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The Journal of Antimicrobial... Feb 2015Antibiotics are commonly classified into bactericidal and bacteriostatic agents based on their antimicrobial action. We aimed to assess whether this distinction is... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Antibiotics are commonly classified into bactericidal and bacteriostatic agents based on their antimicrobial action. We aimed to assess whether this distinction is clinically relevant.
METHODS
OVID MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL) and relevant references and conference proceedings using the Web of Science and Scopus databases were searched for randomized controlled trials comparing bactericidal with bacteriostatic antibiotics for treatment of severe infections. Main outcome measures were clinical cure rates and overall mortality. Abstracts of studies selected in the database search were screened by one reviewer; full-text screening and data extraction were performed by three independent reviewers.
RESULTS
Thirty-three studies were included. Approximately half of patients were treated with bacteriostatic monotherapy. Infections covered were pneumonia (n=13), skin and soft tissue infections (n=8), intra-abdominal infections (n=4) and others (n=8). Neither clinical cure rates [risk ratio (RR), 0.99; 95% CI, 0.97-1.01; P=0.11] nor mortality rates (RR, 0.91; 95% CI, 0.76-1.08; P=0.28) were different between patients treated with bactericidal drugs and those treated with bacteriostatic drugs. Subgroup analyses showed a benefit for clinical cure rates associated with linezolid and increased mortality associated with tigecycline. In meta-regression, clinical cure rates remained higher in patients treated with linezolid (P=0.01); tigecycline displayed a close to significant association with increased mortality (P=0.05) if compared with other bacteriostatic agents.
CONCLUSIONS
The categorization of antibiotics into bacteriostatic and bactericidal is unlikely to be relevant in clinical practice if used for abdominal infections, skin and soft tissue infections and pneumonia. Because we were not able to include studies on meningitis, endocarditis or neutropenia, no conclusion regarding these diseases can be drawn.
Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Recurrence; Severity of Illness Index; Treatment Outcome
PubMed: 25266070
DOI: 10.1093/jac/dku379 -
The Cochrane Database of Systematic... Oct 2012Traditional epidural techniques have been associated with prolonged labour, use of oxytocin augmentation and increased incidence of instrumental vaginal delivery. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Traditional epidural techniques have been associated with prolonged labour, use of oxytocin augmentation and increased incidence of instrumental vaginal delivery. The combined spinal-epidural (CSE) technique has been introduced in an attempt to reduce these adverse effects. CSE is believed to improve maternal mobility during labour and provide more rapid onset of analgesia than epidural analgesia, which could contribute to increased maternal satisfaction.
OBJECTIVES
To assess the relative effects of CSE versus epidural analgesia during labour.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 September 2011) and reference lists of retrieved studies. We updated the search on 30 June 2012 and added the results to the awaiting classification section.
SELECTION CRITERIA
All published randomised controlled trials (RCTs) involving a comparison of CSE with epidural analgesia initiated for women in the first stage of labour. Cluster-randomised trials were considered for inclusion. Quasi RCTs and cross-over trials were not considered for inclusion in this review.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed the trials identified from the searches for inclusion, assessed trial quality and extracted the data. Data were checked for accuracy.
MAIN RESULTS
Twenty-seven trials involving 3274 women met our inclusion criteria. Twenty-six outcomes in two sets of comparisons involving CSE versus traditional epidurals and CSE versus low-dose epidural techniques were analysed.Of the CSE versus traditional epidural analyses five outcomes showed a significant difference. CSE was more favourable in relation to speed of onset of analgesia from time of injection (mean difference (MD) -2.87 minutes; 95% confidence interval (CI) -5.07 to -0.67; two trials, 129 women); the need for rescue analgesia (risk ratio (RR) 0.31; 95% CI 0.14 to 0.70; one trial, 42 women); urinary retention (RR 0.86; 95% CI 0.79 to 0.95; one trial, 704 women); and rate of instrumental delivery (RR 0.81; 95% CI 0.67 to 0.97; six trials, 1015 women). Traditional epidural was more favourable in relation to umbilical venous pH (MD -0.03; 95% CI -0.06 to -0.00; one trial, 55 women). There were no data on maternal satisfaction, blood patch for post dural puncture headache, respiratory depression, umbilical cord pH, rare neurological complications, analgesia for caesarean section after analgesic intervention or any economic/use of resources outcomes for this comparison. No differences between CSE and traditional epidural were identified for mobilisation in labour, the need for labour augmentation, the rate of caesarean birth, incidence of post dural puncture headache, maternal hypotension, neonatal Apgar scores or umbilical arterial pH.For CSE versus low-dose epidurals, three outcomes were statistically significant. Two of these reflected a faster onset of effective analgesia from time of injection with CSE and the third was of more pruritus with CSE compared to low-dose epidural (average RR 1.80; 95% CI 1.22 to 2.65; 11 trials, 959 women; random-effects, T² = 0.26, I² = 84%). There was no significant difference in maternal satisfaction (average RR 1.01; 95% CI 0.98 to 1.05; seven trials, 520 women; random-effects, T² = 0.00, I² = 45%). There were no data on respiratory depression, maternal sedation or the need for labour augmentation. No differences between CSE and low-dose epidural were identified for need for rescue analgesia, mobilisation in labour, incidence of post dural puncture headache, known dural tap, blood patch for post dural headache, urinary retention, nausea/vomiting, hypotension, headache, the need for labour augmentation, mode of delivery, umbilical pH, Apgar score or admissions to the neonatal unit.
AUTHORS' CONCLUSIONS
There appears to be little basis for offering CSE over epidurals in labour, with no difference in overall maternal satisfaction despite a slightly faster onset with CSE and conversely less pruritus with low-dose epidurals. There was no difference in ability to mobilise, maternal hypotension, rate of caesarean birth or neonatal outcome. However, the significantly higher incidence of urinary retention, rescue interventions and instrumental deliveries with traditional techniques would favour the use of low-dose epidurals. It is not possible to draw any meaningful conclusions regarding rare complications such as nerve injury and meningitis.
Topics: Analgesia, Epidural; Analgesia, Obstetrical; Anesthesia, Epidural; Anesthesia, Spinal; Female; Humans; Labor, Obstetric; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 23076897
DOI: 10.1002/14651858.CD003401.pub3 -
Neonatology 2021The diagnosis of neonatal meningitis often rests on microscopic and biochemical findings in the cerebrospinal fluid (CSF). There is ongoing uncertainty about age-related...
BACKGROUND
The diagnosis of neonatal meningitis often rests on microscopic and biochemical findings in the cerebrospinal fluid (CSF). There is ongoing uncertainty about age-related normal values for CSF findings in neonates, and many previous studies have included infants in whom antibiotics were administered before lumbar puncture or in whom viral meningitis was not excluded.
METHODS
A systematic search was done using MEDLINE and EMBASE to identify original studies which investigated CSF normal values in either healthy neonates or febrile neonates in whom bacterial and viral meningitis were reliably excluded.
RESULTS
We identified seven studies investigating 270 term and 96 preterm neonates. There were minimal differences between preterm and term neonates in the CSF white blood cell (WBC) count and glucose concentration. In contrast, the CSF neutrophil count and protein concentration were influenced by gestational and chronological age. In the four studies that reported individual patient data, in 95% of cases the CSF WBC count was <12 cells/μL in preterm and <10 cells/μL in term neonates, the neutrophil count was <16 and 8 cells/μL, and the protein concentration was <210 and 110 mg/dL, respectively.
CONCLUSION
The normal range for CSF parameters in neonates is different to that in older infants, and some parameters are influenced by gestational and chronological age. CSF parameters alone are not sufficiently reliable to exclude meningitis.
Topics: Aged; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Leukocyte Count; Meningitis; Reference Values; Retrospective Studies; Spinal Puncture
PubMed: 34818234
DOI: 10.1159/000517630 -
Virology Journal Mar 2008The morbidity and mortality associated with cytomegalovirus (CMV) infection in immunocompromised patients (especially in HIV-infected patients and transplant... (Review)
Review
BACKGROUND
The morbidity and mortality associated with cytomegalovirus (CMV) infection in immunocompromised patients (especially in HIV-infected patients and transplant recipients), as well as with congenital CMV infection are well known. In contrast, relatively little attention has been paid to the morbidity and mortality that CMV infection may cause in immunocompetent patients.
METHODS
We reviewed the evidence associated with severe manifestations of CMV infection in apparently immunocompetent patients and the potential role of antiviral treatment for these infections. We searched in PubMed, Scopus, and the Cochrane Library for the period of 1950-2007 to identify relevant articles.
RESULTS
We retrieved 89 articles reporting on severe CMV infection in 290 immunocompetent adults. Among these reports, the gastrointestinal tract (colitis) and the central nervous system (meningitis, encephalitis, transverse myelitis) were the most frequent sites of severe CMV infection. Manifestations from other organ-systems included haematological disorders (haemolytic anaemia, thrombocytopenia), thrombosis of the venous or arterial vascular system, ocular involvement (uveitis), and lung disease (pneumonitis). The clinical practice reported in the literature has been to prescribe antiviral treatment for the most severe manifestations of monophasic meningoencephalitis (seizures and coma), ocular involvement, and lung involvement due to CMV.
CONCLUSION
Severe life-threatening complications of CMV infection in immunocompetent patients may not be as rare as previously thought.
Topics: Adolescent; Adult; Aged; Central Nervous System Viral Diseases; Cytomegalovirus; Cytomegalovirus Infections; Female; Gastrointestinal Diseases; Humans; Immunocompetence; Infant; Male; Middle Aged; Pregnancy; Pregnancy Complications, Infectious; Severity of Illness Index
PubMed: 18371229
DOI: 10.1186/1743-422X-5-47 -
The Cochrane Database of Systematic... Aug 2018Tuberculosis (TB) is the world's leading infectious cause of death. Extrapulmonary TB accounts for 15% of TB cases, but the proportion is increasing, and over half a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tuberculosis (TB) is the world's leading infectious cause of death. Extrapulmonary TB accounts for 15% of TB cases, but the proportion is increasing, and over half a million people were newly diagnosed with rifampicin-resistant TB in 2016. Xpert MTB/RIF (Xpert) is a World Health Organization (WHO)-recommended, rapid, automated, nucleic acid amplification assay that is used widely for simultaneous detection of Mycobacterium tuberculosis complex and rifampicin resistance in sputum specimens. This Cochrane Review assessed the accuracy of Xpert in extrapulmonary specimens.
OBJECTIVES
To determine the diagnostic accuracy of Xpert a) for extrapulmonary TB by site of disease in people presumed to have extrapulmonary TB; and b) for rifampicin resistance in people presumed to have extrapulmonary TB.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature (LILACS), Scopus, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number (ISRCTN) Registry, and ProQuest up to 7 August 2017 without language restriction.
SELECTION CRITERIA
We included diagnostic accuracy studies of Xpert in people presumed to have extrapulmonary TB. We included TB meningitis and pleural, lymph node, bone or joint, genitourinary, peritoneal, pericardial, and disseminated TB. We used culture as the reference standard. For pleural TB, we also included a composite reference standard, which defined a positive result as the presence of granulomatous inflammation or a positive culture result. For rifampicin resistance, we used culture-based drug susceptibility testing or MTBDRplus as the reference standard.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data, assessed risk of bias and applicability using the QUADAS-2 tool. We determined pooled predicted sensitivity and specificity for TB, grouped by type of extrapulmonary specimen, and for rifampicin resistance. For TB detection, we used a bivariate random-effects model. Recognizing that use of culture may lead to misclassification of cases of extrapulmonary TB as 'not TB' owing to the paucibacillary nature of the disease, we adjusted accuracy estimates by applying a latent class meta-analysis model. For rifampicin resistance detection, we performed univariate meta-analyses for sensitivity and specificity separately to include studies in which no rifampicin resistance was detected. We used theoretical populations with an assumed prevalence to provide illustrative numbers of patients with false positive and false negative results.
MAIN RESULTS
We included 66 unique studies that evaluated 16,213 specimens for detection of extrapulmonary TB and rifampicin resistance. We identified only one study that evaluated the newest test version, Xpert MTB/RIF Ultra (Ultra), for TB meningitis. Fifty studies (76%) took place in low- or middle-income countries. Risk of bias was low for patient selection, index test, and flow and timing domains and was high or unclear for the reference standard domain (most of these studies decontaminated sterile specimens before culture inoculation). Regarding applicability, in the patient selection domain, we scored high or unclear concern for most studies because either patients were evaluated exclusively as inpatients at tertiary care centres, or we were not sure about the clinical settings.Pooled Xpert sensitivity (defined by culture) varied across different types of specimens (31% in pleural tissue to 97% in bone or joint fluid); Xpert sensitivity was > 80% in urine and bone or joint fluid and tissue. Pooled Xpert specificity (defined by culture) varied less than sensitivity (82% in bone or joint tissue to 99% in pleural fluid and urine). Xpert specificity was ≥ 98% in cerebrospinal fluid, pleural fluid, urine, and peritoneal fluid.Xpert testing in cerebrospinal fluidXpert pooled sensitivity and specificity (95% credible interval (CrI)) against culture were 71.1% (60.9% to 80.4%) and 98.0% (97.0% to 98.8%), respectively (29 studies, 3774 specimens; moderate-certainty evidence).For a population of 1000 people where 100 have TB meningitis on culture, 89 would be Xpert-positive: of these, 18 (20%) would not have TB (false-positives); and 911 would be Xpert-negative: of these, 29 (3%) would have TB (false-negatives).For TB meningitis, ultra sensitivity and specificity against culture (95% confidence interval (CI)) were 90% (55% to 100%) and 90% (83% to 95%), respectively (one study, 129 participants).Xpert testing in pleural fluidXpert pooled sensitivity and specificity (95% CrI) against culture were 50.9% (39.7% to 62.8%) and 99.2% (98.2% to 99.7%), respectively (27 studies, 4006 specimens; low-certainty evidence).For a population of 1000 people where 150 have pleural TB on culture, 83 would be Xpert-positive: of these, seven (8%) would not have TB (false-positives); and 917 would be Xpert-negative: of these, 74 (8%) would have TB (false-negatives).Xpert testing in urineXpert pooled sensitivity and specificity (95% CrI) against culture were 82.7% (69.6% to 91.1%) and 98.7% (94.8% to 99.7%), respectively (13 studies, 1199 specimens; moderate-certainty evidence).For a population of 1000 people where 70 have genitourinary TB on culture, 70 would be Xpert-positive: of these, 12 (17%) would not have TB (false-positives); and 930 would be Xpert-negative: of these, 12 (1%) would have TB (false-negatives).Xpert testing for rifampicin resistanceXpert pooled sensitivity (20 studies, 148 specimens) and specificity (39 studies, 1088 specimens) were 95.0% (89.7% to 97.9%) and 98.7% (97.8% to 99.4%), respectively (high-certainty evidence).For a population of 1000 people where 120 have rifampicin-resistant TB, 125 would be positive for rifampicin-resistant TB: of these, 11 (9%) would not have rifampicin resistance (false-positives); and 875 would be negative for rifampicin-resistant TB: of these, 6 (1%) would have rifampicin resistance (false-negatives).For lymph node TB, the accuracy of culture, the reference standard used, presented a greater concern for bias than in other forms of extrapulmonary TB.
AUTHORS' CONCLUSIONS
In people presumed to have extrapulmonary TB, Xpert may be helpful in confirming the diagnosis. Xpert sensitivity varies across different extrapulmonary specimens, while for most specimens, specificity is high, the test rarely yielding a positive result for people without TB (defined by culture). Xpert is accurate for detection of rifampicin resistance. For people with presumed TB meningitis, treatment should be based on clinical judgement, and not withheld solely on an Xpert result, as is common practice when culture results are negative.
Topics: Antibiotics, Antitubercular; Bacterial Proteins; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; False Negative Reactions; False Positive Reactions; Humans; Mycobacterium tuberculosis; Reagent Kits, Diagnostic; Reference Standards; Rifampin; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Meningeal
PubMed: 30148542
DOI: 10.1002/14651858.CD012768.pub2 -
Infectious Diseases and Therapy Dec 2021A systematic literature review was undertaken to evaluate real-world use of ceftazidime-avibactam for infections due to aerobic Gram-negative organisms in adults with... (Review)
Review
INTRODUCTION
A systematic literature review was undertaken to evaluate real-world use of ceftazidime-avibactam for infections due to aerobic Gram-negative organisms in adults with limited treatment options.
METHODS
Literature searches retrieved peer-reviewed publications and abstracts from major international infectious disease congresses from January 2015 to February 2021. Results were screened using pre-defined criteria to limit the dataset to relevant publications (notable exclusions were paediatric data and outcomes data for bacteria intrinsically resistant to ceftazidime-avibactam). Data for included publications were subjected to qualitative synthesis.
RESULTS
Seventy-three relevant publications (62 peer-reviewed articles; 10 abstracts) comprising 1926 patients treated with ceftazidime-avibactam (either alone or combined with other antimicrobials) and 1114 comparator/control patients were identified. All patients were hospitalised for serious illness and most had multiple comorbidities. The most common infections were pneumonia, bacteraemia, and skin/soft tissue, urinary tract, or abdominal infections; smaller numbers of patients with meningitis, febrile neutropenia, osteomyelitis, and cystic fibrosis were also included. Carbapenem-resistant or carbapenemase-producing Enterobacterales (CRE; n = 1718) and carbapenem-resistant, multidrug-resistant (MDR), and extensively drug-resistant Pseudomonas aeruginosa (n = 150) were the most common pathogens. Most publications reported positive outcomes for ceftazidime-avibactam treatment (clinical success rates ranged from 45 to 100% and reported 30-day mortality from 0 to 63%), which were statistically superior versus comparators in some studies. ceftazidime-avibactam resistance emergence occurred infrequently and mostly in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains.
CONCLUSION
This review provides qualitative evidence of successful use of ceftazidime-avibactam for the treatment of hospitalised patients with CRE and MDR P. aeruginosa infections with limited treatment options.
PubMed: 34379310
DOI: 10.1007/s40121-021-00507-6 -
Clinical Infectious Diseases : An... Apr 2021Cryptococcal antigen (CrAg) detection could direct the timely initiation of antifungal therapy. We searched MEDLINE and Embase for studies where CrAg detection in... (Meta-Analysis)
Meta-Analysis
Cryptococcal Antigen in Serum and Cerebrospinal Fluid for Detecting Cryptococcal Meningitis in Adults Living With Human Immunodeficiency Virus: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies.
Cryptococcal antigen (CrAg) detection could direct the timely initiation of antifungal therapy. We searched MEDLINE and Embase for studies where CrAg detection in serum/cerebrospinal fluid (CSF) and CSF fungal culture were done on adults living with human immunodeficiency virus (HIV) who had suspected cryptococcal meningitis (CM). With Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), we evaluated the risk of bias in 11 included studies with 3600 participants, and used a random-effects meta-analysis to obtain summary sensitivity and specificity of serum and CSF CrAg, as well as agreement between CSF CrAg and CSF culture. Summary sensitivity and specificity of serum CrAg were 99.7% (97.4-100) and 94.1% (88.3-98.1), respectively, and summary sensitivity and specificity of CSF CrAg were 98.8% (96.2-99.6) and 99.3% (96.7-99.9), respectively. Agreement between CSF CrAg and CSF culture was 98% (97-99). In adults living with HIV who have CM symptoms, serum CrAg negativity may rule out CM, while positivity should prompt induction antifungal therapy if lumbar puncture is not feasible. In a first episode of CM, CSF CrAg positivity is diagnostic.
Topics: AIDS-Related Opportunistic Infections; Adult; Antigens, Fungal; Cryptococcus; Diagnostic Tests, Routine; HIV; HIV Infections; Humans; Meningitis, Cryptococcal
PubMed: 32829406
DOI: 10.1093/cid/ciaa1243 -
The Lancet. Infectious Diseases Apr 2010In patients with HIV-1 infection who are starting combination antiretroviral therapy (ART), the incidence of immune reconstitution inflammatory syndrome (IRIS) is not... (Meta-Analysis)
Meta-Analysis Review
In patients with HIV-1 infection who are starting combination antiretroviral therapy (ART), the incidence of immune reconstitution inflammatory syndrome (IRIS) is not well defined. We did a meta-analysis to establish the incidence and lethality of the syndrome in patients with a range of previously diagnosed opportunistic infections, and examined the relation between occurrence and the degree of immunodeficiency. Systematic review identified 54 cohort studies of 13 103 patients starting ART, of whom 1699 developed IRIS. We calculated pooled cumulative incidences with 95% credibility intervals (CrI) by Bayesian methods and did a random-effects metaregression to analyse the relation between CD4 cell count and incidence of IRIS. In patients with previously diagnosed AIDS-defining illnesses, IRIS developed in 37.7% (95% CrI 26.6-49.4) of those with cytomegalovirus retinitis, 19.5% (6.7-44.8) of those with cryptococcal meningitis, 15.7% (9.7-24.5) of those with tuberculosis, 16.7% (2.3-50.7) of those with progressive multifocal leukoencephalopathy, and 6.4% (1.2-24.7) of those with Kaposi's sarcoma, and 12.2% (6.8-19.6) of those with herpes zoster. 16.1% (11.1-22.9) of unselected patients starting ART developed any type of IRIS. 4.5% (2.1-8.6) of patients with any type of IRIS died, 3.2% (0.7-9.2) of those with tuberculosis-associated IRIS died, and 20.8% (5.0-52.7) of those with cryptococcal meningitis died. Metaregression analyses showed that the risk of IRIS is associated with CD4 cell count at the start of ART, with a high risk in patients with fewer than 50 cells per microL. Occurrence of IRIS might therefore be reduced by initiation of ART before immunodeficiency becomes advanced.
Topics: Anti-HIV Agents; Anti-Retroviral Agents; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Probability; Regression Analysis
PubMed: 20334848
DOI: 10.1016/S1473-3099(10)70026-8 -
Journal of Global Health Dec 2015Respiratory syncytial virus (RSV) is the most common pathogen identified in young children with acute lower respiratory infection (ALRI) as well as an important cause of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Respiratory syncytial virus (RSV) is the most common pathogen identified in young children with acute lower respiratory infection (ALRI) as well as an important cause of hospital admission. The high incidence of RSV infection and its potential severe outcome make it important to identify and prioritise children who are at higher risk of developing RSV-associated ALRI. We aimed to identify risk factors for RSV-associated ALRI in young children.
METHODS
We carried out a systematic literature review across 4 databases and obtained unpublished studies from RSV Global Epidemiology Network (RSV GEN) collaborators. Quality of all eligible studies was assessed according to modified GRADE criteria. We conducted meta-analyses to estimate odds ratios with 95% confidence intervals (CI) for individual risk factors.
RESULTS
We identified 20 studies (3 were unpublished data) with "good quality" that investigated 18 risk factors for RSV-associated ALRI in children younger than five years old. Among them, 8 risk factors were significantly associated with RSV-associated ALRI. The meta-estimates of their odds ratio (ORs) with corresponding 95% confidence intervals (CI) are prematurity 1.96 (95% CI 1.44-2.67), low birth weight 1.91 (95% CI 1.45-2.53), being male 1.23 (95% CI 1.13-1.33), having siblings 1.60 (95% CI 1.32-1.95), maternal smoking 1.36 (95% CI 1.24-1.50), history of atopy 1.47 (95% CI 1.16-1.87), no breastfeeding 2.24 (95% CI 1.56-3.20) and crowding 1.94 (95% CI 1.29-2.93). Although there were insufficient studies available to generate a meta-estimate for HIV, all articles (irrespective of quality scores) reported significant associations between HIV and RSV-associated ALRI.
CONCLUSIONS
This study presents a comprehensive report of the strength of association between various socio-demographic risk factors and RSV-associated ALRI in young children. Some of these amenable risk factors are similar to those that have been identified for (all cause) ALRI and thus, in addition to the future impact of novel RSV vaccines, national action against ALRI risk factors as part of national control programmes can be expected to reduce burden of disease from RSV. Further research which identifies, accesses and analyses additional unpublished RSV data sets could further improve the precision of these estimates.
Topics: Acute Disease; Child, Preschool; Developing Countries; Female; Global Health; Hospitalization; Humans; Incidence; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Male; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory Tract Infections; Risk Factors
PubMed: 26682048
DOI: 10.7189/jogh.05.020416 -
The Cochrane Database of Systematic... Sep 2022Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert... (Review)
Review
BACKGROUND
Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects Mycobacterium tuberculosis complex and rifampicin resistance. We previously published a Cochrane Review 'Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for tuberculosis disease and rifampicin resistance in children'. The current review updates evidence on the diagnostic accuracy of Xpert Ultra in children presumed to have tuberculosis disease. Parts of this review update informed the 2022 WHO updated guidance on management of tuberculosis in children and adolescents.
OBJECTIVES
To assess the diagnostic accuracy of Xpert Ultra for detecting: pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance, in children with presumed tuberculosis. Secondary objectives To investigate potential sources of heterogeneity in accuracy estimates. For detection of tuberculosis, we considered age, comorbidity (HIV, severe pneumonia, and severe malnutrition), and specimen type as potential sources. To summarize the frequency of Xpert Ultra trace results.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, three other databases, and three trial registers without language restrictions to 9 March 2021.
SELECTION CRITERIA
Cross-sectional and cohort studies and randomized trials that evaluated Xpert Ultra in HIV-positive and HIV-negative children under 15 years of age. We included ongoing studies that helped us address the review objectives. We included studies evaluating sputum, gastric, stool, or nasopharyngeal specimens (pulmonary tuberculosis), cerebrospinal fluid (tuberculous meningitis), and fine needle aspirate or surgical biopsy tissue (lymph node tuberculosis). For detecting tuberculosis, reference standards were microbiological (culture) or composite reference standard; for stool, we also included Xpert Ultra performed on a routine respiratory specimen. For detecting rifampicin resistance, reference standards were drug susceptibility testing or MTBDRplus.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and, using QUADAS-2, assessed methodological quality judging risk of bias separately for each target condition and reference standard. For each target condition, we used the bivariate model to estimate summary sensitivity and specificity with 95% confidence intervals (CIs). We stratified all analyses by type of reference standard. We summarized the frequency of Xpert Ultra trace results; trace represents detection of a very low quantity of Mycobacterium tuberculosis DNA. We assessed certainty of evidence using GRADE.
MAIN RESULTS
We identified 14 studies (11 new studies since the previous review). For detection of pulmonary tuberculosis, 335 data sets (25,937 participants) were available for analysis. We did not identify any studies that evaluated Xpert Ultra accuracy for tuberculous meningitis or lymph node tuberculosis. Three studies evaluated Xpert Ultra for detection of rifampicin resistance. Ten studies (71%) took place in countries with a high tuberculosis burden based on WHO classification. Overall, risk of bias was low. Detection of pulmonary tuberculosis Sputum, 5 studies Xpert Ultra summary sensitivity verified by culture was 75.3% (95% CI 64.3 to 83.8; 127 participants; high-certainty evidence), and specificity was 97.1% (95% CI 94.7 to 98.5; 1054 participants; high-certainty evidence). Gastric aspirate, 7 studies Xpert Ultra summary sensitivity verified by culture was 70.4% (95% CI 53.9 to 82.9; 120 participants; moderate-certainty evidence), and specificity was 94.1% (95% CI 84.8 to 97.8; 870 participants; moderate-certainty evidence). Stool, 6 studies Xpert Ultra summary sensitivity verified by culture was 56.1% (95% CI 39.1 to 71.7; 200 participants; moderate-certainty evidence), and specificity was 98.0% (95% CI 93.3 to 99.4; 1232 participants; high certainty-evidence). Nasopharyngeal aspirate, 4 studies Xpert Ultra summary sensitivity verified by culture was 43.7% (95% CI 26.7 to 62.2; 46 participants; very low-certainty evidence), and specificity was 97.5% (95% CI 93.6 to 99.0; 489 participants; high-certainty evidence). Xpert Ultra sensitivity was lower against a composite than a culture reference standard for all specimen types other than nasopharyngeal aspirate, while specificity was similar against both reference standards. Interpretation of results In theory, for a population of 1000 children: • where 100 have pulmonary tuberculosis in sputum (by culture): - 101 would be Xpert Ultra-positive, and of these, 26 (26%) would not have pulmonary tuberculosis (false positive); and - 899 would be Xpert Ultra-negative, and of these, 25 (3%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in gastric aspirate (by culture): - 123 would be Xpert Ultra-positive, and of these, 53 (43%) would not have pulmonary tuberculosis (false positive); and - 877 would be Xpert Ultra-negative, and of these, 30 (3%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in stool (by culture): - 74 would be Xpert Ultra-positive, and of these, 18 (24%) would not have pulmonary tuberculosis (false positive); and - 926 would be Xpert Ultra-negative, and of these, 44 (5%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in nasopharyngeal aspirate (by culture): - 66 would be Xpert Ultra-positive, and of these, 22 (33%) would not have pulmonary tuberculosis (false positive); and - 934 would be Xpert Ultra-negative, and of these, 56 (6%) would have tuberculosis (false negative). Detection of rifampicin resistance Xpert Ultra sensitivity was 100% (3 studies, 3 participants; very low-certainty evidence), and specificity range was 97% to 100% (3 studies, 128 participants; low-certainty evidence). Trace results Xpert Ultra trace results, regarded as positive in children by WHO standards, were common. Xpert Ultra specificity remained high in children, despite the frequency of trace results.
AUTHORS' CONCLUSIONS
We found Xpert Ultra sensitivity to vary by specimen type, with sputum having the highest sensitivity, followed by gastric aspirate and stool. Nasopharyngeal aspirate had the lowest sensitivity. Xpert Ultra specificity was high against both microbiological and composite reference standards. However, the evidence base is still limited, and findings may be imprecise and vary by study setting. Although we found Xpert Ultra accurate for detection of rifampicin resistance, results were based on a very small number of studies that included only three children with rifampicin resistance. Therefore, findings should be interpreted with caution. Our findings provide support for the use of Xpert Ultra as an initial rapid molecular diagnostic in children being evaluated for tuberculosis.
Topics: Adolescent; Antibiotics, Antitubercular; Child; Cross-Sectional Studies; HIV Infections; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Rifampin; Sensitivity and Specificity; Sputum; Tuberculosis, Lymph Node; Tuberculosis, Meningeal; Tuberculosis, Pulmonary
PubMed: 36065889
DOI: 10.1002/14651858.CD013359.pub3