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

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.

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Should We Treat Ventilator-Associated Tracheobronchitis with Antibiotics?

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0037-1602582 ◽

2017 ◽

Vol 38 (03) ◽

pp. 264-270 ◽

Cited By ~ 3

Author(s):

John Coakley ◽

Saad Nseir ◽

Ignacio Martin-Loeches

Keyword(s):

Mechanical Ventilation ◽

Respiratory Tract ◽

Antibiotic Treatment ◽

Lower Respiratory Tract ◽

Negative Impact ◽

Antimicrobial Treatment ◽

Organ Support ◽

Resistant Bacteria ◽

Difficult Weaning ◽

Tract Infections

AbstractPatients admitted to intensive care units (ICUs) often require lung organ support. The use of mechanical ventilation, while lifesaving can be associated with subsequent complications. The most common complication in patients under mechanical ventilation is the development of ventilator-associated lower respiratory tract infections (VA-LRTIs). Before the development of VA-LRTI, there is a continuum process that ranges from airway colonization to ventilator-associated pneumonia (VAP). There is an intermediate process called ventilator-associated tracheobronchitis (VAT). Contemporary treatment of VA-LRTI emphasizes the importance of prompt broad-spectrum antimicrobial therapy. Previous studies reported prolonged duration of mechanical ventilation and ICU stay in patients with VAT. This negative impact on outcome is related to increased inflammation of the lower respiratory tract, sputum production, and higher rates of VAP. Extubation failure and difficult weaning have been reported to be associated with increased sputum volume in mechanically ventilated patients. Antibiotic treatment for VAT patients is still a matter for debate. Observational studies suggested a beneficial effect of antimicrobial treatment in VAT patients, including a reduced duration of mechanical ventilation and lower rates of subsequent VAP. Previous studies demonstrated beneficial effects of systemic and aerosolized antibiotics in preventing VAP in critically ill patients. However, antibiotic treatment is a recognized risk factor for the emergence of multidrug-resistant bacteria. Infections related to these bacteria are associated with increased morbidity, mortality, and cost. Therefore, a large well-designed study is warranted to determine whether patients with VAT should receive antimicrobials. Furthermore, a short course of antimicrobials could be sufficient in these patients.

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Investigation of the effect of N-Acetylcysteine on colistin mic values in Acinetobacter Baumannii strains isolated from clinical samples

Journal of Experimental and Clinical Medicine ◽

10.52142/omujecm.38.4.13 ◽

2021 ◽

Vol 38 (4) ◽

pp. 471-473

Author(s):

Fahriye EKŞİ ◽

Mehmet ERİNMEZ

Keyword(s):

Respiratory Tract ◽

Acinetobacter Baumannii ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Clinical Samples ◽

Chronic Obstructive ◽

Identification System ◽

Lower Respiratory Tract Infections ◽

Broth Microdilution Method ◽

Tract Infections

Acinetobacter baumannii is an opportunistic pathogen which colonize inpatients and cause severe infections, septic shock and death. With emergence of multi-drug resistant gramnegative species and being effective in A. baumannii infections, colistin becomes a treatment option again. N-acetylcysteine (NAC), is a mucolitic agent which used commonly in lower respiratory tract infections especially patients who have cronic respiratory disorders like Chronic obstructive pulmonary disease, cystic fibrosis and bronchiectasis. In this study we aim to investigate the effect of NAC, which commonly added in lower respiratory tract infections tratment regime, on MIC values colistin used in A. baumanni tratment. Fifty A.baumannii isolates were included in the study. The isolates were identified by automated identification system. With broth microdilution method, we investigated and compared the MIC (minimum inhibitory concentration) values of colistin and NAC+Colistin combination. Colistin MIC50 value is 0.25 μg/mL and MİK90 value is 1 μg/mL, NAC+Colistin combination MIC50 value is 0.25 μg/mL and MİK90 value is 1 μg/mL. The screening for the effectiveness of clinical drugs may provide clinical strategy to improve treatment outcomes of A. baumannii and reduce hospitalization days.

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The Basics and the Advancements in Diagnosis of Bacterial Lower Respiratory Tract Infections

Diagnostics ◽

10.3390/diagnostics9020037 ◽

2019 ◽

Vol 9 (2) ◽

pp. 37 ◽

Cited By ~ 8

Author(s):

Stephanie Noviello ◽

David Huang

Keyword(s):

Respiratory Tract ◽

Cause Of Death ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Point Of Care ◽

Patient Treatment ◽

Resistant Bacteria ◽

Lower Respiratory Tract Infections ◽

Reactive Protein ◽

Tract Infections

Lower respiratory tract infections (LRTIs) are the leading infectious cause of death and the sixth-leading cause of death overall worldwide. Streptococcus pneumoniae, with more than 90 serotypes, remains the most common identified cause of community-acquired acute bacterial pneumonia. Antibiotics treat LRTIs with a bacterial etiology. With the potential for antibiotic-resistant bacteria, defining the etiology of the LRTI is imperative for appropriate patient treatment. C-reactive protein and procalcitonin are point-of-care tests that may differentiate bacterial versus viral etiologies of LRTIs. Major advancements are currently advancing the ability to make rapid diagnoses and identification of the bacterial etiology of LRTIs, which will continue to support antimicrobial stewardship, and is the focus of this review.

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Multicenter Evaluation of the BioFire FilmArray Pneumonia/Pneumonia Plus Panel for Detection and Quantification of Agents of Lower Respiratory Tract Infection

Journal of Clinical Microbiology ◽

10.1128/jcm.00128-20 ◽

2020 ◽

Vol 58 (7) ◽

Cited By ~ 7

Author(s):

Caitlin N. Murphy ◽

Randal Fowler ◽

Joan Miquel Balada-Llasat ◽

Amanda Carroll ◽

Hanna Stone ◽

...

Keyword(s):

Respiratory Tract ◽

Antimicrobial Stewardship ◽

Lower Respiratory Tract ◽

Diagnostic Testing ◽

Molecular Methods ◽

Marker Genes ◽

Molecular Testing ◽

Sample Treatment ◽

Low Sensitivity ◽

Tract Infections

ABSTRACT The ability to provide timely identification of the causative agents of lower respiratory tract infections can promote better patient outcomes and support antimicrobial stewardship efforts. Current diagnostic testing options include culture, molecular testing, and antigen detection. These methods may require collection of various specimens, involve extensive sample treatment, and can suffer from low sensitivity and long turnaround times. This study assessed the performance of the BioFire FilmArray Pneumonia Panel (PN panel) and Pneumonia Plus Panel (PNplus panel), an FDA-cleared sample-to-answer assay that enables the detection of viruses, atypical bacteria, bacteria, and antimicrobial resistance marker genes from lower respiratory tract specimens (sputum and bronchoalveolar lavage [BAL] fluid). Semiquantitative results are also provided for the bacterial targets. This paper describes selected analytical and clinical studies that were conducted to evaluate performance of the panel for regulatory clearance. Prospectively collected respiratory specimens (846 BAL and 836 sputum specimens) evaluated with the PN panel were also tested by quantitative reference culture and molecular methods for comparison. The PN panel showed a sensitivity of 100% for 15/22 etiologic targets using BAL specimens and for 10/24 using sputum specimens. All other targets had sensitivities of ≥75% or were unable to be calculated due to low prevalence in the study population. Specificity for all targets was ≥87.2%, with many false-positive results compared to culture that were confirmed by alternative molecular methods. Appropriate adoption of this test could provide actionable diagnostic information that is anticipated to impact patient care and antimicrobial stewardship decisions.

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

10.1101/2020.11.04.20216648 ◽

2020 ◽

Author(s):

Virve I Enne ◽

Alp Aydin ◽

Rossella Baldan ◽

Dewi R Owen ◽

Hollian Richardson ◽

...

Keyword(s):

Resistance Genes ◽

Latent Class ◽

Controlled Trial ◽

Turnaround Time ◽

Clinical Samples ◽

Respiratory Pathogens ◽

Icu Patients ◽

Microbiological Investigation ◽

Antimicrobial Resistance Genes ◽

Tract Infections

SummaryBackgroundICU patients with hospital-acquired or ventilator-associated pneumonia (HAP or VAP) have high mortality, so broad-spectrum antibiotics are initiated at clinical diagnosis, then refined after 2-3 days, once microbiology results become available. Unfortunately, culture-based microbiological investigation is also insensitive, with aetiological agents remaining unidentified in many cases. This leads to extended over-treatment of patients with susceptible pathogens, whilst those with highly-resistant pathogens are treated inadequately for prolonged periods. Using PCR to seek pathogens and their resistance genes directly from clinical samples may improve therapy and stewardship. The INHALE study compared two PCR platforms for HAP/VAP diagnosis against routine microbiology (RM), identifying one to progress into a Randomised Controlled Trial (RCT).MethodsSurplus routine sputa, endotracheal tube exudates and bronchoalveolar lavages were collected from ICU patients about to receive new or changed antibiotics for hospital-onset lower respiratory tract infections at 15 UK hospitals. Samples were tested (or frozen for testing) within 72h of collection. Testing was performed using the BioFire FilmArray Pneumonia Panel (bioMérieux) and Unyvero Pneumonia Panel (Curetis). Agreement between machine- and RM-results was categorised as ‘full positive/negative concordance’, ‘partial concordance’ or ‘major/minor discordance’. Bayesian latent class (BLC) analysis was used to estimate the sensitivity and specificity of each test, incorporating information from both PCR panels, 16S rDNA analysis and RM.FindingsIn 652 eligible samples; PCR identified pathogens in considerably more samples compared with RM: 60.4% and 74.2% for Unyvero and FilmArray respectively vs. 44.2%. Both tests also recorded more organisms per sample than routine culture, with the two PCR tests frequently in agreement with each other. For common HAP/VAP pathogens, FilmArray had sensitivity of 91.7-100.0% and specificity of 87.5-99.5%; Unyvero had sensitivity of 83.3-100.0%% except for Klebsiella aerogenes (50.0%) and Serratia marcescens (77.8%), and specificity of 89.4-99.0%. BLC analysis indicated that, compared with PCR, RM had low sensitivity, ranging from 27.0% to 69.4% for common respiratory pathogens. PCR detected more high-consequence antimicrobial resistance genes than would have been predicted by RM and susceptibility testing; around half the host strains could be detected when culture was repeated and they were sought assiduously.InterpretationConventional and BLC analysis demonstrated that both platforms performed similarly and were considerably more sensitive than RM, detecting potential pathogens in patient samples reported as culture negative. FilmArray had slightly higher sensitivity than Unyvero for common pathogens and was chosen for INHALE’s RCT, based on the balance of these results, a swifter turnaround time (75 min vs. 6h), and a smaller footprint. The increased sensitivity of detection realised by PCR offers potential for improved antimicrobial prescribing.

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Impact of immunosuppression on incidence, aetiology and outcome of ventilator-associated lower respiratory tract infections

European Respiratory Journal ◽

10.1183/13993003.01656-2017 ◽

2018 ◽

Vol 51 (3) ◽

pp. 1701656 ◽

Cited By ~ 9

Author(s):

Anne-Sophie Moreau ◽

Ignacio Martin-Loeches ◽

Pedro Povoa ◽

Jorge Salluh ◽

Alejandro Rodriguez ◽

...

Keyword(s):

Respiratory Tract ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Multidrug Resistant ◽

Hazard Ratio ◽

Resistant Bacteria ◽

Ventilator Associated Pneumonia ◽

Immunocompromised Patients ◽

Lower Respiratory Tract Infections ◽

Tract Infections

The aim of this planned analysis of the prospective multinational TAVeM database was to determine the incidence, aetiology and impact on outcome of ventilator-associated lower respiratory tract infections (VA-LRTI) in immunocompromised patients.All patients receiving mechanical ventilation for >48 h were included. Immunocompromised patients (n=663) were compared with non-immunocompromised patients (n=2297).The incidence of VA-LRTI was significantly lower among immunocompromised than among non-immunocompromised patients (16.6% versus 24.2%; sub-hazard ratio 0.65, 95% CI 0.53–0.80; p<0.0001). Similar results were found regarding ventilator-associated tracheobronchitis (7.3% versus 11.6%; sub-hazard ratio 0.61, 95% CI 0.45–0.84; p=0.002) and ventilator-associated pneumonia (9.3% versus 12.7%; sub-hazard ratio 0.72, 95% CI 0.54–0.95; p=0.019). Among patients with VA-LRTI, the rates of multidrug-resistant bacteria (72% versus 59%; p=0.011) and intensive care unit mortality were significantly higher among immunocompromised than among non-immunocompromised patients (54% versus 30%; OR 2.68, 95% CI 1.78–4.02; p<0.0001). In patients with ventilator-associated pneumonia, mortality rates were higher among immunocompromised than among non-immunocompromised patients (64% versus 34%; p<0.001).Incidence of VA-LRTI was significantly lower among immunocompromised patients, but it was associated with a significantly higher mortality rate. Multidrug-resistant pathogens were more frequently found in immunocompromised patients with VA-LRTI.

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