Fakulteit Geneeskunde en Gesondheidswetenskappe

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Faculty of Medicine and Health Sciences

Can we trust the Xpert?

An evaluation of the Xpert MRSA/SA BC System and

an assessment of potential clinical impact

Dr Kessendri Reddy

Division of Medical Microbiology, NHLS Tygerberg

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Background

▪ S. aureus is a common cause of bacteraemia

▪ Rapid differentiation has several benefits▪ Undirected antibiotic use, including vancomycin

▪ Appropriate antimicrobial treatment

▪ Source identification and control

▪ Infection control precautions

Positive blood cultures with Gram positive

cocci in clusters (GPCC) Coagulase-negativestaphylococcus

(CoNS)

Staphylococcus aureus

Methicillin-sensitive S. aureus (MSSA)

Methicillin-resistant S. aureus (MRSA)

The Test

▪ Xpert MRSA/SA BC System (Cepheid, Sunnyvale, CA) ▪ Real-time

▪ Semi-automated

▪ MRSA vs MSSA vs CoNS within ~1h▪ Traditional biochemical-based methods require overnight

incubation

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The Test

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spa mecA SCCmec-orfX

MRSA + + +

MSSA + - +/-

CoNS - +/- -

Interpretation

Research Question

▪ How does the Xpert MRSA/SA BC assay perform in a real-world setting?

▪ What is the potential impact of implementation of this test in Cape Town, South Africa?

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Study Design

▪ Prospective, observational study

▪ Setting and population▪ BacT/Alert 3D Microbial Identification System (bioMérieux, Marcy

L’Étoile, France)

▪ January – June 2016: adults from January – March, then inclusive of paediatric patients

▪ Blood cultures submitted at clinician’s discretion

▪ Ethics▪ Waiver of informed consent

▪ SU Health Research Ethics Committee, reference S14/10/201

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Study Design

▪ Performance▪ Aerobic, anaerobic and paediatric blood culture bottles with

monomorphic GPCC on Gram stain

▪ Operator blinded to culture result

▪ Potential impact▪ Clinician-based interviews

▪ Xpert result not conveyed

Methods: Performance

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BC positive with GPCC

Traditional:

MSA, DNAse, BA, MCC, Kirby-

Bauer disk diffusion

Discrepant results resolved

by PastorexStaph Plus kit

(Bio-Rad)

Xpert:

Stored at 37°C, Xpert MRSA/SA BC assay within

80h

Further identification using Vitek 2 GP ID and/or

AST-P603 (bioMérieux) as

needed

Methods: Potential Impact

▪ Standard practice for calling out positive BCs with GPCC on Gram stain▪ Clinical information available suggested S. aureus sepsis

▪ Previous S. aureus on BC

▪ ICU patient

▪ S. aureus isolated provisionally or on final result

▪ For the study▪ Clinicians contacted in all included cases, when final culture result

indicated CoNS

▪ Basic data and demographic information

▪ Case-by-case assessment of whether earlier knowledge of result would have impacted antibiotic management

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Results: Performance

▪ 231 bottles → 6 failed assays▪ Invalid (loss of SPC): 2

▪ Error (signal loss after initial amplification): 4

▪ Repeat testing: 3 → Resolution of error: 2

▪ Conservative error rate 1.7% (95% CI 0.7-4.4%)

▪ 227 bottles included

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57%

8%

35%

Distribution of BC bottles, in %

FAN Aerobic Plus

FAN Anaerobic Plus

Paediatric FAN Plus

Results: Performance

▪ 4 mixed cultures: ▪ MSSA + CoNS: 3

▪ K. pneumoniae + CoNS: 1

▪ Discrepant result: 1

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Diagnostic accuracy of the Xpert MRSA/SA BC assay (n=227)

Sensitivity(%; 95% CI)

Specificity(%, 95% CI)

PPV(%, 95% CI)

NPV (%, 95% CI)

S. aureus 57/57 (100; 93.7-100)

170/170 (100; 97.8-100)

57/57 (100, 93.7-100)

170/170 (100; 97.8-100)

MRSA 15/15 (100, 79.6-100)

212/212 (100, 98.2-100)

15/15 (100, 79.6-100)

212/212 (100, 98.2-100)

MSSA 42/42(100, 91.6-100)

185/185 (100, 98.0-100)

42/42(100, 91.6-100)

185/185 (100, 98.0-100)

CoNS 170/170 (100, 97.8-100)

57/57 (100, 93.7-100)

170/170 (100, 97.8-100)

57/57 (100, 93.7-100)

100% concordance

Results: Potential Impact

▪ Clinical information in 181 (79.7%)▪ 87.8% started antibiotics at the time of culture collection

▪ β-lactam-based in 150/181 (94.3%)

▪ MSSA-active agent in 125/150 (83.3%)

▪ Targeted antistaphylococcal therapy in 24/181 (13.3%)

▪ S. aureus bacteraemia with known antibiotic history: 46

▪ Targeted antistaphylococcal empiric therapy in 10 (21.7%)12

Demographic data, in % (n = 227)

Age/Ward

Adult (>18y) 66.5

ICU, high care and burns unit (% of adults) 16.6

Paediatric 33.5

ICU (% of paediatric patients) 13.0

Gender

Male 50.6

51,138,3

10,6

Onset of sepsis, in %

Community-acquired

Hospital-acquired

Not known

Results: Potential Impact

▪ Escalation▪ change from an ineffective to a more effective agent, or the addition

of a semisynthetic penicillin (MSSA) or glycopeptide (MRSA)

▪ De-escalation ▪ change in antibiotic to a narrower-spectrum, targeted

antistaphylococcal agent, or cessation of some or all antibiotics

▪ Unclassified: MSSA 1, CoNS 313

Evolution of antimicrobial therapy on Gram stain and culture result availability

MRSA (n=11) MSSA (n=35) CoNS (n=135)

On Gram On Final On Gram On Final On Gram On Final

Escalation 2 6 2 7 7 1

De-escalation 0 7 0 18 0 12

No action 9 3 32 9 125 119

Results: Potential Impact

▪ CoNS▪ Antibiotics stopped in 12/135, additional patient changed from

broad-spectrum β-lactam to alternative agent

▪ 9.6% (95% CI 5.7-15.8% )

▪ Total▪ Potential reduction in antibiotic use in 38/181 (21.0%, 95% CI 15.7-

27.5%)

▪ Further exposure to a broad-spectrum β-lactam in 30 (16.6%, 95% CI 11.9-22.7%)

▪ Further exposure to vancomycin in 4 (2.2%, 95% CI 0.9-5.5%)

▪ >30h potential time saving to final result

▪ Average time between between BC positivity and authorisation of final result 31.3h (IQR 20.7-42.5h)

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Discussion

▪ Patients with unsuspected S. aureus bacteraemia▪ 34/46 patients with known histories (73.9%) changed antibiotics

on release of the final result

▪ >50% of the patients with MRSA bacteraemia and +-22% of all patients with S. aureus bacteraemia could have initiated appropriate therapy earlier

▪ Reduction in broad spectrum agents in 16.6% of the cohort with known antibiotic history

▪ β-lactam-β-lactamase inhibitor combinations

▪ extended-spectrum cephalosporins

▪ carbapenems

▪ vancomycin

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Conclusion

▪ Xpert MRSA/SA BC assay performed well in differentiating between S. aureus and CoNS, and demonstrated a low error rate

▪ Conventional culture should still be performed in parallel

▪ Significant potential benefit of introduction of the assay▪ Appropriate therapy for S. aureus bacteraemia

▪ Modest reduction in antibiotics prescribed

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Acknowledgements

▪ Professor Andrew Whitelaw

▪ NHLS Tygerberg Microbiology Laboratory

▪ NHLS Research Trust

▪ Cepheid

▪ Dr Shima Abdulgader

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