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Lancet (London, England) Feb 2022Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths,...
BACKGROUND
Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen-drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date.
METHODS
We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen-drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. We present final estimates aggregated to the global and regional level.
FINDINGS
On the basis of our predictive statistical models, there were an estimated 4·95 million (3·62-6·57) deaths associated with bacterial AMR in 2019, including 1·27 million (95% UI 0·911-1·71) deaths attributable to bacterial AMR. At the regional level, we estimated the all-age death rate attributable to resistance to be highest in western sub-Saharan Africa, at 27·3 deaths per 100 000 (20·9-35·3), and lowest in Australasia, at 6·5 deaths (4·3-9·4) per 100 000. Lower respiratory infections accounted for more than 1·5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome. The six leading pathogens for deaths associated with resistance (Escherichia coli, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929 000 (660 000-1 270 000) deaths attributable to AMR and 3·57 million (2·62-4·78) deaths associated with AMR in 2019. One pathogen-drug combination, meticillin-resistant S aureus, caused more than 100 000 deaths attributable to AMR in 2019, while six more each caused 50 000-100 000 deaths: multidrug-resistant excluding extensively drug-resistant tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae.
INTERPRETATION
To our knowledge, this study provides the first comprehensive assessment of the global burden of AMR, as well as an evaluation of the availability of data. AMR is a leading cause of death around the world, with the highest burdens in low-resource settings. Understanding the burden of AMR and the leading pathogen-drug combinations contributing to it is crucial to making informed and location-specific policy decisions, particularly about infection prevention and control programmes, access to essential antibiotics, and research and development of new vaccines and antibiotics. There are serious data gaps in many low-income settings, emphasising the need to expand microbiology laboratory capacity and data collection systems to improve our understanding of this important human health threat.
FUNDING
Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.
Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Global Burden of Disease; Global Health; Humans; Models, Statistical
PubMed: 35065702
DOI: 10.1016/S0140-6736(21)02724-0 -
The Cochrane Database of Systematic... Sep 2015In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this inflammatory response.
OBJECTIVES
To examine the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss and neurological sequelae in people of all ages with acute bacterial meningitis.
SEARCH METHODS
We searched CENTRAL (2015, Issue 1), MEDLINE (1966 to January week 4, 2015), EMBASE (1974 to February 2015), Web of Science (2010 to February 2015), CINAHL (2010 to February 2015) and LILACS (2010 to February 2015).
SELECTION CRITERIA
Randomised controlled trials (RCTs) of corticosteroids for acute bacterial meningitis.
DATA COLLECTION AND ANALYSIS
We scored RCTs for methodological quality. We collected outcomes and adverse effects. We performed subgroup analyses for children and adults, causative organisms, low-income versus high-income countries, time of steroid administration and study quality.
MAIN RESULTS
We included 25 studies involving 4121 participants (2511 children and 1517 adults; 93 mixed population). Four studies were of high quality with no risk of bias, 14 of medium quality and seven of low quality, indicating a moderate risk of bias for the total analysis. Nine studies were performed in low-income countries and 16 in high-income countries.Corticosteroids were associated with a non-significant reduction in mortality (17.8% versus 19.9%; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.80 to 1.01, P value = 0.07). A similar non-significant reduction in mortality was observed in adults receiving corticosteroids (RR 0.74, 95% CI 0.53 to 1.05, P value = 0.09). Corticosteroids were associated with lower rates of severe hearing loss (RR 0.67, 95% CI 0.51 to 0.88), any hearing loss (RR 0.74, 95% CI 0.63 to 0.87) and neurological sequelae (RR 0.83, 95% CI 0.69 to 1.00).Subgroup analyses for causative organisms showed that corticosteroids reduced mortality in Streptococcus pneumoniae (S. pneumoniae) meningitis (RR 0.84, 95% CI 0.72 to 0.98), but not in Haemophilus influenzae (H. influenzae) orNeisseria meningitidis (N. meningitidis) meningitis. Corticosteroids reduced severe hearing loss in children with H. influenzae meningitis (RR 0.34, 95% CI 0.20 to 0.59) but not in children with meningitis due to non-Haemophilus species.In high-income countries, corticosteroids reduced severe hearing loss (RR 0.51, 95% CI 0.35 to 0.73), any hearing loss (RR 0.58, 95% CI 0.45 to 0.73) and short-term neurological sequelae (RR 0.64, 95% CI 0.48 to 0.85). There was no beneficial effect of corticosteroid therapy in low-income countries.Subgroup analysis for study quality showed no effect of corticosteroids on severe hearing loss in high-quality studies.Corticosteroid treatment was associated with an increase in recurrent fever (RR 1.27, 95% CI 1.09 to 1.47), but not with other adverse events.
AUTHORS' CONCLUSIONS
Corticosteroids significantly reduced hearing loss and neurological sequelae, but did not reduce overall mortality. Data support the use of corticosteroids in patients with bacterial meningitis in high-income countries. We found no beneficial effect in low-income countries.
Topics: Acute Disease; Adolescent; Adult; Anti-Inflammatory Agents; Child; Developed Countries; Developing Countries; Dexamethasone; Glucocorticoids; Hearing Loss; Humans; Hydrocortisone; Meningitis, Bacterial; Prednisolone; Randomized Controlled Trials as Topic
PubMed: 26362566
DOI: 10.1002/14651858.CD004405.pub5 -
Clinical Microbiology and Infection :... Sep 2021Bacteria colonizing the upper respiratory tract (URT) of young children play a key role in the pathogenesis of lower respiratory tract infection (LRTI). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bacteria colonizing the upper respiratory tract (URT) of young children play a key role in the pathogenesis of lower respiratory tract infection (LRTI).
OBJECTIVES
To systematically review the literature on the association between bacteria colonizing the URT and LRTI among young children.
DATA SOURCES
MEDLINE, Academic Search Premier, Africa-Wide Information and CINAHL, Scopus and Web of Science.
STUDY ELIGIBILITY CRITERIA
Studies published between 1923 and 2020, investigating URT bacteria from LRTI cases and controls.
PARTICIPANTS
Children under 5 years with and without acute LRTI.
METHODS
Three reviewers independently screened titles, abstracts and full texts. Meta-analysis was done using Mantel-Haenszel fixed- or random-effects models.
RESULTS
Most eligible studies (41/50) tested nasopharyngeal specimens when investigating URT bacteria. Most studies were of cross-sectional design (44/50). Twenty-four studies were performed in children in lower- or lower-middle-income countries (LMICs). There was higher prevalence of Haemophilus influenzae (pooled OR 1.60; 95% CI 1.23-2.07) and Klebsiella spp. (pooled OR 2.04; 95% CI 1.17-3.55) from URT specimens of cases versus controls. We observed a positive association between the detection of Streptococcus pneumoniae from URT specimens and LRTI after excluding studies where there was more antibiotic treatment prior to sampling in cases vs. controls (pooled OR 1.41; 95% CI 1.04-1.90). High density colonization with S. pneumoniae (>6.9 log copies/mL) was associated with an increased risk for LRTI. The associations between both Streptococcus and Haemophilus URT detection and LRTI were supported, at genus level, by 16S rRNA sequencing. Evidence for the role of Moraxella catarrhalis and Staphylococcus aureus was inconclusive.
CONCLUSIONS
Detection of H. influenzae or Klebsiella spp. in the URT was associated with LRTI, while evidence for association with S. pneumoniae was less conclusive. Longitudinal studies assessing URT microbial communities, together with environmental and host factors are needed to better understand pathogenesis of childhood LRTI.
Topics: Bacteria; Child; Child, Preschool; Cross-Sectional Studies; Humans; RNA, Ribosomal, 16S; Respiratory Tract Infections
PubMed: 34111578
DOI: 10.1016/j.cmi.2021.05.034 -
PloS One 2018Bacterial meningitis is a global public health concern, with several responsible etiologic agents that vary by age group and geographical area. The aim of this... (Meta-Analysis)
Meta-Analysis
Bacterial meningitis is a global public health concern, with several responsible etiologic agents that vary by age group and geographical area. The aim of this systematic review and meta-analysis was to assess the etiology of bacterial meningitis in different age groups across global regions. PubMed and EMBASE were systematically searched for English language studies on bacterial meningitis, limited to articles published in the last five years. The methodological quality of the studies was assessed using a customized scoring system. Meta-analyses were conducted to determine the frequency (percentages) of seven bacterial types known to cause meningitis: Escherichia coli, Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, group B Streptococcus agalactiae, Staphylococcus aureus, and Listeria monocytogenes, with results being stratified by six geographical regions as determined by the World Health Organization, and seven age groups. Of the 3227 studies retrieved, 56 were eligible for the final analysis. In all age groups, S. pneumoniae and N. meningitidis were the predominant pathogens in all regions, accounting for 25.1-41.2% and 9.1-36.2% of bacterial meningitis cases, respectively. S. pneumoniae infection was the most common cause of bacterial meningitis in the 'all children' group, ranging from 22.5% (Europe) to 41.1% (Africa), and in all adults ranging from 9.6% (Western Pacific) to 75.2% (Africa). E. coli and S. pneumoniae were the most common pathogens that caused bacterial meningitis in neonates in Africa (17.7% and 20.4%, respectively). N. meningitidis was the most common in children aged ±1-5 years in Europe (47.0%). Due to paucity of data, meta-analyses could not be performed in all age groups for all regions. A clear difference in the weighted frequency of bacterial meningitis cases caused by the different etiological agents was observed between age groups and between geographic regions. These findings may facilitate bacterial meningitis prevention and treatment strategies.
Topics: Age Factors; Databases, Factual; Humans; Meningitis, Bacterial; Neisseria meningitidis; Risk Factors; Streptococcus pneumoniae
PubMed: 29889859
DOI: 10.1371/journal.pone.0198772 -
Influenza and Other Respiratory Viruses Sep 2016Coinfecting bacterial pathogens are a major cause of morbidity and mortality in influenza. However, there remains a paucity of literature on the magnitude of coinfection... (Meta-Analysis)
Meta-Analysis Review
AIM
Coinfecting bacterial pathogens are a major cause of morbidity and mortality in influenza. However, there remains a paucity of literature on the magnitude of coinfection in influenza patients.
METHOD
A systematic search of MeSH, Cochrane Library, Web of Science, SCOPUS, EMBASE, and PubMed was performed. Studies of humans in which all individuals had laboratory confirmed influenza, and all individuals were tested for an array of common bacterial species, met inclusion criteria.
RESULTS
Twenty-seven studies including 3215 participants met all inclusion criteria. Common etiologies were defined from a subset of eight articles. There was high heterogeneity in the results (I(2) = 95%), with reported coinfection rates ranging from 2% to 65%. Although only a subset of papers were responsible for observed heterogeneity, subanalyses and meta-regression analysis found no study characteristic that was significantly associated with coinfection. The most common coinfecting species were Streptococcus pneumoniae and Staphylococcus aureus, which accounted for 35% (95% CI, 14%-56%) and 28% (95% CI, 16%-40%) of infections, respectively; a wide range of other pathogens caused the remaining infections. An assessment of bias suggested that lack of small-study publications may have biased the results.
CONCLUSIONS
The frequency of coinfection in the published studies included in this review suggests that although providers should consider possible bacterial coinfection in all patients hospitalized with influenza, they should not assume all patients are coinfected and be sure to properly treat underlying viral processes. Further, high heterogeneity suggests additional large-scale studies are needed to better understand the etiology of influenza bacterial coinfection.
Topics: Adolescent; Adult; Child; Child, Preschool; Coinfection; Drug Resistance, Bacterial; Female; Hospitalization; Humans; Infant; Infant, Newborn; Influenza, Human; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pneumococcal Infections; Staphylococcal Infections; Streptococcus pneumoniae; Young Adult
PubMed: 27232677
DOI: 10.1111/irv.12398 -
Clinical Microbiology and Infection :... Jan 2022Point-of-care tests could be essential in differentiating bacterial and viral acute community-acquired lower respiratory tract infections and driving antibiotic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Point-of-care tests could be essential in differentiating bacterial and viral acute community-acquired lower respiratory tract infections and driving antibiotic stewardship in the community.
OBJECTIVES
To assess diagnostic test accuracy of point-of-care tests in community settings for acute community-acquired lower respiratory tract infections.
DATA SOURCES
Multiple databases (MEDLINE, EMBASE, Web of Science, Cochrane Library, Open Gray) from inception to 31 May 2021, without language restrictions.
STUDY ELIGIBILITY CRITERIA
Diagnostic test accuracy studies involving patients at primary care, outpatient clinic, emergency department and long-term care facilities with a clinical suspicion of acute community-acquired lower respiratory tract infections. The comparator was any test used as a comparison to the index test. In order not to limit the study inclusion, the comparator was not defined a priori.
ASSESSMENT OF RISK OF BIAS
Four investigators independently extracted data, rated risk of bias, and assessed the quality using QUADAS-2.
METHODS OF DATA SYNTHESIS
The measures of diagnostic test accuracy were calculated with 95% CI.
RESULTS
A total of 421 studies addressed at least one point-of-care test. The diagnostic performance of molecular tests was higher compared with that of rapid diagnostic tests for all the pathogens studied. The accuracy of stand-alone signs and symptoms or biomarkers was poor. Lung ultrasound showed high sensitivity and specificity (90% for both) for the diagnosis of bacterial pneumonia. Rapid antigen-based diagnostic tests for influenza, respiratory syncytial virus, human metapneumovirus, and Streptococcus pneumoniae had sub-optimal sensitivity (range 49%-84%) but high specificity (>80%).
DISCUSSION
Physical examination and host biomarkers are not sufficiently reliable as stand-alone tests to differentiate between bacterial and viral pneumonia. Lung ultrasound shows higher accuracy than chest X-ray for bacterial pneumonia at emergency department. Rapid antigen-based diagnostic tests cannot be considered fully reliable because of high false-negative rates. Overall, molecular tests for all the pathogens considered were found to be the most accurate.
Topics: Bias; Biomarkers; Diagnosis, Differential; Humans; Pneumonia, Bacterial; Pneumonia, Viral; Point-of-Care Testing; Sensitivity and Specificity; Ultrasonography
PubMed: 34601148
DOI: 10.1016/j.cmi.2021.09.025 -
Pneumonia (Nathan Qld.) 2020The etiology of community-acquired pneumonia (CAP) has evolved since the beginning of the antibiotic era. Recent guidelines encourage immediate empiric antibiotic... (Review)
Review
BACKGROUND
The etiology of community-acquired pneumonia (CAP) has evolved since the beginning of the antibiotic era. Recent guidelines encourage immediate empiric antibiotic treatment once a diagnosis of CAP is made. Concerns about treatment recommendations, on the one hand, and antibiotic stewardship, on the other, motivated this review of the medical literature on the etiology of CAP.
METHODS
We conducted a systematic review of English-language literature on the etiology of CAP using methods defined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed using a combination of the keywords 'pneumonia', 'CAP', 'etiology', 'microbiology', 'bacteriology', and 'pathogen'. We examined articles on antibiotics that were develop to treat pneumonia. We reviewed all 'related articles' as well as studies referenced by those that came up in the search. After we excluded articles that did not give sufficient microbiological data or failed to meet other predetermined criteria, 146 studies remained. Data were stratified into diagnostic categories according to the microbiologic studies that were done; results are presented as the percentage in each category of all cases in which an etiology was established.
RESULTS
remains the most common cause of CAP although declining in incidence; this decline has been greater in the US than elsewhere. is the second most common cause of CAP, followed by and Gram negative bacilli. The incidence of all bacteria as causes of CAP has declined because, with routine use of PCR for viruses, the denominator, cases with an established etiology, has increased. Viruses were reported on average in about 10% of cases, but recent PCR-based studies identified a respiratory virus in about 30% of cases of CAP, with substantial rates of viral/bacterial coinfection.
CONCLUSION
The results of this study justify current guidelines for initial empiric treatment of CAP. With pneumococcus and continuing to predominate, efforts at antibiotic stewardship might be enhanced by greater attention to the routine use of sputum Gram stain and culture. Because viral/bacterial coinfection is relatively common, the identification of a virus by PCR does not, by itself, allow for discontinuation of the antibiotic therapy.
PubMed: 33024653
DOI: 10.1186/s41479-020-00074-3 -
Pneumonia (Nathan Qld.) 2018is capable of causing multiple infectious syndromes and occasionally causes outbreaks. The objective of this review is to update prior outbreak reviews, identify... (Review)
Review
BACKGROUND
is capable of causing multiple infectious syndromes and occasionally causes outbreaks. The objective of this review is to update prior outbreak reviews, identify control measures, and comment on transmission.
METHODS
We conducted a review of published outbreaks, defined as at least two linked cases of .
RESULTS
A total of 98 articles (86 respiratory; 8 conjunctivitis; 2 otitis media; 1 surgical site; 1 multiple), detailing 94 unique outbreaks occurring between 1916 to 2017 were identified. Reported serotypes included 1, 2, 3, 4, 5, 7F, 8, 12F, 14, 20, and 23F, and serogroups 6, 9, 15, 19, 22. The median attack rate for pneumococcal outbreaks was 7.0% (Interquartile range: 2.4%, 13%). The median case-fatality ratio was 12.9% (interquartile range: 0%, 29.2%). Age groups most affected by outbreaks were older adults (60.3%) and young adults (34.2%). Outbreaks occurred in crowded settings, such as universities/schools/daycares, military barracks, hospital wards, and long-term care facilities. Of outbreaks that assessed vaccination coverage, low initial vaccination or revaccination coverage was common. Most (73.1%) of reported outbreaks reported non-susceptibility to at least one antibiotic, with non-susceptibility to penicillin (56.0%) and erythromycin (52.6%) being common. Evidence suggests transmission in outbreaks can occur through multiple modes, including carriers, infected individuals, or medical devices. Several cases developed disease shortly after exposure (< 72 h). Respiratory outbreaks used infection prevention (55.6%), prophylactic vaccination (63.5%), and prophylactic antibiotics (50.5%) to prevent future cases. PPSV23 covered all reported outbreak serotypes. PCV13 covered 10 of 16 serotypes. For conjunctival outbreaks, only infection prevention strategies were used.
CONCLUSIONS
To prevent the initial occurrence of respiratory outbreaks, vaccination and revaccination is likely the best preventive measure. Once an outbreak occurs, vaccination and infection-prevention strategies should be utilized. Antibiotic prophylaxis may be considered for high-risk exposed individuals, but development of antibiotic resistance during outbreaks has been reported. The short period between initial exposure and development of disease indicates that pneumococcal colonization is not a prerequisite for pneumococcal respiratory infection.
PubMed: 30410854
DOI: 10.1186/s41479-018-0055-4 -
The Lancet. Neurology Aug 2023Although meningitis is largely preventable, it still causes hundreds of thousands of deaths globally each year. WHO set ambitious goals to reduce meningitis cases by...
BACKGROUND
Although meningitis is largely preventable, it still causes hundreds of thousands of deaths globally each year. WHO set ambitious goals to reduce meningitis cases by 2030, and assessing trends in the global meningitis burden can help track progress and identify gaps in achieving these goals. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we aimed to assess incident cases and deaths due to acute infectious meningitis by aetiology and age from 1990 to 2019, for 204 countries and territories.
METHODS
We modelled meningitis mortality using vital registration, verbal autopsy, sample-based vital registration, and mortality surveillance data. Meningitis morbidity was modelled with a Bayesian compartmental model, using data from the published literature identified by a systematic review, as well as surveillance data, inpatient hospital admissions, health insurance claims, and cause-specific meningitis mortality estimates. For aetiology estimation, data from multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature studies were analysed by use of a network analysis model to estimate the proportion of meningitis deaths and cases attributable to the following aetiologies: Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, group B Streptococcus, Escherichia coli, Klebsiella pneumoniae, Listeria monocytogenes, Staphylococcus aureus, viruses, and a residual other pathogen category.
FINDINGS
In 2019, there were an estimated 236 000 deaths (95% uncertainty interval [UI] 204 000-277 000) and 2·51 million (2·11-2·99) incident cases due to meningitis globally. The burden was greatest in children younger than 5 years, with 112 000 deaths (87 400-145 000) and 1·28 million incident cases (0·947-1·71) in 2019. Age-standardised mortality rates decreased from 7·5 (6·6-8·4) per 100 000 population in 1990 to 3·3 (2·8-3·9) per 100 000 population in 2019. The highest proportion of total all-age meningitis deaths in 2019 was attributable to S pneumoniae (18·1% [17·1-19·2]), followed by N meningitidis (13·6% [12·7-14·4]) and K pneumoniae (12·2% [10·2-14·3]). Between 1990 and 2019, H influenzae showed the largest reduction in the number of deaths among children younger than 5 years (76·5% [69·5-81·8]), followed by N meningitidis (72·3% [64·4-78·5]) and viruses (58·2% [47·1-67·3]).
INTERPRETATION
Substantial progress has been made in reducing meningitis mortality over the past three decades. However, more meningitis-related deaths might be prevented by quickly scaling up immunisation and expanding access to health services. Further reduction in the global meningitis burden should be possible through low-cost multivalent vaccines, increased access to accurate and rapid diagnostic assays, enhanced surveillance, and early treatment.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Child; Humans; Global Burden of Disease; Bayes Theorem; Meningitis; Risk Factors; Global Health
PubMed: 37479374
DOI: 10.1016/S1474-4422(23)00195-3 -
Clinical Microbiology and Infection :... Mar 2020The FilmArray® meningitis/encephalitis (ME) panel is a multiplex PCR assay which can detect the most commonly identified pathogens in central nervous system infections.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The FilmArray® meningitis/encephalitis (ME) panel is a multiplex PCR assay which can detect the most commonly identified pathogens in central nervous system infections. It significantly decreases the time to diagnosis of ME and data has yielded several positive outcomes. However, in part, reports of both false positive and false negative detections have resulted in concerns about adoption.
OBJECTIVES
The aim was to evaluate the ME panel in a diagnostic test accuracy review.
DATA SOURCES
The PubMed and EMBASE databases were systematically searched through May 2019.
STUDY ELIGIBILITY CRITERIA
Eligible studies were those providing sensitivity and specificity data for the ME panel compared with a reference standard. Studies providing details on false positive and false negative results of the panel as well as further investigation (adjudication) of the discordant results between the panel and comparator assays were included and assessed separately.
PARTICIPANTS
Patients with suspected ME for whom a panel was ordered were included.
METHODS
The ME panel was compared to reference standard methods for diagnosing community-acquired ME. We performed a meta-analysis and calculated the summary sensitivity and specificity of the ME panel. Moreover, we evaluated the false positive and false negative results of the panel.
RESULTS
Thirteen studies (3764 patients) were included in the review and 8 of them (3059 patients) were pooled in a meta-analysis. The summary estimates of sensitivity and specificity with 95% confidence intervals (CI) was 90% (95% CI 86-93%) and 97% (95% CI 94-99%), respectively. When we looked specifically at studies that assessed further the false positive and false negative results, false positive detections were 11.4% and 4% before and after adjudication, respectively. The highest proportion of false positive was observed for Streptococcus pneumoniae followed by Streptococcus agalactiae. False negative isolates were 2.2% and 1.5% before and after adjudication, respectively. Herpes simplex virus 1 and 2, enterovirus and Cryptococcus neoformans/gattii had the highest proportions of false negative determinations. False negative C. neoformans/gattii were mostly patients with positive antigen titres, on treatment or cleared disease.
CONCLUSIONS
The currently available literature suggests that the ME panel has high diagnostic accuracy. However, the decision for implementation should be individualized based on the needs of the patient population, the capabilities of the laboratory, and the knowledge of the healthcare providers that will utilize the test.
Topics: Encephalitis; Humans; Meningitis; Multiplex Polymerase Chain Reaction; Publication Bias; ROC Curve; Reagent Kits, Diagnostic; Reproducibility of Results; Sensitivity and Specificity
PubMed: 31760115
DOI: 10.1016/j.cmi.2019.11.016