Role of Nasal Decolonization in Preventing Secondary Infections

September 18, 2020

For Healthcare Professionals

Many different types of pathogens can cause infection, including viruses, bacteria, and fungi. Sometimes, getting one infection can lead to a weakening of the immune system or to damage to the respiratory tract, which can result in an increased risk of acquiring an additional infection, known as a secondary infection.

 

What are secondary infections?

A secondary infection develops during or following treatment for a previously diagnosed infection, the first infection [1]. Secondary infections can be a major concern during flu seasons or during pandemics, as they can contribute to increased morbidity and mortality. One common example of a secondary infection is when a patient contracts a viral respiratory infection, such as the flu or a cold, and subsequently develops secondary bacterial pneumonia.

 

Prevalence of secondary infections

The rate of secondary infections is often difficult to estimate because bacterial infections often go unreported in published studies of viral illnesses [2]. This may be due to low testing rates for secondary infections. It is often difficult to distinguish a secondary bacterial infection from a primary viral infection based on symptoms and blood tests.

Secondary infections have been a concern at least since the 1918 influenza pandemic, where up to 95% of deaths were associated with bacterial infection [3]. In the wake of the discovery and increased availability of antibiotics, prevalence rates of secondary infections have decreased but still remain a concern. One recent meta-analysis found that between 11 and 35% of influenza patients may contract secondary bacterial infections, although some studies show rates as high as 65% [4]. During the recent COVID-19 pandemic, secondary infections have been reported in approximately 15% of patients [5,6].

Secondary infections are a major concern when treating viral illnesses because the presence of a bacterial infection typically leads to worse patient outcomes. Studies show that flu patients with secondary infections are more likely to experience longer hospital stays, higher admittance into the ICU, and increased chance of mortality [2,3,7]. Bacterial infections caused an estimated 29-55% of H1N1 influenza deaths, and around half of COVID-related fatalities [5,8]. Preventing and treating secondary infections are key components to improving patient outcomes, especially during times when viral infection rates are high.

Most common secondary bacterial infections

Streptococcus pneumoniae (S. pneumoniae)  and Staphylococcus aureus (S. aureus) are bacteria that commonly colonize influenza patients, contributing to 35% and 28% of secondary infections [4]. In the United States, S. pneumoniae causes 4 million disease cases and 22,000 deaths each year [3]. Other prominent pathogens responsible for secondary infections in flu patients include H. influenzae and group A Streptococcus [2]. In ICU patients, other pneumonia-causing pathogens are also seen: A. baumannii, A. xylosoxidans, methicillin-resistant S. aureus (MRSA), and E. coli [2]. Other bacteria that are often seen in secondary infections include N. meningitides, K. pneumoniae, and bacteria within the ProteusEnterobacter, and Citrobacter genera [8].

Many of these bacterial species can asymptomatically colonize nasal passages. For example, research demonstrates that up to 30% of the population carry S. aureus in their nasal passages, and about 10% are colonized with N. meningitidis [9,10]. Although carriers are often asymptomatic, nasal colonization of such pathogens may cause a secondary infection.

Does contracting a virus increase your risk of a secondary infection?

A great deal of research shows that people who contract viral infections are more likely to develop subsequent bacterial infections [2]. Although the immune system may be able to successfully defend against either a foreign virus or pathogenic bacteria, co-infection leads to an impaired ability to fight off both [8].

Often, bacterial infections arise from nasal colonies. People with S. aureus nasal colonization are two to ten times more likely to develop S. aureus infections, including surgical site infections, catheter-related infections, and ICU-related infections, which lead to a worse prognosis [9,11].

Several immune-related factors likely play a role in acquiring secondary infections. For example, a primary viral infection can disrupt the normal mucociliary clearance process, making a secondary bacterial infection more likely. During mucociliary clearance, foreign particles or pathogens are trapped in the mucus that lines the airway and are subsequently cleared. Viruses can damage the host cells that help clear the mucus, which leads to an increased adherence of bacteria to epithelial cells throughout the respiratory tract [12]. Viral infections also induce pro-inflammatory immune responses. While these responses can help kill bacteria, they can also have detrimental effects, such as upregulation of cellular receptors on host cells that promote bacterial infection [12]. Some studies also show that viral infection may lead to a greater chance of bacterial spread to the lower respiratory tract [3]. Additional mechanisms of secondary infection have been identified in COVID-19 patients. The SARS-CoV-2 virus destroys lung cells, allowing bacteria to reach deep tissue layers; bacteria can also feed off of fluid that fills the lungs during this disease [8].

It is also important to note that the presence of bacteria within the respiratory tract may make people more likely to get viral infections [13]. Bacteria such as S. aureus can elevate the infectivity of the influenza virus [3]. Nasal colonization increases the likelihood of developing both primary and secondary bacterial infections, and thus is a concern when trying to minimize viral diseases.[9,14]

Who is impacted most?

Populations most at risk for contracting secondary infections may vary depending on the type of primary infection. During the 2009 H1N1 influenza pandemic, adults were more likely than children to have secondary infections [2]. In ICU patients with influenza, older, immunocompromised individuals are at a higher risk [15]. For patients with sepsis, risk factors include urinary or deep vein catheters, elevated IL-10 levels, and decreased HLA-DR expression [7]. Additionally, secondary infections may be associated with worse outcomes for certain populations. For example, people who are immunocompromised have an increased risk of severe disease and mortality when they develop a secondary infection [3].

Because secondary infections often develop from existing bacteria in the respiratory tract, it’s also worth considering who is more likely to have pathogenic nasal colonies. Populations with higher rates of nasal colonization include obese patients and diabetic patients on dialysis, as well as patients with diseases such as HIV infections, skin and soft tissue infections, granulomatosis with polyangiitis, rheumatoid arthritis, atopic dermatitis, and recurrent furunculosis [9].

How to safely minimize risk of secondary infections with nasal decolonization

Pathogens can be spread through several modes of transmission, including direct contact with an infected individual or indirect contact with an object they have touched. Frequent hand washing and following hand hygiene measures can help decrease nasal colonization [16].

Transmission of microorganisms can also occur through airborne particles or respiratory droplets produced when an infected person sneezes or coughs. There are up to one million bacterial cells in one cubic meter of air, and the average adult breathes in over 7000 liters of air every day [17]. This leads to a wide variety of pathogens in the nares, including not only gram-positive and gram-negative bacteria but also viruses and fungi [17]. In addition to creating secondary infections within the host, these pathogens can also be spread to others who may in turn get sick. Eliminating these microorganisms may lessen the chances of developing a secondary infection and can reduce morbidity and mortality during the spread of viral illnesses.

One way to reduce nasal colonization is through prophylactic antibiotic treatment, which does lead to a lower rate of secondary infections. However, this strategy is problematic because it contributes to the rise of multi-drug resistant pathogens, and it does not protect patients from secondary infections caused by antibiotic-resistant bacteria [8].

A safer alternative is nasal decolonization using an antiseptic. Research has found that using alcohol-based nasal antiseptics to decolonize high-risk patients decreases surgical site infections by 98%, allowing hospitals to safely reduce contact protections and leading to improved patient outcomes. [18]. Nozin® Nasal Sanitizer® is a patented, alcohol-based antiseptic that can markedly reduce the number of microorganisms within the anterior nasal vestibule. One study found that this alcohol-based product reduced colony-forming units of S. aureus by an average of 99% in healthcare workers [19]. Nozin® Nasal Sanitizer® can also target antibiotic-resistant pathogens, such as MRSA. Additionally, because Nozin kills pathogens without using antibiotics, it does not promote the development of antibiotic-resistant strains.

Summary

Secondary infections are a significant concern for people with primary viral infections because they often lead to a more severe disease course and increased patient fatality rates. These secondary infections often arise from bacterial nasal colonies. Nasal decolonization using an effective antiseptic may improve patient outcomes during flu season or viral pandemics by effectively reducing nasal carriage of pathogenic bacteria and the significant additional risk they pose for respiratory bacterial infection that results in more severe respiratory outcomes of viral illness.

References:

  1. Vyas JM, Zieve D. Secondary infections. MedlinePlus. Reviewed 2019 August 25.
  2. MacIntyre CR, Chughtai AA, Barnes M, et al. The role of pneumonia and secondary bacterial infection in fatal and serious outcomes of pandemic influenza a(H1N1)pdm09. BMC Infect Dis. 2018;18(1):637. Published 2018 Dec 7. doi:10.1186/s12879-018-3548-0
  3. Morris DE, Cleary DW, Clarke SC. Secondary Bacterial Infections Associated with Influenza Pandemics. Front Microbiol. 2017;8:1041. Published 2017 Jun 23. doi:10.3389/fmicb.2017.01041
  4. Klein EY, Monteforte B, Gupta A, et al. The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis. Influenza Other Respir Viruses. 2016;10(5):394-403. doi:10.1111/irv.12398
  5. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-1062. doi:10.1016/S0140-6736(20)30566-3
  6. Langford BJ, So M, Raybardhan S, et al. Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis published online ahead of print, 2020 Jul 22]. Clin Microbiol Infect. 2020;S1198-743X(20)30423-7. doi:10.1016/j.cmi.2020.07.016
  7. Chen Y, Hu Y, Zhang J, et al. Clinical characteristics, risk factors, immune status and prognosis of secondary infection of sepsis: a retrospective observational study. BMC Anesthesiol. 2019;19(1):185. Published 2019 Oct 18. doi:10.1186/s12871-019-0849-9
  8. Manohar P, Loh B, Athira S, et al. Secondary Bacterial Infections During Pulmonary Viral Disease: Phage Therapeutics as Alternatives to Antibiotics?. Front Microbiol. 2020;11:1434. Published 2020 Jun 26. doi:10.3389/fmicb.2020.01434
  9. Sakr A, Brégeon F, Mège JL, Rolain JM, Blin O. Staphylococcus aureus Nasal Colonization: An Update on Mechanisms, Epidemiology, Risk Factors, and Subsequent Infections. Front Microbiol. 2018;9:2419. Published 2018 Oct 8. doi:10.3389/fmicb.2018.02419
  10. Centers for Disease Control and Prevention. Meningococcal Disease: Causes and Spread to Others. Reviewed 2019 May 31.
  11. Perl TM, Golub JE. New approaches to reduce Staphylococcus aureus nosocomial infection rates: treating S. aureus nasal carriage. Ann Pharmacother. 1998;32(1):S7-S16. doi:10.1177/106002809803200104
  12. Hendaus MA, Jomha FA, Alhammadi AH. Virus-induced secondary bacterial infection: a concise review. Ther Clin Risk Manag. 2015;11:1265-1271. Published 2015 Aug 24. doi:10.2147/TCRM.S87789
  13. Madhi SA, Klugman KP; Vaccine Trialist Group. A role for Streptococcus pneumoniae in virus-associated pneumonia. Nat Med. 2004;10(8):811-813. doi:10.1038/nm1077
  14. Reddinger RM, Luke-Marshall NR, Hakansson AP, Campagnari AA. Host Physiologic Changes Induced by Influenza A Virus Lead to Staphylococcus aureus Biofilm Dispersion and Transition from Asymptomatic Colonization to Invasive DiseasemBio. 2016;7(4):e01235-16. Published 2016 Aug 9. doi:10.1128/mBio.01235-16
  15. Martin-Loeches I, J Schultz M, Vincent JL, et al. Increased incidence of co-infection in critically ill patients with influenza. Intensive Care Med. 2017;43(1):48-58. doi:10.1007/s00134-016-4578-y
  16. Genc O, Arikan I. The relationship between hand hygiene practices and nasal Staphylococcus aureus carriage in healthcare workersMed Lav. 2020;111(1):54-62. Published 2020 Feb 24. doi:10.23749/mdl.v111i1.8918
  17. Kumpitsch C, Koskinen K, Schöpf V, Moissl-Eichinger C. The microbiome of the upper respiratory tract in health and disease. BMC Biol. 2019;17(1):87. Published 2019 Nov 7. doi:10.1186/s12915-019-0703-z
  18. Stegmeier, H. (2019). 1238 - Alcohol-based Nasal Antiseptic as Part of a Bundle to Reduce the Incidence of Contact Precautions and Surgical Site Infections. Poster presented at: IDWeek; 2019 October 2-6; Washington D.C.
  19. Steed LL, Costello J, Lohia S, Jones T, Spannhake EW, Nguyen S. Reduction of nasal Staphylococcus aureus carriage in health care professionals by treatment with a nonantibiotic, alcohol-based nasal antiseptic. Am J Infect Control. 2014;42(8):841-846. doi:10.1016/j.ajic.2014.04.008


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