A documented case of Legionella infection presenting with rhabdomyolysis and altered mental status

Ilaria Ricci Iamino*, Pierangelo Coppola*, Enrico Strocchi*, Claudio Borghi*

*Unità Operativa di Medicina Interna, Dipartimento Cardio-Toraco-Vascolare, Università di Bologna

Abstract

Legionnaires’ disease is a form of atypical pneumonia caused by any type of Legionella bacteria. Signs and symptoms include cough, shortness of breath and high fever. Neurological disorders associated with rhabdomyolysis may also, more rarely, occur.
An adult man was admitted to our Internal Medicine Department, with clinical and radiological evidence of pneumonia, then we started a broad-spectrum therapy with beta-lactams and macrolides antibiotics. Patient’s impaired cognition and confusion induced us to perform lumbar puncture which, however, didn’t show any alterations. In addition, he was treated with massive fluid therapy whereas he presented with severely elevated CPK values combined with myalgias, both suggestive of rhabdomyolysis. Detection of soluble Legionella antigen inurine specimen was positive, and consequently antibiotic therapy with levofloxacin was started. After 5 days of therapy the patient recovered completely.

Keywords

Legionella infection, pneumonia, rhabdomyolysis, urine antigen tests, altered mental status.

Introduction

In adults, Legionella infection causes 2-15% of the community acquired pneumonia (CAP) cases that require hospitalization. Association between Legionella and rhabdomyolysis was first described in 1980 by Posner et al. The mechanism is unclear, however, hypotheses include direct invasion of Legionella into the muscles, or the release of endotoxin in the bloodstream with subsequent muscle injury. 
Complications with Legionella infection may arise with central nervous system involvement (up to 50% of patients). It is however rare to observe evidence of infection by neuroimaging or cerebrospinal fluid analysis. While the neurological disorders observed range from peripheral neuropathy, to myositis, isolated nerve palsies and acute disseminated encephalomyelitis, altered mental status and headache are the most frequent neurological symptoms described. [1-3]

Case Report

We report the case of a 73-year-old man who came to the Emergency Department for fever, cough and asthenia. Chest radiography showed pneumonia of the left lower lobe [fig1] and at the blood tests we documented neutrophilic leukocytosis and increase of inflammation indices.

Figure 1

He was hospitalized in the Internal Medicine Department where, initially, he was treated with ceftriaxone and clarithromycin. At the neurological physical exam he appeared confused, unable to speak fluently and demonstrated difficulty with movements and balance. In addition, he reported visual hallucinations. A cranial CT was performed and showed a chronic cerebral vasculopathy [fig 2]. Results from a lumbar puncture did not prove any anomalies and microbiological analysis were negative in both blood and liquor samples. The urine analysis however, resulted positive for legionella infections. So the initial antibiotic therapy of ceftriaxone and clarithromycin was replaced with levofloxacin.

In addition, an increase in CPK levels (highest value 6166 U/L) were observed and treated with hydration therapy. The patient was discharged in good conditions, with a complete resolution of neurological disorders and a diagnosis of Legionella infection, complicated by rhabdomyolysis and acute confusion episode.

Discussion

Legionella bacteria are intracellular pathogens which can cause community-acquired and nosocomial pneumoniae (termed Legionnaires’ disease). When the infection manifests itself with a nonspecific febrile illness, typically self-limited and which resolves without antimicrobial therapy, it is called Pontiac fever.
When associated with pneumonia, infection could include fever, cough and shortness of breath [4-6]. 
Although Legionellaires’ disease has no specific clinical features, certain features can raise the index of probability: gastrointestinal symptoms (nausea, vomiting and diarrhea), altered mental status, hyponatremia, elevated hepatic transaminases, C-reactive protein levels > 100 mg/L, failure to respond to treatment for pneumonia with beta-lactam monotherapy [7-8].
Clinical manifestations range from mild to severe and mortality is about 1-10% [9].
Local complications are uncommon but include empyema and lung abscess. Extrapulmonary infections are rare (described especially in immunocompromised patients) and include cellulitis, skin abscess, septic arthritis, miopericarditis, endocarditis, meningitis and peritonitis. 
There are two different species of Legionella bacteria: Legionella pneumophila which is found worldwide and typically acquired from contaminated water sources and Legionella longbeachae, acquired from soil and with a restricted geographic distribution (Australia and New Zealand).
Laboratory testing is necessary for diagnosis. Testing methods include nucleic acid detection (eg, polymerase chain reaction [PCR] on a lower respiratory tract sample), urine antigen tests and culture. PCR is the preferred test for the diagnosis but it is not easy to obtain an adequate sample from the lower respiratory tract [10-11]. The commonly used alternative test is the urinary test whose sensitivity ranges from 70 to 80 percent and specificity approaches 100 percent in Legionella pneumophila serotype 1. The gold standard for diagnosis of Legionella infections is culture.
Other testing methods include direct fluorescent antibody [DFA] and serology; however, DFA often cross reacts with other respiratory pathogens and serology requires collection of acute and convalescent samples.
Levofloxacin and azithromicin are the preferred agents for the treatment of Legionella infection due to their bactericidal activity, the high intracellular concentrations and lung tissue penetration. Due to these reasons, it is suggested to use one of these agents when selecting an empiric antibiotic regimen for any patient with community-acquired pneumonia and therefore providing a broad spectrum therapy which may cover a potential Legionella infection.
In general, patients with a confirmed Legionnaires’ disease are treated for a minimum of 5 days; anyway, therapy is continued until the patient is clinically stable and afebrile for at least 48 hours. For immunocompromised patients and transplant recipients therapy is longer (minimum 14 days).

Conclusions

Legionella infection is recognized as a frequent cause of both community-acquired pneumonia and nosocomial pneumonia, accounting for between 2 and 15% of pneumonias requiring hospitalization. A rare but demonstrated complication of Legionella infection is rhabdomyolysis. 
Furthermore, the involvement of central nervous system is well described and the most frequent symptoms are altered mental status and headache.
In the case presented above, the only test that resulted positive for infection was the urinary antigen test. In early stages of infection serology can result negative (including IgM antibodies) and should be repeated after four weeks. After diagnosis we replaced the initial antibiotic therapy with levofloxacin; upon introduction of an adequate antibiotic therapy the patient very quickly felt better and the neurological symptoms disappeared.

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