Severe pneumonia due to concurrent Legionella pneumophila and Acinetobacter baumannii infections: a case report

Abstract

Background

Legionella pneumophila is an uncommon pathogen causing community-acquired atypical pneumonia. Acinetobacter baumannii is a major pathogen responsible for hospital-acquired pneumonia, but it rarely causes serious infections in a community setting. Without prompt and appropriate treatments, infection from either of these two pathogens can cause a high mortality rate. Concurrent infection from both L. pneumophila and A. baumannii can cause serious outcomes, but it has rarely been reported previously.

Case presentation

A 45-year-old male presented to our hospital with a productive cough and fever after staying in a local hotel. His chest computed tomography (CT) scan showed bilateral lower-lobe infiltration and left pleural effusion. Empirical antibiotics, including piperacillin-tazobactam, levofloxacin, meropenem, and doxycycline, were administered to him to treat community-acquired pneumonia. However, his condition deteriorated very rapidly, and he required endotracheal intubation and mechanical ventilation for respiratory support. Finally, metagenomic next-generation sequencing (mNGS) of his bronchoalveolar lavage fluid identified L. pneumophila and A. baumannii. The sputum culture demonstrated multidrug-resistant A. baumannii. He was diagnosed with pneumonia by concurrent infections from both L. pneumophila and A. baumannii. After careful consideration of the antibiotic susceptibility results and the antibacterial mechanism of each antibiotic, we switched the antibiotics to omadacycline and cefoperazone/sulbactam. His clinical symptoms gradually subsided. The repeat chest CT image showed no infiltration or pleural effusion.

Conclusions

Community-acquired pneumonia can be caused by concurrent infections of both L. pneumophila and A. baumannii. Close clinical monitoring, early pathogen detection and antibiotic susceptability tests, and appropriate antibiotic regimen adjustments should be applied to these patients who failed initial antibiotic treatments.

Background

Pneumonia is a pulmonary infection that can affect people of all ages. Affected patients can develop respiratory failure, sepsis, multiorgan damage, and death [1]. Legionnaires’ disease, pulmonary infection caused by Legionella pneumophila, is an uncommon type of serious bacterial pneumonia [2]. Recently, its incidence has been reported to be on the rise [3]. More than 70% of Legionnaires’ disease cases are sporadic and acquired in an out-of-hospital setting, with a mortality rate of 5–10% or even up to 80% in untreated immunocompromised patients [4, 5]. However, the initial pathogenic diagnosis of Legionnaires’ disease can be difficult due to its atypical presentation [2].

Acinetobacter baumannii is a Gram-negative aerobic bacillus and a major pathogen responsible for nosocomial infections [6]. The mortality rate of those with A. baumannii infection is reported to be 26–70%, largely due to its resistance to treatments with multiple antimicrobial agents [7, 8]. The diagnosis of A. baumannii pneumonia should consider true infection versus colonization, since A. baumannii is a ubiquitous bacterium found in the environment and human skin [9]. In addition to causing nosocomial infection, A. baumannii can also be responsible for community-acquired infection. A recent study in China has reported that 88.6% of A. baumannii infections originate in out-of-hospital settings [10]. Compared with nosocomial-acquired A. baumannii infection, community-acquired A. baumannii infection causes more severe illness and frequent shock [11]. Co-infection from multiple pathogens can cause more critical outcomes and complications, which require special attention from clinicians.

Here, we report an extremely rare case of concurrent severe pulmonary infection of L. pneumophila and A. baumannii. We share our clinical experience on its diagnosis and management, with the purpose to remind clinicians of this rare mixed infection in critically ill patients.

Case presentation

On July 3, 2022, a 45-year-old male presented to our hospital emergency room with chief complaints of a productive cough for five days and a fever for three days (Fig. 1). The patient reported a medical history of diabetes, chronic hepatitis B, and fatty liver, without treatment compliance. He denied any previous history of hospital admission. Approximately 15 days before presenting to the hospital, he stayed with two roommates in a local hotel. The room was confined with limited space, with the air conditioner outlet right above his bed. The patient went to a medical clinic first and received intravenous cephalosporin administration, but his clinical symptoms did not improve. At presentation to our emergency room, the patient reported a cough with yellow and white sputum, which was sometimes mixed with streaks of blood in the sputum. Meanwhile, he also reported exertional chest tightness, shortness of breath, headache, and muscle aches. The chest computed tomography (CT) scan showed bilateral lower-lobe infiltration with left pleural effusion (Fig. 2A). The patient was admitted to the Department of Respiratory and Critical Care Medicine with the diagnosis of community-acquired pneumonia.

Fig. 1

Clinical timeline. BAL, bronchoalveolar lavage; CT, computed tomography; ICU, intensive care unit; MDR, multidrug resistance; mNGS, metagenomic next-generation sequencing; P/F, partial pressure of oxygen in arterial blood/fraction of inspiratory oxygen concentration

Fig. 2

Chest computed tomography (CT) scans. A, CT at hospital presentation (July 3, 2022), showing bilateral lower-lobe infiltration with left pleural effusion. B, CT scan at two days after hospital admission (July 5, 2022), showing increased bilateral lower-lobe infiltration. C, CT scan at four days after treatment for L. pneumophila and A. baumannii infection (July 12, 2022), showing significantly decreased bilateral lower-lobe infiltration. D, CT scan at nine days after treatment (July 17, 2022), showing almost completely resolved bilateral lower-lobe infiltration. E, CT scan at the clinical follow-up visit on April 15, 2024, showing no infiltration

At hospital admission, the vital signs of the patient were as follows: temperature, 39.9 °C; blood pressure, 131/89 mmHg; pulse, 112 beats/min; respiratory rate, 30 breaths/min; and oxygen saturation under 2 L of oxygen through nasal cannula, 96%. His body mass index was 26.9 kg/m². The laboratory test results are shown in Table 1. The patient received empirical intravenous antibiotic treatment with piperacillin-tazobactam (4.5 g, every 8 h) and levofloxacin (0.5 g, daily). The next day after hospital admission (July 4, 2022), the patient reported an increased cough and shortness of breath, with the respiration rate at 34 breaths/min and the ratio of partial pressure of oxygen in arterial blood to the fraction of inspiratory oxygen concentration (PaO₂/FiO₂) of 146.8 mmHg. The patient was diagnosed with severe pneumonia and type I respiratory failure. Endotracheal intubation and mechanical ventilation were planned for respiratory support, but they were declined by the patient’s family. The patient received high-flow humidified oxygen therapy (temperature, 34 °C; oxygen concentration, 60%; and flow rate, 50 L/min). The sputum was sent for bacterial culture on blood agar and chocolate agar by the four-quadrant streak method in the hospital laboratory. His antibiotics were switched to intravenous meropenem (1.0 g, every 8 h) and oral doxycycline (0.1 g, twice a day). On July 5, 2022, his shortness of breath worsened, with a respiratory rate of > 40 breaths/min. The PaO₂/FiO₂ was 73.8 mmHg. The repeat chest CT demonstrated increased bilateral lower-lobe infiltration (Fig. 2B). The patient received endotracheal intubation and mechanical ventilation, and then he was transferred to the respiratory intensive care unit (RICU).

Table 1 Dynamic changes of important laboratory test results

The next day after the RICU admission (July 6, 2022), a bronchoscopy examination was performed that revealed copious white viscous secretions in the trachea, with congested and edematous bronchial mucosa. A sample of the patient’s bronchoalveolar lavage fluid (BALF) was analyzed by metagenomic next-generation sequencing (mNGS, Q-mNGS™ 2.0 pathogen detection kit, MATRIDX, Hangzhou Jieyi Biotechnology Co., Ltd. China) (Fig. 3). The microorganism examination results are listed in Table 2.

Fig. 3

The metagenomic next-generation sequencing of the bronchoalveolar lavage fluid showing positive results for L. pneumophila and A. baumannii. The sequence read refers to the number of specific sequences that can be uniquely matched to a certain bacterial genus or species. The relative abundance refers to the proportion of a certain microbial genus or species in the microorganisms detected in the entire specimen. A high abundance corresponds to a great proportion of certain bacteria. The Q index refers to the content of different microbial nucleic acids in the specimen, which is calculated through the measured value of the internal standard molecule. A high Q index corresponds to a high microbial content and a high accuracy in pathogen detection

Table 2 Pathogenic test results

On July 8, 2022, after the BALF mNGS identified L. pneumophila, the patient was diagnosed with Legionnaires’ disease and received intravenous omadacycline (100 mg, daily, with a double dosage on the first administration). In addition, the BALF mNGS also found A. baumannii. The sputum culture (started on day 1 of hospitalization) reported multidrug-resistant A. baumannii, which retained sensitivity to polymyxin and had intermediate sensitivity to cefoperazone/sulbactam (Table 3). Since polymyxin was not available, cefoperazone/sulbactam (2.0 g, every 8 h) was administered to the patient.

Table 3 Antibiotic susceptibility test results on Acinetobacter baumannii

After treatment for four days (July 12, 2022), the patient’s temperature gradually returned to normal, with decreased respiratory secretions. The laboratory tests also showed improved results. The PaO₂/FiO₂ increased to 250 mmHg. A repeat chest CT scan found significantly decreased bilateral lower-lobe infiltration (Fig. 2C). The patient was extubated on July 13, 2022, and he was switched to transnasal high-flow humidified oxygen therapy (temperature, 34 °C; oxygen concentration, 35%; flow rate, 40 L/min). Another chest CT was performed on July 17, 2022, showing that the bilateral lower-lobe infiltration had almost completely disappeared (Fig. 2D). The total duration of omadacycline and cefoperazone/sulbactam treatment was 12 days. On July 20, 2022, the patient had no cough, shortness of breath, or fever. He was discharged from our hospital. On the clinic follow-up visit on April 15, 2024, the patient reported no clinical symptoms, and a repeat chest CT scan showed no pulmonary infiltration or pleural effusion (Fig. 2E).

Discussion and conclusions

L. pneumophila commonly causes community-acquired pneumonia. This pathogen resides in water and soil. Humans can develop a respiratory infection once aspirating contaminated aerosolized water or soil. A. baumannii is a common cause of hospital- and ventilator-acquired pneumonia, but its infection can also be acquired in the community. Legionnaires’ disease is reported to have 10–15 cases per million population in Europe, Australia, and the United States per year [12]. Additionally, a systematic review and meta-analysis including 24 articles has reported a pooled estimated incidence of hospital-acquired A. baumannii infection of 56.5 cases per 1,1000 patients in the intensive care unit [13]. In China, an analysis in patients with community-acquired pneumonia found that 11.3% and 5.1% of infections were caused by L. pneumophila and A. baumannii, respectively [14]. However, concurrent infection from L. pneumophila and A. baumannii was extremely rare. Our present case report shows that these two pathogens can cause co-infection. The correct diagnosis and appropriate antibiotics, as well as supportive care, should be administered promptly to save the lives of affected patients.

L. pneumophila was first reported to cause pneumonia in a convention center in 1976 [2]. This pathogen was isolated from the cooling tower of the air conditioning system in the hotel. Patients with mild Legionnaires’ disease usually present with flu-like symptoms, whereas those with severe illness can have a cough, fever, nausea, vomiting, diarrhea, malaise, muscle aches, and headache. The laboratory tests often show hyponatremia, hypophosphate, and elevated hepatic transaminase levels. The possibility of Legionnaire’s disease should be ruled out in patients with these presentations, especially in those with a poor response to macrolide antibiotics [2]. Traditionally, the diagnosis of Legionnaires’ disease depends on the sputum culture or urine Legionella antigen test. The newly developed mNGS technique can greatly increase the diagnostic sensitivity and specificity [15]. mNGS is a high-throughput technique that sequences all of the genetic materials in a specimen and compares the results in a large bioinformatic database to identify potential pathogens. The reported Q index refers to the quality and accuracy of the sequencing data, with a high Q index suggesting a high accuracy in pathogen detection [16]. The first-line recommended antibiotics for Legionnaires’ disease include macrolides and fluoroquinolones. However, L. pneumophila resistant to macrolides and fluoroquinolones has been reported, which is likely due to a drug efflux pump mechanism [17]. Alternatively, tetracycline, trimethoprim, and sulfamethoxazole are also used to treat Legionnaires’ disease in the clinic [2].

A. baumannii is an opportunistic bacterial pathogen that is commonly responsible for nosocomial infections. However, a recent study in China has reported that A. baumannii is the third most common pathogen (following Pseudomonas aeruginosa and Klebsiella pneumoniae) cultured in community-acquired pneumonia [18]. The drug sensitivity tests on these community-acquired A. baumannii infections have shown high resistance profiles to commonly used antibiotics, including beta-lactams (carbapenem and piperacillin) and quinolones, except tigecycline [19]. Affected patients can develop pneumonia, bacterial meningitis, cellulitis, osteomyelitis, or urinary tract infections. In addition, community-acquired A. baumannii infections are frequently identified in elderly adults with a medical history of cardiopulmonary diseases. Affected patients can have a high fever, severe illness, frequent shock, or bilateral multi-lobe pneumonia [11]. The traditional diagnostic method for A. baumannii infection is the culture of bacteria from the sputum, blood, or pus. Similar to L. pneumophila, A. baumannii can also be accurately detected by mNGS [15]. However, different from the diagnosis of L. pneumophila infection, it is important to culture A. baumannii to test its drug sensitivity, since multidrug-resistant A. baumannii has been increasingly reported [20].

Our patient lived in a confined room in a hotel. His bed was also close to an air conditioner outlet. The air conditioner might have been contaminated with L. pneumophila, thus causing his initial Legionnaires’ disease. His clinical symptoms started approximately 10 days after staying in the hotel, which is consistent with the incubation period of 2–10 days for Legionnaires’ disease [2]. In addition, this patient was not compliant with the treatments for his diabetes and chronic liver disease. Patients with poorly controlled diabetes commonly have dysregulated carbohydrate, protein, and lipid metabolisms, with decreased immune responses. The high level of hemoglobin A1C can also stimulate the release of inflammatory cytokines and promote the development of infection. All of these factors could have contributed to the pneumonia in this patient. In addition, the infection can affect the blood glucose control, leading to a vicious cycle and a high severity of Legionnaires’ infectious disease [21]. Moreover, the presence of chronic liver disease with a low albumin level in this patient increased his risk for infection and a poor prognosis [22]. The hyponatremia and hypophosphatemia reported in his laboratory tests also have been frequently reported in other patients with Legionnaires’ disease [23]. The patient in this case report received cephalosporin, piperacillin-tazobactam, levofloxacin, meropenem, and doxycycline treatments, but his condition rapidly deteriorated, which required endotracheal intubation and mechanical ventilation. mNGS on the patient’s BALF detected both L. pneumophila and A. baumannii. The high relative abundance and the Q-index suggested that both pathogens caused infection rather than colonization. The sputum culture started on day 1 after hospitalization grew A. baumannii. The bronchoalveolar lavage was performed on day 4 after hospitalization. The incubation period for an A. baumannii infection commonly ranges from 4 days to 40 days [24]. Therefore, we believe that the patient’s A. baumannii pneumonia was acquired before he presented to our hospital. His medical history of diabetes, existing Legionnaires’ disease, and antibiotic use all placed him at a high risk for A. baumannii infection [25]. The rapid deterioration of the patient’s condition after hospitalization was consistent with a previous description that inappropriately treated Legionnaires’ disease can worsen during the first week [5]. The concurrent infection of A. baumannii could certainly have aggravated his clinical condition. We selected omadacycline to treat the L. pneumophila infection. Omadacycline is a third-generation semisynthetic tetracycline that overcomes two major mechanisms of tetracycline resistance: drug efflux pump and ribosome protection [26]. It has shown a high sensitivity to L. pneumophila [27]. Since A. baumannii is commonly resistant to multiple antibiotics, we referred to the antibiotic susceptability results and selected cefoperazone/sulbactam to treat the A. baumannii infection. Sulbactam is a beta-lactamase inhibitor with an intrinsic activity against A. baumannii. Sulbactam has been combined with ampicillin or cephalosporin to successfully treat A. baumannii infection [28]. Our laboratory did not perform antibiotic susceptibility testing on the tetracycline class of antibiotics to A. baumannii. However, considering the previously reported high sensitivity of omadacycline against A. baumannii and that its antibacterial mechanism (ribosomal inhibition) is different from that of cephalosporin (inhibition of bacterial wall synthesis) [29], omadacycline may have additive or synergistic effects with cefoperazone/sulbactam to treat an infection caused by A. baumannii. Therefore, we finally decided to give both omadacycline and cefoperazone/sulbactam to treat co-infection of L. pneumophila and A. baumannii in our patient, which resulted in a successful full recovery, with resolution of clinical symptoms and normal repeated laboratory test results.

The strength of our study is that we described an extremely rare case of severe pneumonia caused by concurrent infections of L. pneumophila and A. baumannii. We reported the clinical course, diagnostic strategies, and antibiotic selections, which could help clinicans treat patients with similar presentations. The limitation of our study is that it is a single case report. Our findings and suggestions should be used cautiously when treating other patients. We also did not perform drug susceptibility testing on L. pneumophila, which could have facilitated antibiotic selection.

In conclusion, pneumonia is a common but serious respiratory infection. Our present case report demonstrates that community-acquired Legionnaires’ disease can be complicated by A. baumannii infection. Early pathogen detection, antibiotic susceptibility testing, close clinical monitoring, and appropriate antibiotic regimen adjustment are crucial to manage patients with similar symptoms. In addition, mNGS testing can be applied to make an early diagnosis of the infectious pathogen.