Atypical Bacterial Pneumonia


Article Author:
Dustin Stamm


Article Editor:
Holly Stankewicz


Editors In Chief:
Venkat Minnaganti
John Brusch
Janak Koirala


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
3/8/2019 8:27:58 AM

Introduction

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]

Etiology

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]

Epidemiology

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.

Pathophysiology

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.

Evaluation

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.

Prognosis

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]


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Atypical Bacterial Pneumonia - Questions

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Which of the following organisms is a causative agent in nonzoonotic atypical pneumonias?



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Which of the following organisms is a causative agent in zoonotic atypical pneumonias?



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Which of the following is not a causative organism for atypical pneumonia?



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A 21-year-old male presents for evaluation of 4 days of subjective fevers, headache, nonproductive cough and myalgias. He states he didn’t want to come, but he has been fatigued and cannot perform his job duties. He notes other sick contacts and that he is up to date on all immunizations. He has no significant medical history. On exam, he is febrile to 100.6 degrees Fahrenheit; heart rate is 78 beats per minute, respiratory rate is 18 per minute, and oxygen saturation is 99% on room air. He well appears, with normal mentation and faint crackles scattered throughout the lower fields bilaterally. Which of the following organisms is the most likely cause of the patient’s symptoms?



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A 78-year-old male present from an apartment building for evaluation of cough, malaise, subjective fevers, and diarrhea. He appears well unremarkable vital signs. On physical exam, he appears to have faint crackles in the right lower lobe. On chest x-ray, he has an interstitial infiltrate pattern in the right lower lobe. He mentions that he has a water reservoir sitting at his window. He also has a humidifier unit he no longer uses secondary to the water container being full, and he has been too weak to empty it. An atypical etiology of his infiltrate is suspected. What is the most likely pathogen?



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Which of the following findings are more frequently associated with atypical bacterial pneumonia as opposed to pneumococcal pneumonia?



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Which of the following imaging or laboratory findings is most commonly seen with atypical bacterial pneumonia?



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Atypical Bacterial Pneumonia - References

References

Jain V,Bhardwaj A, Pneumonia, Pathology null. 2018 Jan     [PubMed]
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]
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]
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]
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]
Theodorsson E, [Laboratory diagnosis of rare diseases]. Lakartidningen. 2018 Nov 27;     [PubMed]
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]
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]
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]
Arnold FW, How Antibiotics Should be Prescribed to Hospitalized Elderly Patients with Community-Acquired Pneumonia. Drugs     [PubMed]
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]

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