Introduction

Pneumonia is an infection that affects the lower respiratory tract causing the alveoli, the small air sacs in the lungs, to become inflamed and filled with fluid and pus. Different pathogens (organisms that cause diseases) can be responsible for pneumonia, including bacteria, viruses, or fungi. Pneumonia can be a life-threatening disease, with symptoms ranging from mild to severe. According to the World Health Organisation (WHO), pneumonia ranked among the top 10 leading causes of death worldwide in 2021 and was responsible for 39 million deaths.¹ 

Pneumonia presents with a range of symptoms like:

• Cough
• Fever
• Chills
• Sweats
• Shortness of breath
• Chest pain
• Low energy
• Fatigue
• Muscle aches
• Stiff joints 

The typical bacterial strains responsible for pneumonia are detectable using standardised bacteriological testing. On the other hand, atypical pathogens contribute to the instances of atypical pneumonia observed.²

Understanding atypical pneumonia and its pathogens

Many Pathogens can cause atypical pneumonia; however, the most common bacterium is Mycoplasma pneumoniae.² Other atypical pathogens that cause atypical pneumonia include Chlamydia pneumoniae, Coxiella burnetii, Francisella tularensis, and the most pathogenic of the group is Legionella pneumoniae, which causes severe lung infections.²

Bacterial classifications

Bacteria can be classified into two categories based on the cell wall: a protective multilayered structure that envelops the bacterium. Bacteria can be either gram-positive or gram-negative. Gram-positive bacteria comprise a thick peptidoglycan layer that surrounds the cell wall, while the peptidoglycan layer in gram-negative bacteria is thinner and located between the membranes. 

On this basis, antibiotics are designed to target the peptidoglycan layer of bacterial cell walls to kill them or hinder their replication. However, atypical bacteria do not respond typically to antibiotics, primarily due to the rise in antibiotic resistance.

Additionally, these microbes are not easily detectable by bacteriological testing methods, such as culturing on standard media or gram staining. This ultimately creates a challenge in determining the pathogen responsible for atypical pneumonia.

How is atypical pneumonia diagnosed?

A detailed patient medical history and physical examination are conducted. Further diagnostic testing, including a complete blood count (CBC), urine analysis, and chest X-rays to rule out bronchitis, is considered for a patient suspected of atypical pneumonia. Molecular-based diagnostic tests are performed on throat or sputum swabs to pinpoint the exact organism causing the illness.

Why is accurate diagnosis important?

Given the wide variety of organisms that can cause atypical pneumonia, it is crucial to pinpoint the exact pathogen responsible for the illness and ensure that treatment regimens are specific and effective. To achieve this, molecular-based methods have replaced time-consuming traditional bacteriological methods, in which atypical organisms tend to be undetectable.

What is PCR testing?

Polymerase Chain Reaction (PCR) is a molecular biology technique used in labs to make thousands of copies of a specific region of DNA for further analysis.³ It works by using specific molecules called primers that flank the section of DNA being investigated, with enzymes called polymerases that copy it repeatedly in a short time frame. This technique is sensitive enough to detect very small amounts of genetic material from bacteria or viruses. Scientists can design experiments using PCR to target specific genes and identify the exact microbes responsible for atypical pneumonia.

How PCR testing works for atypical pneumonia

Sample collection and testing processes

A healthcare provider (HCP) obtains samples of saliva (from the throat) and nasal secretion (from the nose). Swabs are used for this process which is done by tilting the patient’s head backward. Then, the inserted swab is gently rotated a few times.

Depending on the type of testing, the specimen type required may vary between a nasopharyngeal swab, a throat swab, or a respiratory tract specimen such as sputum. The specimen is transported to the lab under optimal conditions to preserve it for the duration of the journey.

How samples are tested in the lab

In the lab, based on the specimen type and suspected diagnosis, specific experiments are conducted to extract and isolate the DNA of the pathogen present in the sample. Then the sample undergoes PCR testing, and the results are interpreted.

Results and their significance

Unlike standard culture-based tests that require bacteria to grow over for several days, PCR is an automated process typically completed in a few hours. However, the turnaround time for patient results may still take a few days. Nevertheless, PCR testing significantly reduces the wait time, ensuring the patient can begin treatment plans as soon as possible. PCR quickly identifies the specific microbe causing the infection, guiding healthcare providers in developing targeted treatment plans to eradicate the pathogen and alleviate symptoms.

Advantages of PCR testing in treating atypical pneumonia

There are several advantages of using PCR testing to diagnose atypical pneumonia.

Faster diagnosis, faster treatment

PCR testing helps doctors initiate targeted treatment more quickly. Atypical bacteria can be difficult to grow on standard culture media, significantly limiting the usefulness of this type of testing for diagnosing atypical pneumonia. PCR testing can detect pathogens and allows for the accurate and rapid identification of microbes, promptly enabling the next steps in patient care. 

Targeted treatment

Trial and error to identify whether a bacterium or virus is causing the infection can be eliminated, as the exact organism responsible can be readily identified. This avoids the unnecessary administration of antibiotics and antivirals, which could contribute to the growing problem of antimicrobial resistance.

Improved patient outcomes

Since PCR enables the correct treatment to be administered more quickly, it ultimately results in improved patient outcomes, with faster recoveries and fewer complications.

Benefits of PCR testing

While X-ray imaging provides insight into infections present in the lungs, imaging alone cannot conclusively pinpoint the exact underlying pathogen.

Limitations of PCR testing 

Although PCR testing has greatly improved diagnostic processes, limitations to its use are there.

Potential downsides

PCR runs the risk of producing false positive results because it is such a sensitive technique, as it can amplify DNA contaminants present in the sample. For example, if the microorganism of interest shares similar DNA sequences with another, false positives could occur as amplification of both organisms’ DNA may take place.

On the flip side, false negatives can also occur. While this issue is significantly reduced by using appropriate controls and adhering to good laboratory practices and procedures, false positives and false negatives remain one of the main limitations of PCR testing. 

Another downside of PCR testing is that if the pathogen causing the illness is unknown, PCR cannot be used to detect it. This is because PCR experiments are designed to target specific DNA sequences for amplification, therefore PCR can only confirm the presence of suspected pathogens, not identify unknown ones.

Availability and cost

Not all hospitals or clinics have access to PCR testing, and in some cases, acquiring the necessary reagents and equipment for PCR testing can be expensive.

Summary

Atypical pneumonia is a type of pneumonia caused by pathogens that are not usually responsible for the condition. It presents as a respiratory tract infection, with symptoms ranging from mild to severe. Common symptoms of atypical pneumonia include: coughing, sweats, chills, fever, muscle aches, and chest pains.

Diagnosing atypical pneumonia involves a physical examination and a review of the patient’s medical history. The physician may also order a complete blood test and chest X-rays to detect signs of infection. Although traditional bacteriological culture tests are used, these pathogens are difficult to grow in cases of atypical pneumonia, making accurate diagnosis a challenge.

PCR is a vital tool for quickly and accurately identifying the cause of atypical pneumonia, allowing doctors to provide optimal care. As PCR technology continues to advance, it will play an increasingly important role in improving pneumonia diagnosis and treatment, leading to better outcomes for patients.