BACKGROUND: Legionnaires\' disease (LD) is a common but under-diagnosed cause of community-acquired pneumonia (CAP), although rapid detection of urine antigen testing (UAT) and advances in molecular testing have improved the diagnosis. LD entails intensive care unit (ICU) admission in almost one-third of cases, and the mortality rate ranges from 4% to 40%. This review aims to discuss recent advances in the study of this condition and to provide an update on the diagnosis, pathogenesis and management of severe LD.
RESULTS: The overall incidence of LD has increased worldwide in recent years due to the higher number of patients with risk factors, especially immunosuppression, and to improvements in diagnostic methods. Although LD is responsible for only around 5% of all-cause CAP, it is one of the three most common causes of CAP requiring ICU admission. Mortality in ICU patients, immunocompromised patients or patients with a nosocomial source of LD can reach 40% despite appropriate antimicrobial therapy. Regarding pathogenesis, no Legionella-specific virulence factors have been associated with severity; however, recent reports have found high pulmonary Legionella DNA loads, and impairments in immune response and lung microbiome in the most severe cases. The clinical picture includes severe lung injury requiring respiratory and/or hemodynamic support, extrapulmonary symptoms and non-specific laboratory findings. LD diagnostic methods have improved due to the broad use of UAT and the development of molecular methods allowing the detection of all Lp serogroups. Therapy is currently based on macrolides, quinolones, or a combination of the two, with prolonged treatment in severe cases.
CONCLUSIONS: Numerous factors influence the mortality rate of LD, such as ICU admission, the underlying immune status, and the nosocomial source of the infection. The host immune response (hyperinflammation and/or immunoparalysis) may also be associated with increased severity. Given that the incidence of LD is rising, studies on specific biomarkers of severity may be of great interest. Further assessments comparing different regimens and/or evaluating host-directed therapies are nowadays needed.

Legionella pneumophila, the leading cause of Legionnaires\' disease in the United States, is found in lakes, ponds, and streams but poses a health risk when it grows in building water systems. The growth of L. pneumophila in hot water systems of healthcare facilities poses a significant risk to patients, staff, and visitors. Hospitals and long-term care facilities account for 76% of reported Legionnaires\' disease cases with mortality rates of 25%. Controlling L. pneumophila growth in hot water systems serving healthcare and hospitality buildings is currently achieved primarily by adding oxidizing chemical disinfectants. Chemical oxidants generate disinfection byproducts and can accelerate corrosion of premise plumbing materials and equipment. Alternative control methods that do not generate hazardous disinfection byproducts or accelerate corrosion are needed. L. pneumophila is an obligate aerobe that cannot sustain cellular respiration, amplify, or remain culturable when dissolved oxygen (DO) concentrations are too low (< 0.3 mg/L). An alternative method of controlling L. pneumophila growth by reducing DO levels in a hot water model system using a gas transfer membrane contactor was evaluated. A hot water model system was constructed and inoculated with L. pneumophila at DO concentrations above 0.5 mg/L. Once the model system was colonized, DO levels were incrementally reduced. Water samples were collected each week to evaluate the effect of reducing dissolved oxygen levels when all other conditions favored Legionella amplification. At DO concentrations below 0.3 mg/L, L. pneumophila concentrations were reduced by 1-log over 7 days. Under conditions in the hot water model system, at favorable temperatures and with no residual chlorine disinfectant, L. pneumophila concentrations were reduced by 1-log, indicating growth inhibition by reducing DO levels as the sole control measure. In sections of the model system where DO levels were not lowered L. pneumophila continued to grow. Reducing dissolved oxygen levels in hot water systems of healthcare and other large buildings to control L. pneumophila could also lower the risk of supplemental chemical treatment methods currently in use.

OBJECTIVE: The effectiveness of monotherapy and combination therapy with quinolones and macrolides for treating Legionnaires\' disease remains uncertain; this study aimed to assess the comparative effectiveness of three treatment approaches.
METHODS: Using a nationwide inpatient database, we analyzed 3560 eligible patients hospitalized for Legionnaires\' disease between April 1, 2014, and March 31, 2021; patients were divided into combination therapy, quinolone monotherapy, and macrolide monotherapy groups according to the antibiotics administered within 2 days of admission. We compared in-hospital mortality, total hospitalization costs, and length of stay across these groups using multiple propensity score analysis with inverse probability of treatment weighting.
RESULTS: Of the 3560 patients, there were 564 (15.8%), 2221 (62.4%), and 775 (21.8%) patients in the combination therapy, quinolone monotherapy, and macrolide monotherapy groups, respectively. No significant differences were observed in in-hospital mortality between combination therapy and quinolone monotherapy groups, and between combination therapy and macrolide monotherapy groups. There were no significant differences in total hospitalization costs or length of stay among the three groups.
CONCLUSIONS: The study suggests that there may not be a significant advantage in using a combination of quinolones and macrolides over monotherapy for the treatment of Legionnaires\' disease. Given the potential for increased side effects, careful consideration is advised when choosing this combination therapy.

OBJECTIVE: The occurrence of bacteria of the genus Legionella sp. in hot water supply systems in buildings is a real threat to human health, especially for patients in hospitals and residents of nursing homes. The aim of the study was determination of the degree of colonization of hot water systems in hospitals and nursing homes in the Świętokrzyskie Province in south-east Poland.
METHODS: Between 2014 - 2018, samples were collected from hot water systems in 30 hospitals and 32 nursing homes in order to determine the degree of contamination. 631 samples collected of the bacteria Legionella sp were analyzed.
RESULTS: Excessive contamination (≥ 100CFU/100 ml) with the bacteria Legionella sp. was detected in 12.12% (n=71) of samples. Contamination was significantly more frequently detected in samples from hot water systems in nursing homes, compared to hospitals (16.48% vs. 10.37%). Above-standard contamination of hot water systems with Legionella sp. bacteria occurred in 34.43% of the facilities, and was more frequent in hospitals (41.38%) than in the nursing homes (28.13%). In 21.3% of the facilities, contamination was detected many times during the study period.
CONCLUSIONS: Excessive contamination of hot water systems with Legionella sp. bacteria in the examined facilities was a common phenomenon. The presence of the pathogen in the installations of these facilities may constitute a considerable health hazard for patients and residents.

We determined whether the incidence rates of travel-associated Legionnaires\' disease (TALD) in hotels in Germany increased after a previous occurrence and whether control measures required by the European Legionnaires\' Disease Surveillance Network after a cluster (>2 cases within 2 years) restored the rate to baseline. We analyzed TALD surveillance data from Germany during 2015-2019; a total of 307 TALD cases (163 domestic, 144 nondomestic) in hotels were reported. The incidence rate ratio was 5.5 (95% CI 3.6-7.9) for a second case and 25 (95% CI 11-50) for a third case after a cluster had occurred, suggesting that control measures initiated after the occurrence of TALD clusters might be inadequate to restore the incidence rate to baseline. Our findings indicate that substantial LD preventive measures should be explored by hotels or other accommodations after the first TALD case occurs to reduce the risk for future infections.

UNASSIGNED: A case admitted with dysarthria and syncope and hyperintense lesion in the splenium of the corpus callosum, diagnosed as Legionnaires\' disease by detecting Legionella antigen in the urine, and recovered only with antibiotic treatment is presented because it is rare in the literature.
UNASSIGNED: When a 64-year-old female patient was admitted to the emergency department with complaints of sudden loss of consciousness and fainting at home, she had speech impairment, and her pulse oxygen saturation in room air was 88%. In the neurological examination, there was no pathological finding except dysarthria in the patient with no motor deficit. The patient had no respiratory complaints and had a recent travel history. In laboratory examinations, hyponatremia was detected with increased C-reactive protein and liver enzymes. Consolidation was observed in the lower right zone on chest computed tomography. Ampicillin + sulbactam (4x1 gr, intravenous) and clarithromycin (2 × 500 mg orally) were initiated. On cranial magnetic resonance, a hyperintense lesion was observed in the splenium of the corpus callosum in the oval T2 sequence. Legionella pneumophila serogroup 1 antigen in urine was reported as positive. On the fourth day of her hospitalization, the patient, whose CRP and liver enzyme values regressed, her hyponatremia improved, her pulse oxygen saturation increased to 92% in room air, and her speech became comprehensible, was discharged after oral antibiotic treatment was arranged. On the 12th day, the speech ability of the patient completely returned to normal.
UNASSIGNED: Legionella infection should be suspected in the presence of pneumonia and corpus callosum splenium lesion.

BACKGROUND: Legionnaires\' Disease (LD) rarely evolves into pulmonary abscesses. The current systematic review has been designed to explore therapeutical strategies in pulmonary cavitary LD.
METHODS: A research strategy was developed and applied to the databases Embase, Pubmed, and Web of Science from the 1st of January 2000 to the 1st of November 2022. Original articles, case series, case reports, and guidelines written in English, French, German, Italian, and Dutch were considered. Furthermore, medical records of patients treated at the University Hospital UZ Brussel for LD cavitary pneumonia, between the 1st of January 2016 to the 1st of January 2022, were reviewed.
RESULTS: Two patients were found by the UZ Brussel\'s medical records investigation. Through the literature review, 23 reports describing 29 patients, and seven guidelines were identified. The overall evidence level was low.
UNASSIGNED: The median age was 48 years and 65% were male. A polymicrobial infection was detected in 11 patients (44%) with other aerobic bacteria being the most commonly found. At diagnosis, 52% of patients received combination therapy, and fluoroquinolones were the preferred antimicrobial class. Anaerobic coverage was neglected in 33% of patients.
UNASSIGNED: Three guidelines favor monotherapy with fluoroquinolones or macrolides, while one suggested an antimicrobial combination in case of severe LD. Four guidelines recommended anaerobic coverage in case of lung abscesses.
CONCLUSIONS: To date, the evidence supporting cavitary LD treatment is low. Monotherapy lowers toxicity and might be as effective as combination therapy. Finally, anaerobes should not be neglected.

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.
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.
Among the 84 patients, a higher secretion of plasmatic MCP-1, MIP1-β, 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.
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.

UNASSIGNED: The aim of this study is to compare the epidemiological situation of legionellosis in Poland in 2018-2021 to prior years, taking into account the impact of the COVID-19 pandemic in 2020-2021.
UNASSIGNED: The assessment is based on national surveillance data published in the annual bulletin \"Infectious Diseases and Poisons in Poland\" from 2013 to 2021, as well as data from Legionnaires\' disease case reports collected and sent to the Department of Epidemiology of Infectious Diseases and Surveillance NIPH NIH - NRI by sanitary and epidemiological stations or submitted to EpiBase.
UNASSIGNED: In Poland, both Legionnaires\' disease (an acute infection that progresses to pneumonia) and Pontiac fever (a mild, flu-like sickness) are reported. In 2018-2021, a total of 255 cases of legionellosis were registered, including 236 cases of Legionnaires\' disease and 19 cases of Pontiac fever. Each year, there was an increase in the number of notifications compared to the annual median number of cases from 2013-2017. The annual incidence rate in 2019 (0.23 per 100,000 population) was the highest since the start of legionellosis case registration in Poland. It declined again during the years of the COVID-19 pandemic. The notifications occurred throughout the country, but the highest notification rate was observed in the western belt of voivodeships. Pomorskie reported the highest incidence, accounting for more than 20% of all registered cases. The median incidence of Legionnaires\' disease in men (0.23 per 100,000) was more than twice that of women (0.10), with the highest incidence (0.58) recorded in men 65 years of age or older. All indigenous cases of Legionnaires\' disease were sporadic; all but three patients were hospitalized. State Sanitary Inspection reported 26 fatal cases of Legionnaires\' disease (mortality = 11%). Twenty-four cases were linked to contaminated water systems in health-care settings, and 21 cases were likely associated with travel abroad.
UNASSIGNED: Although the number of notifications has increased in recent years, Legionnaires\' disease is still an infrequently diagnosed respiratory infection in Poland, and the reported incidence remains one of the lowest in the entire EU. The most affected demographic group is men aged 65 and older. Improving the early diagnosis of Legionnaires\' disease in healthcare settings remains a priority.

Legionella, the bacterium that causes Legionnaires\' disease, can grow and spread in building water systems and devices. The COVID-19 pandemic impacted building water systems through reductions in water usage. Legionella growth risk factors can be mitigated through control measures, such as flushing, to address stagnation, as part of a water management program (WMP). A national lodging organization (NLO) provided WMP data, including Legionella environmental testing results for periods before and during the pandemic. The statistical analysis revealed an increased risk of water samples testing positive for Legionella during the pandemic, with the greatest increase in risk observed at the building\'s cold-water entry test point. Sample positivity did not vary by season, highlighting the importance of year-round Legionella control activities. The NLO\'s flushing requirements may have prevented an increased risk of Legionella growth during the pandemic. However, additional control measures may be needed for some facilities that experience Legionella detections. This analysis provides needed evidence for the use of flushing to mitigate the impacts of building water stagnation, as well as the value of routine Legionella testing for WMP validation. Furthermore, this report reinforces the idea that WMPs remain the optimal tool to reduce the risk of Legionella growth and spread in building water systems.