Analysis of the effectiveness of combination antimicrobial therapy for Legionnaires' disease: A nationwide inpatient database study.

OBJECTIVES: 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. CONCLUSION: 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.

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.

Association between the Timing of Urinary Antigen Testing and Outcomes in Legionella Pneumonia Patients: A Nationwide Database Study.

Objective Recommendations on the timing of Legionella urinary antigen tests for community-acquired pneumonia patients differ among guidelines in Japan, the United States, and European nations. We therefore evaluated the association between the timing of urinary antigen tests and in-hospital mortality in patients with Legionella pneumonia. Methods We conducted a retrospective cohort study using the Diagnosis Procedure Combination database, a nationwide database of acute care inpatients in Japan. Patients who underwent Legionella urinary antigen tests on the day of admission formed the tested group. Patients who were tested on day 2 of admission or later or were unexamined formed the control group. We performed a propensity score matching analysis to compare in-hospital mortality, length of hospital stay and duration of antibiotics use between the two groups. Results Of the 9,254 eligible patients, 6,933 were included in the tested group. One-to-one propensity score matching generated 1,945 pairs. The tested group had a significantly lower 30-day in-hospital mortality than the control group (5.7 vs. 7.7%; odds ratio, 0.72; 95% confidence intervals, 0.55-0.95; p=0.020). The tested group also showed a significantly shorter length of stay and duration of antibiotics use than the control group. Conclusion Urine antigen testing upon admission was associated with better outcomes in patients with Legionella pneumonia. Urine antigen tests upon admission may be recommended for all patients with severe community-acquired pneumonia.

A Novel Case of Legionnaire's Disease after Staying at Home Rentals.

Case of a 44-year-old woman with past medical history of dermatomyositis who had been on Methrotexate therapy who became infected with Legionella pneumophila after staying at a home rental, known commercially as an Airbnb. The patient presented to the ER with complaints of general malaise and subsequently developed sepsis with respiratory failure requiring intubation. CT scan confirmed the diagnosis of pneumonia and through extensive research L. pneumophila was identified using a pneumonia panel that works by identifying nucleic acids of fastidious organisms that are difficult and take long to grow by culture. As the patient's pneumonia progressed to ARDS and her clinical impression worsened, pronation technique was begun in addition to her course of antibiotics that were already being administered. The patient began showing significant improvement in her clinical picture and was extubated with progressive recovery.

Therapeutical strategies in cavitary legionnaires' disease, two cases from the field and a systematic review.

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. RESULT OF SYNTHESIS (CASE REPORTS): 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. RESULT OF SYNTHESIS (GUIDELINES): 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. CONCLUSION: 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.

Early discontinuation of combination antibiotic therapy in severe community-acquired pneumonia: a retrospective cohort study.

BACKGROUND: Severe community-acquired pneumonia (SCAP) is commonly treated with an empiric combination therapy, including a macrolide, or a quinolone and a ß-lactam. However, the risk of Legionella pneumonia may lead to a prolonged combination therapy even after negative urinary antigen tests (UAT). METHODS: We conducted a retrospective cohort study in a French intensive care unit (ICU) over 6 years and included all the patients admitted with documented SCAP. All patients received an empirical combination therapy with a ß-lactam plus a macrolide or quinolone, and a Legionella UAT was performed. Macrolide or quinolone were discontinued when the UAT was confirmed negative. We examined the clinical and epidemiological features of SCAP and analysed the independent factors associated with ICU mortality. RESULTS: Among the 856 patients with documented SCAP, 26 patients had atypical pneumonia: 18 Legionella pneumophila (LP) serogroup 1, 3 Mycoplasma pneumonia (MP), and 5 Chlamydia psittaci (CP). UAT diagnosed 16 (89%) Legionella pneumonia and PCR confirmed the diagnosis for the other atypical pneumonia. No atypical pneumonia was found by culture only. Type of pathogen was not associated with a higher ICU mortality in the multivariate analysis. CONCLUSION: Legionella pneumophila UAT proved to be highly effective in detecting the majority of cases, with only a negligible percentage of patients being missed, but is not sufficient to diagnose atypical pneumonia, and culture did not provide any supplementary information. These results suggest that the discontinuation of macrolides or quinolones may be a safe option when Legionella UAT is negative in countries with a low incidence of Legionella pneumonia.

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.

[4.3.1]Bicyclic FKBP Ligands Inhibit Legionella Pneumophila Infection by LpMip-Dependent and LpMip-Independent Mechanisms.

Legionella pneumophila is the causative agent of Legionnaires' disease, a serious form of pneumonia. Its macrophage infectivity potentiator (Mip), a member of a highly conserved family of FK506-binding proteins (FKBPs), plays a major role in the proliferation of the gram-negative bacterium in host organisms. In this work, we test our library of >1000 FKBP-focused ligands for inhibition of LpMip. The [4.3.1]-bicyclic sulfonamide turned out as a highly preferred scaffold and provided the most potent LpMip inhibitors known so far. Selected compounds were non-toxic to human cells, displayed antibacterial activity and block bacterial proliferation in cellular infection-assays as well as infectivity in human lung tissue explants. The results confirm [4.3.1]-bicyclic sulfonamides as anti-legionellal agents, although their anti-infective properties cannot be explained by inhibition of LpMip alone.

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.

Effects of corticosteroids in hospitalized patients with Legionella pneumonia: A retrospective cohort study.

INTRODUCTION: Legionella pneumophila is an important cause of pneumonia, however there is scant literature assessing the therapeutic benefit of corticosteroids in treatment. We sought to investigate the association between corticosteroid use and in-hospital mortality for patients hospitalized with Legionella pneumonia. METHODS: Data was collected retrospectively from January 2012 to July 2019 at a 705 bed hospital in New York City. Patients were included if they received a positive Legionella test. Exclusion criteria included age <18, concurrent immunosuppression, and HIV diagnosis. We assessed the relationship between corticosteroid use and in-hospital mortality. Statistical analyses were performed in RStudio. RESULTS: The study included 160 patients, among which 32 (20%) received steroids. Overall mortality was 7.5% (12.5% among steroid recipients, 6.2% among controls). 25% of patients were admitted to the ICU (37.5% among steroid recipients, 21.9% among controls). Adjusted analysis showed steroid recipients did not have significantly different mortality (aOR = 2.56, p = 0.436). Steroid use was not significantly associated with longer LOS (p = 0.22). Steroid use was significantly associated with hyperglycemia (aOR = 2.91, p = 0.018) and GI bleed (OR = 9.0, p = 0.014). CONCLUSIONS: We found that in patients hospitalized with Legionella pneumonia, corticosteroid administration was not significantly associated with longer hospitalization or mortality. All findings held true when adjusting for known predictors of pneumonia severity. Corticosteroid use was associated with increased rates of hyperglycemia and GIB requiring blood transfusion. The results of this study are consistent with guidelines recommending against routine use of corticosteroids in CAP.

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.

The Different Clinical Courses of Legionnaires' Disease in Newborns from the Same Maternity Hospital.

In children, the incidence of Legionnaires' disease (LD) is unknown, hospital-acquired LD is associated with clinical risk factors and environmental risk, and children with cell-mediated immune deficiency are at high risk of infection. Both newborns were born in the same delivery room; stayed in the same hospital room where they were cared for, bathed, and breastfed; were male; were born on time, with normal birth weight, and with high Apgar score at birth; and survived this severe infection (L. pneumophila, serogroup 2-15) but with different clinical courses. In neonate 1, bleeding in the brain, thrombosis of deep pelvic veins, and necrosis of the lungs, which left behind cystic and cavernous changes in the lungs, were found, while neonate 2 suffered from pneumonia alone. The only difference in risk factors for LD between these two newborns is the number of days of illness until the start of azithromycin treatment (sixth versus the third day of illness). We suggest that a change in the guidelines for diagnosing and treating community-acquired pneumonia and hospital-acquired pneumonia in newborns is needed in terms of mandatory routine testing for Legionella pneumophila. Early initiation of macrolide therapy is crucial for the outcome of LD in the newborn.

Proteome Exploration of Legionella pneumophila To Identify Novel Therapeutics: a Hierarchical Subtractive Genomics and Reverse Vaccinology Approach.

Legionella pneumophila is the causative agent of a severe type of pneumonia (lung infection) called Legionnaires' disease. It is emerging as an antibiotic-resistant strain day by day. Hence, identifying novel drug targets and vaccine candidates is essential to fight against this pathogen. Here, attempts were taken through a subtractive genomics approach on the complete proteome of L. pneumophila to address the challenges of multidrug resistance. A total of 2,930 proteins from L. pneumophila proteome were investigated through diverse subtractive proteomics approaches, e.g., identification of human nonhomologous and pathogen-specific essential proteins, druggability and "anti-target" analysis, subcellular localization prediction, human microbiome nonhomology screening, and protein-protein interaction studies to find out effective drug and vaccine targets. Only three fulfilled these criteria and were proposed as novel drug targets against L. pneumophila. Furthermore, outer membrane protein TolB was identified as a potential vaccine target with a better antigenicity score. Antigenicity and transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis, and a molecular docking approach were adopted to generate the most potent epitopes. The final vaccine was constructed by the combination of highly immunogenic epitopes, along with suitable adjuvant and linkers. The designed vaccine construct showed higher binding interaction with different major histocompatibility complex (MHC) molecules and human immune TLR-2 receptors with minimum deformability at the molecular level. The present study aids the development of novel therapeutics and vaccine candidates for efficient treatment and prevention of L. pneumophila infections. However, further wet-lab-based phenotypic and genomic investigations and in vivo trials are highly recommended to validate our prediction experimentally. IMPORTANCE Legionella pneumophila is a human pathogen distributed worldwide, causing Legionnaires' disease (LD), a severe form of pneumonia and respiratory tract infection. L. pneumophila is emerging as an antibiotic-resistant strain, and controlling LD is now difficult. Hence, developing novel drugs and vaccines against L. pneumophila is a major research priority. Here, the complete proteome of L. pneumophila was considered for subtractive genomics approaches to address the challenge of antimicrobial resistance. Our subtractive proteomics approach identified three potential drug targets that are promising for future application. Furthermore, a possible vaccine candidate, "outer membrane protein TolB," was proposed using reverse vaccinology analysis. The constructed vaccine candidate showed higher binding interaction with MHC molecules and human immune TLR-2 receptors at the molecular level. Overall, the present study aids in developing novel therapeutics and vaccine candidates for efficient treatment of the infections caused by L. pneumophila.

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.

Validating a clinical prediction score for Legionella-related community acquired pneumonia.

BACKGROUND: Legionella-related community acquired pneumonia (CAP) is a disease with an increasing incidence and a high mortality rate, especially if empirical antibiotic therapy is inadequate. Antibiotic treatment highly relies on clinical symptoms, although proven non-specific, because currently available diagnostic techniques provide insufficient accuracy for detecting Legionella CAP on admission. This study validates a diagnostic scoring system for detection of Legionella-related CAP, based on six items on admission (Legionella prediction score). METHODS: We included patients with Legionella-related CAP admitted to five large Dutch hospitals between 2006 and 2016. Controls were non-Legionella-related CAP patients. The following six conditions were rewarded one point if present: fever > 39.4 °C; dry cough; hyponatremia (sodium) < 133 mmol/L; lactate dehydrogenase (LDH) > 225 mmol/L; C-reactive protein (CRP) > 187 mg/L and platelet count < 171 × 109/L. The accuracy of the prediction score was assessed by calculating the area under the curve (AUC) through logistic regression analysis. RESULTS: We included 131 cases and 160 controls. A score of 0 occurred in non-Legionella-related CAP patients only, a score of 5 and 6 in Legionella-related CAP patients only. A cut-off ≥ 4 resulted in a sensitivity of 58.8% and a specificity of 93.1%. The AUC was 0.89 (95% CI 0.86-0.93). The strongest predictors were elevated LDH, elevated CRP and hyponatremia. CONCLUSIONS: This multi-centre study validates the Legionella prediction score, an easily applicable diagnostic scoring system, in a large group of patients and finds high diagnostic accuracy. The score shows promise for future prospective validation and could contribute to targeted antibiotic treatment of suspected Legionella CAP.

Legionnaires' disease - a qualitative study on Swiss physicians' approaches to the diagnosis and treatment of community-acquired pneumonia.

BACKGROUND: The number of reported cases of Legionnaires' disease has increased significantly over the last decade in Switzerland and abroad. Along with the number of cases, the volume of testing has increased as well, which has been partially attributed to a change in awareness of the disease. Yet, while there are numerous guidelines and recommendations for the case management of community-acquired pneumonia, little is known about how physicians in Switzerland perceive and manage Legionnaires' disease. METHODS: This study aimed to investigate physicians' awareness of Legionnaires' disease, their information resources and their approach to the diagnosis and treatment of pneumonia (and thus Legionnaires' disease). Using a semi-structured interview guide, we conducted in-depth interviews with physicians from different levels of care and from the German-, French- and Italian-speaking regions of Switzerland. RESULTS: We conducted 46 interviews with physicians from university, cantonal and regional hospitals as well as with general practitioners (GPs) from all three language regions. Overall, the physicians working in hospitals indicated a similar level of awareness of Legionnaires' disease, and comparable diagnosis and treatment approaches. The Legionella urine antigen test (UAT) was reported to be routinely performed in inpatients. In contrast, GPs indicated lower levels of awareness, reflecting the fact that they treat pneumonia cases empirically without identification of the causative agent, in accordance with current guidelines. The value of the diagnostic tests in general and the Legionella UAT in particular was considered to be dependent on the (preferred) antibiotic treatment approach. Some physicians saw the test as redundant, as its result would not influence treatment. This was tied to concerns about the UAT's sensitivity and its limited use for the detection of Legionella pneumophila serogroup 1. Lastly, extrinsic constraints, such as financial and time considerations also affected physicians' testing and treatment preferences. CONCLUSION: Awareness of Legionnaires' disease is overall high, yet cases are mainly diagnosed and reported by hospitals. Improved diagnostic tools are needed to support physicians in reducing underestimation of Legionnaires' disease and optimise antibiotic stewardship without compromising patient health outcomes.

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.

Blockade of Cycloxygenase-2 ameliorates sepsis induced immune-suppression by regulating myeloid-derived suppressor cells.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) and cyclooxy-genase-2 (COX-2)/Prostaglandin E2 (PGE2) axis are important contributors to sepsis-induced immune-suppression. The purpose of present study is to explore whether COX-2 inhibitor can improve immunological disorder after sepsis via regulating MDSCs. METHODS: A ''two-hit'' model reflecting clinical sepsis development was performed. Cecal ligation and puncture (CLP) and Legionella pneumophila infection were used as the first and the second hit, respectively. NS398, a selective COX-2 inhibitor, was utilized to treat septic mice. The motality, bacterial counts in the lung, systematic inflammatory reaction and CD4 + T cells response after sepsis were assessed, so as the frequency and function of MDSCs. In some experiments, the number of MDSCs was manipulated by adoptive transfer or neutralizing antibody before induction of secondary infection. RESULTS: Mice surviving CLP showed a marked expansion and activation of MDSCs in spleen, accompanied by suppressed proliferating capability, impaired secreting functionand increased apoptosis of CD4 + T cells. Majority of CLP survivors became succumbed to L. pneumophila invasion, associated with defective bacteria elimination ability. NS398 treatment was found to ameliorate these adverse outcomes significantly. CONCLUSION: MDSCs contribute greatly to the sepsis-induced immune dysfunction. Inhibiting COX-2 may become a promising therapy that targets MDSCs-induced immunosuppression.