephalopathy to subtle domain-specific cognitive impairments, as well as psychological disorders that are compounded by HIV-related stigma and sociodemographic factors that disproportionately affect PHIV children. Early commencement and consistent use of combination antiretroviral therapy (cART) has resulted in a dramatic improvement in neuropsychological outcomes for PHIV children; however, they remain vulnerable to cognitive impairment and psychological disorders, as evidenced by imaging findings, randomised clinical trials and observational studies. An optimal neuroprotective cART regimen remains elusive in children, but systemic viral suppression, regular neurocognitive and psychological screening and ready access to neuropsychological management strategies are key components for optimising neuropsychological outcomes. However, a lack of standardised and validated screening tools, particularly in resource-limited settings, hinders a precise understanding of the nature, prevalence and associations between neuropsychological symptomatology and HIV health. This article reviews the natural history, cellular pathophysiology and structural and functional imaging findings for children growing up with HIV, as well as summarising management strategies related to antiretroviral therapy, screening tools and specific interventions for neurocognitive impairments and psychological disorders.
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HIV Infections , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Brain/diagnostic imaging , Brain/drug effects , Brain/growth & development , Brain/virology , Child , HIV Infections/complications , HIV Infections/diagnostic imaging , HIV Infections/drug therapy , HIV Infections/psychology , Humans , Mental Disorders/diagnosis , Mental Disorders/etiology , Mental Disorders/therapy , PrevalenceABSTRACT
As the SARS-CoV-2 pandemic unfolds across the globe, consistent themes are emerging with regard to aspects of SARS-CoV-2 infection and its associated disease entities in children. Overall, children appear to be less frequently infected by, and affected by, SARS-CoV-2 virus and the clinical disease COVID-19. Large epidemiological studies have revealed children represent less than 2% of the total confirmed COVID-19 cases, of whom the majority experience minimal or mild disease that do not require hospitalisation. Children do not appear to be major drivers of SARS-CoV-2 transmission, with minimal secondary virus transmission demonstrated within families, schools and community settings. There are several postulated theories regarding the relatively low SARS-CoV-2 morbidity and mortality seen in children, which largely relate to differences in immune responses compared to adults, as well as differences in angiotensin converting enzyme 2 distribution that potentially limits viral entry and subsequent inflammation, hypoxia and tissue injury. The recent emergence of a multisystem inflammatory syndrome bearing temporal and serological plausibility for an immune-mediated SARS-CoV-2-related disease entity is currently under investigation. This article summarises the current available data regarding SARS-CoV-2 and the paediatric population, including the spectrum of disease in children, the role of children in virus transmission, and host-virus factors that underpin the unique aspects of SARS-CoV-2 pathogenicity in children.
Subject(s)
COVID-19/transmission , Host-Pathogen Interactions/physiology , SARS-CoV-2/pathogenicity , COVID-19/immunology , COVID-19/virology , Child , Child, Preschool , Female , Humans , Infant , Male , SARS-CoV-2/immunologyABSTRACT
Multidrug-resistant infections present a treatment challenge for pediatric clinicians and these infections have been associated with increased morbidity and mortality. There are very limited published data to support safe and effective treatment regimens for carbapenemase-producing Enterobacteriaceae (CPE) infections, particularly in children. We report the successful treatment of three children with invasive CPE infections using a combination of extended-infusion meropenem and amikacin.
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Aminoglycosides/therapeutic use , Anti-Bacterial Agents/therapeutic use , Carbapenem-Resistant Enterobacteriaceae/isolation & purification , Carbapenems/therapeutic use , Enterobacteriaceae Infections/drug therapy , Aminoglycosides/administration & dosage , Aminoglycosides/pharmacology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Carbapenem-Resistant Enterobacteriaceae/drug effects , Carbapenems/administration & dosage , Carbapenems/pharmacology , Child , Female , Humans , Infant , Male , Microbial Sensitivity TestsABSTRACT
PURPOSE: Antimicrobial resistance (AMR) is of increasing global concern, threatening to undermine recent progress in reducing child and neonatal mortality. Repurposing older antimicrobials is a prominent strategy to combat multidrug-resistant sepsis. A potential agent is fosfomycin, however, there is scarce data regarding its in vitro activity and pharmacokinetics in the paediatric population. METHODOLOGY: We analysed a contemporary, systematically collected archive of community-acquired (CA) and hospital-acquired (HA) paediatric Gram-negative bacteraemia isolates for their susceptibility to fosfomcyin. MICs were determined using agar serial dilution methods and validated by disk diffusion testing where breakpoints are available. Disk diffusion antimicrobial susceptibility testing was also conducted for current empirical therapies (ampicillin, gentamicin, ceftriaxone) and amikacin (proposed in the literature as a new combination empirical therapeutic option). RESULTS: Fosfomycin was highly active against invasive Gram-negative isolates, including 90 â% (202/224) of Enterobacteriaceae and 96 â% (22/23) of Pseudomonas spp. Fosfomycin showed high sensitivity against both CA isolates (94 %, 142/151) and HA isolates (81 %, 78/96; P =0.0015). CA isolates were significantly more likely to be susceptible to fosfomycin than the current first-line empirical therapy (96â % vs 59 â%, P <0.0001). Extended spectrum ß-lactamases (ESBL) production was detected in 34 â% (85/247) of isolates with no significant difference in fosfomycin susceptibility between ESBL-positive or -negative isolates [73/85 (86â %) vs 147/162 (91 â%) respectively, P =0.245]. All isolates were susceptible to a fosfomycin-amikacin combination. CONCLUSION: Gram-negative paediatric bacteraemia isolates are highly susceptible to fosfomycin, which could be combined with aminoglycosides as a new, carbapenem-sparing regimen to achieve excellent coverage to treat antimicrobial-resistant neonatal and paediatric sepsis.
Subject(s)
Anti-Bacterial Agents/pharmacology , Fosfomycin/pharmacology , Gram-Negative Bacteria/drug effects , Bacteremia/drug therapy , Child, Preschool , Community-Acquired Infections/microbiology , Cross Infection/drug therapy , Enterobacteriaceae/drug effects , Enterobacteriaceae Infections/drug therapy , Escherichia coli Infections/drug therapy , Female , Humans , Infant , Infant, Newborn , Klebsiella pneumoniae/drug effects , Male , Microbial Sensitivity Tests , Pseudomonas/drug effects , Sepsis/drug therapy , Sepsis/microbiologyABSTRACT
Background Severe acute malnutrition (SAM) affects nearly 20 million children worldwide and is responsible for up to 1 million deaths per year in children under the age of 5 years. Current WHO guidelines recommend oral amoxicillin for children with uncomplicated malnutrition and parenteral benzylpenicillin and gentamicin for those with complicated malnutrition. Because of cost pressures and increasing antimicrobial resistance, the administration of empirical antibiotics for children with SAM has recently been debated. Methods A systematic review of the current published literature was undertaken to assess 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. Results The initial search found 712 papers, eight of which met the inclusion criteria. Quality assessment of the studies was performed as per the Grading of Recommendations Assessment, Development and Evaluation guidelines. International guidelines and clinical data registries were also reviewed which identified inconsistencies in current first- and second-line therapies and dosing regimens. Conclusion Current evidence supports the continued use of broad-spectrum oral amoxicillin for treating children with uncomplicated SAM as outpatients. There is no strong evidence to justify changing the current parenteral therapy guidelines for children admitted with complicated SAM, although they should be clarified to harmonise the dosage regimen of amoxicillin for the treatment of SAM to 40 mg/kg twice daily, and to continue parenteral antimicrobials beyond 2 days if indicated by the clinical condition.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Severe Acute Malnutrition/drug therapy , Administration, Oral , Amoxicillin/administration & dosage , Amoxicillin/adverse effects , Amoxicillin/economics , Amoxicillin/pharmacokinetics , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/economics , Anti-Bacterial Agents/pharmacokinetics , Child, Preschool , Cost-Benefit Analysis , Drug-Related Side Effects and Adverse Reactions/epidemiology , Guidelines as Topic , Humans , Infant , Injections, Intramuscular , World Health OrganizationABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Cholera/drug therapy , Adolescent , Azithromycin/administration & dosage , Child , Child, Preschool , Drug Resistance, Bacterial , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/pathology , Erythromycin/administration & dosage , Guidelines as Topic , Humans , Infant , Infant, Newborn , Treatment Outcome , Vibrio cholerae/drug effects , World Health OrganizationABSTRACT
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), ß-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 ß-lactamase-producing organisms.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Dysentery, Bacillary/drug therapy , Adolescent , Anti-Bacterial Agents/adverse effects , Child , Child, Preschool , Drug Resistance, Bacterial , Guidelines as Topic , Humans , Infant , Infant, Newborn , World Health OrganizationABSTRACT
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 67â451 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 ß-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.