A 64 year-old woman presenting with fever, confusion, ophthalmoplegia and pneumonia.
Legionella pneumophila is a major cause of atypical community-acquired pneumonia, which is commonly severe enough to require hospitalization. (1,2) Though primarily a respiratory infection, Legionellosis involves the central nervous system (CNS) in up to 50% of patients, and diagnosis can be obscured by the absence of obvious respiratory symptomatology. (3) A reversible diffuse encephalopathy is the most common neurologic complication, but focal CNS involvement can sometimes be the initial presentation. (4,5,6) We report a case of a woman infected with Legionella pneumophila presenting with vague symptomatology and focal neurologic findings. This report highlights the challenges of early recognition of Legionella infection when neurologic symptoms predominate.
We describe the case of a 64-year-old woman with a past medical history of chronic hepatitis C infection and hypertension presenting to the emergency department with several days of generalized weakness, lethargy, subjective fevers, chills, and poor oral intake. The patient's family mentioned that she was also confused during this period. On initial presentation, the physical exam was significant for a left lateral gaze palsy, slowed mentation, and crackles on auscultation of the base of the left lung. Laboratory values were significant for a serum sodium of 128 mmol/L (normal 135-145 mmol/L) and a platelet count of 89,000/[micro]L (normal 130,000-400,000/[micro]L). There was also a mild elevation in creatinine to 1.12 mg/dL. Chest radiograph was significant for an infiltrate in the area of the left lower lobe, consistent with pneumonia (Figure 1).
The patient was initially admitted to the medical intensivecare unit for close monitoring of her focal neurologic findings. The patient was empirically started on ceftriaxone, ampicillin, acyclovir, and vancomycin to treat a potential central nervous system (CNS) infection. A lumbar puncture was attempted at the bedside, but was unsuccessful. The patient later refused a lumbar puncture attempt with interventional ra diolog y. Due to the pneumonia, she was also started on ciprofloxacin and oseltamavir. Blood cultures, sputum culture, and legionella urine antigen were collected prior to administration of antibiotics. Overnight the ophthalmoplegia resolved spontaneously, and on day two of admission, the patient was transferred to the medicine ward. Antibiotics were de-escalated to ceftriaxone and levofloxacin, and the patient's mental status was noted to have improved. Her hyponatremia and elevated creatinine normalized by the third day of hospitalization. By day four of her hospital stay, the patient's presenting symptoms had completely resolved, and she was discharged to complete a fourteen-day course of levofloxacin. One week after admission, her urine legionella antigen resulted as positive and the diagnosis of Legionellosis was confirmed.
Legionella pneumophila was first recognized as a causative pathogen of severe pneumonia in 1976 after an outbreak among American Legion conventioneers at Philadelphia's Bellevue Stratford Hotel. (7) Legionella species are aerobic Gram-negative bacteria found naturally in fresh water environments, and Legionnaires' disease outbreaks are usually associated with manmade fresh-water reservoirs, such as building-associated water systems. (8) There has been a recent increase in reported cases of Legionellosis since the turn of the century, but it is still unclear whether this represents a true increase in incidence or changes in testing and reporting practices. (8) The most common presenting symptoms are cough, dyspnea, and high fevers, but extrapulmonary manifestations such as diarrhea and neurologic deficits can also be seen. (9)
Here we describe a patient presenting with lethargy, confusion, and an ophthalmoplegia, who was subsequently diagnosed with a Legionella infection. Legionellosis involves the CNS in up to 50% of patients, commonly presenting with headache, somnolence, and varying degrees of encephalopathy. (3) Focal neurologic findings are uncommon, but cerebellar dysfunction, pyramidal dysfunction, and psychiatric symptoms have been reported. (6,10-15) Legionellosis presenting with an ophthalmoplegia or cranial nerve palsy as in our patient is even less frequent. (14,16-18) Proposed theories for the pathogenesis of Legionellaassociated neurologic dysfunction include direct invasion of brain parenchyma, (14,16) neurotoxin production, and autoimmune mechanisms. (4,14,16) The prognosis of neurologic deficits associated with Legionella infection is not well studied, but there are numerous case reports and case series of persistent neurologic symptoms. (4,6,14) Our patient's neurologic symptoms resolved with antibiotics, an outcome that has also been reported in other cases in the literature. (3,5,11,14,16)
Timely diagnosis of Legionella infection can be challenging when there is a lack of sputum production, only mild respiratory symptoms, or a predominance of extrapulmonary manifestations. (9) Early recognition of the disease is important, as delay in appropriate therapy has been associated with increased mortality. (19) Diagnosis of serotype 1 Legionella infection can be confirmed by urinary antigen tests, which have a specificity of 99% but a lower sensitivity of 74%. (20) Due to poor sensitivity, limited detection of non-serotype 1 Legionella, and the inability in certain settings to obtain these results rapidly, empiric antibiotic coverage is often needed before a diagnosis can be confirmed.
Though the heterogeneity of clinical presentation can make recognition of Legionella infection challenging, there are some unique clinical predictors which can help assess the likelihood of Legionella pneumonia. Higher fevers (sometimes with a relative bradycardia), absence of sputum production, hyponatremia, elevated LDH, and low platelets have been shown to be independent predictors of Legionella-associated community-acquired pneumonia (CAP). (9) In addition, highly elevated serum ferritin levels (mean level at initial presentation 1698 ng/ mL) have been associated with Legionella CAP while matched patients with non-Legionella CAP had levels less than twice the normal value. (21)
Treatment & Prognosis
Macrolides and fluoroquinolones are the IDSA-recommended first-line treatment for Legionella pneumonia. (22) Although studies showed superiority of respiratory fluoroquinolones to the older macrolides, (23,24) more recent trials comparing azithromycin and levofloxacin have shown no difference in mortality or length of hospital stay. (25,26) Also shorter antibiotic courses (7-14 days) have been found to have the same cure rates as the previously recommended duration of 21 days. (27,28) A large-scale study from the CDC showed a decrease in the case-fatality rate for Legionella CAP from 26%-10% for the period 1980-1998. (29) Implementation of community-acquired pneumonia (CAP) guidelines, which recommend empiric use of either azithromycin or a respiratory fluoroquinolone, could be a reason for the dramatic mortality reduction seen in community-acquired Legionella pneumonia. (30) With recent data showing 90-day mortality non-inferiority of beta lactam monotherapy compared to beta-lactam-macrolide combination or fluoroquinolone monotherapy for communityacquired pneumonia, (31) empiric use of therapy effective against Legionella may decline. This would make clinical recognition of Legionella infection even more important.
Legionella is an atypical pneumonia pathogen that can present with extrapulmonary symptoms including neurologic deficits. Early recognition and initiation of appropriate therapy against Legionella species improves mortality. Awareness of the unique clinical presentations of Legionella-associated infections is essential for the appropriate antimicrobial management of patients with community-acquired pneumonia.
(1.) Stout JE, Yu VL. Legionellosis. N Engl J Med. 1997; 337(10):682-7.
(2.) Muder RR, Yu VL, Fang GD. Community-acquired Legionnaires' disease. Semin Respir Infect. 1989; 4(1):32-9.
(3.) Robbins NM, Kumar A, Blair BM. Legionella pneumophila infection presenting as headache, confusion and dysarthria in a human immunodeficiency virus-1 (HIV-1) positive patient: case report. BMC Infect Dis. 2012; 12:225.
(4.) Alici O, Agalar C. Cerebellar involvement that occurred during treatment of Legionella pneumonia: A case report. J Microbiol Infect Dis 2013; 3 (2): 83-85.
(5.) Kulkarni KH, Thorat SB, Wagle SC, Khadilkar SV. Focal neurological manifestations in Legionellosis. J Assoc Physicians India. 2005; 53:731-3.
(6.) Baker PC, Price TR, Allen CD. Brain stem and cerebellar dysfunction with Legionnaires' disease. J Neurol Neurosurg Psychiatry 1981; 44:1054-1056.
(7.) Fraser DW, Tsai TR, Orenstein W, Parkin WE, Beecham HJ, Sharrar RG, Harris J, Mallison GF, Martin SM, McDade JE, Shepard CC, Brachman PS. Legionnaires' disease: description of an epidemic of pneumonia. N Engl J Med. 1977; 297(22):1189-97.
(8.) Neil K, Berkelman R. Increasing incidence of legionellosis in the United States, 1990-2005: changing epidemiologic trends. Clin Infect Dis. 2008; 47(5):591-9.
(9.) Fiumefreddo R, Zaborsky R, Haeuptle J, Christ-Crain M, Trampuz A, Steffen I, Frei R, Muller B, Schuetz P. Clinical predictors for Legionella in patients presenting with community-acquired pneumonia to the emergency department. BMC Pulm Med. 2009; 9:4.
(10.) Weir AI, Bone I, Kennedy DH. Neurological involvement in legionellosis. J Neurol Neurosurg Psychiatry 1982; 45:603- 608.
(11.) Morgan JC, Cavaliere R, Juel VC. Reversible corpus callosum lesion in legionnaires' disease. J Neurol Neurosurg Psychiatry 2004; 75:651-654.
(12.) Maskill MR, Jordan EC. Pronounced cerebellar features in Legionnaires' disease. Br Med J (Clin Res Ed) 1981; 283(6286):276.
(13.) Shetty KR, Cilyo CL, Starr BD, Harter DH. Legionnaires'disease with profound cerebellar involvement. Arch Neurol 1980; 37:379-380.
(14.) Johnson JD, Raff MJ, Van Arsdall JA. Neurologic manifestations of Legionnaires' disease. Medicine (Baltimore) 1984; 63:303-310.
(15.) Plaschke M, Strohle A, Then Bergh F, Backmund H, Trenk- walder C. Neurologic and psychiatric symptoms of Legionella infection. Case report and overview of the clinical spectrum. Nervenarzt. 1997; 68:342-345.
(16.) Basani SR, Ahmed SM, Habte-Gabr E. Legionnaires' disease with facial nerve palsy. Case Rep Med. 2011; 2011:916859. doi: 10.1155/2011/916859. Epub 2011 Mar 10.
(17.) JA Munoz, A Diaz Ortuno, et al. Paralysis of the third cranial nerve in legionellosis. Revista Clinica Espanola; 1988; 182(1):57.
(18.) Konno S, Kono H, Kitazono H, Murata M, Nakazora H, Nomoto N, Sugimoto H, Sanno K, Fujioka T. Legionellosis presenting as singultus and external ophthalmoplegia. Neurol Sci. 2012; 33(6):1435-7.
(19.) Heath CH, Grove DI, Looke DF. Delay in appropriate therapy of Legionella pneumonia associated with increased mortality. Eur J Clin Microbiol Infect Dis. 1996 ; 15(4):286-90.
(20.) Shimada T, Noguchi Y, Jackson JL, Miyashita J, Hayashino Y, Kamiya T, Yamazaki, S, Matsumura T, Fukuhara S. Systematic review and metaanalysis: urinary antigen tests for Legionellosis. Chest. 2009 ; 136(6):1576-85.
(21.) Cunha BA. Highly elevated serum ferritin levels as a diagnostic marker for Legionella pneumonia. Clin Infect Dis. 2008; 46(11):1789-91.
(22.) Victor, L. Y., Ramirez, J., Roig, J., & Sabria, M. Legionnaires disease and the updated IDSA guidelines for community-acquired pneumonia. Clinical infectious diseases; 2004; 39(11), 1734-1737.
(23.) Blazquez Garrido RM, Espinosa Parra FJ, Alemany Frances L, Ramos Guevara RM, Sanchez-Nieto JM, Segovia Hernandez M, Serrano Martinez JA, Huerta FH. Antimicrobial chemotherapy for Legionnaires disease: levofloxacin versus macrolides. Clin Infect Dis. 2005; 40(6):800-6.
(24.) Sabria M, Pedro-Botet ML, Gomez J, Roig J, Vilaseca B, Sopena N, Banos V; Legionnaires Disease Therapy Group. Fluoroquinolones vs macrolides in the treatment of Legionnaires disease. Chest. 2005; 128(3):1401-5.
(25.) Gershengorn HB, Keene A, Dzierba AL, Wunsch H. The association of antibiotic treatment regimen and hospital mortality in patients hospitalized with legionella pneumonia. Clin Infect Dis. 2015; 60(11):e66-79.
(26.) Griffin AT, Peyrani P, Wiemken T, Arnold F. Macrolides versus quinolones in Legionella pneumonia: results from the Community-Acquired Pneumonia Organization international study. Int J Tuberc Lung Dis. 2010; 14(4):495-9.
(27.) Yu VL, Greenberg RN, Zadeikis N, et al. Levofloxacin efficacy in the treatment of community-acquired legionellosis. Chest 2004; 125:2135-9.
(28.) Plouffe JF, Breiman RF, Fields BS, et al. Azith- romycin in the treatment of Legionella pneu- monia requiring hospitalization. Clin Infect Dis 2003; 37:1475-80.
(29.) Benin AL, Benson RF, Besser RE. Trends in legionnaires disease, 19801998: declining mortality and new patterns of diagnosis. Clin Infect Dis. 2002; 35(9):1039-46. Epub 2002 Oct 14.
(30.) Mandell, L. A., Wunderink, R. G., Anzueto, A., Bartlett, J. G., Campbell, G. D., Dean, N. C., et. al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clinical infectious diseases; 44 (Supplement 2); 2007; S27-S72.
(31.) Postma DF, van Werkhoven CH, van Elden LJ, Thijsen SF, Hoepelman AI, Kluytmans JA, Boersma WG, Compaijen CJ, van der Wall E, Prins JM, Oosterheert JJ, Bonten MJ; CAP-START Study Group. Antibiotic treatment strategies for community-acquired pneumonia in adults. N Engl J Med. 2015; 372(14):1312-23.
Dr. Johnson is a chief resident in the Department of Internal Medicine at Louisiana State University Health Sciences Center in New Orleans; Dr. Modica is a second-year resident in the Department of Internal Medicine at LSUHSC-New Orleans; Dr. Coleman is a chief resident in the Department of Internal Medicine at LSUHSC-New Orleans; Dr. Sanders is the Chairman of the Department of Medicine, the Edgar Hull Professor
of Medicine, and a Professor of Microbiology, Immunology, and Parasitology at the LSUHSC-New Orleans; Dr. Lopez is the Richard Vial Professor and Vice Chair of Education in the Department of Internal Medicine at LSUHSC-New Orleans.
|Printer friendly Cite/link Email Feedback|
|Title Annotation:||CLINICAL CASE OF THE MONTH|
|Author:||Johnson, Daniel H.; Modica, Michael; Coleman, Rachel; Sanders, Charles V.; Lopez, Fred A.|
|Publication:||The Journal of the Louisiana State Medical Society|
|Article Type:||Clinical report|
|Date:||Sep 1, 2016|
|Previous Article:||Telemedicine and telepsychology: a medicolegal dilemma clarifying standard of care for the physicians emergency certificate: a case report.|
|Next Article:||Heart failure in a man from Chile.|