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We read with interest the review by Kreitmann et al. on intensive care unit (ICU)-acquired infections in immunocompromised patients [1]. The authors nicely discussed conditions associated with immunosuppression in ICU and mechanisms of infections. Their review offers also an up-to-date description of epidemiology and diagnostic–therapeutic management of ventilator-associated lower respiratory tract infections (VA-LRTIs) in this population.
However, we do not agree with the authors’ view on the role of multiplex polymerase chain reaction (mPCR)-based tests in VA-LRTIs. While they stated that mPCR pneumonia tests are probably less useful for ICU-acquired than for community-acquired infections, we believe they are actually quite the opposite. Recent guidelines on community-acquired pneumonia suggest mPCR testing only “whenever nonstandard antibiotics are prescribed or considered” [2]. Conversely, multicenter randomized controlled trials on nosocomial pneumonia showed that mPCR-based tests could increase the sensitivity of microbial sampling and/or shorten the duration of inappropriate antibiotic therapy, supporting their use to improve antibiotic stewardship in ICU [3].
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In the prospective cohort study CoV-AP, we previously evaluated the concordance between mPCR-based test BIOFIRE®FILMARRAY® Pneumonia Panel plus (BALFAPPP) and standard cultures (BALCX) on bronchoalveolar lavage (BAL) of ICU patients with coronavirus disease 2019 (COVID-19) and suspected ventilator associated pneumonia (VAP) [4].
Based on a secondary analysis of the CoV-AP study, here we want to share some food for thought on the impact of mPCR-based tests on therapeutic decisions of VA-LRTIs in real-life settings.
1.
Strength point #1: very short turnaround time.
In the CoV-AP cohort, the median time from BAL acquisition to definitive microbiological results differed greatly between techniques (6.3h, interquartile range (IQR) 4.5–7.7h for BALFAPPP and 70.6h, IQR 49.7–77.8h for BALCX results).
2.
Strength point #2: ability to anticipate (the majority of) therapeutic choices.
Therapeutic decisions based on BALFAPPP were confirmed at the arrival of BALCX in 81.6% of cases (confirmation of prescribed antibiotics in 57.2% of cases; confirmation of antibiotics withheld in 24.5% of cases) (Figure 1).
3.
Limitation #1: be aware of what is missing.
As the authors stated, an intrinsic limitation of mPCR-based tests is the (relatively) limited number of targets. In the CoV-AP study, BALFAPPP was not able to microbiologically characterize VAP caused by Corynebacterium spp and Aspergillus spp (12.2% of total cases) [4]. Beyond COVID-19, in our clinical practice, the main limitation of BALFAPPP is the absence of detection of uncommon Enterobacterales and non-fermenting gram-negative bacteria (i.e., Stenotrophomonas maltophilia), which are a rare but possible cause of LRTIs in patients with long ICU stay or immunocompromised hosts such as solid organ transplant.
4.
Limitation #2: all that glitters is not gold.
In the CoV-AP cohort, the prevalence of VAP caused by multidrug-resistant organisms was low (7% with BALFAPPP and 3% with BALCX). Interestingly, of the three cases with resistance mechanisms detected in BALFAPPP, only one was confirmed by BALCX. Although uncommon, discrepant results between BALFAPPP and standard cultures or other molecular methods have been reported [5].
Fig. 1
Therapeutic choices based on BALFAPPP and BALCX in patients with suspected VAP of the CoV-AP study. *16/49 patients (32.6%) were already on antimicrobial therapy at the time of BAL acquisition. **Therapeutic choices based on BALCX considered decisions guided by BALFAPPP as baseline
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Most likely, mPCR-based tests will change the management of VA-LRTIs, if is not already happening. While waiting for further trials to assess their impact on antibiotic consumption and clinical outcomes, physicians should be aware of their strengths and limitations.
Declarations
Conflicts of interest
MT declared there are no conflicts of interest; DM received speaker’s honoraria from Pfizer and MSD and received travel grants from Pfizer; MP declared there are no conflicts of interest; CM declared there are no conflicts of interest; and AB received speaker’s honoraria and fees for attending advisory boards from AstraZeneca, bioMérieux, Janssen-Cilag, Nordic Pharma, Pfizer, QIAGEN, Sobi, and ViiV and received research grants from Gilead.
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Ethical approval and consent to participate
This clinical study was approved by the Milan Area 2 Ethical Committee (#97_2021). We received informed consent from participants or their proxies. All data processing was performed according to the Declaration of Helsinki.
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
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