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.

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.

Clinical predictors and outcomes for Legionnaire's disease versus bacteremic pneumococcal pneumonia.

BACKGROUND: Legionnaires' disease (LD) is a serious sometimes fatal pneumonia caused by Legionella pneumophila. The clinical manifestations of LD may be similar to those by caused by Streptococcus pneumoniae. As both conditions can be serious illnesses but requiring different antimicrobial therapies, factors that can help differentiate these types of pneumonias can be helpful in the clinical management of hospitalized patients with bacterial pneumonia. This study aimed to compare clinical features and indicators of disease progression in hospitalized patients with community-acquired pneumonia caused by L. pneumophila and bacteremic S. pneumoniae. METHODS: We conducted a retrospective case comparison study of adult patients hospitalized with LD or S. pneumoniae. Data collected included demographic, clinical characteristics, and comorbidities, and outcomes. Data were analyzed using SPS vs 24.0. Multivariable analysis was done using logistic regression with a forward stepwise algorithm. RESULTS: A total of 106 patients met study criteria. The incidence of LD peaked in summer months and S. pneumoniae peaked in the winter quarter. From multivariable analysis predictors of LD were male gender (OR=21.6, p < 0.001), diarrhea (OR=4.5, p = 0.04), body mass index (BMI) (OR=1.13, p = 0.02), hyponatremia (OR=5.6, p = 0.03 and Charlson weighted index of comorbidity (CWIC) score (OR=0.61, p = 0.01). Patients with S. pneumoniae had higher rates of mechanical ventilation, septic shock, and death than those with LD. CONCLUSIONS: Our data suggests that variables that may distinguish LD from S. pneumoniae include male gender, diarrhea, hyponatremia, higher temperature on admission, higher BMI and fewer comorbidities. Bacteremic S. pneumoniae was associated with poorer outcomes than LD including higher rates of septic shock, mechanical ventilation, ICU admission, and death.

ECMO Support in Pre-B-Cell ALL for Disseminated Legionnaire's Disease.

Legionella pneumophila is a common cause of community- and hospital-acquired pneumonia. Its increasing frequency and reemergence as a pathogen of interest in the intensive care unit is likely due to increased awareness, recognition, and diagnostic test availability (1). Extracorporeal Membrane Oxygenation (ECMO) is increasingly used in the pediatric intensive care unit (PICU) for refractory cardiopulmonary failure and acute respiratory distress syndrome (ARDS) in concert with conventional modalities or when these have failed to adequately support the patient. The breadth of applications for this technology are ever-expanding as our collective knowledge and experience grows. With a particularly high mortality rate among immunocompromised patients, Legionnaires' disease should be considered early in the differential diagnosis and appropriate antimicrobials initiated (1). We present the case of an adolescent patient with pre-B-cell acute lymphoblastic leukemia (pre-B ALL) requiring ECMO support for septic shock and ARDS due to disseminated Legionella. To our knowledge, this is the first case describing an immunocompromised pediatric patient supported with ECMO for Legionnaires' disease.

Bacterial Long-Range Warfare: Aerial Killing of Legionella pneumophila by Pseudomonas fluorescens.

Legionella pneumophila, the causative agent of Legionnaires' disease, is mostly found in man-made water systems and is one of the most closely monitored waterborne pathogens. With the aim of finding natural ways to control waterborne pathogens and thus further reduce the impact of disinfection by-products on human health, some studies have demonstrated the ability of bacteria to kill Legionella through the production of secondary metabolites or antimicrobial compounds. Here, we describe an unexpected growth inhibition of L. pneumophila when exposed to a physically separated strain of Pseudomonas fluorescens, designated as MFE01. Most of the members of the Legionellaceae family are sensitive to the volatile substances emitted by MFE01, unlike other bacteria tested. Using headspace solid-phase microextraction GC-MS strategy, a volatilome comparison revealed that emission of 1-undecene, 2-undecanone, and 2-tridecanone were mainly reduced in a Tn5-transposon mutant unable to inhibit at distance the growth of L. pneumophila strain Lens. We showed that 1-undecene was mainly responsible for the inhibition at distance in vitro, and led to cell lysis in small amounts, as determined by gas chromatography-mass spectrometry (GC-MS). Collectively, our results provide new insights into the mode of action of bacterial volatiles and highlight them as potent anti-Legionella agents to focus research on novel strategies to fight legionellosis. IMPORTANCE Microbial volatile compounds are molecules whose activities are increasingly attracting the attention of researchers. Indeed, they can act as key compounds in long-distance intrakingdom and interkingdom communication, but also as antimicrobials in competition and predation. In fact, most studies to date have focused on their antifungal activities and only a few have reported on their antibacterial properties. Here, we describe that 1-undecene, naturally produced by P. fluorescens, is a volatile with potent activity against bacteria of the genus Legionella. In small amounts, it is capable of inducing cell lysis even when the producing strain is physically separated from the target. This is the first time that such activity is described. This molecule could therefore constitute an efficient compound to counter bacterial pathogens whose treatment may fail, particularly in pulmonary diseases. Indeed, inhalation of these volatiles should be considered as a possible route of therapy in addition to antibiotic treatment.

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.

Case report: fatal pneumonia caused by new sequence type Legionella pneumophilia serogroup 1.

INTRODUCTION: Legionnaires' disease is caused by Legionella bacteria, and commonly manifests as pneumonia and has a high fatality rate. PATIENT CONCERNS: This case study reports on the fatal incident of a patient, initially diagnosed with pneumonia, and subsequently diagnosed with Legionnaires' disease caused by a new sequence type (ST) of Legionella. DIAGNOSIS: It is speculated that the patient acquired Legionnaires' disease from a contaminated water source. Legionnaires' disease was diagnosed using the Legionella urinary antigen assay and bacterial cultures of respiratory secretions; Legionella pneumophilia Type 1 was also identified through serological testing. Sequence-based typing of the cultured bacterium revealed it to be a previously unidentified species, and it was named ST2345 new-type. INTERVENTIONS: In addition to the treatment of Legionnaires' disease, blood samples taken on the second day of admission showed a co-infection of Candida tropicalis, which was treated with anti-fungal treatment. The patient improved after a week, however, on the seventh day of administration lower respiratory secretions showed the growth of Klebsiella pneumonia, indicative of ventilator-associated pneumonia. OUTCOMES: Despite active treatment, the patient passed away due to multiple organ failure. As this was a fatal case, further research is needed to determine whether the critical condition of this case was related to the virulence of the novel Legionella strain. CONCLUSION: A key finding of this study is that treatment for suspected Legionnaires' disease must be administered rapidly, as infection with Legionella may give rise to secondary pathogenic infections.

[Severe community-acquired pneumonia caused by Legionella pneumophila with acute respiratory failure: clinical characteristics and prognosis of 34 cases].

Objective: To describe the clinical characteristics and treatment of severe community-acquired pneumonia(SCAP) caused by Legionella pneumophila with acute respiratory failure and to analyze the risk factors for mortality. Methods: From October 2011 to October 2019, 34 patients were diagnosed with SCAP caused by Legionella pneumophila with acute respiratory failure.There were 25 males and 9 females, aged from 17 to 82 years, with a median age of 61 (48, 69) years. According to the prognosis, the patients were divided into a survival group and a death group for comparative analysis.The survival group included 24 patients, 17 males and 7 females, with a median age of 65 (55, 70) years. There were 10 cases in the death group, 8 males and 2 females, with a median age of 53 (50, 58) years. Multivariable logistic regression analysis was used for risk factors of ICU mortality. Results: The median time of admission to ICU was 7 (5, 11) days, the median time of stay in RICU was 12 (7, 22) days, and the PaO(2)/FiO(2) was 134 (91, 216) mmHg(1 mmHg=0.133 kPa). Ten patients died during ICU hospitalization, with a mortality of 29%. Sequential organ failure assessment (SOFA) of death group was 9 (7, 12), which was significantly higher than that of the survival group [4 (3, 8)], P=0.018. The time from onset of pneumonia symptoms to initiation of targeted treatment of the death group was 10 (7, 14) d, which was significantly longer than that of the survival group of [4 (3, 7) d], P=0.019. Multivariable logistic regression analysis showed that SOFA score (OR=1.461, 95%CI 1.041-2.051, P=0.028) and the time from onset of pneumonia symptoms to initiation of targeted treatment (OR=1.293, 95%CI 1.029-1.625, P=0.027) were independent risk factors for hospital mortality. Conclusions: The ICU mortality of severe legionella pneumonia was high. Critical organ dysfunctions and delayed initial targeted treatment were related with the increase of ICU mortality.

ECLS for Legionella: All Ages Welcome in the ELSO Registry.

We describe the use of extracorporeal life support (ECLS) for Legionellosis in the pediatric and adult populations and report complications, morbidity, and mortality by conducting a retrospective review of patients from the Extracorporeal Life Support Organization registry, including two cases at our pediatric institution. A total of 194 patients with ECLS for Legionella pneumophila infection who received ECLS were included in the analysis. Overall survival was 71%. Lower body weight and VA ECLS were associated with lower survival. ECLS complications including central nervous system (CNS) hemorrhage, cardiopulmonary resuscitation, pulmonary infection, and documented infections were rare but more common among nonsurvivors. Mortality in children (64%) was significantly higher than for adults (27%, p = 0.015). Infants fared very poorly with a mortality of 88%. As demonstrated, ECLS can successfully support patients with severe respiratory failure caused by L. pneumophila infection. Consideration should be given to its use in high-risk pediatric patients with severe acute hypoxemic respiratory failure of unclear etiology. ECLS is a beneficial tool for appropriate candidates with rare disease. Pulmonary respite may provide time for diagnosis and lung recuperation.

The relevance of molecular genotyping to allocate cases in a suspected outbreak of Legionella pneumonia in patients with prolonged immunosuppressive therapy.

Three cases of pneumonia caused by Legionella pneumophila serogroup 1 (Lp1) in immunosuppressed patients with repeated hospitalization were suspected as a healthcare-associated cluster. The environmental investigation did not reveal the presence of legionellae in the hospital patient rooms. Water samples collected from the homes of two patients were also negative for Legionella spp. In the absence of environmental strains potentially involved in the infections, we proceeded to genotype environmental Lp1 strains isolated in the hospital during routine water sampling during the decade 2009-2019 and recovered after long-term storage at -20°C. These 'historical' strains exhibited a high grade of similarity and stability over time, regardless of the disinfection systems. The different molecular profiles shown among the clinical and environmental strains excluded a nosocomial outbreak. The study suggests that the application of molecular typing may be a useful tool to discriminate hospital vs community-acquired cases, mostly for severely immunosuppressed patients in whom the symptomatology could be insidious and the incubation period could be prolonged. Moreover, the genotyping allowed us to exclude any link between the cases.

[Legionella spp: An update]. / Actualités sur les infections à Legionella.

Legionella-related disease is caused by an intracellular bacteria mainly living in water. Contamination results from inhalation of Legionella sp containing aerosolized water. Main risk factors are tobacco, immunodeficiency, and advanced age. Antigenuria is the cornerstone of the diagnosis. Immunocompromised patients, more commonly infected with non pneumophilaLegionella, present negative antigenuria, and culture and PCR are essential for the diagnosis. Legionnaires' disease may be severe, especially in elderly and/or immunocompromised patients. Mortality rate varies from 10 % in the general population to 50 % in intensive care. Treatment is based on macrolides or fluoroquinolones. Antibiotic resistance is very rare.

Legionella Pneumonia Following the Heavy Rain Event of July 2018 in Japan.

We herein report the case of a 62-year-old man diagnosed with Legionella pneumonia while engaged in recovery work in a flooded area after the Heavy Rain Event of July 2018 in Japan. The patient was intubated and maintained on mechanical ventilation and continuous hemodiafiltration. He was also administered antimicrobial therapy with ciprofloxacin and azithromycin. After 53 days in the hospital, he was discharged. It is important to recognize the risk of Legionella infection and to take measures to prevent it during recovery work that involves exposure to water and soil after a flood disaster.

Prosthetic Valve Legionella Endocarditis.

This report describes the case of an 80-year-old man with culture-negative prosthetic valve endocarditis who ultimately was given a diagnosis of Legionella pneumophila endocarditis.

[Successful extracorporeal membrane oxygenation (ECMO) treatment in Legionella pneumonia]. / Sikeres extracorporalis membránoxigenizációs (ECMO-) kezelés Legionella-pneumoniában.

The mortality of severe ARDS is almost 60%. Ventilation-associated lung-injury can be avoided by low-pressure, low-volume ventilation. Potential use of ECMO in case of refractory hypoxemia beside modern ventilatory therapy can be considered. Increasing numbers of respiratory ECMO runs are seen worldwide, though the efficacy remains controversial. The authors present the first successful venovenous-ECMO treatment in severe ARDS in our Institute. We report the case of a 67-year-old male who was admitted with community-acquired pneumonia caused by Legionella. Despite empirical and later targeted antibiotic therapy, severe ARDS with sepsis evolved. Neither ventilation nor prone position resulted in permanent improvement in oxygenation. The patient was referred to our Institute for extracorporeal life support (ECLS) therapy. On admission, blood gas showed severe hypoxemia with mild hypercapnia (PaO2/FiO2: 60, pCO2: 53 mmHg at PEEP: 14 mmHg, PIP: 45 mmHg). X-ray showed bilateral patchy infiltrates while cardiac impairment (EF: 45%) and dilated right ventricle were seen on echocardiography. Elevated pulmonary artery pressure (mPAP: 41 mmHg) was measured. After implantation of femoral-jugular VV ECMO, oxygen saturation was appropriate with lung protective ventilation (FiO2: 0.5, TV: 3-4 ml/kg). Improving lung function enabled us to stop ECMO after 8 days and further 5 days later the patient was weaned off ventilation. After 21 days of intensive care we discharged him to the referral hospital. By reporting this case we emphasise the potential role of respiratory ECMO. Consideration should be given to increase the contingent of this modality in the Hungarian intensive care in accordance with international practice. Orv Hetil. 2019; 160(6): 235-240.

Outcome and Management of Refractory Respiratory Failure With Timely Extracorporeal Membrane Oxygenation: Single-Center Experience With Legionella Pneumonia.

OBJECTIVE:: To analyze the management and outcome of patients with refractory respiratory failure complicating severe Legionella pneumonia rescued with extracorporeal membrane oxygenation (ECMO) in our Center. DESIGN AND SETTING:: Observational study of patients with refractory respiratory failure treated with ECMO in Hospital S.João (Porto, Portugal), between November 2009 and September 2016. PARTICIPANTS:: A total of 112 patients rescued with ECMO, of which 14 had Legionella pneumonia. RESULTS:: Patients with Legionella pneumonia were slightly older than patients with acute respiratory failure of other etiologies (51 [48-56] vs 45 [35-54]), but with no significant differences in acute respiratory failure severity between groups: Pao2/Fio2 ratio 67 (60-75) versus 69 (55-85) and Respiratory Extracorporeal Membrane Oxygenation Survival Prediction score 4 (1-5) versus 2 (-1-4), respectively. Legionella pneumonia was associated with earlier ECMO initiation (days of invasive mechanical ventilation [IMV] before ECMO: 2.0 [1.0-4.0] vs 5.0 [2.0-9.5]). After IMV adjustment to "lung rest" settings, this group presented higher respiratory system (RS) static compliance (28.7 [18.8-37.4] vs 16.0 [10.0-20.8] mL/cmH2O) but required higher ECMO support (blood flow 5.0 [4.3-5.4] vs 4.2 [3.6-4.8]). Patients with Legionella pneumonia had shorter IMV (16 [14-23] vs 27 [20-42] days) and lower incidence of intensive care unit nosocomial infections (35.7% vs 64.3%), with a trend to higher hospital survival (85.7% vs 62.2%; P = .13). CONCLUSION:: In Legionella pneumonia complicated by refractory respiratory failure, ECMO support allowed patient stabilization under lung protective ventilation and high survival rates. Timely ECMO referral should be considered for Legionella pneumonia failing conventional treatment.

[ARDS - An Update - Part 2: Therapy and Outcome]. / ARDS ­ Ein Update ­ Teil 2: Therapie und Outcome.

The Acute Respiratory Distress Syndrome (ARDS) is defined by hypoxemic respiratory failure due to inflammatory response within the lung usually requiring invasive mechanical ventilation. Despite more than 50 years of scientific research numerous issues especially regarding mechanical ventilation as the most important treatment option remain unclear. Most important, adjustment of mechanical ventilation is challenging due to desirable beneficial effects on pulmonary gas exchange on the one hand and deleterious effects in terms of ventilator-associated lung injury on the other. Specifically, optimal settings of positive end-expiratory pressure and the role of spontaneous breathing activity are still controversial. Because no specific pharmacological therapy revealed beneficial effects until today, adjunctive treatment is actually limited to prone positioning and restrictive fluid balance. Long-term outcome of ARDS survivors is often affected by anxiety and mental health disorders.

Legionella pneumophila Pneumonia in Two Infants Treated with Adrenocorticotropic Hormone.

Patients with infantile spasms, an intractable epileptic disorder, often are treated with adrenocorticotropic hormone. Legionella pneumophila is a rare cause of pneumonia in children. We describe 2 infants with Legionella pneumonia whose infection occurred within 1 month after starting adrenocorticotropic hormone.

Legionnaires' disease caused by Legionella longbeachae: Clinical features and outcomes of 107 cases from an endemic area.

BACKGROUND AND OBJECTIVE: Legionella longbeachae is a predominant cause of Legionnaires' disease in some parts of the world, particularly in Australasia. Clinical reports of L. longbeachae infection are limited to case reports or small case series, and culture-confirmed cases. METHODS: We reviewed the clinical characteristics and outcomes of L. longbeachae pneumonia in a large case series from Christchurch, New Zealand during a 4-year period when both PCR and cultures were used as routine diagnostic tools for Legionnaires' disease. Cases of Legionella pneumophila pneumonia were reviewed for comparison. RESULTS: A total of 107 cases of L. longbeachae infection were identified by PCR and/or culture. The median age was 65 years (range 25-90 years), 63% were male, and most became unwell during spring or summer. Presenting clinical features were similar to those reported for community-acquired pneumonia, with headache, myalgia and diarrhoea being common. Elevated C-reactive protein, hyponatraemia and abnormal liver function tests were also common. History of productive cough, involvement of both lungs, and high bacterial load were independently associated with culture of Legionella from lower respiratory samples. One quarter required intensive care unit admission, and 5% died. Among patients given antimicrobial therapy before admission, those given agents without anti-Legionella activity were more likely to be admitted to the intensive care unit. Limited comparisons were made with the 19 L. pneumophila cases over the same time period. CONCLUSION: Characteristics of L. longbeachae pneumonia are broadly similar to those reported for community-acquired pneumonia from a variety of other populations, except for the spring/summer seasonality.