A 73-Year-Old Man With a Pneumonia Syndrome and Mental Changes

Ronald N. Rubin, MD
Volume 56 - Issue 4 - April 2016

A 73-year-old man was brought to an urgent care center by his family. He lived alone in a small apartment and was able to care for himself and manage his financial and other affairs. He enjoyed recreational golf with his friends. However, the past week he had been unable to do so, and when his family checked in on him as they frequently did, they found him lethargic and less mentally sharp than usual.

During the visit, he said that a “dry” cough had been troubling him, and that he had a bit more shortness of breath than at baseline. He had moderate chronic obstructive pulmonary disease related to a prior 40 pack-year cigarette smoking history. He also had been having mild diarrhea for the past 72 hours.

His medications included a bronchodilator and a corticosteroid inhaler. He is a retired machinist who saw active duty in the war in Vietnam.

On physical examination, the man was subtly but definitely somewhat lethargic and confused, although he was able to answer coherently to direct questioning. His temperature was 40.2°C, his blood pressure was 110/60 mm Hg, and his pulse was 78 beats/min. There were no enlarged lymph nodes.

Chest examination revealed diffuse expiratory wheezing and signs of consolidation of the right lower lobe (RLL). His abdomen was nontender without masses. Results of a stool guaiac test were negative for heme. Neurologic examination revealed subtle mental acuity changes but otherwise was nonfocal.

Laboratory test abnormalities included a white blood cell count of 13,900/µL with a left shift. Chest radiographs revealed mild to moderate hyperinflation and RLL consolidation.

Which ones of the following statements about this patient's diagnosis and management is most accurate?

A. The chest radiograph can be expected to demonstrate at least one of several findings typical of and specific for Legionella pneumophila infection.
B. The patient’s presentation of severe community-acquired pneumonia in the absence of an associated cluster of cases is atypical of L pneumophila infection.
C. Legionella urinary antigen testing is relatively inexpensive and rapid but has poor sensitivity and specificity.
D. A macrolide should be included in this patient’s antibiotic regimen.

Answer on next page

Correct Answer: D

This case exemplifies the demographics, findings, and clinical therapeutics of an important etiology of severe community-acquired pneumonia (CAP): legionnaires disease caused by organisms of the genus Legionella, most commonly L pneumophila.

Epidemiology

Legionnaires disease received much notoriety and, indeed, its name in 1976 when a major outbreak involving hundreds of cases and with a 30% mortality rate occurred in Philadelphia, Pennsylvania, at an American Legion convention. Subsequent research has shown that the setting of that famous outbreak was a “perfect storm,” bringing together components of epidemiology that explain that outbreak of clustered cases. This included the affected population’s risk factors of cigarette smoking, age above 50 years, and the presence of existing chronic lung disease. An additional very important risk factor that is more prevalent today than in earlier descriptions is host immunosuppression such as that occurring with the use of glucocorticoids, biologic immune suppressive agents, and chemotherapy.1-3

Also contributing to the perfect storm was the mode of transmission. Legionella species have an optimum temperature of 35°C, slightly cooler than human body temperature. They thrive in aquatic biosystems and, in fact, often live within and symbiotically with fresh-water amoebae.2,3 Thus, exposure to these organisms occurs most commonly by way of aerosolized droplets of contaminated water, such as from air conditioning systems, cooling towers, and, iatrogenically, respiratory therapy equipment.2,3 Whenever a cluster of cases are encountered, either in the community or in a hospital, such sources need to be aggressively explored. However, Legionella also is an important cause of sporadic CAP, with prevalence figures ranging from 2% to 15% of cases of CAP,2 as was the situation in the patient’s case presented here. The community-acquired sporadic cases far outnumber the cluster outbreaks, and Answer B is not a correct statement.

Clinical Findings

Despite earlier reports in the literature of “typical” findings associated with Legionella infection, in 2016 Legionella pneumonia most often will be a nonspecific pneumonia syndrome, with the pneumonia dominating the picture. Still, certain ancillary findings are more frequent in Legionella cases than with other community-acquired infections and include the following: (1) unusual severity characterized by high temperature (> 40°C) and mental changes such as confusion and obtundation; (2) gastrointestinal tract findings, especially diarrhea in 20% to 40% of cases; and (3) hyponatremia, with serum sodium less than 130 mEq/L.1-3 The presence of abnormalities on chest radiographs are almost universal and cover a variety of changes including lobar consolidation, nodular infiltrates, and pleural effusions. However, chest radiography findings are nonspecific and cannot be used to confirm or exclude Legionella as a potential cause of CAP, and Answer A thus is not a correct statement.

Diagnosis

Legionella is not an easy organism to grow in the laboratory, but in recent decades excellent surrogate methods have been developed. The optimal diagnostic methods when considering speed, availability, cost, sensitivity (70%) and specificity (100%) seems to be the urinary antigen assay, which is the most commonly used diagnostic method today. A criticism of this test is its limitation to infections caused by L pneumophila serogroup 1 and not other Legionella species. However, because 90% or more of human Legionella infections are with L pneumophila serogroup 1, for now this assay is considered the standard of diagnosis.2,3 Answer C greatly underestimates the sensitivity and specificity of this test and is an incorrect statement.

Clinical Therapeutics

The poor results and high mortality rate seen in earlier epidemics and sporadic experiences with Legionella can be attributed to the high-risk characteristics on the host side, as well as the use of antibiotics to which Legionella are not sensitive. However, currently available newer macrolides (azithromycin), quinolones, and rifampin all have good efficacy against Legionella.2-4 Parenteral forms are indicated in severe cases, such as patients requiring intensive care unit admission. The duration of therapy can be 3 to 5 days in mild cases but as long as 14 days in severe, intensive-care or immunosuppression-related cases.2,3 Thus, Answer D is the most appropriate one here.

Patient Follow-Up

Within 8 hours, a urinary antigen test for Legionella was reported as positive, confirming the diagnosis of legionellosis. Intravenous azithromycin was given, and by day 4 the patient had become afebrile. Oral azithromycin was given for a total of 10 days, with eventual complete clinical and radiologic resolution of all abnormal findings. 

Ronald Rubin, MD, is a professor of medicine at the Temple University School of Medicine and is chief of clinical hematology in the Department of Medicine at Temple University Hospital, both in Philadelphia, Pennsylvania.

References:

  1. Roig J, Domingo C, Morera J. Legionnaries’ disease. Chest. 1994;105(6): 1817-1825.
  2. Stout JE, Yu VL. Legionellosis. N Engl J Med. 1997;337(10):682-687.
  3. Cunha BA, Burillo A, Bouza E. Legionnaries’ disease. Lancet. 2016; 387(10016):376-385.
  4. Postma DF, van Werkhoven CH, van Elden LJR, et al; CAP-START Study Group. Antibiotic treatment strategies for community-acquired pneumonia in adults. N Engl J Med. 2015;372(14):1312-1323.