Normal Respiratory Microbiota in Health and Disease

Feb. 17, 2020

Serious respiratory infections are a risk for all hospitalized patients, but are particularly common in the intensive care unit (ICU). Patients admitted to the (ICU) are at a greater risk of developing nosocomial pneumonia than patients admitted to other wards in the hospital, and ventilated patients are at a 3-10 times increased risk of developing nosocomial pneumonia compared with those who are not ventilated. This is in part because many ICU patients require ventilator support to help with obstructed pathways or other conditions that prevent them from breathing on their own. Ventilation involves placing an endotracheal tube down the windpipe to deliver oxygen directly to the lungs, which is a life-saving procedure but not one without risks. For many reasons, mechanically ventilated patients are especially susceptible to developing pneumonia. In fact, pneumonia is the second most common nosocomial infection affecting critically ill patients in the ICU.

Ventilator-Associated Pneumonia and The Role of Normal Respiratory Flora

Patients are at most at risk of developing ventilator-associated pneumonia (VAP) in the first 48 hours after an endotracheal tube has been placed. The placement of the tube disrupts the normal anatomy of the respiratory tract, and prevents the patient from swallowing, coughing or clearing mucus and other secretions normally. As these secretions pool in the oropharynx, bacteria that live in the respiratory tract can begin to accumulate along the endotracheal tube. If the patient aspirates these bacteria, they may cause infection within the lungs.

Depiction of endotracheal tube placement in a critically ill patient.
Depiction of endotracheal tube placement in a critically ill patient. Source:

Organisms that normally live within the respiratory tract may end up being the same organisms that cause pneumonia in these patients. Understanding that a single organism may be either normal microbiota or a pathogen encourages the microbiologist and clinician to consider other key factors when making a VAP diagnosis such as which organisms constitute normal respiratory flora and what makes some members of the respiratory microbiota more pathogenic than others.

Commensal Organisms Have The Potential to Cause Harm

Like all human skin and mucosal surfaces, the respiratory tract is colonized with commensal bacteria that protect the host from disease, increase epithelial cell renewal rates, and promote production of mucosal immunoglobulins. The difficulty in diagnosing the cause of VAP comes from the fact that many of these organisms have the potential to cause disease. Are organisms present simply colonizing the endotracheal tube and surrounding airway without causing harm, or are they the cause of infection? Table 1 lists the organisms most commonly isolated from the respiratory tract and the roles they may play in both harmless colonization and disease.

Commonly Isolated Organisms by Site of Detection

Oropharynx and Nasopharynx

Group C or G Streptococci

  • Most commonly represents colonization, but can cause isolated cases and outbreaks of symptomatic pharyngitis.

Group A Streptococcus

Streptococcus pneumoniae
  • A large range (6% to 100%) of infants and toddlers are colonized.
  • Approximately 25% of children between 3 months and 4 years of age are colonized, and 5-10%% of older and younger people.
  • Can persist for weeks to months at this site.
  • Growing S. pneumoniae from a culture of the oropharynx/nasopharynx is of no significance, but about 15% of children will develop clinical infections within one month of acquiring a new strain.
  • A child who develops a viral upper respiratory tract infection while colonized may develop acute otitis media or sinusitis.
Nontypeable Haemophilus influenzae and Moraxella catarrhalis Neisseria meningitidis
Lower Respiratory Tract

Streptococcus pneumoniae

  • Common contaminant from the upper respiratory tract (where this is a colonizing organism), but also a common cause of lower respiratory tract disease. The significance of the presence of this organism in culture will rely heavily on the clinical picture, other diagnostic testing and predominance in culture.

Staphylococcus aureus

Nontypeable Haemophilus influenzae, Moraxella catarrhalis and Enterococcus species.

Enterobacteriaceae and nonfermenting gram-negative bacilli

Any Respiratory Tract Site

Viridans group streptococci, nonhemolyic streptococci, coagulase-negative staphylococci, nonpathogenic Neisseria species, Corynebacterium species, Lactobacillus species, Micrococcus species, Stomatococcus species and Bacillus species 

Many respiratory pathogens live normally in the host without causing disease. Identifying one of these organisms as the cause of infection must be done in the context of clinical signs and symptoms of pneumonia*. Treating all organisms identified from respiratory tract cultures can lead to antibiotic overuse and encourage the development of antibiotic resistant organisms. What makes these seemingly normal bacteria so dangerous, and how can they live within humans and not cause disease most of the time, but occasionally cause lethal infections? It is important to understand how some of the most common causes of pneumonia transition from colonizers to opportunistic pathogens. Below are 3 major bacteria associated with VAP and the traits that allow them to do so.

Gram stain of a respiratory specimen from a patient without pneumonia
Gram stain of a respiratory specimen from a patient without pneumonia. Source: Andrea Prinzi.

Streptococcus pneumoniae as a Lower Respiratory Tract Pathogen

Streptococcus pneumoniae is a normal colonizer of the respiratory tract, yet it is the leading cause of pneumonia mortality globally. The World Health Organization (WHO) estimates that this organism is responsible for killing half a million children worldwide each year.

Virulence trait: Polysaccharide capsule.
  • Helps the bacterium evade host defenses.
  • Capsule, which is negatively charged, allows the bacterium to avoid getting stuck in mucous, reach and attach to epithelial cells.
Virulence trait: surface proteins (such as hyaluronate lyase)
  • Encourage and promote attachment.
  • Promote biofilm production so that more organisms can attach and proliferate.

If colonizing S. pneumoniae organisms are allowed to make their way into the lower respiratory tract, as a result of anatomical disturbance like an endotracheal tube, primary viral infection such as influenza, or aspiration, the bacteria use a variety of pathogenic factors to attach to alveolar cells and ignite an inflammatory host response, resulting in pneumonia.

Mucoid S. pneumoniae colonies on a blood agar plate. The mucoid appearance is due to particularly abundant capsule production in this strain of S. pneumoniae.
Mucoid S. pneumoniae colonies on a blood agar plate. The mucoid appearance is due to particularly abundant capsule production in this strain of S. pneumoniae. Source:

Pseudomonas aeruginosa as a Lower Respiratory Tract Pathogen

Pseudomonas aeruginosa is not commonly part of the microbiota of the respiratory tract, but it can become a colonizer in patients who have been admitted to the hospital for an extended period of time. This is also true for other Gram-negative rods including the Enterobacterales. In a hospitalized patient, particularly an intubated patient, it is not safe to assume that the presence of P. aeruginosa in a respiratory culture automatically equals infection. That said, in patients with confirmed VAP, P. aeruginosa is the most common bacterial cause. If P. aeruginosa is the predominant organism growing in a tracheal aspirate culture from a ventilated patient with symptoms of pneumonia, it is likely the causative pathogen.

The effect P. aeruginosa has on an intubated patient will differ depending on serotype:

  • Isolates with the serotypes O6 and O11 colonize humans more often than other serotypes but 60% of patients resolve VAP infections with these serotypes.
  • Serotypes O1 and O2 are less common and are associated with higher mortality.

The pathogenicity of P. aeruginosa is very complex, and the organism uses several mechanisms to adhere to living and nonliving surfaces. Its many adhesion properties allow P. aeruginosa to form biofilms, particularly on medical devices; biofilm formation on endotracheal tubes increases the patient risk of acquiring VAP should the organism move into the lungs.

Staphylococcus aureus as a Lower Respiratory Tract Pathogen

Nearly one-third of adults are colonized with Staphylococcus aureus in their respiratory tracts. While many people will never develop complications as a result of their S. aureus colonization, adults who are colonized and intubated are at a 15-fold greater risk of developing S. aureus pneumonia as compared to those who were not colonized. Additionally, S. aureus is responsible for >20% of VAP cases, 50% of which are caused by MRSA.

Virulence trait: bacterial surface proteins, particularly Protein A, are essential for the organism to be able to cause pneumonia-related mortality.

While these numbers are frightening, it is important to remember that a large portion of the population is colonized with this organism, and the presence of it in culture does not immediately suggest infection.

Respiratory Commensals as Pathogens: All Things Considered

The relationships between humans and bacteria are immensely complex. Normal respiratory microbiota can play a key role in human health, but can also play a part in severe respiratory disease. Understanding these relationships can help the clinical microbiology and infectious disease community better understand how to decipher diagnostic results when it comes to hospital-acquired pneumonia.

*How can a clinical microbiologist make a diagnosis in the context of clinical signs and symptoms? Be sure to catch the next article in this series which will discuss the challenges and benefits of pneumonia diagnostics.

The above represents the views of the author and does not necessarily reflect the opinion of the American Society for Microbiology.

Author: Andrea Prinzi, Ph.D., MPH, SM(ASCP)

Andrea Prinzi, Ph.D., MPH, SM(ASCP)
Andrea Prinzi, Ph.D., MPH, SM(ASCP) is a field medical director of U.S. medical affairs and works to bridge the gap between clinical diagnostics and clinical practice.