<i>Mycobacterium tuberculosis</i>and Rifampin Resistance, United Kingdom

Sam, I‐Ching; Drobniewski, Francis; More, P G; Kemp, Melanie; Brown, Timothy J.

doi:10.3201/eid1205.041339

Cited by 33 publications

(33 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After the first phase of screening, 557 papers were identified as being potentially eligible for the review (Figure 1). A total of 56 studies contained sufficient information on the performance of the rapid diagnostic tests to be included in the review. These studies were divided into five categories, depending on the rapid test investigated: INNO-LiPA studies (n = 9), 33,35,[51][52][53][54][55][56][57] GeneXpert studies (n = 6), 29,38,[58][59][60][61] MTBDRplus …”

Section: Details Of Included and Excluded Studiesmentioning

confidence: 99%

Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis

Drobniewski

Cooke

Jordan

et al. 2015

Health Technology Assessment

Self Cite

View full text Add to dashboard Cite

BackgroundDrug-resistant tuberculosis (TB), especially multidrug-resistant (MDR, resistance to rifampicin and isoniazid) disease, is associated with a worse patient outcome. Drug resistance diagnosed using microbiological culture takes days to weeks, as TB bacteria grow slowly. Rapid molecular tests for drug resistance detection (1 day) are commercially available and may promote faster initiation of appropriate treatment.ObjectivesTo (1) conduct a systematic review of evidence regarding diagnostic accuracy of molecular genetic tests for drug resistance, (2) conduct a health-economic evaluation of screening and diagnostic strategies, including comparison of alternative models of service provision and assessment of the value of targeting rapid testing at high-risk subgroups, and (3) construct a transmission-dynamic mathematical model that translates the estimates of diagnostic accuracy into estimates of clinical impact.Review methods and data sourcesA standardised search strategy identified relevant studies from EMBASE, PubMed, MEDLINE, Bioscience Information Service (BIOSIS), System for Information on Grey Literature in Europe Social Policy & Practice (SIGLE) and Web of Science, published between 1 January 2000 and 15 August 2013. Additional ‘grey’ sources were included. Quality was assessed using quality assessment of diagnostic accuracy studies version 2 (QUADAS-2). For each diagnostic strategy and population subgroup, a care pathway was constructed to specify which medical treatments and health services that individuals would receive from presentation to the point where they either did or did not complete TB treatment successfully. A total cost was estimated from a health service perspective for each care pathway, and the health impact was estimated in terms of the mean discounted quality-adjusted life-years (QALYs) lost as a result of disease and treatment. Costs and QALYs were both discounted at 3.5% per year. An integrated transmission-dynamic and economic model was used to evaluate the cost-effectiveness of introducing rapid molecular testing (in addition to culture and drug sensitivity testing). Probabilistic sensitivity analysis was performed to evaluate the impact on cost-effectiveness of diagnostic and treatment time delays, diagnosis and treatment costs, and associated QALYs.ResultsA total of 8922 titles and abstracts were identified, with 557 papers being potentially eligible. Of these, 56 studies contained sufficient test information for analysis. All three commercial tests performed well when detecting drug resistance in clinical samples, although with evidence of heterogeneity between studies. Pooled sensitivity for GenoType®MTBDRplus (Hain Lifescience, Nehren, Germany) (isoniazid and rifampicin resistance), INNO-LiPA Rif.TB®(Fujirebio Europe, Ghent, Belgium) (rifampicin resistance) and Xpert®MTB/RIF (Cepheid Inc., Sunnyvale, CA, USA) (rifampicin resistance) was 83.4%, 94.6%, 95.4% and 96.8%, respectively; equivalent pooled specificity was 99.6%, 98.2%, 99.7% and 98.4%, respectively. Results of the transmission model suggest that all of the rapid assays considered here, if added to the current diagnostic pathway, would be cost-saving and achieve a reduction in expected QALY loss compared with current practice. GenoType MTBDRplus appeared to be the most cost-effective of the rapid tests in the South Asian population, although results were similar for GeneXpert. In all other scenarios GeneXpert appeared to be the most cost-effective strategy.ConclusionsRapid molecular tests for rifampicin and isoniazid resistance were sensitive and specific. They may also be cost-effective when added to culture drug susceptibility testing in the UK. There is global interest in point-of-care testing and further work is needed to review the performance of emerging tests and the wider health-economic impact of decentralised testing in clinics and primary care, as well as non-health-care settings, such as shelters and prisons.Study registrationThis study is registered as PROSPERO CRD42011001537.FundingThe National Institute for Health Research Health Technology Assessment programme.

show abstract

Section: Details Of Included and Excluded Studiesmentioning

confidence: 99%

Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis

Drobniewski

Cooke

Jordan

et al. 2015

Health Technology Assessment

Self Cite

View full text Add to dashboard Cite

show abstract

“…Sensitivities are significantly lower for pleural, ascitic or cerebrospinal fluid. The parameters for detecting rifampicin resistance were 99.1, 95.0, 99.6, 92.7, and 99.7%, respectively [67].…”

Section: Identificationmentioning

confidence: 98%

“…Laboratories should aim to identify isolates as MTBC and perform rifampicin resistance in 90% of isolates within 1-2 working days. This is technologically feasible [53][54][55][56][57][58][59][60][61][62][63][64][65][66][67].…”

Section: Identificationmentioning

confidence: 99%

“…This is technologically feasible but challenging. In a recent analysis of a routine national nontrial service, 1,997 primary clinical specimens, including 658 nonrespiratory specimens were analysed [67]. The overall adjusted concordance, sensitivity, specificity, positive predictive value, and negative predictive value for detecting MTBC were 91.2, 85.2, 96.2, 95.7, and 86.7%, respectively (unadjusted, 86.7, 85.2, 88.2, 86.9, and 86.7%, respectively), when false-positive samples from patients (n583) with a known microbiological diagnosis of MTBC or patients receiving current or recent antituberculous treatment were excluded [67].…”

Section: Identificationmentioning

confidence: 99%

See 1 more Smart Citation

Recommended standards for modern tuberculosis laboratory services in Europe

Drobniewski¹,

Hoffner²,

Rüsch-Gerdes³

et al. 2006

Eur Respir J

View full text Add to dashboard Cite

The principles underpinning these standards are that any tuberculosis laboratorybased diagnostic procedure should be performed by appropriately trained staff, working to standardised operating procedures in appropriately equipped and safe laboratories, against clear national and international proficiency and quality standards. Quality should be the pre-eminent criteria, not cost.The standards are technologically feasible, but initially may not be within the financial capacity of all laboratories. There is a requirement for government and international donors to adequately fund an appropriate safe infrastructure to enable staff to deliver accurate and timely results at whatever level of activity they are performing.There is a need for national reference laboratories to train a new cadre of mycobacterial laboratory experts. This will require the funding of appropriate individuals at these centres to train and assist in the implementation of good laboratory practice and evaluation to build sustainable capacity. Further operational research is needed to establish the optimal configuration of new technologies to determine isoniazid, rifampicin and second-line drug susceptibility in mycobacterial cultures and also, increasingly, directly on specimens.Improved integration of laboratory medicine as a core part of all tuberculosis programmes is needed to achieve and maximise the potential of new developments.

show abstract

“…Rifampin resistance is a notable global health problem concern (11), since it is the front line drug for treating tuberculosis (4) and preventing meningococcal diseases (13). More than 90% of rifampin resistance is due to mutational alterations in an 81-bp rifampin resistance determining region of the rpoB gene (9).…”

mentioning

confidence: 99%

Detection of New arr-4 and arr-5 Gene Cassettes in Clinical Pseudomonas aeruginosa and Klebsiella pneumoniae Strains from Brazil

Fonseca

Freitas

Amorim

et al. 2008

Antimicrob Agents Chemother

View full text Add to dashboard Cite

New arr alleles emerged in class 1 integrons from a clinical Pseudomonas aeruginosa strain (arr-4) and four Klebsiella pneumoniae strains (arr-5) in Brazil/American continent. arr-4 was preceded by aacA7-catB3, whereas arr-5 was the unique cassette. The putative proteins shared 75% (Arr-5) and 78% (Arr-4) identities with Arr-2.Rifampin resistance is a notable global health problem concern (11), since it is the front line drug for treating tuberculosis (4) and preventing meningococcal diseases (13). More than 90% of rifampin resistance is due to mutational alterations in an 81-bp rifampin resistance determining region of the rpoB gene (9). However, resistance may also arise by horizontal acquisition of arr genes, which code for ADP-ribosyltransferases responsible for the drug inactivation. The arr-1 gene was first described in the Mycobacterium smegmatis chromosome (10). Subsequently, arr-2 and arr-3 alleles were described as gene cassettes in class 1 integrons present in gram-negative isolates from Europe and Asia (1,6,8,14), showing high-level rifampin MICs ranging from 32 to Ͼ256 g/ml.We report here the identification and characterization of two new arr alleles, arr-4 and arr-5, and the emergence of this class of gene in the American continent as gene cassettes from class 1 integrons present in clinical Pseudomonas aeruginosa and Klebsiella pneumoniae strains.One P. aeruginosa (PS1111) and four K. pneumoniae (K56, K224, K688, and K830) isolates recovered from different inpatients of a Brazilian hospital (Rio de Janeiro city) in 2005 tested positive for class 1 integron signatures (3). DNA macrorestriction using SpeI, followed by pulsed-field gel electrophoresis, was performed as previously described (3) and demonstrated four distinct profiles among the K. pneumoniae strains. Sequence analysis of the class 1 integron variable regions showed the presence of a 453-bp open reading frame, encoding a predicted protein of 150 amino acid residues in all integrons. These sequences from the K. pneumoniae strains and from isolate PS1111 shared 78% amino acid identity, and 75 and 78% amino acid identity, respectively, with ADP-ribosyltransferase Arr-2 (Fig. 1). Therefore, these open reading frames were named arr-4 (PS1111) and arr-5 (the K. pneumoniae strains). The genes were assigned to be parts of cassettes due to the presence of attC sites. The arr-4 gene cassette was preceded by a aacA7-catB3 array, which confer resistance to aminoglycosides and chloranphenicol, respectively, and arr-5 was the unique cassette inserted in all K. pneumoniae integrons. The arr-4 gene cassette is 516 bp long and presented an attC site only 22 bp in length due to the loss of 2L and 2R simple sites (Fig. 2). The arr-5 gene cassette is 555 bp, presenting a classical attC of 61 bp, encompassing the core site sequences that make up the left-hand and right-hand consensus sites composed of 1L, 2L, 1R, and 2R simple sites (Fig. 2) (12).arr-2 and arr-3 gene cassettes share 99% nucleotide identity and, moreover, present identical attC site sequence...

show abstract

Mycobacterium tuberculosisand Rifampin Resistance, United Kingdom

Abstract: A national diagnostic service identified M. tuberculosis and rifampin resistance in primary clinical specimens faster than conventional techniques.

Cited by 33 publications

References 24 publications

Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis

Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis

Recommended standards for modern tuberculosis laboratory services in Europe

Detection of New arr-4 and arr-5 Gene Cassettes in Clinical Pseudomonas aeruginosa and Klebsiella pneumoniae Strains from Brazil

Contact Info

Product

Resources

About