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Annals of Intensive Care Apr 2024Legionnaires' disease (LD) is a common but under-diagnosed cause of community-acquired pneumonia (CAP), although rapid detection of urine antigen testing (UAT) and... (Review)
Review
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.
PubMed: 38565811
DOI: 10.1186/s13613-024-01252-y -
Annals of Agricultural and... Mar 2024is the primary etiological agent of Legionnaires' disease. These are opportunistic pathogens causing lung infections by inhalation of contaminated aerosols. Controlling...
INTRODUCTION
is the primary etiological agent of Legionnaires' disease. These are opportunistic pathogens causing lung infections by inhalation of contaminated aerosols. Controlling the presence of these bacteria in domestic distribution water systems (mainly hot water systems) is important for reducing the threat they pose to human health. pathogens are detected and quantified during routine testing of water samples according to procedures included in PN-EN ISO 11731:2017. However, these procedures are labour-intensive, and the results are obtained after a relatively long time. Implementing the Legiolert™/Quanti-Tray test as an alternative method may constitute a good solution: it simplifies the testing procedure and significantly reduces the time necessary to obtain the final result.
OBJECTIVE
The aim of the study was to compare the relative recovery of from water samples tested according to PN-EN ISO 11731:2017, and the alternative method of the most probable number (MPN) with the Legiolert™/Quanti-Tray (IDEXX) test, and to assess the suitability of the alternative method for routine testing.
MATERIAL AND METHODS
Parallel testing was conducted of 38 hot water samples to detect and determine acc. to PN-EN ISO 11731:2017 and the Legiolert™/Quanti-Tray test. Statistical analysis of the results was performed according to PN-EN ISO 17994:2014 and the McNemar's test.
RESULTS
The Legiolert™ test was confirmed to be comparable in performance to the reference standardized method in both qualitative and quantitative detection of in hot water samples.
CONCLUSIONS
The study confirmed that the Legiolert™ test is specific and easy to use, and may constitute an alternative to standardized procedures used in the quantification of in water.
Topics: Humans; Legionella pneumophila; Water Microbiology; Respiratory Aerosols and Droplets; Legionnaires' Disease; Drinking Water; Legionella
PubMed: 38549473
DOI: 10.26444/aaem/173402 -
European Journal of Clinical... Jun 2024In case of pneumonia, some biological findings are suggestive for Legionnaire's disease (LD) including C-reactive protein (CRP). A low level of CRP is predictive for... (Observational Study)
Observational Study
INTRODUCTION
In case of pneumonia, some biological findings are suggestive for Legionnaire's disease (LD) including C-reactive protein (CRP). A low level of CRP is predictive for negative Legionella Urinary-Antigen-Test (L-UAT).
METHOD
Observational retrospective study in Nord-Franche-Comté Hospital with external validation in Besançon University Hospital, France which included all adults with L-UAT performed during January 2018 to December 2022. The objective was to determine CRP optimal threshold to predict a L-UAT negative result.
RESULTS
URINELLA included 5051 patients (83 with positive L-UAT). CRP optimal threshold was 131.9 mg/L, with a negative predictive value (NPV) at 100%, sensitivity at 100% and specificity at 58.0%. The AUC of the ROC-Curve was at 88.7% (95% CI, 86.3-91.1). External validation in Besançon Hospital patients showed an AUC at 89.8% (95% CI, 85.5-94.1) and NPV, sensitivity and specificity was respectively 99.9%, 97.6% and 59.1% for a CRP threshold at 131.9 mg/L; after exclusion of immunosuppressed patients, index sensitivity and NPV reached also 100%.
CONCLUSION
In case of pneumonia suspicion with a CRP level under 130 mg/L (independently of the severity) L-UAT is useless in immunocompetent patients with a NPV at 100%. We must remain cautious in patients with symptoms onset less than 48 h before CRP dosage.
Topics: Humans; Legionnaires' Disease; Legionella pneumophila; C-Reactive Protein; Retrospective Studies; Male; Female; Middle Aged; Aged; Sensitivity and Specificity; Serogroup; Adult; France; ROC Curve; Predictive Value of Tests
PubMed: 38530466
DOI: 10.1007/s10096-024-04814-x -
Journal of Clinical Microbiology Apr 2024The unprecedented precision and resolution of whole genome sequencing (WGS) can provide definitive identification of infectious agents for epidemiological outbreak...
The unprecedented precision and resolution of whole genome sequencing (WGS) can provide definitive identification of infectious agents for epidemiological outbreak tracking. WGS approaches, however, are frequently impeded by low pathogen DNA recovery from available primary specimens or unculturable samples. A cost-effective hybrid capture assay for WGS analysis directly on primary specimens was developed. DNA from a diverse range of sputum and autopsy specimens PCR-positive for serogroup 1 (LPSG1) was enriched with this method, and WGS was performed. All tested specimens were determined to be enriched for reads (up to 209,000-fold), significantly improving the discriminatory power to compare relatedness when no clinical isolate was available. We found the WGS data from some enriched specimens to differ by less than five single-nucleotide polymorphisms (SNPs) when compared to the WGS data of a matched culture isolate. This testing and analysis retrospectively provided previously unconfirmed links to environmental sources for clinical specimens of sputum and autopsy lung tissue. The latter provided the additional information needed to identify the source of these culture-negative cases associated with the South Bronx 2015 Legionnaires' disease (LD) investigation in New York City. This new method provides a proof of concept for future direct clinical specimen hybrid capture enrichment combined with WGS and bioinformatic analysis during outbreak investigations.IMPORTANCELegionnaires' disease (LD) is a severe and potentially fatal type of pneumonia primarily caused by inhalation of -contaminated aerosols from man-made water or cooling systems. LD remains extremely underdiagnosed as it is an uncommon form of pneumonia and relies on clinicians including it in the differential and requesting specialized testing. Additionally, it is challenging to obtain clinical lower respiratory specimens from cases with LD, and when available, culture requires specialized media and growth conditions, which are not available in all microbiology laboratories. In the current study, a method for using hybrid capture by RNA baiting was developed, which allowed us to generate sufficient genome resolution from serogroup 1 PCR-positive clinical specimens. This new approach offers an additional tool for surveillance of future LD outbreaks where isolation of is not possible and may help solve previously unanswered questions from past LD investigations.
Topics: Humans; Legionnaires' Disease; Retrospective Studies; Legionella pneumophila; Legionella; Whole Genome Sequencing; Disease Outbreaks; Pneumonia; DNA
PubMed: 38511938
DOI: 10.1128/jcm.01305-23 -
Journal of Clinical Microbiology Apr 2024Many pneumonia patients do not produce sputum, and it is unknown whether purulent sputum is required for the identification of species. This study aimed to evaluate...
Many pneumonia patients do not produce sputum, and it is unknown whether purulent sputum is required for the identification of species. This study aimed to evaluate the identification rate of species based on sputum quality and the factors predictive of infection. This study included pneumonia patients at Kurashiki Central Hospital from November 2000 to December 2022. Sputum quality, based on gram staining, was classified as the following: Geckler 1/2, 3/6 and 4/5. Geckler 4/5 was defined as purulent sputum. The sputa of 104 of 124 pneumonia patients were cultured. Fifty-four patients (51.9%) were identified with species, most of which were serogroup 1 (81.5%). The identification rates of species according to sputum quality were 57.1% (16/28) in Geckler 1/2 sputum, 50.0% (34/68) in Geckler 3/6 sputum, and 50.0% (4/8) in Geckler 4/5 sputum, which were not significantly different ( = 0.86). On multivariate analysis, pre-culture treatment with anti- antimicrobials (odds ratio [OR] 0.26, 95% confidence interval [CI] 0.06-0.91), Pneumonia Severity Index class ≥IV (OR 2.57 [95% CI 1.02-6.71]), and intensive care unit admission (OR 3.08, 95% CI 1.06-10.09) correlated with the ability to identify species, but sputum quality did not (OR 0.88, 95% CI 0.17-4.41). The identification rate of species in non-purulent sputum was similar to that in purulent sputum. For the diagnosis of pneumonia, sputum should be collected before administering anti- antibiotics and cultured regardless of sputum quality.
Topics: Humans; Legionella; Sputum; Legionnaires' Disease; Legionella pneumophila; Pneumonia
PubMed: 38501659
DOI: 10.1128/jcm.01665-23 -
PNAS Nexus Mar 2024Legionnaires' disease (LD) is a severe form of pneumonia (∼10-25% fatality rate) caused by inhalation of aerosols containing , a pathogenic gram-negative bacteria....
Legionnaires' disease (LD) is a severe form of pneumonia (∼10-25% fatality rate) caused by inhalation of aerosols containing , a pathogenic gram-negative bacteria. These bacteria can grow, spread, and aerosolize through building water systems. A recent dramatic increase in LD incidence has been observed globally, with a 9-fold increase in the United States from 2000 to 2018, and with disproportionately higher burden for socioeconomically vulnerable subgroups. Despite the focus of decades of research since the infamous 1976 outbreak, substantial knowledge gaps remain with regard to source of exposure and the reason(s) for the dramatic increase in LD incidence. Here, we rule out factors indicated in literature to contribute to its long-term increases and identify a hitherto unexplored explanatory factor. We also provide an epidemiological demonstration that the occurrence of LD is linked with exposure to cooling towers (CTs). Our results suggest that declining sulfur dioxide air pollution, which has many well-established health benefits, results in reduced acidity of aerosols emitted from CTs, which may prolong the survival duration of in contaminated CT droplets and contribute to the increase in LD incidence. Mechanistically associating decreasing aerosol acidity with this respiratory disease has implications for better understanding its transmission, predicting future risks, and informed design of preventive and interventional strategies that consider the complex impacts of continued sulfur dioxide changes.
PubMed: 38476666
DOI: 10.1093/pnasnexus/pgae085 -
Virulence Dec 2024() is a prevalent pathogenic bacterium responsible for significant global health concerns. Nonetheless, the precise pathogenic mechanisms of have still remained...
() is a prevalent pathogenic bacterium responsible for significant global health concerns. Nonetheless, the precise pathogenic mechanisms of have still remained elusive. Autophagy, a direct cellular response to infection and other pathogens, involves the recognition and degradation of these invaders in lysosomes. Histone deacetylase 6 (HDAC6), a distinctive member of the histone deacetylase family, plays a multifaceted role in autophagy regulation. This study aimed to investigate the role of HDAC6 in macrophage autophagy via the autophagolysosomal pathway, leading to alleviate -induced pneumonia. The results revealed a substantial upregulation of HDAC6 expression level in murine lung tissues infected by . Notably, mice lacking HDAC6 exhibited a protective response against -induced pulmonary tissue inflammation, which was characterized by the reduced bacterial load and diminished release of pro-inflammatory cytokines. Transcriptomic analysis has shed light on the regulatory role of HDAC6 in infection in mice, particularly through the autophagy pathway of macrophages. Validation using -induced macrophages from mice with HDAC6 gene knockout demonstrated a decrease in cellular bacterial load, activation of the autophagolysosomal pathway, and enhancement of cellular autophagic flux. In summary, the findings indicated that HDAC6 knockout could lead to the upregulation of p-ULK1 expression level, promoting the autophagy-lysosomal pathway, increasing autophagic flux, and ultimately strengthening the bactericidal capacity of macrophages. This contributes to the alleviation of -induced pneumonia.
Topics: Animals; Mice; Autophagy; Histone Deacetylase 6; Legionella; Legionella pneumophila; Legionnaires' Disease; Macrophages; Pneumonia
PubMed: 38466143
DOI: 10.1080/21505594.2024.2327096 -
Clinical Case Reports Mar 2024Legionnaires' disease, often presenting as pneumonia, can uncommonly manifest with extrapulmonary symptoms such as cerebellar involvement and rhabdomyolysis. This case...
KEY CLINICAL MESSAGE
Legionnaires' disease, often presenting as pneumonia, can uncommonly manifest with extrapulmonary symptoms such as cerebellar involvement and rhabdomyolysis. This case emphasizes the successful resolution of dysarthria and renal dysfunction with prompt Legionella treatment, underscoring the importance of vigilance for diverse manifestations in Legionella infections.
ABSTRACT
Legionnaires' disease usually presents with pneumonia and a few extrapulmonary manifestations, such as neurological, musculoskeletal, and cutaneous manifestations. However, cerebellar involvement and rhabdomyolysis as an association with Legionella are not frequently encountered. We present a case of Legionella-induced rhabdomyolysis requiring hemodialysis and dysarthria that resolved with Legionella treatment.
PubMed: 38464574
DOI: 10.1002/ccr3.8628 -
Medicina (Kaunas, Lithuania) Jan 2024: Legionnaires' disease (LD) is an acute respiratory disease with increasing annual numbers of reported domestic and global cases. This study aimed to establish...
: Legionnaires' disease (LD) is an acute respiratory disease with increasing annual numbers of reported domestic and global cases. This study aimed to establish foundational data for the prevention and control of LD by investigating the occurrence and infection routes of reported and suspected cases of LD in Gyeonggi Province, Korea, from January 2016 to December 2022, and by and analyzing the risk factors for death. : A sex-and-age standardization was performed on LD patients and suspected cases reported in Gyeonggi Province. The monthly average number of confirmed cases was visualized using graphs, and a survival analysis was performed using Kaplan-Meier survival curves. The mortality risk ratio was estimated using the Cox proportional hazards model. : The incidence of LD in Gyeonggi Province mirrored the national trend, peaking in July with the highest number of confirmed and suspected cases. While there was no significant difference in survival rates by age, the survival rate was higher for suspected cases when analyzed separately. Comparing the death ratio by infection route, nosocomial infections showed the highest death ratio, and intensive care unit (ICU) admission and the presence of coinfections were significantly correlated with mortality. Factors such as nosocomial infection, admission within 1 to 3 days following diagnosis, and the development of complications were factors contributing to a higher risk of death. : The general characteristics of patients with LD were similar to those suggested by previous studies. The proportion of community-acquired infections was lower than in previous studies, but the length of hospital stay was similar for survivors and the deceased, and the mortality rate within 30 days after diagnosis was higher for nosocomial infections. In conclusion, nosocomial infection, a period of up to 3 days from admission to diagnosis, and complications were significantly related to the mortality rate of LD.
Topics: Humans; Legionnaires' Disease; Legionella pneumophila; Cross Infection; Epidemiologic Studies; Risk Factors; Republic of Korea
PubMed: 38399516
DOI: 10.3390/medicina60020227