A Case of Legionella Pneumonia Suspected as Typical Pneumonia After Lung Cancer Surgery, Diagnosed by a Repeat Urinary Legionella Antigen Test.

Introduction
A prevalence of atypical pneumonia of 8.1% has been reported, with the estimated prevalence of Legionella in patients with severe pneumonia at 4.0% (95% confidence interval: 2.8%-5.3%) [1]. Patient factors that increase the risk of developing a Legionella infection include male gender, age over 50, smoking, surgery, intubation, nasogastric tube use, ventilator management, and an immunocompromised state (post-organ transplant, cancer treatment, steroid use) [2]. Most cases of Legionnaires' pneumonia are caused by Legionella pneumophila serotype one, with the mortality rate estimated to be approximately 27% if not treated appropriately [3]. It has been reported that if postoperative pneumonia is resistant to standard antibiotics or if the symptoms and blood test results are atypical of usual pneumonia, it is extremely important to consider the possibility of atypical pneumonia [2].
We encountered a case in which early retesting of the urinary Legionella antigen saved the life of a patient with Legionella pneumonia. We report this case to highlight the importance of early retesting in situations where atypical pneumonia cannot be ruled out, even if the initial test is negative.

Case presentation
A 74-year-old man with a history of smoking presented with fever. He had previously undergone thoracoscopic partial resection of the left lower lobe for left lower lobe lung adenocarcinoma (pathological stage 0) and was discharged on postoperative day (POD) six with a favorable outcome (no complications). However, on POD 27, he developed a fever and presented to our department on POD 28. He was diagnosed with right upper lobe pneumonia and started on oral treatment with garenoxacin (Figure 1). On POD 30, his pneumonia worsened, and he was urgently admitted to our hospital (Figure 2). His past medical history included pathological-stage IB right lower lobe squamous cell carcinoma of the lung (he underwent right lower lobectomy and mediastinal lymph node dissection five years and two months earlier; there were no postoperative adverse events, and he was discharged on POD six), diabetes mellitus, and moderate aortic stenosis. After surgery for squamous cell carcinoma of the right lower lobe of the lung, the patient received oral UFT for two years as postoperative adjuvant chemotherapy. Subsequent periodic CT scans showed no evidence of recurrence.
Table 1 displays the blood test results at the time of admission. Both influenza and coronavirus tests were negative. Although β-D-glucan was elevated at 35.6 pg/mL, serum Aspergillus and Cryptococcus antigens were negative. Serum Mycobacterium avium complex antibody was negative, and TSPOT.TB was indeterminate. Pleural fluid TB/PCR was negative, and pleural fluid acid-fast bacillus culture was also negative. Urinary antigen tests performed in the outpatient clinic the day before admission were negative for both pneumococcus and Legionella.
After admission, sulbactam/ampicillin was administered from day one to day three; however, the fever persisted, and the inflammatory response significantly increased. Therefore, the antibiotics were switched to tazobactam/piperacillin on day three. Additionally, chest CT revealed an increased right pleural effusion accompanied by hypoxia. The CT scan did not reveal any lesions that suggested a recurrence of lung cancer. Right pleural effusion drainage was performed for both diagnostic and therapeutic purposes (Figure 3).
The pleural fluid pH was 7.2, lactate dehydrogenase 246 U/L, albumin 2.0 g/dL, glucose 200 mg/dL, and total protein 3.1 g/dL. Pleural fluid culture showed no bacterial growth, and pleural fluid cytology revealed no malignant cells. On day four, blood tests showed rising infective markers, and a CT of the thorax confirmed worsening right upper lobe consolidation along with worsening hypoxia. Since Legionnaires' pneumonia could not be ruled out, levofloxacin was added to the regimen. Urinary Legionella antigen (R70829, MIZUHO MEDY Co., Ltd., Tosu, Japan) was measured again on day five and returned positive, confirming the diagnosis of Legionnaires' pneumonia. Azithromycin was administered concomitantly on days 6-8 and 13-15. Oxygen was adjusted to 1-5 L to maintain SpO2 above 90%. In this case, pneumonia was widespread, and we set the target oxygen saturation lower than usual, fearing that high oxygen concentrations could cause interstitial pneumonia or hypercapnia. The treatment course is summarized in Table 2. The patient had been experiencing renal dysfunction since admission and was receiving 1000 mL of intravenous fluid. Fluid management was based on daily blood and weight measurements. As renal dysfunction progressed, the patient underwent two hemodialysis sessions at our hospital's nephrology department. CK levels began to rise on the fourth day after the start of hemodialysis, peaking at 1,563 U/L on the sixth day.
Legionella urinary antigen (R70829, MIZUHO MEDY Co., Ltd.) testing was performed twice, with the second test returning positive. The patient's temperature peaked on the third day of hospitalization and subsided by day 24. Oxygen administration was discontinued on day 32. After the initiation of levofloxacin, the WBC count decreased from its peak. Hemodialysis was performed twice.
Bacterial culture of the pleural fluid was negative, and the patient was diagnosed with parapneumonic pleural effusion. The right chest drain was removed on day 21. Oxygen therapy was discontinued on day 31, and the patient was transferred to a long-term care hospital on day 54. Chest X-ray findings during the treatment course and the most recent chest X-ray are shown in Figures 4, 5.

Discussion
This patient developed Legionnaires' disease 27 days after surgery. The initial urinary Legionnaires' antigen test was negative, and the patient was diagnosed with community-acquired pneumonia, with treatment initiated. However, continuing broad-spectrum antibiotics targeting typical pneumonia proved ineffective, and atypical pneumonia could not be ruled out based on the clinical course. Therefore, urinary Legionella antigen testing was repeated, and the results were positive, confirming the diagnosis of Legionnaires' disease.
Although no clear environmental factors associated with Legionnaires' disease were identified in this case, known risk factors include male gender, age over 50, smoking, and the effects of surgery [2]. Antibiotics remain the cornerstone of treatment, with macrolides and fluoroquinolones being the recommended drug classes [4].
Legionnaires' disease can lead to serious extrapulmonary complications, including acute kidney injury (AKI), rhabdomyolysis, and damage to the heart and liver, highlighting the importance of rapid diagnosis and prompt treatment [5]. A previous case report describes a patient with renal dysfunction due to Legionella infection who required intermittent hemodialysis for 16 days during hospitalization and was discharged 23 days after admission [6].
In our case, renal function improved following two hemodialysis sessions. There are two hypotheses regarding the pathogenesis of AKI: immune-related and infection-related mechanisms. Some suggest that AKI may be indirectly related to Legionella pneumophila via rhabdomyolysis, while others propose that it may be directly caused by the pathogen itself [7].
Kidney biopsies from patients with Legionella infection have revealed a wide range of cytopathological findings, from tubulointerstitial nephritis (TIN) to acute tubular necrosis (ATN) to glomerulonephritis [8]. Hemodialysis is required in 55.5% of cases of acute renal failure associated with Legionnaires' disease, and the mortality rate is reported to reach 51% (compared with 15% in patients without signs of acute renal failure) [7]. In cases of tubulointerstitial nephritis, steroids have been shown to be effective in restoring kidney function [8]. In this case, CK levels began to rise on the fourth day after the start of dialysis and peaked on the sixth day. The increase in CK levels after renal dysfunction began suggests that Legionella pneumophila itself may be directly involved in the renal dysfunction, rather than rhabdomyolysis being the primary cause.
Although a renal biopsy was not performed in this case and steroid treatment was not administered, renal function improved with hemodialysis and appropriate antibiotic treatment. Urinary antigen tests primarily target lipopolysaccharide present in the cell wall of Legionella pneumophila and are widely used as first-line screening methods due to their speed, low cost, relatively simple procedures, and ease of specimen collection [9].
Approximately 8% of patients with Legionnaires' disease do not excrete antigens in their urine [10], and approximately 60% excrete antigens intermittently [11]. Therefore, a negative urinary antigen test does not rule out Legionella infection, and retesting is recommended when necessary [9]. The overall mortality rate for Legionnaires' disease is 10%, increasing to 27% in patients who are not initially treated with erythromycin [12].
During the course of the disease, the patient developed renal failure and underwent temporary dialysis. However, by re-measuring urinary Legionella antigen early and providing appropriate treatment, the patient was able to discontinue dialysis and ultimately survive. This patient had a history of heart disease (aortic valve stenosis) following lung cancer surgery, placing him at very high risk for reduced pulmonary reserve and worsening heart failure. However, early diagnosis saved his life.
When antibiotic treatment for typical pneumonia is ineffective and imaging findings cannot rule out atypical pneumonia, we recommend re-measuring urinary Legionella antigen within at least one week.

Conclusions
We present a case in which typical pneumonia was initially suspected after lung cancer surgery, but a retest for urinary Legionella antigen revealed Legionella pneumonia, leading to lifesaving treatment. If antibiotic treatment is ineffective and imaging findings suggest Legionella pneumonia, retesting is necessary, even if the initial urinary Legionella antigen test is negative.