Multicentre evaluation of two multiplex PCR platforms for the rapid microbiological investigation of nosocomial pneumonia in UK ICUs: the INHALE WP1 study

Abstract

BackgroundCulture-based microbiological investigation of hospital-acquired or ventilator-associated pneumonia (HAP or VAP) is insensitive, with aetiological agents often unidentified. This can lead to excess antimicrobial treatment of patients with susceptible pathogens, while those with resistant bacteria are treated inadequately for prolonged periods. Using PCR to seek pathogens and their resistance genes directly from clinical samples may improve therapy and stewardship.MethodsSurplus routine lower respiratory tract samples were collected from intensive care unit patients about to receive new or changed antibiotics for hospital-onset lower respiratory tract infections at 15 UK hospitals. Testing was performed using the BioFire FilmArray Pneumonia Panel (bioMérieux) and Unyvero Pneumonia Panel (Curetis). Concordance analysis compared machine and routine microbiology results, while Bayesian latent class (BLC) analysis estimated the sensitivity and specificity of each test, incorporating information from both PCR panels and routine microbiology.FindingsIn 652 eligible samples; PCR identified pathogens in considerably more samples compared with routine microbiology: 60.4% and 74.2% for Unyvero and FilmArray respectively vs 44.2% by routine microbiology. PCR tests also detected more pathogens per sample than routine microbiology. For common HAP/VAP pathogens, FilmArray had sensitivity of 91.7%–100.0% and specificity of 87.5%–99.5%; Unyvero had sensitivity of 50.0%–100.0%%, and specificity of 89.4%–99.0%. BLC analysis indicated that, compared with PCR, routine microbiology had low sensitivity, ranging from 27.0% to 69.4%.InterpretationConventional and BLC analysis demonstrated that both platforms performed similarly and were considerably more sensitive than routine microbiology, detecting potential pathogens in patient samples reported as culture negative. The increased sensitivity of detection realised by PCR offers potential for improved antimicrobial prescribing.

Potential of Multiplex Polymerase Chain Reaction Performed on Protected Telescope Catheter Samples for Early Adaptation of Antimicrobial Therapy in ARDS Patients

“…Still, it can also lead to overdiagnosis and over-prescription of antibiotics since fourteen mPCR-positive samples were culture-negative (below the threshold). Additionally, we showed, in accordance with previous studies, that false positives of mecA/C and MREJ were not exceptional [ 14 , 15 ].…”

“…mPCR performance with PTC is consistent with the findings of previous studies that examined mPCR with other sampling methods where a direct examination was available [ 14 , 15 ]. This result is important for daily practice since PTC is the main diagnostic sampling technique in intubated patients in France [ 6 ].…”

“…A potential concern of PCR-based methods is that they may detect residual nucleic acids rather than viable material. In our study, four samples were mPCR-positive and culture-negative, and showed the same microorganisms that had already been found in the culture of previous samples, i.e., mPCR detected their residue [ 15 ]. Detecting residual materials can be advantageous for patients previously treated with antibiotics (e.g., CAP).…”

Performance of PCR‐based syndromic testing compared to bacterial culture in patients with suspected pneumonia applying microscopy for quality assessment

“…This finding indicates that indiscriminate use of BF could pose a risk of overdiagnosis and overuse of antibiotics and agrees with the concerns of Cohen et al, thus underlining the importance of diagnostic stewardship [31]. Several studies have reported a potential for improved antimicrobial prescribing [32][33][34]. However, since the impact on patient outcome (e.g., length of stay, time on ventilator support, and use of antimicrobials) by BF have so far not been investigated by randomized, prospective outcome studies, the costeffectiveness of a more expensive rapid syndromic molecular panel test compared to culture for diagnosing pneumonia is unknown and should be considered before implementation as routine diagnostics.…”

Ventilator-associated pneumonia

“…A pilot RCT using the polymerase chain reaction (PCR) to detect methicillin-resistant S. aureus (MRSA) in the bronchoalveolar lavage (BAL) of mechanically ventilated patients has demonstrated better diagnostic performance and antibiotic management than with traditional methods [12]. Other multicenter studies show a very good sensitivity and good concordance of rapid molecular tests for both MRSA and Gram-negative bacilli with conventional cultures [13,14].…”