October - December 2007: 
Volume 20, Issue 4

Click on the image to download the Issue in PDF format.


Fulminant multiorgan failure due to legionella pneumophila Diagnostic and therapeutic problems in the ICU
SUMMARY. We describe a case of severe community-acquired systemic Legionella pneumophila infection which manifested abruptly as pneumonia, septic shock, and acute respiratory distress syndrome (ARDS) severe myocardyopathy and was successfully treated in the Intensive Care Unit. The favorable outcome of this case is based, in part, on some important diagnostic and therapeutic procedures that are explicitly discussed. Pneumon 2007; 20(4):412–417
Full text


Legionnaire’s disease is usually caused by the intracellular gram-negative bacterium Legionella pneumophila. The clinical manifestations include acute febrile syndrome and respiratory tract symptoms ranging from mild problems to life-threatening pneumonia1,2. The mortality rate of Legionella pneumonia among immunocompetent patients is 5-25%3. Extrapulmonary manifestations, although uncommon, may be extremely serious. In these cases, there is a prodromal phase with systemic infection with bacteraemia4.

This is a case report of severe community-acquired systemic Legionella infection, which presented abruptly with pneumonia, septic shock, adult respiratory distress syndrome (ARDS) and severe myocardyopathy, and was treated in the intensive care unit (ICU). The favourable outcome of this case was based, in part, on certain specific diagnostic and therapeutic procedures that are discussed.

Figure 1. Chest X-ray in the Emegerncy Department: Consolidation and pulmonary oedema due to acute heart failure, increased cardiothoracic ratio, redistribution of circulation due to venous hypertension.


A 54 year-old civil servant was brought to the emergency department (ED) in acute respiratory failure, with a five-day history of worsening dyspnoea and a two-day history of fever of up to 39°C, accompanied by productive cough with yellowish sputum. He was being treated for hypertension with enalapril and amlodipine, he had hypercholesterolaemia, and he had undergone prostatectomy six months earlier. He was an active smoker and heavy drinker.

Physical examination revealed central cyanosis with signs of severe respiratory distress (respiratory rate 30 per minute with use of auxiliary muscles), pulse rate 130 per minute, blood pressure 70/40 mmHg and temperature 39.2°C.

On lung auscultation, some diffuse rales were audible bilaterally on deep inspiration, followed by prolongation of expiration. A third heart sound was evident on cardiac auscultation. The patient also had mild pitting oedema of the lower extremities, but no other clinical findings. His consciousness level was excellent (Glasgow Coma Scale, 15). Paraclinical examinations revealed impaired gas exchange: pH 7.26, PO2 20mmHg, PCO2 61mmHg, HCO3 27.4 mEq/L with FiO2 21%, indicating profound hypoxaemia and uncompensated hypercapnia (type II acute respiratory failure).

The electrocardiogram (ECG) revealed sinus tachycardia and altered depolarization patterns in leads I, II, III, aVL, V5 and V6. Chest X-ray showed diffuse bilateral opacities with an alveolar pattern, increased cardiothoracic index, portal accentuation and signs of venous hypertension (Figure 1). Echocardiogram revealed no abnormalities in the movement, size and shape of heart chambers and the function of heart valves, and no presence of pericardial effusion, but there was a left-sided pleural effusion.

Laboratory tests revealed leukocytosis with polymorphonucleosis: Ht 41.4%, Hb 14.2 g/dL, WBC 24,460/Μl (P 93%, L 5%, Μ 2%), abnormal renal indices: PLT 240 K/μL, Urea 50mg/dL, Creatinine 1.7mg/dL, CRP 13.6mg/dL, K+ 3.8 mmol/L, Na+ 144 mmol/L, Ca2+ 7.9mg/dL, PO43- 2.9mg/dL, and slightly impaired hepatic indices: LDH 748 U/L, SGOT 80 U/L, SGPT 85 U/L, γGT 153 U/L, CPK 184 U/L, CPK-MB 28 U/L, Total Protein 6.3g/dL, Albumin 3.3g/ dL, Total Bilirubin 0.8 mg/dL, Direct Bilirubin 0.6mg/dL, Amylase 25 U/L, slight increase of D-Dimmers, 504 ng/ml and negative troponin test.

On admission to the ICU (19.00 pm) non-invasive mechanical ventilation support was applied initially as the patient was conscious despite the severe hypoxaemia, but this failed to improve the clinical status or the arterial blood gas profile. The patient was then intubated and propofol and remifentanil were administered to maintain sedation in case of need for co-administration of cisatracurium for neuromuscular paralysis because of patient-ventilator asynchrony.

Despite the use of controlled mandatory ventilation [IPPV with FiO2 1, respiratory frequency (f ) 20/min, tidal volume (TV) 500 ml and PEEP of 8 cm H2O] according to the ARDS Network5, there was a gradual deterioration of the blood gas profile: pH 7.12, PO2 55 mmHg, PCO2 64mmHg.

At this time, the alveolar recruitment maneouvre (ARM) was performed with continuous positive pressure ventilation (CPAP) of 40cm H2O for 40 sec, which improved the oxygenation remarkably (SpO2 89-98%). The new PEEP value providing adequate oxygenation (SpO2 ≥90%) was set at 20 cm H2O.

The ECG demonstrated ST segment depression, ST >2 mm in leads ΙΙ, ΙΙΙ, aVF, aVL, V4, V5, and V6, and the patient developed haemodynamic instability and anuria. For this reason, a Swan-Ganz catheter was inserted into the pulmonary artery and the measurements showed high pulmonary capillary wedge pressure (PCWP), low cardiac output (CO) and a fall in mixed venous oxygen saturation (SvO2), [PCWP 24 cm H2O, CO 4,2 L/min, CI 1,8 L/m2/min, SvO2 55% respectively].

This haemodynamic profile was considered to be an indication for administration of β-adrenergic drugs (dobutamine 15μg/kg/min) and vasopressors (norepinephrine 1μg/kg/min) in combination with intravenous crystalloids (-5L positive equilibrium in 4 hours) and continuous infusion furosemide 50 mg/h, which resulted in haemodynamic stabilization and normalization of the urination pattern.

A diagnostic pleural tap was performed which revealed fluid consistent with a complex parapneumonic exudate. According to Light, every pleural effusion related to pneumonia or lung abscess is called parapneumonic, whether the complex effusion requires, by definition, invasive treatment (i.e thoracotomy tube insertion) or is positive on culture6. Effusions with pH <7.2, Glucose <60 mg/dL and LDH >3 times the superior normal range in blood levels need drainage, while the pH is considered the most sensitive diagnostic index. The presence of pus (empyema) is an absolute indication for invasive treatment (drainage by needle or thoracotomy tube insertion)7. In this case, the pleural fluid had the appearance of viscous pus with pH <7.2 and glucose <60 mg/dL. Culture of blood, urine, pleural fluid and bronchial secretions were ordered, along with Legionella Urinary Antigen (Ag) Test determination, and empirical antibiotic treatment was initiated (imipenem-cilastatin 1g×3, moxifloxacin 400mg×1, linezolid 600 mg×2 and azithromycin 500mg×1).

Figure 2. Chest X-ray on the 2nd day of hospitalization: Persisting picture of pulmonary oedema. Swan Ganz catheter in the right pulmonary artery. Haemodynamics findings point to mixed oedema, hydrostatic + ARDS (see text).

After a 12-hour stay in ICU, despite the continuous resuscitation measures, the patient’s respiratory function deteriorated (pH 7.16, PCO2 79mmHg, PO2 40mmHg on IPPV with f 28/min, TV 500 ml with FiO2 1.0 and PEEP 20 cm H2O). The haemodynamic instability resulted in oliguria and finally anuria with further worsening of the renal indices (Urea 67mg/dL, Creatinine 2.3 mg/dL). Eight hours later, the haemodynamic status was: CO 14 L/min, CI 6.2 L/m2/min, PCWP 20 mmHg, systemic vascular resistance (SVR) 244 dynes sec cm-5, pulmonary vascular resistance (PVR) 113 dynes sec cm-5, SVΟ2 55%, oxygen delivery (DO2) 591ml/min, oxygen consumption (VO2) 297 ml/min, shunt fraction (Qs/Qt) 41.2%.

A transoesophageal echocardiogram was performed but no pathological features were found. Further deterioration was noted on the chest X-ray (Figure 2). Based on the above findings, the gradual discontinuation of dobutamine and escalation of the dosage of furosemide and norepinephrine were ordered.

A few hours later, the diagnosis of Legionella infection was confirmed by the Legionella Urinary Antigen (Ag) Test, so the antibiotic treatment was switched to imipenemcilastatin 1g×3, moxifloxacin 400 mg×1, rifampicin 600mg ×2 and azithromycin 500mg×1.

At this stage, the diagnosis was made of severe Legionella pneumonia complicated by ADRS, septic shock and acute heart failure, which ultimately progressed in multisystem organ failure.

On the 2nd day post admission, due to progressive deterioration of renal function and worsening metabolic acidosis, renal replacement therapy with continuous veno-venous haemofiltration (CVVH) was initiated. Six CVVH sessions were adequate for the partial recovery of renal function. At the same time, intravenous treatment was commenced with activated protein C (APC-Xigris 24 μg/kgr/h). The cultures of urine, pleural fluid and bronchial secretions failed to identify any pathogenic organisms.

On day 4, APC was discontinued because of upper gastrointestinal bleeding. The ventilation and oxygenation improved progressively (pH 7.33, PO2 66 mmHg, PCO2 51mmHg on IPPV with f 27/min, TV 650 ml, FiΟ2 0.6 and PEEP 12 cm Η2Ο) and by the end of day 4 there was a gradual decrease of core temperature (37°C), remission of leukocytosis (11,810/μL) and improvement of the chest X-ray.

On the 7th day post admission, the patient again became febrile (39.5°C) with increased WBC count (16,820 → 24,500/Μl with 87% polymorphonuclear leucocytes) and required increased doses of inotropic drugs (norepinephrine 0.2 → 1 μg/kg/min), although the chest X-ray was improved (Figure 3).

The central venous catheter was replaced immediately and blood, urine, catheter-tip and bronchial secretions samples were taken for culture, and the antimicrobial treatment was switched to colistin 1×106 ×1, meropenem 1gr×3, moxifloxacin 400mg×1, rifampicin 600mg×2 in order to cover possible nosocomial bloodstream infection by Gram-negative pathogens. Clinical and laboratory improvement was noted within 48 hours as the patient responded to the treatment, although no causative pathogen was isolated.

Urination patterns were restored to normal on day 7 and the renal indices improved by day 8. Diuretics were discontinued on day 13, and the last CVVH session performed on day 12. Inotropics were discontinued the same day, while the sedation was gradually decreased and eventually discontinued on day 14. The patient recovered consciousness on day 15 and ventilatory weaning was started on day 16. There was no need for tracheostomy but only periodic support with noninvasive positive pressure ventilation (NIPPV) for the following 48 hours.

On day 24, the patient was transferred to a general ward with blood gases pH 7.47, PO2 67mmHg, PCO2 48mmHg, with Venturi mask 50%, in a stable haemodynamic state, without fever and with normal urination patterns.

Figure 3. Chest X-ray on the 7th day of hospitalization: Significant improvement of pulmonary oedema. Incomplete expansion and atelectasis at the base of both lungs


Despite the publication of diagnostic criteria for severe community pneumonia by both the American Thoracic Society (ATS) and the British Thoracic Society (BTS), a universally accepted definition is still lacking8,9. However, it is commonly believed that every case of pneumonia that needs treatment in an ICU can be characterized as severe. Its high mortality rate (20-50%) makes early detection and urgent treatment a primary concern for definitive management.

The following reasons indicate the need for admission of patients with severe community pneumonia to the ICU:

1. Severe acute respiratory failure (which may need mechanical ventilatory support).

2. Haemodynamic instability (usually due to concomitant septic shock).

3. Need for management of multi-organ failure.

The case presented here was characterized as typical severe community pneumonia due to Legionella pneumophila that led to the development (within hours) of multiple organ failure, affecting concurrently:
1. The lungs (ARDS)
2. The cardiovascular system (septic shock and acute heart failure due to myocarditis).
3. The kidneys (acute tubular necrosis-ATN).

The primary concern of the attending physician is the systematic support of vital functions of the critically ill patient, but various diagnostic and therapeutic dilemmas arise during the early course of the disease, which need to be addressed as quickly as possible in order to ensure the best possible management:

Firstly, the causative micro-organisms of the severe infection must be detected early because this may dictate changes in the initial, empirical antimicrobial treatment. It is believed that delay in the initial diagnosis and inappropriate early antimicrobial treatment can affect the final outcome negatively. Particularly in cases caused by Legionella pneumophila, the wrong antimicrobial treatment can lead to increased mortality10, and for this reason, the ATS guidelines for the early management of community pneumonia in 1993 recommended the addition of specific treatment for this micro-organism11. In cases of Legionella, the early detection of the specific antigens of Legionella pneumophila in the urine, in combination with the traditional methods, makes diagnosis easier, especially as the test remains positive for many days and is not affected by the administration of antibiotics12.

A second question raised during this patient’s ICU stay concerned the primary cause of the pulmonary oedema, namely whether it was of cardiac origin (due to overhydration for the management of septic shock) or part of the primary respiratory insult (ARDS) in the context of severe pneumonia and septic shock. In many cases, it is difficult to differentiate these two types of oedema in the clinical setting13. The radiological findings (bilateral infiltrates on the chest X-ray), the reduced respiratory index (PaO/FiO2 <200), and the positive outcome of alveolar recruitment were not diagnostic of ARDS14,15. The exclusion of over-resuscitation with fluid administration or acute severe cardiovascular compromise related to septic myocardiopathy was of mandatory importance for the management of fluid balance. The Swan-Ganz catheter permitted the diagnosis of cardiogenic pulmonary oedema with increased occlusion pressure (PCWP: 24 mmHg) and severely decreased cardiac index (CO: 4.2 L/min, CI: 1.8 L/m2/min), despite the concomitant administration of high doses of inotropes and vasopressor agents. This led to the explanation of a mixed form of ARDS with secondary pulmonary oedema, caused by septic myocardiopathy. However, high PCWP values are not always indicative of left ventricular dysfunction. Increased pleural pressure (mechanical ventilation, high PEEP values and abdominal muscle contraction) might increase PCWP and decrease cardiac output due to diminished venous return (along with hypovolaemia)16. In such cases, measurement of extravascular lung water (EVLW) using the transpulmonary thermodilution technique can be of value for definitive diagnosis and treatment, particularly in terms of fluid management17.

A third issue that emerged concerned the administration of APC. Recombinant APC is the only therapeutic factor that has recently been proved to reduce mortality in patients with severe sepsis and septic shock18. Its advantages are attributed to its anti-thrombotic, antiinflammatory and anti-apoptotic actions19. The most serious side effect of APC is an increased risk of severe haemorrhage. Because of the failure of conservative treatment, and in the absence of risk factors given in the exclusion criteria selected in the initial PROWESS study18, it was decided to include APC in the therapeutic armamentarium for this patient. The acute renal failure that emerged is not considered a contradiction for APC administration, in contrast with chronic renal failure needing haemodialysis or peritoneal dialysis. Finally his platelet count was definitely higher than the lower accepted value (≥30,000/mm3). In the literature there is only one published case of successful administration of APC in a patient with ARDS, severe sepsis and myocarditis due to Legionella pneumophila infection20. It was necessary to withdraw APC treatment after 48 hours, because of a mild haemorrhage from the upper gastrointestinal tract, despite concomitant administration of gastroprophylaxis (proton pump inhibitors).

CVVH with or without haemodialysis is considered to be the most successful method for extra-renal substitution therapy in acute renal failure (ARF), and is widely used in the ICU setting21. In cases of ARF due to sepsis, CVVH has been shown to ameliorate the haemodynamic status, but its impact on mortality is still debated22. In the case described, CVVH led to rapid restoration of renal function within approximately 9 days.

Finally, it is important to recognize the significance of early, targeted and aggressive treatment for the management of severe sepsis and septic shock. Rivers et al, in a recently published randomized prospective study of medical patients with early signs of sepsis conducted in the ED of a tertiary hospital, demonstrated that early and aggressive administration of fluids, vasopressor agents and red blood cell transfusions, significantly reduced mortality (from 46.5% to 30.5%, p=0.009), especially when specific target values of arterial blood pressure, haematocrit and saturation of venous blood from the superior vena cava (ScvO2) were reached23. The authors are of the opinion that the application of such therapeutic protocols is of paramount importance for successful management of these patients in the ED setting.

In conclusion

Severe pneumonia from Legionella pneumophila, if undiagnosed, and in the case of significant delay of specific antimicrobial treatment, may progress rapidly to generalized sepsis and septic shock. The presentation of this patient to the ED with hypoxaemia and hypercapnia of such an advanced degree was indicative of delay in diagnosis and treatment, leading to serious deterioration of his clinical status. Early aetiologic diagnosis and aggressive resuscitation, specifically on arrival at the ΕD and during the whole ICU stay, may have significantly improved the prognosis and the final outcome, as in the case of this patient.


1. Fraser DW, Tsai TR, Orestein W, et al. Leggionnaries disease: description of an epidemic pneumonia. N Engl J Med 1977; 297:1189-1197.
2. Stout JE, Yu VL. Legionellosis N Engl J Med 1997; 337:682- 687.
3. Mandell LA, Bartlett JG, Dowell SF, File TMJr, Musher DM, Whitney C. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis 2003; 37:1405-1433.
4. Richs JD, Yu VL, Zuranleff JJ, Goetz A, Muder RR. Isolation of Legionella pneumophilla from blood using the BACTEC: a prospective study yielding positive results. J Clin Microbiol 1985; 22:422-424.
5. ARDS network. N Engl J Med 2000; 342:1301-1308.
6. Light RW. Pleural Diseases, 4th Edition. Baltimore: Lippincott, Williams and Wilkins; 2001. 7. Light RW. Parapneumonic effusions and empyema. Proc Am Thorac Soc 2006; 3: 75-80.
8. Αmerican Thoracic Society. Guidelines for the management of adults with community acquired pneumonia. Am J Respir Crit Care Med 2001; 163:1730-1754.
9. BTS Guidelines for the management of community acquired pneumonia in adults. Thorax 2001; 58(suppl4):IV1-64.
10. Heath CH, Grove DI, Looke DFM. Delay in appropriate therapy of Legionella pneumophila associated with increased mortality. Eur J Clin Microbiol Infect Dis 1996; 15: 286-290.
11. Niederman MS, Bass JB, Cambell GD, et al. Guidelines for the initial management of adults with community acquired pneumonia: diagnosis, assessment of severity and initial antimicrobial therapy. Am Rev Respir Dis 1993; 148:1418-1426.
12. Kazandjian D, Chiew R, Gilbert GL. Rapid diagnosis of Legionella pneumophila serogroup 1 infectionwith the Binax enzyme immunoassay urinary antigen test. J Clin Microbiol 1997; 35:954-956.
13. Μartin GS, Eaton S, Mealer M, Moss M. Extravascular lung water in patients with severe sepsis: a prospective cohort study Crit Care 2005; 9:R74-R82.
14. Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 149(3 Pt 1):818-24.
15. Mols G, Priebe HJ, Guttmann J. Alveolar recruitment in acute lung injury. Br J Anaesth 2006; 96 (2):156-66.
16. Pinsky MR. Clinical significance of pulmonary artery occlusion pressure. Applied Physiology in Intensive Care Medicine, Springer-Verlang Ed, 2006; p 51-56.
17. Monnet X, Anquel N, Oaman D, Hamzaoui O, Richard C, Temboul JL. Assessing pulmonary permeability by transpulmonary thermodilution allows differentiation of hydrostatic pulmonary edema from ALI/ARDS Intensive Care Med 2007; 33(3):448- 453.
18. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis N Engl J Med 2001; 344:699-709.
19. Mathay MA. Severe Sepsis — A New Treatment with Both Anticoagulant and Antiinflammatory Properties N Engl J Med 2001; 344:759-762.
20. Bodur H, Sarvan Y, Koca U, et al. Legionella pneumonia with acute respiratory distress syndrome, myocarditis and septic shock successfully treated with Drotrecogin Alpha (activated). Eur J Anaesthesiol 2006; 23(9):808-10.
21. Continuous hemofiltration in the treatment of acute renal failure. N Engl J Med 1997; 336:1303-1309.
22. Klouche K, Cavadore P, Portales P, Clot J, Canaud B, Beraud JJ. Continuous veno-venous hemofiltration improves hemodynamics in septic shock with acute renal failure without modifying TNF* and IL6 plasma concentrations. J Nephrol 2002; 15(2):150-157.
23. Rivers E, Ngugen B, Havstad S, et al. Early goal directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368-1377.