Incidence and risk factors associated with progression to severe pneumonia among adults with non-severe Legionella pneumonia

Jin-Young Huh; Sang-Ho Choi; Kyung-Wook Jo; Jin Won Huh; Sang-Bum Hong; Tae Sun Shim; Chae-Man Lim; Younsuck Koh

doi:10.4266/acc.2022.00521

Articles

Page Path: HOME > Acute Crit Care > Volume 37(4); 2022 > Article

Original Article Pulmonary Incidence and risk factors associated with progression to severe pneumonia among adults with non-severe Legionella pneumonia: Jin-Young Huh^1,2, Sang-Ho Choi³, Kyung-Wook Jo², Jin Won Huh¹, Sang-Bum Hong¹, Tae Sun Shim¹, Chae-Man Lim¹, Younsuck Koh¹; Acute and Critical Care 2022;37(4):543-549.
DOI: https://doi.org/10.4266/acc.2022.00521
Published online: October 21, 2022

¹Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

²Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, Korea

³Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Corresponding author: Younsuck Koh Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Tel: +82-2-3010-3130 Fax: +82-2-3010-6960 E-mail: yskoh@amc.seoul.kr

• Received: April 14, 2022 • Revised: August 17, 2022 • Accepted: August 26, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

3,491 Views
123 Download
6 Web of Science
6 Crossref
4 Scopus

prev next

Full Article

Download PDF

Abstract
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
HIGHLIGHTS
NOTES
REFERENCES

Abstract

Background
Legionella species are important causative organisms of severe pneumonia. However, data are limited on predictors of progression to severe Legionella pneumonia (LP). Therefore, the risk factors for LP progression from non-severe to the severe form were investigated in the present study.
Methods
This was a retrospective cohort study that included adult LP patients admitted to a 2,700-bed referral center between January 2005 and December 2019.
Results
A total of 155 patients were identified during the study period; 58 patients (37.4%) initially presented with severe pneumonia and 97 (62.6%) patients with non-severe pneumonia. Among the 97 patients, 28 (28.9%) developed severe pneumonia during hospitalization and 69 patients (71.1%) recovered without progression to severe pneumonia. Multivariate logistic regression analysis showed platelet count ≤150,000/mm³ (odds ratio [OR], 2.923; 95% confidence interval [CI], 1.100–8.105; P=0.034) and delayed antibiotic treatment >1 day (OR, 3.092; 95% CI, 1.167–8.727; P=0.026) were significant independent factors associated with progression to severe pneumonia.
Conclusions
A low platelet count and delayed antibiotic treatment were significantly associated with the progression of non-severe LP to severe LP.
Keywords: antibiotics; Legionella; pneumonia; prognosis; thrombocytopenia

INTRODUCTION

Legionella species (spp.) are small Gram-negative bacilli usually found in natural aqueous environments [1,2]. The bacteria can cause respiratory infection in humans and are an important causative organism of pneumonia [3,4]. Legionella pneumonia (LP) accounts for 2.4%–12.5% of community-acquired pneumonia (CAP) cases [5,6]. In the last decade, the incidence of LP has rapidly increased worldwide [7-9]. The number of cases reported to the Korea Centers for Disease Control and Prevention was 6 in 2006 in contrast to 501 in 2019 [10]. The reasons for such a sharp increase include widespread nucleic acid amplification, urinary antigen testing, and the introduction of mandatory reporting systems for the disease in several countries [11-13]. Furthermore, an aging population, infrastructure, and changes in the global climate have been suggested as factors contributing to this increase [14].

In prior studies, 20.7%–78.6% of LP patients were shown to initially have or eventually progress to severe pneumonia requiring intensive care unit (ICU) admission [15-18]. Despite the growing importance of LP in public health, the issues associated with the progression of LP have been addressed in only a few studies. Therefore, in the present study, the risk factors associated with the progression of non-severe LP to severe LP in adults were investigated.

MATERIALS AND METHODS

The study protocol was approved by the Institutional Review Board of Asan Medical Center (No. 2021-2424). The requirement for informed consent was waived due to the retrospective nature of the analysis.

Study Population and Data Collection

Patients whose clinical specimens yielded positive results for Legionella spp. between January 2005 and December 2019 at Asan Medical Center, a 2,700-bed tertiary hospital, were screened for this study. Using the clinical microbiology electronic database of the hospital, 170 LP patients >18 years of age were identified, their medical records were reviewed, and patients treated in-hospital for LP were selected. Finally, a total of 155 patients were included in the present study (Figure 1). Data on demographics, underlying diseases or conditions, clinical manifestations, laboratory and radiologic findings, pathogens, treatment, and outcomes were retrospectively collected from the electronic records. Survival data were obtained from the National Health Insurance records.

Definitions

A LP case was defined as a patient with pneumonia whose specimens yielded microbiologic evidence of Legionella spp. The diagnosis of pneumonia was confirmed if the patient presented with new or increased cough, sputum, fever or hypothermia, abnormal white blood cell count, or elevated C-reactive protein as well as new pulmonary infiltration on radiologic examination. Legionella spp. were detected based on serology (type-specific immunofluorescence antibody assay conducted at the Seoul Research Institute of Public Health and Environment), BinaxNOW urinary antigen testing (Abbott Diagnostic Medical, Lake Forrest, CA, USA), PCR with the AmpliSens Legionella pneumophila-FRT PCR kit (InterLabService Ltd., Moscow, Russia), Seeplex PneumoBacter ACE Detection assay (Seegene, Seoul, Korea), or culture of respiratory tract specimens using buffered charcoal yeast extract agar (bioMérieux, Marcy-l'Étoile, France).

Severe pneumonia was defined as septic shock with the need for vasopressor administration, respiratory failure requiring mechanical ventilation, as defined in the American Thoracic Society and Infectious Disease Society of America’s guidelines [19], or PaO₂/FiO₂ (partial pressure of arterial oxygen/fraction of inspired oxygen) ratio <200. The criteria for clinical stability were temperature ≤37.8℃, heart rate ≤100 beats/min, respiratory rate ≤24 breaths/min, systolic blood pressure ≥90 mm Hg, arterial oxygen saturation ≥ 90% or pO₂ ≥60 mm Hg on room air, ability to maintain oral intake, and normal mental status [20].

Adequate antibiotic treatment was defined as the use of macrolides or fluoroquinolones. Although other classes of empirical antibiotics were also frequently administered, they were not categorized as “adequate” due to their lack of efficacy against LP. The macrolides used in this study were clarithromycin and azithromycin. The fluoroquinolones included ciprofloxacin, levofloxacin, and moxifloxacin. Chronic lung diseases included chronic obstructive pulmonary disease, interstitial lung disease, bronchiectasis, emphysema, asthma, and chronic bronchitis.

Statistical Analysis

Continuous variables were compared using Student t-test or Mann-Whitney test as appropriate. Categorical variables were compared using chi-square test or Fisher’s exact test. The relationship among risk factors for progression to severe pneumonia was evaluated using logistic regression analysis. Factors with P<0.1 in univariate analysis were selected for multivariate analysis. Statistical analysis was performed using R version 3.6.0 (R Foundation for Statistical Computing, Vienna, Austria). All tests of significance were two-sided, and P<0.05 was considered statistically significant (two-tailed).

RESULTS

Baseline Characteristics

The baseline characteristics of the 155 included patients are presented in Table 1. The mean number of patients per year increased from 5.2 per year between 2005 and 2009 to 12.9 per year between 2010 and 2019. The mean age was 64.9 years and 76.1% of patients were male. CAP was the most common (45.2%) and 34.8% and 20.0% of patients had healthcare-associated pneumonia and hospital-acquired pneumonia, respectively. A total of 89 patients (57.4%) were immunocompromised. The most common symptom was fever (67.1%), followed by sputum (63.9%) and cough (62.6%). A total of 22 patients (14.2%) had altered mental status. At LP diagnosis, the median serum sodium concentration was 134.0 mmol/L and the median C-reactive protein level was 16.8 mg/dl. The median leukocyte and platelet counts were 9,200/mm³ and 174,000/mm³, respectively. A total of 65 patients had thrombocytopenia (<150,000/mm³). Radiologic examination revealed bilateral lung involvement in 58.7% of patients and pleural effusion in 16.1% of patients.

Treatment and Clinical Outcomes of LP

During hospitalization, most patients (98.7%) were treated with macrolides, fluoroquinolones, or both for LP. Fluoroquinolone therapy, without macrolide was administered to 102 patients (65.8%) and macrolide therapy without fluoroquinolone was administered to 11 patients (7.1%). A combination of both was administered to 40 patients (25.8%). At presentation, 58 patients (37.4%) had severe pneumonia. Among the 97 patients without severe pneumonia (62.6%, 97/155), 28 patients (28.9%, 28/97) progressed to severe pneumonia and 69 patients (71.1%, 69/97) recovered without deterioration (Figure 1). At presentation, leukocyte and platelet counts were lower in the progressed group than in the non-progressed group; however, other baseline characteristics were comparable (Table 2). Clinical stability was achieved in 60 patients and the median time since the presentation of LP was 6 days (interquartile range, 4–11 days). The 90-day mortality rates of patients with non-severe LP, initially severe LP, and severe LP after progression were 17.4% (12/69), 53.4% (31/58), and 75.0% (21/28), respectively (P=0.001).

Risk Factors for Progression to Severe Pneumonia in LP

Table 3 shows analysis of the risk factors for progression to severe pneumonia for the 97 patients with initially non-severe LA. In univariate analysis, platelet count ≤150,000/mm³ (odds ratio [OR], 3.30; 95% confidence interval [CI], 1.34–8.43; P=0.010) and delayed antibiotic treatment >1 day (OR, 2.75; 95% CI, 1.11–7.10; P=0.032) were significant factors associated with the development of severe pneumonia during hospitalization. In addition, immunocompromised state (OR, 2.35; 95% CI, 0.93–6.38; P=0.078) and bilateral involvement on radiologic examination (OR, 2.13; 95% CI, 0.88–5.35; P=0.098) were included for multivariate analysis. Multivariate analysis identified platelet count ≤150,000/mm³ (adjusted OR [aOR], 2.92; 95% CI, 1.10–8.11; P=0.034) and delayed antibiotic treatment >1 day (aOR, 3.09; 95% CI, 1.17–8.73; P=0.026) as independent risk factors for severe disease in LP.

DISCUSSION

In the present study, approximately one-third of patients initially had severe LP at the time of hospital presentation. Among the remaining two-thirds of patients with non-severe LP, one-quarter progressed to severe pneumonia during hospitalization. Risk factors associated with the development of severe pneumonia were low platelet count and delayed antibiotic treatment. Overall, the death rate was high among patients who progressed to severe LP.

The high percentage of severe pneumonia among patients with LP in this study is comparable to the findings in several previous studies. In a prospective study conducted in Spain, among 30 hospitalized LP patients, 50% had respiratory failure [15]. The outcomes of 14 LP patients were reported in a Canadian study and 78.6% (11/14) required ICU admission [16]. However, conflicting results have also been reported. In a large prospective French study, 27.4% (30/540) of 540 community-acquired LP patients required ICU care [17]. In a study in Italy, 20.7% (24/116) of 116 patients retrospectively analyzed required ICU admission [18]. These discrepancies may be attributed to differences in the patient population and number of participants. The present study was relatively large and performed at a tertiary care hospital. The inclusion of immunocompromised patients may have contributed to the relatively high rate of severe LP.

A low platelet count has been associated with the progression of non-severe LP. In a recent prospective cohort study involving 250 hospitalized CAP patients, both ICU admission rate and the rate of mechanical ventilation were higher in the thrombocytopenia group (<100,000/mm³) [21]. In another retrospective cohort study involving 500 hospitalized patients with CAP, thrombocytopenia was significantly associated with death [22]. The present study results are in agreement with these studies, indicating a low platelet count might be predictive of non-severe LP progressing to severe LP. Platelets play various roles in the immune response; they can recognize pathogenic bacteria or toxins, induce the acute phase response, and promote the innate immune cell response [23]. Recently, streptococcal M1 protein was shown to activate platelets, resulting in the acquisition of C1q on the surface of the platelets and increase apoptosis and phagocytosis [24]. A similar mechanism for enhancing complement activity may be present in Legionella spp. The L. pneumophila lipopolysaccharide activates the classical complement pathway [25]. In a study of samples from infected patients, an activation of platelets and thrombocytopenia was observed [26]. In addition, L. pneumophila is an intracellular organism that utilizes complement receptors for entry into monocytes for replication [27]. A decreased platelet count may indirectly indicate susceptibility to Legionella infection.

In the present study, delayed antibiotic treatment >1 day was a risk factor for progression to severe pneumonia, which is consistent with a recent Italian study [10]. The investigators showed macrolide/levofloxacin administration within 24 hours of admission was associated with fewer transfers to the ICU (OR, 0.20; 95% CI, 0.05–0.73). In a Taiwanese study, the ICU admission rate was also reportedly higher in patients who received delayed treatment compared with subjects who received timely antibiotic treatment (68.7% vs. 31.2%) [28]. The importance of administering antibiotics in a timely manner has also been demonstrated for all-cause pneumonia [29]. Our finding reemphasizes the importance of adequate early therapy for non-severe LP as well as severe LP.

The present study had several limitations. First, this was a retrospective study performed at a single referral center. Approximately half the patients were immunocompromised. Due to the possibility of selection bias of the study population, the results may not be generalizable to other patient populations. Second, patients who were not hospitalized were excluded from the analysis which may have been a source of bias. However, the number of excluded patients was relatively small. In conclusion, severe pneumonia frequently occurs among patients with LP and the mortality rate is high. The risk of progression to severe pneumonia is higher among patients with subnormal platelet counts and delayed antibiotic treatment >1 day. Thus, that early administration of antibiotics against Legionella spp. may be beneficial for LP patients, especially those with low platelet counts.

HIGHLIGHTS

▪ Among 155 patients with Legionella pneumonia at presentation, 58 patients (37.4%) had severe pneumonia and 97 patients (62.6%) had non-severe pneumonia; 28 of the 97 patients (28.9%) progressed to severe pneumonia.

▪ Platelet count ≤150,000/mm³ and delayed antibiotic treatment >1 day were factors associated with progression to severe pneumonia in initially non-severe Legionella pneumonia patients.

NOTES

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

AUTHOR CONTRIBUTIONS

Conceptualization: JYH, SHC, YK. Data curation: JYH, SHC, KWJ, TSS. Formal analysis: JYH, SHC. Methodology: JYH, SHC, YK. Project administration: JWH, SBH, CML. Visualization: JYH, SHC. Writing–original draft: JYH, SHC. Writing–review & editing: JYH, SHC, YK.

Figure 1.

Flowchart of study findings.

Table 1.

Baseline characteristics of 155 Legionella pneumonia patients included in the study

Characteristics	Value
Number of patients	155
Age (yr)	64.9±12.9
Male	118 (76.1)
Body mass index (kg/m²)	22.2±3.4
Current smoker	19 (12.3)
Category of pneumonia
Community-acquired pneumonia	70 (45.2)
Healthcare-associated pneumonia	54 (34.8)
Hospital-acquired pneumonia	31 (20.0)
Comorbidity
Immunocompromised state^a)	89 (57.4)
Diabetes mellitus	39 (25.2)
Chronic lung disease	30 (19.4)
Chronic obstructive pulmonary disease	12 (40.0)
Interstitial lung disease	8 (26.7)
Bronchiectasis	5 (16.7)
Emphysema	3 (10.0)
Chronic bronchitis	1 (3.3)
Asthma	1 (3.3)
Chronic kidney disease	26 (16.8)
Chronic heart disease	18 (11.6)
Liver cirrhosis	13 (8.4)
Clinical finding
Fever	104 (67.1)
Sputum	99 (63.9)
Cough	97 (62.6)
Dyspnea	80 (51.6)
Altered mental status	22 (14.2)
Chest discomfort	17 (11.0)
Diarrhea	17 (11.0)
Headache	5 (6.9)
Laboratory finding
Leukocytes (/mm³)	9,200 (4,100–13,500)
Platelets (×10³/mm³)	174.0 (91.5–238.5)
Blood urea nitrogen (mg/dl)	24.0 (17.5–37.5)
Sodium (mmol/L)	134.0 (130.0–137.0)
Lactate dehydrogenase (U/L)	362.0 (255.0–481.0)
C-reactive protein (mg/dl)	16.8 (8.3–27.2)
PaO₂/FiO₂ ratio	276.2 (206.7–342.8)
Radiologic finding
Multilobar involvement	104 (67.1)
Bilateral involvement	91 (58.7)
Pleural effusion	25 (16.1)
Pneumonia severity
CURB-65 score	2 (1–2)

Values are presented as mean±standard deviation, number (%), or median (interquartile range).

PaO₂: partial pressure of arterial oxygen; FiO₂: fraction of inspired oxygen; CURB-65: confusion, uremia, blood pressure, age ≥65 years.

^a)An immunocompromised state was defined if one of the following criteria were met: (1) receiving immunosuppressants daily, including corticosteroids; (2) infection with human immunodeficiency virus; (3) receiving solid organ or hematopoietic stem cell transplantation; (4) receiving chemotherapy for underlying malignancy during the previous 6 months; and (5) presence of other underlying immunodeficiency disorders.

Table 2.

Baseline characteristics of Legionella pneumonia patients who progressed or did not progress to severe pneumonia

Characteristics	Progressed	Non-progressed	P-value
Number of patients	28	69	-
Age (yr)	66.0±11.2	63.0±14.2	0.327
Male	24 (85.7)	49 (71.0)	0.207
Body mass index (kg/m²)	23.5±3.4	22.2±3.4	0.098
Current smoker	2 (7.1)	10 (14.5)	0.512
Immunocompromised state^a)	20 (71.4)	34 (51.5)	0.119
Chronic lung disease	5 (17.9)	15 (21.7)	0.880
Leukocytes (/mm³)	7,850 (3,150–10,775)	9,800 (6,500–15,100)	0.040
Platelets (×10³/mm³)	102 (44.5–180.5)	193 (131–269)	<0.001
Protein (mg/dl)	5.9±0.9	6.3±1.0	0.361
Albumin (mg/dl)	2.5±0.6	2.8±0.6	0.203
Sodium (mmol/L)	134.5 (131.8–136.2)	134.0 (130.0–137.0)	0.984
Blood urea nitrogen (mg/dl)	20.5 (18.0–29.0)	22 (22.0–34.0)	0.837
PaO₂/FiO₂ ratio <300	12 (42.9)	18 (26.1)	0.169
Bilateral involvement	17 (60.7)	29 (42.0)	0.148
Pleural effusion	2 (7.1)	10 (14.5)	0.512
Fluoroquinolone use	24 (85.7)	60 (87.0)	>0.999
Macrolide use	10 (35.7)	24 (34.8)	>0.999
Both fluoroquinolone and macrolide use	15 (21.7)	8 (28.6)	0.650
CURB-65 score	2 (1–2)	1 (1–2)	0.236

Values are presented as mean±standard deviation, number (%), or median (interquartile range).

PaO₂: partial pressure of arterial oxygen; FiO₂: fraction of inspired oxygen; CURB-65: confusion, uremia, blood pressure, age ≥65 years.

Table 3.

Risk factors for progression to severe pneumonia among 97 patients who were initially presented with non-severe Legionella pneumonia

Risk factor	Univariate analysis			Multivariate analysis
Risk factor	OR	95% CI	P-value	Adjusted OR	95% CI	P-value
CURB-65 score	1.311	0.782–8.231	0.308
Body mass index	1.121	0.982–1.296	0.101
Current smoker	0.454	0.067–1.877	0.329
Chronic lung disease	0.783	0.233–2.293	0.669
Immunocompromised state	2.353	0.934–6.377	0.078	2.104	0.767–6.150	0.157
Leukocytes <4,000/mm³	2.250	0.817–6.179	0.115
Platelets ≤150,000/mm³	3.302	1.344–8.427	0.010	2.923	1.100–8.105	0.034
PaO₂/FiO₂ ratio ≤300	2.125	0.839–5.365	0.109
Bilateral involvement on CXR	2.132	0.879–5.345	0.098	2.081	0.785–5.776	0.147
Delayed antibiotic treatment >1 day	2.746	1.109–7.103	0.032	3.092	1.167–8.727	0.026
Fluoroquinolone use	0.900	0.265–3.574	0.871
Macrolide use	1.042	0.406–2.583	0.931
Both fluoroquinolone and macrolide use	1.440	0.512–3.864	0.475

OR: odds ratio; CI: confidence interval; CURB-65: confusion, uremia, blood pressure, age ≥65 years; PaO₂: partial pressure of oxygen; FiO₂: fraction of inspired oxygen; CXR: chest X-ray.

REFERENCES

1. Diederen BM. Legionella spp. and Legionnaires’ disease. J Infect 2008;56:1-12.Article PubMed
2. Cunha BA, Burillo A, Bouza E. Legionnaires’ disease. Lancet 2016;387:376-85.Article PubMed
3. Carratalà J, Garcia-Vidal C. An update on Legionella. Curr Opin Infect Dis 2010;23:152-7.Article PubMed
4. Morgan AJ, Glossop AJ. Severe community-acquired pneumonia. BJA Educ 2016;16:167-72.Article PubMed PMC
5. Chong YP, Jung KS, Lee KH, Kim MN, Moon SM, Park S, et al. The bacterial etiology of community-acquired pneumonia in Korea: a nationwide prospective multicenter study. Infect Chemother 2010;42:397-403.Article
6. Sopena N, Sabrià M, Pedro-Botet ML, Manterola JM, Matas L, Domínguez J, et al. Prospective study of community-acquired pneumonia of bacterial etiology in adults. Eur J Clin Microbiol Infect Dis 1999;18:852-8.Article PubMed PDF
7. Centers for Disease Control. Notice to readers: final 2014 reports of nationally notifiable infectious diseases. MMWR Morb Mortal Wkly Rep 2015;64:1019. Article
8. European Centre for Disease Prevention and Control. Legionnaires’ disease: annual epidemiological report for 2019. Stockholm: European Centre for Disease Prevention and Control; 2019.
9. Fukushima S, Hagiya H, Otsuka Y, Koyama T, Otsuka F. Trends in the incidence and mortality of legionellosis in Japan: a nationwide observational study, 1999-2017. Sci Rep 2021;11:7246. Article PubMed PMC PDF
10. Korea Disease Control and Prevention Agency. Legionellosis [Internet]. Cheongju: Korea Disease Control and Prevention Agency; 2020 [cited 2022 Sep 1]. Available from: https://www.kdca.go.kr/npt/biz/npp/ist/simple/simplePdStatsMain.do.
11. Cassell K, Thomas-Lopez D, Kjelsø C, Uldum S. Provincial trends in Legionnaires’ disease are not explained by population structure in Denmark, 2015 to 2018. Euro Surveill 2021;26:2000036. Article PubMed PMC
12. Diederen BM, Kluytmans JA, Vandenbroucke-Grauls CM, Peeters MF. Utility of real-time PCR for diagnosis of Legionnaires’ disease in routine clinical practice. J Clin Microbiol 2008;46:671-7.Article PubMed PMC PDF
13. Han BS, Lee MJ, Kwon YH, Lee WC. A comparative study of the epidemiological aspects of Legionnaires’ disease: outbreaks in Korea and Japan, 2010 - 2014. J Clin Med Res 2017;9:67-70.Article PubMed PMC
14. Rubin R. Why are Legionnaires disease diagnoses becoming more common in the United States? JAMA 2018;319:1753-4.Article PubMed
15. Falcó V, Fernández de Sevilla T, Alegre J, Ferrer A, Martínez Vázquez JM. Legionella pneumophila: a cause of severe community-acquired pneumonia. Chest 1991;100:1007-11.Article PubMed
16. Cargnelli S, Powis J, Tsang JL. Legionella pneumonia in the Niagara region, Ontario, Canada: a case series. J Med Case Rep 2016;10:336. Article PubMed PMC PDF
17. Chidiac C, Che D, Pires-Cronenberger S, Jarraud S, Campèse C, Bissery A, et al. Factors associated with hospital mortality in community-acquired legionellosis in France. Eur Respir J 2012;39:963-70.Article PubMed
18. Falcone M, Russo A, Tiseo G, Cesaretti M, Guarracino F, Menichetti F. Predictors of intensive care unit admission in patients with Legionella pneumonia: role of the time to appropriate antibiotic therapy. Infection 2021;49:321-5.Article PubMed PMC PDF
19. Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, et al. Diagnosis and treatment of adults with community-acquired pneumonia: an official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med 2019;200:e45-67.Article PubMed PMC
20. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44(Suppl 2):S27-72.Article PubMed PMC
21. Ghoneim AH, Mohammad MA, Elghamrawy MA, Embarak S. Platelet count as a predictor of outcome of hospitalized patients with community-acquired pneumonia at Zagazig University Hospitals, Egypt. Egypt J Bronchol 2020;14:11. Article PDF
22. Mirsaeidi M, Peyrani P, Aliberti S, Filardo G, Bordon J, Blasi F, et al. Thrombocytopenia and thrombocytosis at time of hospitalization predict mortality in patients with community-acquired pneumonia. Chest 2010;137:416-20.Article PubMed
23. Eriksson O, Mohlin C, Nilsson B, Ekdahl KN. The human platelet as an innate immune cell: interactions between activated platelets and the complement system. Front Immunol 2019;10:1590. Article PubMed PMC
24. Palm F, Sjöholm K, Malmström J, Shannon O. Complement activation occurs at the surface of platelets activated by Streptococcal M1 protein and this results in phagocytosis of platelets. J Immunol 2019;202:503-13.Article PubMed
25. Mintz CS, Schultz DR, Arnold PI, Johnson W. Legionella pneumophila lipopolysaccharide activates the classical complement pathway. Infect Immun 1992;60:2769-76.Article PubMed PMC PDF
26. Larsson A, Nilsson B, Eriksson M. Thrombocytopenia and platelet microvesicle formation caused by Legionella pneumophila infection. Thromb Res 1999;96:391-7.Article PubMed
27. Chauhan D, Shames SR. Pathogenicity and virulence of Legionella: intracellular replication and host response. Virulence 2021;12:1122-44.Article PubMed PMC
28. Kao WF, Wang JT, Sheng WH, Chen YC. Community-acquired Legionnaires’ disease at a medical center in northern Taiwan. J Microbiol Immunol Infect 2019;52:465-70.Article PubMed
29. Zasowski EJ, Bassetti M, Blasi F, Goossens H, Rello J, Sotgiu G, et al. A systematic review of the effect of delayed appropriate antibiotic treatment on the outcomes of patients with severe bacterial infections. Chest 2020;158:929-38.Article PubMed

Figure & Data

References

Citations

Citations to this article as recorded by

Understanding the Correlation between Blood Profile and the Duration of Hospitalization in Pediatric Bronchopneumonia Patients: A Cross-Sectional Original Article
Dessika Listiarini, Dev Desai, Yanuar Wahyu Hidayat, Kevin Alvaro Handoko
The Journal of Critical Care Medicine.2024; 10(3): 254. CrossRef
An Investigation of Mortality Associated With Comorbid Pneumonia and Thrombocytopenia in a Rural Southwest Missouri Hospital System
Tabitha Ranson , Hannah Rourick , Rajbir Sooch , Nicole Ford, Nova Beyersdorfer, Kerry Johnson, John Paulson
Cureus.2024;[Epub] CrossRef
Legionella Pneumonia Undetected by Repeated Urinary Antigen Testing With Ribotest® Legionella
Yasushi Murakami, Mika Morosawa, Yasuhiro Nozaki, Yoshio Takesue
Cureus.2024;[Epub] CrossRef
Atraumatic Splenic Rupture in Legionella pneumophila Pneumonia
Elliott Worku, Dominic Adam Worku, Salim Surani
Case Reports in Infectious Diseases.2023; 2023: 1. CrossRef
Short- and long-term prognosis of patients with community-acquired Legionella or pneumococcal pneumonia diagnosed by urinary antigen testing
Leyre Serrano, Luis Alberto Ruiz, Silvia Perez-Fernandez, Pedro Pablo España, Ainhoa Gomez, Beatriz Gonzalez, Ane Uranga, Sonia Castro, Milagros Iriberri, Rafael Zalacain
International Journal of Infectious Diseases.2023; 134: 106. CrossRef
Case report: Fatal Legionella infection diagnosed via by metagenomic next-generation sequencing in a patient with chronic myeloid leukemia
Chunhong Bu, Shuai Lei, Linguang Chen, Yanqiu Xie, Guoli Zheng, Liwei Hua
Frontiers in Medicine.2023;[Epub] CrossRef

PubReader
ePub Link

Cite

CITE: export Copy Format; Close

Download Citation

Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

Format:

RIS — For EndNote, ProCite, RefWorks, and most other reference management software
BibTeX — For JabRef, BibDesk, and other BibTeX-specific software

Include:

Citation for the content below
Citation and abstract for the content below

Incidence and risk factors associated with progression to severe pneumonia among adults with non-severe Legionella pneumonia

Acute Crit Care. 2022;37(4):543-549. Published online October 21, 2022

DOI: https://doi.org/10.4266/acc.2022.00521

XML Download

Figure

Related articles

Incidence and risk factors associated with early death in patients with emergency department septic shock

Incidence and risk factors associated with progression to severe pneumonia among adults with non-severe Legionella pneumonia

Figure 1. Flowchart of study findings.

Figure 1.

Incidence and risk factors associated with progression to severe pneumonia among adults with non-severe Legionella pneumonia

Characteristics	Value
Number of patients	155
Age (yr)	64.9±12.9
Male	118 (76.1)
Body mass index (kg/m²)	22.2±3.4
Current smoker	19 (12.3)
Category of pneumonia
Community-acquired pneumonia	70 (45.2)
Healthcare-associated pneumonia	54 (34.8)
Hospital-acquired pneumonia	31 (20.0)
Comorbidity
Immunocompromised state^a)	89 (57.4)
Diabetes mellitus	39 (25.2)
Chronic lung disease	30 (19.4)
Chronic obstructive pulmonary disease	12 (40.0)
Interstitial lung disease	8 (26.7)
Bronchiectasis	5 (16.7)
Emphysema	3 (10.0)
Chronic bronchitis	1 (3.3)
Asthma	1 (3.3)
Chronic kidney disease	26 (16.8)
Chronic heart disease	18 (11.6)
Liver cirrhosis	13 (8.4)
Clinical finding
Fever	104 (67.1)
Sputum	99 (63.9)
Cough	97 (62.6)
Dyspnea	80 (51.6)
Altered mental status	22 (14.2)
Chest discomfort	17 (11.0)
Diarrhea	17 (11.0)
Headache	5 (6.9)
Laboratory finding
Leukocytes (/mm³)	9,200 (4,100–13,500)
Platelets (×10³/mm³)	174.0 (91.5–238.5)
Blood urea nitrogen (mg/dl)	24.0 (17.5–37.5)
Sodium (mmol/L)	134.0 (130.0–137.0)
Lactate dehydrogenase (U/L)	362.0 (255.0–481.0)
C-reactive protein (mg/dl)	16.8 (8.3–27.2)
PaO₂/FiO₂ ratio	276.2 (206.7–342.8)
Radiologic finding
Multilobar involvement	104 (67.1)
Bilateral involvement	91 (58.7)
Pleural effusion	25 (16.1)
Pneumonia severity
CURB-65 score	2 (1–2)

Characteristics	Progressed	Non-progressed	P-value
Number of patients	28	69	-
Age (yr)	66.0±11.2	63.0±14.2	0.327
Male	24 (85.7)	49 (71.0)	0.207
Body mass index (kg/m²)	23.5±3.4	22.2±3.4	0.098
Current smoker	2 (7.1)	10 (14.5)	0.512
Immunocompromised state^a)	20 (71.4)	34 (51.5)	0.119
Chronic lung disease	5 (17.9)	15 (21.7)	0.880
Leukocytes (/mm³)	7,850 (3,150–10,775)	9,800 (6,500–15,100)	0.040
Platelets (×10³/mm³)	102 (44.5–180.5)	193 (131–269)	<0.001
Protein (mg/dl)	5.9±0.9	6.3±1.0	0.361
Albumin (mg/dl)	2.5±0.6	2.8±0.6	0.203
Sodium (mmol/L)	134.5 (131.8–136.2)	134.0 (130.0–137.0)	0.984
Blood urea nitrogen (mg/dl)	20.5 (18.0–29.0)	22 (22.0–34.0)	0.837
PaO₂/FiO₂ ratio <300	12 (42.9)	18 (26.1)	0.169
Bilateral involvement	17 (60.7)	29 (42.0)	0.148
Pleural effusion	2 (7.1)	10 (14.5)	0.512
Fluoroquinolone use	24 (85.7)	60 (87.0)	>0.999
Macrolide use	10 (35.7)	24 (34.8)	>0.999
Both fluoroquinolone and macrolide use	15 (21.7)	8 (28.6)	0.650
CURB-65 score	2 (1–2)	1 (1–2)	0.236

Risk factor	Univariate analysis			Multivariate analysis
Risk factor	OR	95% CI	P-value	Adjusted OR	95% CI	P-value
CURB-65 score	1.311	0.782–8.231	0.308
Body mass index	1.121	0.982–1.296	0.101
Current smoker	0.454	0.067–1.877	0.329
Chronic lung disease	0.783	0.233–2.293	0.669
Immunocompromised state	2.353	0.934–6.377	0.078	2.104	0.767–6.150	0.157
Leukocytes <4,000/mm³	2.250	0.817–6.179	0.115
Platelets ≤150,000/mm³	3.302	1.344–8.427	0.010	2.923	1.100–8.105	0.034
PaO₂/FiO₂ ratio ≤300	2.125	0.839–5.365	0.109
Bilateral involvement on CXR	2.132	0.879–5.345	0.098	2.081	0.785–5.776	0.147
Delayed antibiotic treatment >1 day	2.746	1.109–7.103	0.032	3.092	1.167–8.727	0.026
Fluoroquinolone use	0.900	0.265–3.574	0.871
Macrolide use	1.042	0.406–2.583	0.931
Both fluoroquinolone and macrolide use	1.440	0.512–3.864	0.475

Table 1. Baseline characteristics of 155 Legionella pneumonia patients included in the study

Values are presented as mean±standard deviation, number (%), or median (interquartile range).

PaO₂: partial pressure of arterial oxygen; FiO₂: fraction of inspired oxygen; CURB-65: confusion, uremia, blood pressure, age ≥65 years.

An immunocompromised state was defined if one of the following criteria were met: (1) receiving immunosuppressants daily, including corticosteroids; (2) infection with human immunodeficiency virus; (3) receiving solid organ or hematopoietic stem cell transplantation; (4) receiving chemotherapy for underlying malignancy during the previous 6 months; and (5) presence of other underlying immunodeficiency disorders.

Table 2. Baseline characteristics of Legionella pneumonia patients who progressed or did not progress to severe pneumonia

Values are presented as mean±standard deviation, number (%), or median (interquartile range).

PaO₂: partial pressure of arterial oxygen; FiO₂: fraction of inspired oxygen; CURB-65: confusion, uremia, blood pressure, age ≥65 years.

Table 3. Risk factors for progression to severe pneumonia among 97 patients who were initially presented with non-severe Legionella pneumonia

OR: odds ratio; CI: confidence interval; CURB-65: confusion, uremia, blood pressure, age ≥65 years; PaO₂: partial pressure of oxygen; FiO₂: fraction of inspired oxygen; CXR: chest X-ray.