Legionella Pneumophila Pneumonia Research Articles

Legionella-induced acute lung injury in the setting of hyperoxia: protective role of tumour necrosis factor-alpha.

Among the main characteristics of Legionella pneumophila pneumonia are acute lung injury and severe hypoxemia. Although high oxygen supplementation is a valuable supportive therapy in these patients, oxygen itself is known to be a risk factor for acute lung injury. The effects of hyperoxia on lung injury of mice with Legionella pneumonia were examined. Hyperoxia treatment reduced survival of the infected mice in an oxygen concentration- and exposure time-dependent manner. The enhanced lethality was associated with an increase in total lung weight and apoptosis markers, but not with bacterial burden in the lungs. Hyperoxia decreased the levels of the antioxidant glutathione (GSH) in infected lungs. Exogenous tumour necrosis factor-alpha (TNF-alpha) improved the survival of infected mice kept under hyperoxia. TNF-alpha effects were associated with restoration of total lung weight and histone DNA and GSH levels on day 2, whereas the lung bacterial burden did not differ significantly. Moreover, upregulation of GSH by TNF-alpha was observed in the lungs of mice without infection. These results demonstrate that hyperoxia exacerbates L. pneumophila pneumonia. The data suggest that TNF-alpha may be a potential therapeutic candidate for these individuals, not only through modulating host antibacterial systems, but also by mediating induction of the antioxidant GSH.

Bronchoalveolar lavage findings in severe community-acquired pneumonia due to Legionella pneumophila serogroup 1

Background: No specific data are available in the literature on the bronchoalveolar lavage (BAL) findings of Legionella pneumophila pneumonia. We report on the cytological and immunophenotypical BAL data of three immunocompetent patients with severe community-acquired pneumonia due to L. pneumophila serogroup 1. Methods: Retrospective chart review. The microbiologial diagnosis was obtained by BAL culture or/and urinary antigen assay. Results: All patients presented with high-grade fever, bilateral chest infiltrates and severe respiratory failure requiring ventilatory support. The cytological BAL pattern at presentation showed in all patients the association of a marked neutrophilia with a variable but remarkable percentage of lymphoblasts. Increased levels of activated T-lymphocytes (both HLA-DR+ and CD25+ cells) and, in 2 out of 3 patients, of T-cells bearing the γ/ δ T-cell receptor were the main immunophenotypical findings on flow cytometric analysis. Conclusions: We suggest that the association of lymphoblasts with a marked neutrophilia in BAL fluid of patients with a clinical-radiological setting compatible with acute pneumonia should suggest L. pneumophila as a possible etiologic agent.

Reactantes de fase aguda en la neumonía adquirida en la comunidad

We aimed to study the usefulness of acute-phase proteins in the evolution and microbial diagnosis of community-acquired pneumonia (CAP). One-year prospective study of CAP. Plasma levels of C reactive protein (CRP), erythrocyte sedimentation rate (ESR) and fibrinogen were measured on admission in all patients with CAP. 240 cases of CAP were included in the study. ESR was higher in patients who developed pleural effusion (p = 0.03). A value of ESR > 120 mm/h was associated with a higher likelihood of having a CAP complicated with pleural effusion (odds ratio = 3.80; 95% confidence interval, 1.37-10.49, p = 0.006). Baseline concentrations of CRP, ESR and fibrinogen were higher in patients who developed empyema. CRP and fibrinogen levels were significantly higher in patients with Legionella pneumophila pneumonia, while pneumococcal pneumonia was associated with a higher ESR value. Some frequently used acute-phase proteins can be useful in the prediction of pleural complications and in the approach to the etiological diagnosis of CAP.

家庭用24時間風呂が感染源と特定できたレジオネラ肺炎の1例

A 88 year old female with active rheumatoid arthritis treated by low dose of prednisolone and methotrexate was admitted to our hospital because of severe bilateral pulmonary infiltration and acute respiratory distress syndrome. On admission, she had consciousness disturbance and was intubated because of severe respiratory failure. We heard from her family of her habit she had taking a private whirlpool bath 2 or 3 times everyday. So, we suspected a Legionella pneumophila infection. We started intravenous erythromycin (EM) (1,500mg/day) and methylprednisolone pulse therapy (1,000mg x 3days) and full controlled mechanical ventilation supported with PEEP. Her respiratory failure was gradually improved and she was discharged on the 44 the hospital day. Legionella pneumophila (serogroup 6) was isolated in her sputum by B-CYE alpha culture. Legionella pneumophila (serogroup 6) was isolated in her private whirlpool bath too. Both samples revealed the same by genetic analysis with pulse field gel electrophoresis (PFGE). This is the first adult case of Legionella pneumophila pneumonia infected from a private whirlpool bath confirmed by genetic analysis. We should always suspect Legionella pneumonia as one of the severe community-acquired pneumonia, because Legionella pneumophila were frequently detected among various water sources including the private whirlpool bath.

C-reactive protein levels in community-acquired pneumonia.

The diagnostic value of C-reactive protein (CRP) admission serum levels as an indicator of the aetiology of community-acquired pneumonia (CAP) was evaluated. A cohort of 1,222 patients with CAP was assessed. CRP levels were analysed in 258 patients with a single aetiological diagnosis. The mean CRP values in patients with pyogenic, atypical, viral and Legionella pneumophila pneumonia were: 16 mg x dL(-1), 13 mg x dL(-1), 14 mg x dL(-1) and 25 mg x dL(-1), respectively. CRP levels were not significantly different among patients outcome research team (PORT) groups (19 mg x dL(-1) in groups I-II, 16 mg x dL(-1) in group III and 16 mg x dL(-1) in groups IV-V). A cut-off point of 25 mg x dL(-1) had a sensibility, specificity, positive predictive value and negative predictive value of 0.6, 0.83, 0.3, and 0.94, respectively. After controlling for age and PORT score, the odds of having a CRP level >25 mg x dL(-1) was 6.9 times higher in patients with L. pneumophila pneumonia than in those with non-L. pneumophila pneumonia. Patients with Legionella pneumophila pneumonia had higher C-reactive protein levels than those with pneumonia of any other aetiology, independently of severity of infection. Being a cheap and readily available test, C-reactive protein may be a useful adjunctive procedure in the diagnosis of community-acquired pneumonia.

Clinical Utility of a Legionella pneumophila Urinary Antigen Test in a Large University Teaching Hospital

To determine the clinical utility of diagnosing Legionella pneumonia by urinary antigen testing (LPUAT) in a low prevalence centre. The results of LPUATs were abstracted and analyzed from the authors' laboratory information system. Medical records were reviewed in detail for all positive tests and a random sample of 50 negative tests. The Queen Elizabeth II Health Sciences Centre, a large university hospital complex. Patients who were admitted from the emergency room with pneumonia or who had developed pneumonia in hospital and who had a LPUAT performed between April 1998 and October 2000. One thousand one hundred fifty-four tests were performed on 1007 patients. Seven patients had nine positive LPUATs. Three of these patients had confirmed Legionella pneumophila pneumonia. Three others had probable or possible L pneumophila pneumonia. There was one probable false positive. Six of the seven patients were already on empirical anti-L pneumophila therapy. Of the 50 negative tests reviewed in detail, 31 patients were on one of the antibiotics of choice for L pneumophila at the time the test was ordered; in 21 (68%) of these patients the negative result did not lead to a change in therapy. The cost to diagnose each case of Legionella pneumonia by LPUAT was approximately $5,770 and most patients were already on appropriate antibiotics. In patients with negative tests, antibiotics were often not changed in response to the test result. Rigorous screening of patients is required to increase pretest probability for LPUAT to be justified.

Factors related to persistence of Legionella urinary antigen excretion in patients with legionnaires' disease.

The aim of this prospective study was to compare patient characteristics, clinical data, and evolution of Legionella pneumophila pneumonia according to the duration of Legionella urinary antigen excretion. Urine samples from 61 patients with Legionella pneumonia diagnosed by detection of urinary antigen were obtained periodically until urinary antigen could no longer be detected. Cases were divided into two groups based on the duration of urinary antigen excretion: group I (46 patients, <60 days) and group II (15 patients, >or=60 days). Groups were compared for patient characteristics, clinical data, and evolution of pneumonia. Antigen excretion >or=60 days was observed significantly more frequently in immunosuppressed patients ( P=0.001) in whom the time to apyrexia was >72 h ( P=0.002), although only the time to apyrexia remained significant on multivariate analysis ( P=0.006). In conclusion, the duration of Legionella urinary antigen excretion was <60 days in most patients but was longer in immunosuppressed patients with a longer time to defervescence of fever.

Culture Proven Legionella Pneumophila Pneumonia in a HIV-infected Patient: Case Report and Review

We report the first culture proven case of Legionella pneumonia in a HIV-positive patient in Italy. The laboratory diagnosis was obtained by isolation of Legionella pneumophila serogroup 1, serology, urinary antigen detection and PCR. Culture first allowed diagnosis of the infection, that probably would have been unrecognized. Since Legionellosis in HIV-positive patients with respiratory symptoms is rare and difficult to confirm, we strongly suggest that all available laboratory tests, and particularly culture, should be performed. A review of literature on culture proven cases is also provided.

Legionella Pneumonia and Bacteraemia in Association with Protein-losing Enteropathy after Fontan Operation

A 20-year-old young man suffered from severe protein-losing enteropathy 4 years after Fontan operation. His postoperative haemodynamics were unfavourable in terms of poor myocardial contractility and moderate atrioventricular prosthetic paravalvar leakage. A 2-week trial of steroid therapy for protein-losing enteropathy was given without success. The clinical course was complicated by Legionella pneumophila pneumonia and bacteraemia, which respond to the combination therapy with intravenous erythromycin and ciprofloxacin. The vulnerability of the patient to infection was related to an immuno-deficiency state secondary to protein-losing enteropathy and steroid therapy. Steroids should be used with caution in the management of protein-losing enteropathy after Fontan operation.

Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia.

The contribution of neutrophils to lethal sensitivity and cytokine balance governing T1 and T2 host responses was assessed in a murine model of Legionella pneumophila pneumonia. Neutrophil depletion by administration of granulocyte-specific mAb RB6-8C5 at 1 day before infection rendered mice approximately 100-fold more susceptible to lethal pneumonia induced by L. pneumophila. However, this treatment did not alter early bacterial clearance, despite a substantial decrease in neutrophil influx at this time point. Cytokine profiles in the lungs of control mice demonstrated strong T1 responses, characterized by an increase of IFN-gamma and IL-12. In contrast, neutrophil-depleted mice exhibited significantly lower levels of IFN-gamma and IL-12, and elevation of T2 cytokines, IL-4 and IL-10. Immunohistochemistry of bronchoalveolar lavage cells demonstrated the presence of IL-12 in neutrophils, but not alveolar macrophages. Moreover, IL-12 was detected in lavage cell lysates by ELISA, which was paralleled to neutrophil number. However, intratracheal administration of recombinant murine IL-12 did not restore resistance, whereas reconstitution of IFN-gamma drastically improved bacterial clearance and survival in neutrophil-depleted mice. Taken together, these data demonstrated that neutrophils play crucial roles in primary L. pneumophila infection, not via direct killing but more immunomodulatory effects. Our results suggest that the early recruitment of neutrophils may contribute to T1 polarization in a murine model of L. pneumophila pneumonia.

Legionella pneumophila Pneumonia in Cancer Patients: Case Report and Review

Tsambiras, Petros E.; Tsambiras, Belen M.; Greene, John N.; Sandin, Ramon L.; Vincent, Albert L.; Gompf, Sandra

Prognostic factors of severe Legionella pneumonia requiring admission to ICU.

Despite the fact that the epidemiology of community-acquired pneumonia and nosocomial Legionella infection is well known, there are no specific reports dealing with severe cases of Legionella pneumophila pneumonia admitted to intensive care units. We undertook a prospective study upon 84 patients with a reliable diagnosis of L. pneumophila pneumonia that required ICU admission. The study assessed the prognostic factors, clinical, radiological and outcome variables of both nosocomial (n = 33) and community-acquired (n = 51) cases of L. pneumophila pneumonia. The following variables were more common in nosocomial acquired as compared to community-acquired Legionella pneumonia: Chronic obstructive pulmonary disease (COPD) (64 versus 41%), cardiac disease (39 versus 10%), chronic renal failure (21 versus 4%), alcoholism (54 versus 18%), septic shock (33 versus 16%), and unilateral chest X-ray involvement (61 versus 39%). The crude mortality rate in this study was 30% (25 of 84) with no differences when comparing mortality between nosocomial (9, 27%) to community-acquired (16, 31%) types. The univariate analysis showed that cardiac disease, diabetes mellitus, creatinine > or = 1.8 mg/dl, septic shock, chest X-ray extension, mechanical ventilation, hyponatremia < or = 136 mEq/L, PACO2/FIO2 < 130, and blood urea levels > or = 30 mg/dl were factors related to poor outcome. On the other hand, the following two variables were related to better outcome: adequate treatment for Legionella and pneumonia improvement. The logistic regression analysis demonstrated that APACHE II score > 15 at admission (RR: 11.5; 95% CI 1.75 to 76.1; p = 0.025), and serum Na levels < or = 136 (RR: 21.3; 95% CI 1.11 to 408; p = 0.023), were the only independent factors related to death. On the other hand, improving pneumonia is associated with better outcome in Legionnaires' disease than for patients not having improving pneumonia (RR: 0.019; 95% CI: 0.036 to 0.106; p < 0.0001). A better understanding of the prognostic factors in cases of severe Legionella pneumonia will optimize our therapeutic approach in this disease and help to decrease both its mortality and morbidity rates.

Tremendous high plasma lipopolysaccharide concentrations in a patient with Legionella pneumophila pneumonia

We describe a patient suffering from nosocomial Legionella pneumophila pneumonia with extremely high lipopolysaccharide (LPS) concentrations (peak concentration = 725 EU/ml). This unexpectedly high LPS load led to an exaggerated response of the cytokine network. Although immediate treatment with macrolides was instituted, the patient developed an adult respiratory distress syndrome. Despite application of nitric oxide and porcine natural surfactant factor, the patient died 5 days after admission to the ICU. Because of this dramatic case, we emphasize physicians to be aware of L. pneumophila and to include this organism into the diagnosis and antibiotic therapy in patients with nosocomial pneumonia.

Recurrent Infection Due to Legionella pneumophila in a Patient with AIDS

We report a patient with AIDS who presented with community-acquired cavitary Legionella pneumophila pneumonia. The patient recovered after an extended course of treatment with macrolide antibiotics. He returned to the hospital 4 months later with a febrile illness. Chest radiograms appeared normal. Cultures of blood yielded L. pneumophila. The isolate from blood was indistinguishable from the isolate from sputum taken during the first infection, as shown by restriction-endonuclease analysis and pulsed-field gel electrophoresis. These data suggest that the second infection represented reactivation of a persistent focus of infection that was not apparent when the patient had pneumonia.

Colonisation of the respiratory tract with Legionella pneumophila for 63 days before the onset of pneumonia

We report the case of a 70-year-old man who was admitted to hospital A 66 days before developing Legionella pneumophila pneumonia 6 days after open heart surgery at hospital C. The strain of L. pneumophila recovered from the patient's sputum was of the same subtype (monoclonal antibody type, enzyme type, plasmid profile, and restriction endonuclease pattern) as a strain of L. pneumophila in the potable water supplied to the room where he stayed in hospital A. We conclude that the patient's respiratory tract became colonised by L. pneumophila while he was in hospital A and persisted for at least 63 days until he developed pneumonia requiring antibiotic treatment while in hospital C.

Radiographic appearance of nosocomial legionnaires' disease after erythromycin treatment.

Radiographic features of 71 patients (48 men, 23 women) with nosocomial Legionella pneumophila pneumonia were assessed and compared with those of other nosocomial series of L pneumophila pneumonia. Sixteen patients were assessed retrospectively and 55 prospectively. Chest radiographs were assessed at the onset of the illness, 10 days later, and at 3 months. Erythromycin was given to 67 patients at the time of the diagnosis and to the remaining four at a later stage. Forty eight patients were over the age of 60. On the initial chest radiograph 53 of the 71 patients had unilateral shadowing (23 of them in the right lung); 35 had unilobar shadowing and the remaining 36 had more than one affected lobe. Pleural effusion was present in 24 cases and cavitation in 2. One patient had evidence of a pericardial effusion. At 10 days 21 patients had evidence of radiographic progression (14 ipsilateral), but 28 had improved. At 3 months 36 patients had an abnormal radiograph, 30 showing residual scarring, 15 loss of volume, six pleural shadows and two cavitation. Our series shows a lesser incidence of unilateral shadowing and pleural effusion than other nosocomial series and a lesser tendency to progression, but more patients had radiographic abnormalities at long term follow up.

Bactericidal effects of ticarcillin-clavulanic acid against Legionella pneumophila pneumonia in immunocompromised weanling rats

A model of acute Legionella pneumophila pneumonia in neutropenic weanling rats was developed as a means of assessing the efficacies in vivo of the beta-lactams ticarcillin, ticarcillin-clavulanic acid, and clavulanic acid, agents active against the organism in vitro. Weanling rats were dosed with cyclophosphamide 3 days before and immediately prior to infection by intrabronchial intubation with L. pneumophila. The bacteria persisted in the lungs of untreated animals at high counts (5.0 to 7.0 log10 CFU/g of lung tissue) for up to 168 h after infection, and the histological characteristics of the infection were similar to those of the disease in humans. Transmission electron micrography revealed the presence of L. pneumophila multiplying within alveolar macrophages. Therapy with ticarcillin was ineffective in reducing the bacterial numbers in the lung tissue, whereas ticarcillin-clavulanic acid and clavulanic acid were active, producing bactericidal effects similar to those of erythromycin. The ticarcillin-clavulanic acid combination was significantly more efficacious (P less than 0.01) than corresponding doses of clavulanic acid alone. Synergistic activity between ticarcillin and clavulanic acid against L. pneumophila has been demonstrated in vivo, and the combination showed activity similar to that of erythromycin.

Correction of neutropenia associated with chronic lymphocytic leukaemia following treatment with granulocyte-macrophage colony-stimulating factor

A patient with chronic lymphocytic leukaemia (CLL) and severe persisting neutropenia due to marrow infiltration of his leukaemia, developed bilateral Legionella pneumophila pneumonia for which he was treated with erythromycin, rifampin and ciprofloxacin. To increase the number of circulating polymorphonuclear neutrophils, the patient was treated with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) at a dose of 2 micrograms protein/kg bodyweight s.c./12 h. GM-CSF therapy resulted in a sustained rise of the neutrophil count from the fifth day of treatment onwards, without showing an effect on the number of circulating leukemic cells. The patient completely recovered from his pneumonia. It is suggested that the rise of the neutrophil count, due to GM-CSF, contributed to the improvement of the infection of this patient. Our observation illustrates that GM-CSF can be given safely to CLL-patients and that it can be used effectively in CLL patients with severe bacterial infections to restore neutropenia.

Reduction in Legionella pneumophila through Heat Flushing Followed by Continuous Supplemental Chlorination of Hospital Hot Water

An increase in endemic rate of nosocomial Legionella pneumophila pneumonia prompted an investigation that revealed 16.2% (12/74) of patient care hot-water sites surveyed were culture-positive for L. pneumophila. No positive cultures were recovered from cooling towers, air intakes, or construction areas. Heat flushing of hospital hot-water outlets to temperatures greater than 60 degrees C for 30 min achieved a 66% reduction in positive Legionella cultures. After 4 1/2 months, different serotypes recurred in previously eradicated areas and there were new positive cultures. Continuous supplemental chlorination of the hot-water system (2 parts per million [ppm]) significantly reduced the number of culture-positive samples from 37.4% (43/115) to 7.0% (8/115) after 6 weeks (P less than .005). Of 30 sites surveyed 6 months after hot-water chlorination, 67% (20) were still culture-negative. Of those positive, 70% had less than or equal to 150 L. pneumophila/ml and 90% were from bathtubs. Adverse effects of chlorination on users and plumbing have not been seen. There have been no definite cases of nosocomial L. pneumophila in areas served by supplemental chlorine during the first 17 months of the chlorination project. Technology allowing tighter regulation of chlorine and use of silicates to control corrosion have made continuous hot-water chlorination a safe and effective option in Legionella control.

Legionella: An infrequent cause of adult community acquired pneumonia in Dublin

The commonest infectious agents identified in community acquired pneumonia (CAP) amongst 50 patients admitted to a Dublin hospital were Streptococcus pneumoniae and Haemophilis influenzae. Legionella pneumophila pneumonia occurred in only one patient who acquired infection abroad. A serological screen of blood bank donors and renal transplant recipients failed to detect antibody to Legionella pneumophila supporting the clinical findings of a low prevalence of infection in this community. It is concluded that initial antibiotic therapy for patients with CAP need not routinely include cover for Legionella.