Atypical Bacterial Pneumonia

Article Author:
Dustin Stamm
Article Editor:
Holly Stankewicz
3/8/2019 8:27:58 AM
PubMed Link:
Atypical Bacterial Pneumonia


Pneumonia is a lower respiratory tract infection, specifically involving the pulmonary parenchyma. Viruses, fungi and bacteria can cause pneumonia. The severity of pneumonia can range from mild to life-threatening, with uncomplicated disease resolving with outpatient antibiotics and complicated cases progressing to septic shock, acute respiratory distress syndrome (ARDS) and death.[1] It affects all age groups, accounts for over 2 million emergency visits annually, and is a leading cause of mortality in both adults and children. Atypical micro-organisms are known to cause a disproportionate disease burden in children and adolescents. Atypical organisms are difficult to culture.  They present subacutely and with progressive constitutional symptoms.[2]


Pneumonia is acquired when a sufficient volume of a pathogenic organism bypasses the body’s cough and laryngeal reflexes and makes its way into the parenchyma. This can occur from being exposed to large volumes of pathogens in inspired air, increasingly virulent pathogen exposure, aspiration or impaired host defenses. Given the different environments in which one may acquire pneumonia, the diagnosis is often broadly classified into community-acquired or hospital-acquired.[1] It may be further classified as viral, bacterial, or atypical bacteria based on the suspected pathogen requiring treatment.  Atypical pneumonia is acquired from various sources. There are a vast number of pathogens that are considered atypical, but the most commonly identified are mycoplasma pneumoniae which are associated with close living conditions like at school and military barracks, legionella from stagnant water sources, Chlamydophila pneumoniae, Coxiella burnettii, and Francisella tularensis from various mammalian sources.[3]


It is estimated that 7% to 20% of community-acquired pneumonia is secondary to atypical bacterial microorganisms. Given their intra-cellular nature, they are not visible on gram stain and are difficult to culture[4]; therefore, the true number of cases is unknown, but given similar treatments, specific etiology is often unnecessary. There is a preference for younger individuals, with age being the only reliable predictor in adults.


When the inoculating organisms overwhelm the host defenses, it causes a proliferation of the infectious agent. The pathogen replicating initiates the host immune response, and further inflammation, alveolar irritation, and impairment occur. This leads to the following signs and symptoms; cough, sputum production, dyspnea, tachypnea, and hypoxia.[1] Atypical infections result in less lobar consolidation. Therefore, patients do not usually appear toxic; hence the common term “walking pneumonia.”

Atypical organisms are an inclusive term for organisms difficult to culture and not apparent on gram stain. Given their intracellular nature, they are difficult to isolate and often challenging to treat because antibiotics must be able to penetrate intracellularly to reach their intended target. They are also grouped based on their subacute presentation and similar constitutional symptoms.

History and Physical

Patients often present with prolonged constitutional symptoms. Although not found to be predictive, it is traditionally taught that patients with atypical infections will present gradually and have a viral prodrome including a sore throat, headache, nonproductive cough, and low-grade fevers.[2] They rarely have an obvious area of consolidation on auscultation/imaging compared to pneumococcal pneumonia. Additionally, extra-cardiopulmonary symptoms are often seen; for example, mycoplasma infections are loosely associated with rashes, and bullous myringitis and Legionella is classically associated with gastrointestinal ailments and electrolyte abnormalities.


In a nontoxic-appearing patient, especially in the outpatient setting, a high clinical suspicion is all that is needed to pursue empiric treatment. In ill-appearing individuals or patients in whom the diagnosis is uncertain, a chest x-ray is the diagnostic gold standard.  Lab work often complements and further serves to help risk stratify individuals and direct treatment. Decision-making is only supplemented by lab studies. Some providers may check a complete blood count to test for leukocytosis and a left-shift, or complete a pro-calcitonin test to help differentiate viral versus bacterial etiology.  [5][6][7]Patients who are admitted to the hospital have urinary antigen tests and viral PCRs, allowing for detection of legionella, chlamydia, and mycoplasma. When patients appear toxic, it is also important to obtain blood cultures and sputum cultures, if possible,[2] to help with antimicrobial stewardship and the de-escalation of antibiotics.

Classic imaging findings in atypical pneumonia include patchy infiltrates, sometimes bilateral in distribution, and interstitial patterns.  They are less commonly associated with lobar consolidations and complicated parenchymal findings such as empyema and ARDS.

Treatment / Management

Atypical organisms such as M. pneumoniae, which is the most common, lack cell walls; therefore, beta-lactam antibiotics are not recommended.  First-line treatment is the macrolide family of antibiotics, although resistance is emerging. Azithromycin is the most common and is available in intravenous and oral formulations; the short treatment course of just 5 days increases patient compliance. Alternate outpatient antibiotics include fluoroquinolone and tetracycline. These are frequently utilized in older or more toxic-appearing individuals when more pyogenic organisms are also considered. In patients requiring hospital admission for presumed community-acquired pneumonia, a broadened approach is frequently utilized, and a beta-lactam such as ceftriaxone is added to azithromycin.[1]

Clinician tools such as the CURB 65 score and the pneumonia severity index are frequently utilized to determine if outpatient or inpatient medical treatment is most appropriate. [5][8]Well-appearing individuals in whom an atypical organism is suspected can be managed with outpatient antibiotics and symptomatic care.

Differential Diagnosis

The differential diagnosis for pneumonia typically spans cardiac, respiratory, and musculoskeletal systems. From the cardiac system, pericarditis and myocarditis can present in the setting of viral symptoms and should be considered. In the respiratory system, one must differentiate between upper and lower respiratory tree. The upper respiratory system includes pharyngitis, sinusitis and more emergent conditions such as epiglottitis and retropharyngeal abscess. For the lower respiratory tree, a chest x-ray will differentiate bronchitis/bronchiolitis versus pneumonia. It further complicates the diagnosis when an abnormal infiltrate is found on chest x-ray; in these cases, one must differentiate between atypical/viral/bacterial pneumonia, polymicrobial aspiration, and sterile chemical pneumonitis. Other noninfectious respiratory mimickers include asthma and COPD.[2] Lastly, it is important to consider musculoskeletal complaints such as costochondritis and rib dysfunction; however, they frequently lack constitutional symptoms.


The vast majority of patients in whom an atypical infection is suspected can be managed successfully as an outpatient. There is usually a complete resolution of symptoms and a low morbidity and mortality. Treatment is often uneventful in the absence of significant comorbid conditions, vital sign abnormalities, and a toxic appearance.  As with all clinical disease, not every case follows the expected course. Close follow-up and compliance are necessary to monitor for disease progression.

Enhancing Healthcare Team Outcomes

The diagnosis and management of atypical pneumonia is often difficult because laboratory results are not always immediately available, hence clinical acumen is necessary. The infection is best managed by a multidisciplinary team that includes an emergency department physician, infectious disease consultant, nurse practitioner, internist, radiologist, and a pharmacist. The majority of patients are managed as outpatients without sequelae. However, some atypical pneumonia may not follow the usual course and may result in severe symptoms, which require admission. [9][10][9]To avoid the morbidity and mortality, it is important to follow these patients until full resolution of symptoms is obtained. [11]


[1] Jain V,Bhardwaj A, Pneumonia, Pathology null. 2018 Jan     [PubMed PMID: 30252372]
[2] Mahashur A, Management of lower respiratory tract infection in outpatient settings: Focus on clarithromycin. Lung India : official organ of Indian Chest Society. 2018 Mar-Apr     [PubMed PMID: 29487250]
[3] Wagner K,Springer B,Imkamp F,Opota O,Greub G,Keller PM, Detection of respiratory bacterial pathogens causing atypical pneumonia by multiplex Lightmix{sup}®{/sup} RT-PCR. International journal of medical microbiology : IJMM. 2018 Apr     [PubMed PMID: 29397298]
[4] Ota K,Iida R,Ota K,Sakaue M,Taniguchi K,Tomioka M,Nitta M,Takasu A, An atypical case of atypical pneumonia. Journal of general and family medicine. 2018 Jul     [PubMed PMID: 29998043]
[5] McLaren SH,Mistry RD,Neuman MI,Florin TA,Dayan PS, Guideline Adherence in Diagnostic Testing and Treatment of Community-Acquired Pneumonia in Children. Pediatric emergency care. 2019 Feb 14;     [PubMed PMID: 30829848]
[6] Theodorsson E, [Laboratory diagnosis of rare diseases]. Lakartidningen. 2018 Nov 27;     [PubMed PMID: 30480747]
[7] Valade S,Biard L,Lemiale V,Argaud L,Pène F,Papazian L,Bruneel F,Seguin A,Kouatchet A,Oziel J,Rouleau S,Bele N,Razazi K,Lesieur O,Boissier F,Megarbane B,Bigé N,Brulé N,Moreau AS,Lautrette A,Peyrony O,Perez P,Mayaux J,Azoulay E, Severe atypical pneumonia in critically ill patients: a retrospective multicenter study. Annals of intensive care. 2018 Aug 13;     [PubMed PMID: 30105627]
[8] Eljaaly K,Alshehri S,Aljabri A,Abraham I,Al Mohajer M,Kalil AC,Nix DE, Clinical failure with and without empiric atypical bacteria coverage in hospitalized adults with community-acquired pneumonia: a systematic review and meta-analysis. BMC infectious diseases. 2017 Jun 2;     [PubMed PMID: 28576117]
[9] Postma DF,van Werkhoven CH,Oosterheert JJ, Community-acquired pneumonia requiring hospitalization: rational decision making and interpretation of guidelines. Current opinion in pulmonary medicine. 2017 May;     [PubMed PMID: 28198726]
[10] Arnold FW, How Antibiotics Should be Prescribed to Hospitalized Elderly Patients with Community-Acquired Pneumonia. Drugs     [PubMed PMID: 27928779]
[11] El Seify MY,Fouda EM,Ibrahim HM,Fathy MM,Husseiny Ahmed AA,Khater WS,El Deen NN,Abouzeid HG,Hegazy NR,Elbanna HS, Microbial Etiology of Community-Acquired Pneumonia Among Infants and Children Admitted to the Pediatric Hospital, Ain Shams University. European journal of microbiology     [PubMed PMID: 27766169]