Ventilators
In hospitals, 80% of infections that can be traced back to medical equipment happen because the bacteria on that equipment are able to grow and persist in biofilms. Infections caused by biofilms on equipment such as ventilators and catheters, have remained under-researched for decades despite their potential for influencing the outcome of therapies.
The bacterial pathogen, Klebsiella pneumoniae is a common cause of hospital-acquired infections and is considered a priority pathogen by the World Health Organisation. Recently it has been shown that, not only can K. pneumoniae grow as a biofilm, but it is simultaneously resistant to numerous different antibiotics including carbapenem, making it a global threat to health. Reports suggest that as many as 42% of people infected with carbapenem-resistant K. pneumoniae die due to this infection.
The biochemical and metabolic characteristics of K. pneumoniae that enable it to grow as a biofilm are under the control of specific genes, for instance genes that control the production of allantoin, aerobactin, type I & III fimbriae, adhesins, capsular polysaccharides, or enable quorum sensing and colanic acid secretion. Recent research has demonstrated a relationship between genes controlling biofilm formation and genes controlling antibiotic resistance in K. pneumoniae, and that some of these genes were inherited together.
Klebsiella pneumoniae causes some of the deadliest hospital-acquired infections. Its genetic code harbours both virulence factors essential for the pathogen to escape the host immune system and for successful biofilm formation (Li et al., 2014). Biofilms of K. pneumoniae formed in medical devices such as catheters and ventilators are expected to be coated with host cellular factors in situ, leading to hospital-acquired infections (Murphy and Clegg, 2012).
Multi-drug resistant K. pneumoniae are particularly difficult to treat, restricting doctors to a limited number of antimicrobials, such as colistin, tigecycline and minocycline. Furthermore, bacteria within biofilms are persistent, requiring higher than standard doses of antimicrobials, or a combination therapy, for effective removal. Under-dosing can encourage development of resistance during treatment and induce biofilm formation (Cadavid et al., 2018), leading to further complexity in patient management.
Newer combinations of antimicrobials, such as ceftazidime/avibactam (FDA approved) with aztreonam and cefepime/Zidebactam (in pipeline for development) might be effective against K. pneumoniae biofilms.
Research has shown that in the USA 9% of 9000 patients using a ventilator in 1998 acquired ventilator-associated pneumonia, which increased the average hospital stay costs by $40 000 in the US (Shirtliff M.& Leid J. G. (eds), 2009 and Millar M., 2005).
Further reading on biofilms and ventilators
Cadavid, E., Robledo, S.M., Quiñones, M. and Echeverri, F. (2018) ‘Induction of Biofilm Formation in Klebsiella pneumoniae ATCC 13884 by Several Drugs: The Possible Role of Quorum Sensing Modulation’, Antibiotics, vol. 7(4), https://doi.org/10.3390/antibiotics7040103.
Li, B., Zhao, Y., Liu, C., Chen, Z. and Zhou, D. (2014) ‘Molecular pathogenesis of Klebsiella pneumoniae‘, Future Microbiology, vol. 9(9), pp. 1071-81, https://doi.org/10.2217/fmb.14.48.
Murphy, C.N. and Clegg, S. (2012) ‘Klebsiella pneumoniae and type 3 fimbriae: nosocomial infection, regulation and biofilm formation’, Future Microbiology, vol. 7(8), pp. 991-1002, https://doi.org/10.2217/fmb.12.74.
Shirtliff M.& Leid J. G. (eds) 2009. The role of biofilms in device-related infections. Berlin, Germany: Springer-Verlag. The Role of Biofilms in Device-Related Infections | SpringerLink.
Millar M. 2005. Microbial biofilms and clinical implants. Surfaces and interfaces for biomaterials (ed. & Vadgama P.), pp. 619–631. Boca Raton, FL: CRC Press. https://doi.org/10.1533/9781845690809.4.619.