The Challenges of Diagnosing and Treating Secondary Infections

by | Clinical, Molecular

Publish Date: November 15, 2023

In the past two decades, there have been six major global outbreaks of infectious diseases. While these infections may be treated, treatment can get more difficult when a secondary infection may take advantage of an already weakened immune system (Manohar, et al, 2020). Four of the six outbreaks were respiratory viruses, which commonly involve secondary infections. A secondary infection, not to be confused with a co-infection, is caused by an opportunistic pathogen that flourishes within a weakened immune system resulting from a primary infection (Boskey, 2021). Secondary infections can occur from more than just a weakened immune system; they can also be the result of compromised skin such as open sores from a long hospital stay or the use of a treatment such as broad-spectrum antibiotics (Boskey, 2021). In some situations, it can be a challenge to diagnose some respiratory secondary infections when the primary infection is also a respiratory infection and some symptoms may overlap. Secondary infections can make diagnosis difficult, posing risks for the patient when it comes to the correct treatment plan.

Often secondary infections are associated with respiratory diseases. Viruses such as Influenza or SARS-CoV-2 can make mammalian cells more vulnerable to bacterial inundation and can result in a disease such as bacterial pneumonia (Manohar, et al, 2020). Patients infected with Respiratory Syncytial virus (RSV), Influenza, or Rhinovirus are more likely to develop a secondary infection from Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae. The mechanism behind the secondary respiratory infection is due to a virus damaging the respiratory mucosal layer which makes it easier for the bacterial pathogens to form biofilms in the respiratory airways (Manohar, et al, 2020).

The 1918 Spanish Flu Pandemic is an example of a respiratory secondary infection causing a major impact. In a 2008 study, researchers observed 96 military and civilian autopsy series samples preserved from the 1918 Spanish flu. The samples were reexamined, and 92.7% of the lung cultures were positive for at least one species of bacteria (Morens, et all, 2008). Many of the bacterial species observed were pneumopathogens, such as pneumococci, streptococci and staphylococci, known to cause bacterial pneumonia. Based on all the data that was gathered from reexamining the tissue and looking back at postmortem reports, the researchers concluded that bacterial infections were the cause of majority of the deaths during the 1918-1919 influenza pandemic. The scientists hypothesized that, without the secondary infections, many would have recovered from the influenza (Morens, et all, 2008).

In some situations, hospital associated infections (HAIs) can be considered secondary infections, since they may be opportunistic pathogens growing within weakened immune systems. As also defined in a secondary infection, HAIs are infections acquired by an opportunistic pathogen. These infections are typically manifested within 48 hours of admission to the hospital. The risk of acquiring an HAI not only has to do with the practices of the facility but also the status of the patients’ immune system (Monegro, et al, 2022).  While antibiotics are effective in killing the disease-causing bacteria, they cannot distinguish between good bacteria and disease-inducing bacteria. This means that the administration of certain antibiotics can alter the gut microbiota and make the digestive tract more susceptible to HAIs such as Clostridium difficile. While studies show that the innate immune system can combat C. difficile, the gut microbiome can directly suppress the spores ingested by the patients Ubeda, C., & Pamer, E. G. (2012).

According to the CDC, it is estimated that nearly 500,000 people are diagnosed with C. difficile each year (CDC, 2022). In one study, 1883 patients with community-acquired pneumonia (CAP) were analyzed for C. difficile. Of the 1883 patients, all patients were given antibiotics as a form of treatment for CAP, and 365 patients were tested for Clostridium difficile infections (CDI) due to symptoms displayed by the patient. Overall, there were 61 patients who had tested positive for C. difficile and those who did test positive fit an older demographic or had longer hospital stays. The patients with CAP had a mortality rate of 8.6%. The mortality rate for patients with CAP plus secondary CDI infections was 21.3%, more than double those without secondary infections (Chalmers, et al, 2016).

The world of testing and diagnosing infections is ever changing and evolving. Scientists are finding better and more efficient ways to test patients for secondary infections. During the COVID-19 pandemic, as the number of patients admitted into the intensive care unit (ICU) grew exponentially, researchers worked to develop faster methods for diagnosing secondary infections. Prior to the COVID-19 pandemic, patients with ventilator-acquired secondary infections would wait approximately 2-4 days to receive test results. During those 2-4 days, patients would be treated with a general antibiotic and thus increase the risk for multi-drug resistant pathogens (Hickman, 2021).

Scientists from Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London ran studies using samples from patients intubated and exhibiting secondary nosocomial infections. In the study, the scientists collaborated with Quadram Institute in Norwich, Oxford Nanopore Technologies, & Viapath to improve the role of diagnostics in reducing antibiotic resistance. They used nanopore metagenomics sequencing on 43 respiratory samples over a 9-week period to identify several species of bacteria and fungus producing respiratory infections. Understanding the challenges of secondary infections, the researchers were able to begin proper treatment within a day after identifying and sequencing the causative organisms using rapid sequencing technology. With the sample sequence available, two strains of multi-drug-resistant organisms were identified, and every patient was treated with a different antibiotic from the one initially prescribed and (Hickman, 2021).

In the future, researchers hope to become even more efficient at diagnosing secondary infections. Presently, it is important to remain vigilant in acknowledging that secondary infections can pose serious risks and to recognize changing symptoms that may indicate the need for further testing. Running multiplex testing can help identify more than one infectious agent that may be coursing through the body. Recognizing and diagnosing secondary infections can be a critical step in saving the lives of patients.

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Boskey, E. (2021, September 16). Secondary Infections Occur When a Primary Infection Goes Wrong. Verywell Health.

CDC. (2022, September 7). Could you or your loved one have C. diff? Centers for Disease Control and Prevention.

Chalmers, J. D., Akram, A. R., Singanayagam, A., Wilcox, M. H., & Hill, A. T. (2016). Risk factors for Clostridium difficile infection in hospitalized patients with community-acquired pneumonia. Journal of Infection73(1), 45–53.

Hickman, D. (2021, November 18). Faster testing possible for secondary ICU infections. The Hospitalist.

Manohar, P., Loh, B., Nachimuthu, R., Hua, X., Welburn, S. C., & Leptihn, S. (2020). Secondary Bacterial Infections in Patients With Viral Pneumonia. Frontiers in Medicine7.

‌Monegro, A. F., Muppidi, V., & Regunath, H. (2022). Hospital Acquired Infections.; StatPearls Publishing.

Morens, David M., Taubenberger, Jeffery K., & Fauci, Anthony S. (2008). Predominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for Pandemic Influenza Preparedness. The Journal of Infectious Diseases198(7), 962–970.

Ubeda, C., & Pamer, E. G. (2012). Antibiotics, microbiota, and immune defense. Trends in Immunology33(9), 459–466.


Written by Angie Otto

Angie has been a part of Microbiologics® Technical Support team since June 2021, and in her current role as Technical Support Scientist II for a year. During her time at Microbiologics, she has provided technical support to Microbiologics’ customers internationally and domestically for our products used as Quality Control reference materials in various industries such as the Pharmaceutical, Food, Cosmetic and Clinical. She addresses how they are used and implemented in Quality Control testing for multiple regulations including but not limited to the USP, BAM, CLSI, FDA, and others. Other duties include investigation of product complaints, planning and executing laboratory investigations, and assisting and developing training programs on the use of our products and specific test methods. Angie obtained her Bachelor of Science degree from St. Cloud State University in Life Science.

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