Omadacycline for the treatment of severe Legionella pneumophila pneumonia complicated with multiple organ dysfunction: a case report.

Omadacycline is a novel tetracycline antibiotic that has a strong in vitro antibacterial activity against atypical pathogen such as Legionella. It is approved for the treatment of adults with community-acquired bacterial pneumonia, including Legionella pneumonia. However, clinical data on the use of omadacycline in Legionella pneumonia is limited. In the present paper, we report a case of severe pneumonia induced by Legionella pneumophila (L.pneumophila) presenting with septic shock and multiple organ dysfunction including lung, liver and kidney. With omadacycline treaetment, inflammation indices of the patient markedly decreased, and the patient significantly improved with multiple organ dysfunction and was discharged from home. Due to its strong antibacterial activity against L.pneumophila, good safety profile and no dosage adjustment in patients with severe hepatic or renal impairment, omadacycline can be considered as an optimal treatment strategies for severe infections by such special pathogen. Whereas, more case reports are needed to support this conclusion.

Legionella pneumonia in hospitalized adults with respiratory failure: Quinolones or macrolides?

The optimal antimicrobial regimen for adults with respiratory failure due to Legionella pneumonia remains controversial. A systematic review was performed to assess the impact on outcomes comparing quinolones versus macrolides. A literature search was conducted in PubMed, Cochrane Library and Web of Science between 2012 and 2022. It yielded 124 potentially articles and ten observational studies met the inclusion criteria. A total of 4271 patients were included, 2879 (67 %) were male. A total of 1797 (42 %) subjects required intensive care unit (ICU) admission and 942 (52 %) mechanical ventilation. Fluoroquinolones and macrolides alone were administered in 1397 (33 %) and 1500 (35 %) subjects, respectively; combined therapy in 204 (4.8 %) patients. Overall mortality was 7.4 % (319 patients), with no difference between antibiotics. When data from the three studies with severe pneumonia were pooled together, mortality with fluoroquinolones alone was statistically superior to macrolides alone (72.8 % vs 30.8 %, p value 0.027). Hospital length of stay and complications were comparable. Our findings suggest that macrolides and quinolones were comparable for hospitalized Legionella pneumonia. However, in severe pneumonia, a randomized clinical trial is an unmet clinical need. PROSPERO registration number: CRD42023389308.

Hyper-inflammatory profile and immunoparalysis in patients with severe Legionnaires' disease.

Introduction: Severe Legionnaires' disease (LD) can lead to multi-organ failure or death in 10%-30% of patients. Although hyper-inflammation and immunoparalysis are well described in sepsis and are associated with high disease severity, little is known about the immune response in LD. This study aimed to evaluate the immune status of patients with LD and its association with disease severity. Methods: A total of 92 hospitalized LD patients were included; 19 plasmatic cytokines and pulmonary Legionella DNA load were measured in 84 patients on the day of inclusion (day 0, D0). Immune functional assays (IFAs) were performed from whole blood samples collected at D2 and stimulated with concanavalin A [conA, n = 19 patients and n = 21 healthy volunteers (HV)] or lipopolysaccharide (LPS, n = 14 patients and n = 9 HV). A total of 19 cytokines (conA stimulation) and TNF-α (LPS stimulation) were quantified from the supernatants. The Sequential Organ Failure Assessment (SOFA) severity score was recorded at D0 and the mechanical ventilation (MV) status was recorded at D0 and D8. Results: Among the 84 patients, a higher secretion of plasmatic MCP-1, MIP1-ß, IL-6, IL-8, IFN-γ, TNF-α, and IL-17 was observed in the patients with D0 and D8 MV. Multiparametric analysis showed that these seven cytokines were positively associated with the SOFA score. Upon conA stimulation, LD patients had a lower secretion capacity for 16 of the 19 quantified cytokines and a higher release of IL-18 and MCP-1 compared to HV. IL-18 secretion was higher in D0 and D8 MV patients. TNF-α secretion, measured after ex vivo LPS stimulation, was significantly reduced in LD patients and was associated with D8 MV status. Discussion: The present findings describe a hyper-inflammatory phase at the initial phase of Legionella pneumonia that is more pronounced in patients with severe LD. These patients also present an immunoparalysis for a large number of cytokines, except IL-18 whose secretion is increased. An assessment of the immune response may be relevant to identify patients eligible for future innovative host-directed therapies.

A Lethal Combination: Legionnaires' Disease Complicated by Rhabdomyolysis, Acute Kidney Injury, and Non-Occlusive Mesenteric Ischemia.

BACKGROUND Legionnaires' disease is one of the most common types of community-acquired pneumonia. It can cause acute kidney injury and also occasionally become severe enough to require continuous renal replacement therapy (CRRT). Non-occlusive mesenteric ischemia (NOMI) is a condition characterized by ischemia and necrosis of the intestinal tract without organic obstruction of the mesenteric vessels and is known to have a high mortality rate. CASE REPORT A 72-year-old man with fatigue and dyspnea was diagnosed with Legionnaires' disease after a positive result in the Legionella urinary antigen test pneumonia confirmed by chest radiography and computed tomography. He developed acute kidney injury, with anuria, rhabdomyolysis, septic shock, respiratory failure, and metabolic acidosis. We initiated treatment with antibiotics, catecholamines, mechanical ventilation, CRRT, steroid therapy, and endotoxin absorption therapy in the Intensive Care Unit. Despite ongoing CRRT, metabolic acidosis did not improve. The patient was unresponsive to treatment and died 5 days after admission. The autopsy revealed myoglobin nephropathy, multiple organ failure, and NOMI. CONCLUSIONS We report a fatal case of Legionnaires' disease complicated by rhabdomyolysis, acute kidney injury, myoglobin cast nephropathy, and NOMI. Legionella pneumonia complicated by acute kidney injury is associated with a high mortality rate. In the present case, this may have been further exacerbated by the complication of NOMI. In our clinical practice, CRRT is a treatment option for septic shock complicated by acute kidney injury. Thus, it is crucial to suspect the presence of NOMI when persistent metabolic acidosis is observed, despite continuous CRRT treatment.

Severe Cavitary Pneumonia Caused by Legionella pneumophila: a Case Report.

BACKGROUND: Pulmonary cavities caused by Legionella occur mainly in immunocompromised patients, and clinical information in patients with normal immune function is therefore limited. METHODS: We report a 64-year-old female who developed a Legionella pulmonary cavity without any immunological abnormality. RESULTS: She suffered severe pneumonia complicated by acute respiratory failure and acute renal insufficiency. Despite long-term antibiotic therapy, she showed signs of a life-threatening infection and a progressive pulmonary cavity. CONCLUSIONS: Our case report provided clinical data regarding the diagnosis and therapy of patients who develop Legionella pulmonary cavities without any underlying disease.

Legionella associated rhabdomyolysis: a case report.

BACKGROUND: Infections have been recognized as an uncommon cause of rhabdomyolysis, with evidence indicating a worse prognosis when compared to rhabdomyolysis caused by other etiologies. Diseases caused by Legionella pneumophila can present variably, ranging from mild to severe illness, as is sometimes the case with pneumonia. In particular, the triad of Legionnaire's disease, rhabdomyolysis, and acute kidney injury is associated with a significant increase in the morbidity and mortality, with most patients requiring initiation of renal replacement therapy such as hemodialysis. While the exact mechanism of both the muscle and kidney injury in this setting remains unknown, several hypotheses exist, with some research suggesting multiple yet distinct processes occurring in both target organs. CASE PRESENTATION: In this case report, we describe a 53-year-old African American man who presented with Legionella pneumophila pneumonia complicated by rhabdomyolysis and acute kidney injury. He was treated with aggressive fluid resuscitation and a 2-week course of azithromycin. His clinical status improved without necessitating renal replacement therapy or mechanical ventilation. We postulate that early recognition and treatment were key to his recovery. He was discharged 10 days later without recurrence of rhabdomyolysis at the time of this report. CONCLUSION: While there are several well-established and more common causes of rhabdomyolysis, clinicians should recognize Legionella sp. as an etiology, given its association with significant morbidity and mortality.

Metagenomic next-generation sequencing confirms the diagnosis of Legionella pneumonia with rhabdomyolysis and acute kidney injury in a limited resource area: a case report and review.

Background: Legionella pneumonia, rhabdomyolysis, and acute kidney injury are called the Legionella triad, which is rare and associated with a poor outcome and even death. Early diagnosis and timely treatment are essential for these patients. Case presentation: A 63-year-old man with cough, fever, and fatigue was initially misdiagnosed with common bacterial infection and given beta-lactam monotherapy but failed to respond to it. Conventional methods, including the first Legionella antibody test, sputum smear, and culture of sputum, blood, and bronchoalveolar lavage fluid (BALF) were negative. He was ultimately diagnosed with a severe infection of Legionella pneumophila by metagenomics next-generation sequencing (mNGS). This patient, who had multisystem involvement and manifested with the rare triad of Legionella pneumonia, rhabdomyolysis, and acute kidney injury, finally improved after combined treatment with moxifloxacin, continuous renal replacement therapy, and liver protection therapy. Conclusion: Our results showed the necessity of early diagnosis of pathogens in severe patients, especially in Legionnaires' disease, who manifested with the triad of Legionella pneumonia, rhabdomyolysis, and acute kidney injury. mNGS may be a useful tool for Legionnaires' disease in limited resource areas where urine antigen tests are not available.

Case of clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) due to Legionella pneumonia.

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinicoradiologic syndrome diagnosed by temporary hyperintense lesion in the area, including the splenium of the corpus callosum, on diffusion-weighted imaging and neuropsychiatric symptoms that recover without sequelae. MERS is rare in adults, especially elderly people. We herein report a man in his 60s diagnosed with MERS caused by Legionella pneumonia. He completely recovered with only the administration of levofloxacin and azithromycin despite the risk factors of an advanced age, medical history of untreated hypertension, bilateral spontaneous pneumothoraxes, smoking and drinking habits and pulmonary emphysema. To our knowledge, this is the oldest case of MERS due to Legionella pneumonia and extremely old among total MERS cases. Our research revealed that Legionella species are the most common pathogens of adult-onset MERS, while viruses are the main causative factors in children. This case helps clarify the features of MERS in high-risk adults.

Legionella: An uncommon cause of community-acquired pneumonia.

ABSTRACT: Legionnaires disease is an important, relatively uncommon, yet well known form of atypical community-acquired pneumonia (CAP). If not appropriately treated in the early stage of infection, it can be fatal. Several factors increase the risk of contracting Legionnaires disease, including age over 50 years, chronic cardiovascular disease, underlying respiratory disease, chronic renal disease, diabetes, smoking, any immunosuppressing condition, travel history, and certain types of employment. Legionnaires disease can present without the usual symptoms associated with pneumonia. The incidence of Legionnaires disease is increasing, and because of its morbidity and mortality, clinicians should consider it in the differential when treating patients with CAP. This article reviews the pathophysiology and treatment of Legionnaires disease and when to refer patients to tertiary centers for higher levels of care, including extracorporeal membrane oxygenation.

Clinical Presentation of Legionella pneumophila Serogroup 1-Associated Pneumonia and Diffuse Alveolar Hemorrhage: A Case Report and Literature Review.

BACKGROUND We report a case of diffuse alveolar hemorrhage (DAH) caused by Legionella pneumophila serogroup (SG) 1 and review the existing literature to identify risk factors and determine the prognosis of patients with Legionella pneumonia-associated DAH. CASE REPORT A 44-year-old woman was admitted to our hospital following the presentation of dyspnea for a few days. Chest computed tomography (CT) findings revealed "crazy-paving" pattern in the right upper lobe implicating DAH and consolidation in the lower lobe. Analysis of the bronchoalveolar lavage (BAL) fluid revealed DAH, with further analyses identifying L. pneumophila SG 1 as the causative agent. The patient was successfully treated with levofloxacin and a red blood cell transfusion and discharged on the 32nd day of hospitalization. A literature review of 6 reported cases (including our case) of Legionella pneumonia-associated DAH revealed that the median age of patients with DAH was 59 years (range, 44-75 years), involving female patients in 4 cases (67%) and the use of immunosuppressive drugs in 2 cases (33%). Three cases were BAL Legionella polymerase chain reaction (PCR)-positive and 4 cases were diagnosed using a urinary Legionella antigen test (one case was simultaneously PCR-positive). These infections were caused by L. pneumophila SG 1 in three cases and SG 3 in one case. Mechanical ventilation was used in 5 cases (83%) and one patient had an unfavorable prognosis. Steroids for DAH were used in 5 cases (83%), and 2 cases responded to this treatment. CONCLUSIONS Our case highlights that clinicians should be aware of Legionella spp. as a cause of DAH in an immunocompetent host with "crazy-paving" pattern on chest CT, and perform a urinary antigen test and BAL PCR for diagnosis.

The Triad of Legionnaires' Disease, Rhabdomyolysis, and Acute Kidney Injury: A Case Report.

BACKGROUND Legionella infection is a common cause of atypical pneumonia, known as Legionnaires' disease when infection extends to extrapulmonary involvement, which often leads to hospitalization. The triad of Legionella pneumonia, rhabdomyolysis, and renal failure displays a rare yet fatal complication without prompt management. CASE REPORT Our patient was a 62-year-old man with no significant medical history who developed Legionnaires' disease with severely elevated creatinine phosphokinase (CPK) of 9614 mcg/L, consistent with rhabdomyolysis. He experienced severe headache, anorexia, and hematuria, which prompted him to seek medical care. Pertinent social history included recent flooding in his neighborhood, which surrounded the outer perimeter of his home. His clinical manifestations and laboratory findings were consistent with Legionella infection, with concomitant acute kidney injury. A chest X-ray revealed hazy left perihilar opacities concerning for atypical pneumonia. Immediate interventions of hydration and antigen-directed azithromycin were initiated to prevent rapid decompensation. His clinical symptoms resolved without further complications, and he was not transferred to the Intensive Care Unit (ICU). CONCLUSIONS Legionella-induced rhabdomyolysis is an uncommon association that can lead to acute kidney failure and rapid clinical deterioration. Early and aggressive management with fluid repletion and appropriate antibiotics can improve clinical manifestations and hospital length of stay. Our patient's reduction in CPK levels and clinical improvement confirmed that extrapulmonary involvement in Legionella infection can lead to rhabdomyolysis. It is important for healthcare providers to recognize the clinical triad of Legionella pneumonia, rhabdomyolysis, and renal failure as prompt and timely management to reduce associated morbidity.

Cerebellar syndrome associated with legionellosis: A case report and literature review.

INTRODUCTION: Legionnaire's disease is a community-acquired pneumonia caused by the Gram-negative bacterium Legionella pneumophila. This disease is often associated with neurological symptoms, the clinical presentation of which can be very varied. CASE REPORT: We report a 47-year-old female patient who developed Legionnaires' disease with cerebellar symptoms (ataxia, dysarthria and hypermetria). Laboratory tests revealed a biological inflammatory syndrome. The cerebrospinal fluid was sterile. Urinary antigen test and serology were positive for L. pneumophila. An interstitial syndrome of the right upper lobe was detected on chest computed tomography (CT) scan. Brain imaging (magnetic resonance imaging and CT angiography) showed no abnormalities. The outcome was favourable after treatment with spiramycin, levofloxacin and corticosteroids. DISCUSSION: Few cases only (n=110) of Legionnaires' disease with cerebellar symptoms have been reported in the literature. The pathogenic mechanism behind neurological dysfunction in patients with Legionnaires' disease is unknown. Neurological symptoms improve with antibiotic therapy and corticosteroids. Extra-pulmonary forms of Legionnaires' disease are frequent, with neurological symptoms being the most common symptoms. Cerebellar dysfunction may be underestimated and requires appropriate management with antibiotic therapy and corticosteroid therapy. Recommendations for the management of Legionnaire's disease with severe extra-pulmonary symptoms are needed.

Acute fibrinous and organizing pneumonia in a patient with Sjögren's syndrome and Legionella pneumonia: a case report and literature review.

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare clinicopathological condition. Studies in the literature have reported that AFOP may be associated with respiratory infections, such as respiratory syncytial virus, influenza virus, Pneumocystis jirovecii, Penicillium citrinum, and Chlamydia infections. However, AFOP associated with Legionella infection has not been reported previously. Here, we report a case of a patient with AFOP secondary to Sjögren's syndrome and Legionella infection. CASE PRESENTATION: A 47-year-old man was admitted to the hospital because of fever, expectoration, and shortness of breath. Lung imaging showed irregular patchy consolidation. A diagnosis of Legionella pneumonia was initially considered on the basis of the patient's history of exposure to soil before disease onset, signs of extrapulmonary involvement, and a positive Legionella urine antigen test result. However, the patient's symptoms and lung imaging did not improve after treatment with levofloxacin, moxifloxacin, and tigecycline for Legionella infection. In addition, Sjögren's syndrome was diagnosed on the basis of clinical manifestations and immunological indicators. Pathological changes associated with AFOP were confirmed from the results of ultrasound-guided percutaneous lung biopsy. The patient's clinical symptoms improved rapidly after a short course of low-dose corticosteroid therapy, and lung imaging showed significant improvement. CONCLUSIONS: The possibility of secondary AFOP should be considered when Legionella pneumonia does not improve after standard antibiotic therapy. Lung biopsy and histopathological examination are important for the adjustment of treatment strategy. Our case also highlights the importance of screening for autoimmune diseases in patients with AFOP.

Concomitance of COVID-19 and legionnaires' disease - a case series.

Coronavirus disease-2019 (COVID-19) and legionnaires disease (LD) caused by Gram-negative water-born bacteria Legionella pneumophila show certain similarities, including a predisposition to pulmonary involvement and extrapulmonary manifestations in some of the patients infected. One disease can mimic the other, both can rarely coexist. CASE SERIES REPORT: The authors describe 7 such cases (5 females), aged 51-90 years (mean 69.7 years) detected while screening 133 subjects with moderate to severe pneumonia and confirmed COVID- 19, which constituted 5.3% of the patients in whom urinary antigen test (UAT) for L. pneumophila was performed. The patients had multiple concomitant disorders: hypertension (6), heart failure (4), diabetes (4), obesity (4), coronary heart disease (3), chronic kidney disease (3), chronic obstructive pulmonary disease (3), anemia (3). Positive UAT was obtained at admission in 4 patients, and on 3rd, 11th and 14th days of hospitalization in the remaining 3 patients. One patient also had positive UAT for Streptococcus pneumoniae. We analyzed: radiological imaging, laboratory data (CRP, interleukin-6, procalcitonin, troponin I, BNP), ECG, echocardiography, treatment and outcome. Three patients required a modification of initial antibiotic therapy, two developed Clostridioides difficile infection. The duration of hospitalization ranged from 13 to 59 days (mean 24.3 days); two patients died. CONCLUSIONS: The authors suggest that the coexistence of COVID- 19 and LD may result in prolonged hospitalization, in increased mortality risk and in subsequent cardiovascular complications, including takotsubo syndrome (TTS) which was found in 2 cases, both presented as focal TTS (fTTS).

Complement-mediated autoimmune haemolytic anaemia as an initial presentation of Legionnaires' disease.

A 42-year-old diabetic man presented to the hospital with severe sepsis and multiorgan dysfunction. A probable respiratory source of sepsis was suspected because of suggestive clinical and radiological findings. He was critically ill and was therefore admitted to intensive care for further management including ventilatory support and renal replacement therapy. He was also found to have marked anaemia requiring multiple blood transfusions with clinical and laboratory evidence pointing towards severe haemolysis. Further workup for the aetiology of pneumonia established a diagnosis of Legionella by confirmatory tests namely legionella antigen in the urine and exponentially rising serum antibody titres. The cause for the severe haemolysis was found to be complement-mediated autoimmune haemolysis as determined by direct antiglobulin test positive for complement components C3 and negative for IgG. Such clinically significant autoimmune haemolysis as a presenting feature, rather than a late complication, has never before been reported in the literature.

Probable caso de reinfección grave por SARS-CoV-2 con coinfección por Legionella pneumophila / Probable case of severe SARS-CoV-2 reinfection with Legionella pneumophila co-infection

Resumen La inmunidad conferida luego de una primera infección por SARS-CoV-2 y el riesgo consiguiente de infección persistente o reinfección no están completamente dilucidados. Existen reportes internacionales de casos de reinfección, incluyendo el primer caso publicado en Sudamérica. Por otra parte, las comunicaciones de casos de coinfecciones han ido en aumento, incluyendo las asociadas a Legionella pneumophila . Presentamos el caso de un varón de 47 años de edad, personal de salud, que luego de cuatro meses de una primera infección por SARS-CoV-2, presenta una neumonía grave, certificándose una nueva infección por SARS-CoV-2 y una coinfección por L. pneumophila mediante detección de antígeno urinario. Fue tratado en UCI, requiriendo ventilación mecánica, dexametaxona y moxifloxacino, con buena respuesta clínica. Actualmente se encuentra en rehabilitación respiratoria y motora.

Abstract The immunity conferred after a first SARS-CoV-2 infection and the consequent risk of persistent infection or reinfection are not fully elucidated. There are reports both in Europe and in North America of reinfection cases, recently highlighting the first case published in South America. On the other hand, reports of co-infections have been increasing, including those associated with Legionella pneumophila . We present the case of a 47-year-old male, health personnel who, after four months of a first SARS-CoV-2 infection, suffers a severe pneumonia certifying a new SARS-CoV-2 infection and a L. pneumophila co-infection by urinary antigen detection. He was treated in the ICU, requiring mechanical ventilation, dexamethasone, and moxifloxacin, with a good response. He is currently in respiratory and motor rehabilitation.

Legionnaires' disease arising with hirsutism: case report of an extremely confusing event.

BACKGROUND: Legionella bacteria is a common cause of pneumonia, but the infection may affect several organs in the most serious cases. A systemic involvement ab initio could be non-specific, leading to a diagnostic misinterpretation. CASE PRESENTATION: A 33-year-old woman had been complaining of mental confusion, restlessness, aggressiveness, and, subsequently, hirsutism. After 3 weeks, the patient developed pneumonia and died during the hospitalization. The autopsy examination revealed a multi-organ necrotizing exudative disease involving the lung, the heart and the brain. The microbiological tests of tracheal aspirate were positive for Legionella pneumophila serotype 1. CONCLUSION: The Legionella infection may show a proteiform clinical course and an extra-pulmonary manifestation may be the first sign of the disease. Herein, we report a case of Legionella infection in a young female, presenting with non-specific neurological symptoms and hirsutism at onset, misdiagnosed as a metabolic disease.

Legionella pneumophila in Patients with Pneumonia at a Referral Hospital, New Delhi, India, 2015-2020.

Legionnaires' disease (LD) is an established cause of pneumonia, and the disease remains largely underdiagnosed. Even though LD has been reported from many parts of the world, only sporadic cases have been reported in India. During February 2015-January 2020, we enrolled 597 patients with radiographically confirmed pneumonia and tested respiratory secretions for Legionella spp. by using real-time PCR, and culture. A commercial urinary antigen test (UAT) was also used to detect the Legionella pneumophila (Lp) serogroup 1 antigen in urine. An LD case was defined as a patient with pneumonia and positive results for Legionella spp. infections determined by real-time PCR (from any respiratory specimen) or culture or UAT. Demographic data, risk factors, clinical, radiological, and outcome data of Lp-positive and Lp-negative patients were compared using logistic regression. Over the study period, 14 (2.3%) patients were positive for Legionella spp. infections by real-time PCR and UAT; eight (57%) were admitted to the intensive care unit, and four (28.6%) in-hospital deaths occurred. Bivariate analysis showed that renal disease, neurological conditions, confusion, leukocytosis, and requirement of oxygen support were more common in the Lp-positive group than in the Lp-negative group. However, multivariate analysis failed to confirm most of these differences; renal disease was the only independent variable remaining significant. All test methods have intrinsic limitations in identifying Legionella; therefore, more than one testing method should be used. Application of molecular assays including real-time PCR has great value because of its high sensitivity, specificity, and rapid diagnostic potency. Increased awareness and improved diagnostic testing could facilitate early detection of cases, pathogen-directed therapy, and improved outcomes for patients.