Introduction

Overview of Atypical Pneumonia

Pneumonia is an infection of the lower respiratory tract, the lung parenchyma. Causes usually are of bacteria, viral, or fungi origin. Pneumonia can be mild, moderate, severe, or life-threatening. Treatment ranges from outpatient treatment to intensive care management depending on the severity of the Pneumonia.¹ Pneumonia is termed typical when it is caused by typical pathogens like Streptococcus pneumonia, Staphylococcus spp, and Haemophilus influenzae. 

Pathogens causing atypic pneumonia include:

• Mycoplasma spp
• Chlamydia pneumoniae
• Legionella species
• Coxiella burnetii (Q fever)²

Atypic pathogens causing pneumonia are intracellular organisms that lack the cell wall that makes typical pathogens susceptible to typical forms of treatment with β-lactam antimicrobial therapy.²

Significance of Studying Immunocompromised Patients

Definition of immunocompromised states

Immunocompromised states, also known as immunosuppressed patients, are patients with weakened immune systems, usually caused by infections and disease conditions like AIDS, cancer, diabetes, malnutrition, and certain genetic disorders. Reduced immune systems can also be caused by certain medications or therapies such as anticancer drugs, radiation therapy, and stem cell or organ transplants. These patients have little ability to fight disease or infections.³

Susceptibility to atypical pathogens and severity of infections

Atypical pneumonia is noted to cause severe to life-threatening pneumonia. This has been demonstrated by Dr Wang and collaborators in 2023 that with an overall frequency of 8.1% of atypical pneumonia, 

• Chlamydia pneumoniae causes 1.8% of severe pneumonia
• Mycoplasma Tuberculosis causes 2.8% of severe pneumonia
• Legionella spp causes 4.0% of severe pneumonia⁴

Atypic pneumonia in immunosuppressed patients is mostly severe to life-threatening as these patients' immune systems have a reduced ability to fight this microorganism.⁵

Background on Immunocompromised Populations

Types of Immunocompromised Conditions

• AIDS/HIV 

HIV destroys mostly human CD4+T cells along with other immune cells like monocytes, macrophages, and B cells, leaving the human body with a reduced immune system that is unable to fight against disease conditions or opportunistic infections.⁶

• Organ transplant recipients

In patients undergoing organ transplants, the transplanted organ may be rejected by the recipient's body. This manifests as the recipient's immune system attacking the transplanted organ as a foreign body. To prevent this, immunosuppressant medications reduce the recipient's immunity, preparing the recipient for the transplantation process.

This, however, causes an immunocompromised state in organ transplant recipients, making them vulnerable to opportunistic infections.⁷

• Cancer patients

Cancers like lymphoma and leukemia, which affect the bone marrow as well as other types of cancer with metastasis to the bone marrow, prevent immune cell development, thus leading to a weakened immune system.⁸ Cancer treatment by chemotherapy, radiotherapy, targeted cancer cell therapy, and steroids can also lead to immunosuppression through the reduced quantity of white blood cell production by bone marrow. End-stage cancerous diseases are treated by organ transplantation, which is also associated with immune suppression.^7,8

• Autoimmune diseases

Autoimmune diseases are conditions in which the immune system attacks healthy body cells as invaders or foreign bodies. Examples include Graves’ disease, Systemic Lupus, Rheumatoid arthritis, Crohn's disease, Ulcerative colitis, etc. Treatment involves long-term use of steroids, which suppresses the immune system.⁹

• Medication-related immunosuppression

Medications known to cause immunosuppression include steroids, anti-cancer medications, and immunosuppressants.¹⁰

Clinical Presentation of Atypical Pneumonia in Immunocompromised Patients

Clinical presentations of atypical pneumonia in immunocompromised patients vary depending on the causative agent. Mycobacterium tuberculosis usually manifests in a chronic form, whereas Pneumocystis pneumonia presents in an acute form.¹¹

Symptoms and Signs

The signs and symptoms include

• Low or high-grade fever
• Cough (dry or productive)
• Shortness of breath
• Hemoptysis
• Altered state of consciousness, especially in elderly patients
• Dullness during percussion
• On auscultation: Crepitation, rhonchi, and bronchial breath sounds¹¹

Laboratory findings also vary depending on the causal agent. The Laboratory evaluations include:

• Complete blood count showing leukocytosis with raised neutrophils in cases where immune suppression is not caused by neutropenia
• Increased C-reactive protein as a sign of inflammation
• Sputum smear and culture in cases of productive cough to identify causal agents,
• Blood culture to identify the causal agent
• CD4 counts in HIV-infected persons¹¹ 

Morphological evaluations include:

• Chest X-ray for every suspected case of Pneumonia
• Computer tomography of the chest¹¹ 

Case Studies

HIV-positive patient with Mycoplasma pneumonia

Mycoplasma pneumoniae is a significant concern in HIV-positive patients, with studies showing a higher prevalence compared to HIV-negative individuals. In HIV-positive adults with community-acquired pneumonia, M. pneumoniae prevalence was found to be 17% in induced sputum and 11.3% in throat swab cultures.¹³ 

Clinical presentations associated with M. pneumoniae in HIV-positive patients include: 

• Respiratory symptoms such as cough, shortness of breath, chest pain, 
• fever
• rales, 
• pharyngeal erythema, 
• cervical adenopathy, and 
• skin rash¹³

Diagnosis of atypical pneumonia in HIV patients can be challenging due to compromised antibody responses; as such, we may find normal X-ray results. This has led to the necessity of the use of PCR-based methods. Despite advances in antiretroviral therapy, bacterial pneumonia remains a significant cause of death in HIV-infected individuals. A 7–10 day course of treatment with macrolides (clarithromycin, erythromycin, or azithromycin), doxycycline, or fluoroquinolones (levofloxacin or moxifloxacin) is used for atypic pneumonia infections in HIV patients.¹⁴

Organ transplant recipient with Legionella pneumonia

Dr. McGinnis and collaborators described 2 cases of organ transplant recipients with Legionella pneumonia in: 

• Donor: A 30-39-year-old person, born male, who drowned in a river. He was declared brain dead after resuscitation attempts, his organs were collected for transplant¹²
• Recipient A: A 70-79-year-old person, born female, received a right lung transplant from the above donor in May 2022. Nine days following the transplantation procedure, laboratory results showed elevated white cell counts and acute anemia. Further exploration with a CT scan revealed consolidation of the middle lobe of the transplanted right lung, which later formed a cavitatory lesion in the subsequent weeks. A sputum specimen was collected through bronchioloalveolar lavage, which tested positive for Legionella species. Treatment was immediately initiated with doxycycline, and the patient fully recovered¹²
• Recipient B: A 60-69-year-old, born male, was the recipient of the left lung from the above-mentioned donor. The transplantation procedure was done on the same day as recipient A. Recipient B experienced severe complications in the postoperative period. He was administered antibiotic treatment with the initiation of doxycycline on day 15 post-surgery. After recipient A’s case was discovered, a sputum specimen was collected in early June and tested positive for L. pneumophila by culture¹²

Challenges and Limitations

Diagnostic Challenges

Diagnosing atypical pneumonia in immunosuppressed conditions is still a challenging task and becomes even more so when the patient is severely immunocompromised. Due to the lack of data, the lack of consideration, and the current subpar diagnostic methods, atypical bacterial pneumonia is often left undiagnosed in HIV-infected individuals.¹⁴

Treatment Limitations

Due to the atypical nature of the pathogens causing atypical pneumonia, there are increased problems with antibiotic resistance. These atypic germs do not respond to Beta-lactams, aminoglycosides, and sulfa drugs used in treating typical pneumonia. The growing antibody resistance in individuals will cause difficulties in the treatment of atypical pneumonia.¹⁴

Complications from immunosuppressive treatments in cases of organ transplant can cause adverse drug reactions with antibiotics used to treat atypical pneumonia.⁷

Summary

Atypic pneumonia is caused by atypic germs, which lack a cell wall. Patients with immunocompromised states have severe to life-threatening cases of atypical pneumonia. Clinical presentation varies due to the causal agent. Diagnostic criteria are limited as PCR methods are the surest way to identify the causal pathogens. Treatment is essentially done with fluoroquinolones.