Procalcitonin and Innovation in Pneumonia
Healthcare Innovaton
Introduction
This is my favourite part! I have listed some of my thoughts on the existing lacunae in the management of pneumonia. Feel free to discuss these and others in the forum. You are also welcome to email me at medbookprof@themedbook.com with any questions or suggestions you have. Trust me, this is not just welcomed but craved!
The holy grail of pneumonia management is getting an accurate diagnosis and differentiating between viral and bacterial aetiology which helps in deciding whether to use antibiotics or not. Failing this, a good second prize would be to at least know when to de-escalate or stop antibiotics earlier. Historically, Streptococcus pneumoniae and Haemophilus influenzae formed the bulk of community acquired pneumonia (CAP) and empiric antibiotic therapy was directed at it. With increasing targeted vaccinations, their incidence is however falling which is another reason to urgently evaluate our antibiotic choices (1,2).
1. Accurate diagnosis of infectious aetiology
- Urine legionella and pneumococcal antigen testing
Quick turnaround, point of care tests can certainly help in tailoring therapy to narrow spectrum antibiotics. Access to these tests in primary care would also help. The test also remains positive up to three days after starting treatment. The benefits are obvious but the disadvantage is that we don’t get sensitivity results. Will this help ensure appropriate use of antibiotics?
- PCR tests to help choose appropriate antibiotics earlier in the course of illness
Multiplex PCR tests on sputum or lower respiratory tract sampling have shown some promise (3). However, they are far too sensitive thereby increasing false positives with contaminants and normal commensals (remember virulent pathogens can sometimes be a part of normal microbiome). One way of getting around this problem is to quantify the colony counts which might help. Indeed, this study found that quantifying the bacterial load could help de-escalation in the number or spectrum of antibiotics in up to 77% of patients.
- Role of the lung microbiome in the pathogenesis of pneumonia
Read my blog for a fuller discussion of this topic and why this is important.
2. Bacterial versus viral infection
- Role of procalcitonin
Normally procalcitonin is only produced by the thyroid gland. However, cytokine stimulation with TNF-α, IL-6 etc secondary to systemic inflammation results in almost all tissues producing procalcitonin. Viruses tend to inhibit TNF-α production resulting in a lack of procalcitonin rise.
On face value, procalcitonin appears very promising but as soon as you go into a little bit of depth you realise that it has the same flaws as any other test. It has false positives, false negatives and similar to CRP can also be raised in non-infective systemic inflammation. It rises within 24-48 hours of injury and falls at a roughly similar rate. But this is prolonged in the presence of renal impairment. Seems like we are back to square one isn’t it?
In terms of antibiotic initiation for CAP, procalcitonin does not reliably distinguish between bacterial and viral aetiologies. What has been shown so far is that, the higher the procalcitonin level the greater is the probability of typical bacteria than atypical or viral aetiology (4). There is no magic number that can be used as a cut-off for distinguishing bacteria from viruses.
- Procalcitonin to help stop antibiotics
It has been shown that procalcitonin is most useful in reducing unnecessary antibiotic use in the context of stopping antibiotics. A fall in procalcitonin levels has been used in algorithms to guide antibiotic cessation (5).
3. Choosing the right antibiotic
Should we develop clinical scores in pneumonia that take into account risk factors that predict the likely pathogen? This will ensure that appropriate antibiotic therapy is started at presentation. Read my blog on the utility of pneumonia severity scores in order to understand the background for this discussion.
Ultimately, despite the advances in technology, real-world decisions continue to rely on clinicians who have to integrate clinical information with all the test results with their inherent shortcomings to come up with the appropriate regimen. Innovative solutions to tackle different aspects of antibiotic therapy in pneumonia are urgently needed as empiric management is unsustainable. One way forward is to pick apart each issue and address them separately i.e. diagnosis, decision for starting antibiotics, spectrum of choice, decision to de-escalate and stop.
References
- Vadlamudi NK, Chen A, Marra F. Impact of the 13-valent pneumococcal conjugate vaccine among adults: A systematic review and meta-analysis [Internet]. Vol. 69, Clinical Infectious Diseases. Oxford University Press; 2019 [cited 2021 May 3]. p. 34–49. Available from: https://pubmed.ncbi.nlm.nih.gov/30312379/
- Pilishvili T, Lexau C, Farley MM, Hadler J, Harrison LH, Bennett NM, et al. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis [Internet]. 2010 Jan [cited 2021 May 3];201(1):32–41. Available from: https://pubmed.ncbi.nlm.nih.gov/19947881/
- Gadsby NJ, Russell CD, Mchugh MP, Mark H, Conway Morris A, Laurenson IF, et al. Comprehensive molecular testing for respiratory pathogens in community-acquired pneumonia. Clin Infect Dis [Internet]. 2016 Apr 1 [cited 2021 May 2];62(7):817–23. Available from: /pmc/articles/PMC4787606/
- Self WH, Balk RA, Grijalva CG, Williams DJ, Zhu Y, Anderson EJ, et al. Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community-Acquired Pneumonia. Clin Infect Dis [Internet]. 2017 Jul 15 [cited 2019 Jun 9];65(2):183–90. Available from: https://academic.oup.com/cid/article/65/2/183/3605415
- Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane database Syst Rev [Internet]. 2017 Oct 12 [cited 2019 Aug 4];10:CD007498. Available from: http://doi.wiley.com/10.1002/14651858.CD007498.pub3
Like what you read? Subscribe now for more fun and accessible medical snippets.
Join 57 other subscribers