Community-acquired pneumonia associated with influenza co-infection caused by fusobacterium necrophorum: a case report and literature review

Abstract

Background

Fusobacterium necrophorum is a rare pathogen associated with community-acquired pneumonia (CAP), particularly among healthy adults. This case report presents a rare documented case of CAP caused by F. necrophorum in a young individual, providing valuable insights for the diagnosis and treatment of similar cases.

Case presentation

The patient was initially diagnosed with influenza, and subsequently developed CAP caused by F. necrophorum. Despite one week of outpatient treatment with moxifloxacin, the symptoms persisted, leading to hospitalisation. Treatment with piperacillin tazobactam/imipenem and doxycycline, which target atypical pathogens, did not result in improvement after admission. Conventional diagnostic methods failed to identify the causative pathogen; however, metagenomic next-generation sequencing of bronchoalveolar lavage fluid confirmed it to be F. necrophorum. The patient showed significant improvement after ten days of targeted treatment with ornidazole and imipenem/piperacillin tazobactam, and was discharged.

Conclusion

Uncommon pathogens, such as F. necrophorum, should be considered as potential culprits in young individuals with CAP when conventional cultures yield negative results but there is a strong suspicion of infection, especially if initial antibiotic therapy is ineffective.

Background

Community-acquired pneumonia (CAP) poses a significant health burden and is associated with considerable morbidity and mortality [1]. It can be caused by bacteria, viruses, or fungi [2]. However, the distribution of pathogens responsible for CAP varies across regions, age groups, and study periods. Anaerobic organisms are rarely reported as causative agents of CAP [3]. Fusobacteriu. necrophorum is a common cause of Lemierre’s syndrome and sometimes a pathogen of necrotising pneumonia [4, 5]. In this study, we present a case of CAP caused by F. necrophorum, which co-occurred with influenza infection. This case report, along with a relevant literature review, aims to improve the clinical awareness, diagnosis, and treatment of this disease.

Case presentation

A thirty-year-old man was admitted to the hospital on December 27th, 2023, due to a persistent cough lasting over 20 days, recurrent fever (Fig. 1D), and progressive pain in the right chest for more than 10 days.

Fig. 1

Illustrates the changes in inflammatory markers and temperature of the patient from onset to discharge. The horizontal line represents the normal reference range. A: white blood cell (WBC) count, B: neutrophil percentage, C: C-reactive protein (CRP), D: Temperature

Nine days prior to admission, the patient had visited a fever clinic presenting with flu-like symptoms, including sore throat, runny nose, and cough. He attempted to self-treat with baloxavir marboxil, but experienced no improvement. Upon physical examination, his temperature was 39.2 °C, blood pressure was 132/94 mmHg, heart rate was 107 bpm, and oxygen saturation was 97%, respectively. Laboratory investigations indicated a markedly elevated white blood cell (WBC) count of 21.9 × 10⁹/L (normal range 4– 10 × 10⁹/L), with a neutrophil percentage of 89.5% (normal range 50– 70%). The patient also exhibited an international normalised ratio of 1.5 (normal range 0.9– 1.1), an activated partial thromboplastin time of 53.2s (normal range 30–45 s), a D-dimer level of 2880 µg/L (normal range < 500 µg/L), and a C-reactive protein (CRP) level of 175.4 mg/L (normal range < 10 mg/L). Other blood tests did not reveal any significant abnormalities. Result of the influenza A virus antigen test was positive. The doctor then initiated empirical treatment with moxifloxacin for seven days (Table 1).

Table 1 Medication since the onset of illness

On the day before admission, the patient’s blood tests still indicated persistently high levels, with a WBC count of 21.7 × 10⁹/L, neutrophil percentage of 84.8%, and CRP level of 159.6 mg/L. Chest computed tomography (CT) revealed further progression of inflammation and consolidation in the lower right lung (Fig. 2A, B). The patient was subsequently admitted to the hospital for further evaluation and management, and his medication was switched to piperacillin-tazobactam.

Fig. 2

Chest CT images. A, B: Multiple inflammations in both lungs with partial consolidation; C, D: Improvement of lesions in the lower lobes of both lungs after identifying the cause and administering appropriate treatment

After admission, a series of tests were performed to detect bacteria, fungi, and viruses. The pathogen test results were negative for all except influenza A virus nucleic acid (Table 2). Despite the addition of oseltamivir on the third day of admission and doxycycline the next day due to the patient’s persistent fever, the fever did not subside. Consequently, on January 3rd, 2024, the patient underwent bronchoscopy examination, during which bronchoalveolar lavage fluid (BALF) specimens were collected for metagenomic next-generation sequencing (mNGS) to identify potential pathogens.

Table 2 Inspection during the process from onset to identification of the pathogens

During the bronchoscopy, a small amount of white secretion was observed in the right lower lobe cavity, whereas no apparent abnormalities were detected in the bronchial segments on either side. The mNGS analysis revealed presence of F. necrophorum (sequence number 6421) and influenza A virus (sequence number 1) (Fig. 3). The bilateral internal jugular vein colour Doppler ultrasound examination (Fig. 4) and blood culture results were normal, ruling out Lemierre’s syndrome. After treatment with ornidazole and imipenem, the patient’s temperature and inflammatory indicators returned to normal (Fig. 1), and chest CT showed significant improvement in absorption (Fig. 2C, D). The patient was discharged after 17 days in the hospital and switched to a four-week course of oral amoxicillin clavulanic acid and oral ornidazole.

Fig. 3

Pathogen detection results of metagenomics next-generation sequencing. The number of sequences in parentheses

Fig. 4

Bilateral internal jugular vein color Doppler ultrasound examination. A: Internal jugular vein diameter; B, C: Intravenous color Doppler blood flow

Discussion and conclusions

Studies investigating the cause of community-acquired pneumonia (CAP) can yield varying results owing to variations in patient selection and research methods. In China, Respiratory syncytial virus is the predominant viral cause of CAP in children, Streptococcus pneumoniae is the primary bacterial pathogen in children, Mycoplasma pneumoniae in adolescents, and Haemophilus influenzae in adults [6]. Anaerobes are believed to play a significant role in the development of aspiration pneumonia, which predominantly affects the elderly [7, 8]. However, reports associating anaerobes with CAP are scarce [9, 10]. In this specific case, a young man initially diagnosed with influenza was subsequently found to have CAP caused by F. necrophorum. F. necrophorum is a non-spore forming obligate anaerobic Gram-negative bacillus that is part of the normal flora in the upper respiratory tract of humans and animals [11]. Influenza can weaken the immune system, damage the respiratory epithelium, and impair the normal clearance mechanisms of the respiratory tract [12], thereby facilitating the migration of bacteria like F. necrophorum from the upper respiratory tract to the lower respiratory tract. F. necrophorum is occasionally responsible for osteitis [13] and is the most common cause of Lemierre’s syndrome [14]. A clinical survey in Denmark revealed that the incidence of Lemierre’s syndrome was higher than previously reported, with a distinct age distribution. Early suspicion and prompt antibiotic therapy, often combined with surgical drainage, are crucial to reduce mortality [15]. In this patient, Lemierre’s syndrome was ruled out based on negative results from bilateral internal jugular vein colour Doppler ultrasound examination and blood culture. F. necrophorum is considered a rare cause of CAP [16] and does not grow under normal aerobic cultivation methods, which often leads to its oversight by physicians. The use of inappropriate antibiotics can also prolong hospital stays [17]. If patients are not promptly diagnosed and treated, they can develop severe pneumonia and multiple organ failure, which can be fatal [18]. Treatment should include a prolonged course of intravenous beta-lactam antibiotics in combination with metronidazole [19]. In this case, the patient was initially treated with moxifloxacin, which does not target F. necrophorum, resulting in recurrent fever and elevated inflammatory markers. Even after admission and use of piperacillin tazobactam/imipenem, the fever persisted. It was only after utilizing metagenomic next-generation sequencing (mNGS) to identify the pathogen and adding ornidazole to the treatment that the patient’s temperature normalized.

mNGS is a rapid and accurate method for identifying potential pathogens and has shown great promise in diagnosing infectious diseases [20]. It can detect non-viable DNA, making it particularly useful for patients who have already received prolonged antimicrobial therapy. This case demonstrates the value of mNGS in aiding the diagnosis of infections caused by difficult to culture bacteria or in cases where prior antibiotic use has compromised organism recovery. While the cost and availability of mNGS currently limit its widespread use, it is important to consider it when conventional cultures are negative but infection is strongly suspected.

In conclusion, F. necrophorum is an uncommon pathogen typically associated with CAP, especially in previously healthy adults. This case underscores the need for clinicians to consider atypical pathogens like F. necrophorum in young individuals with CAP when standard cultures are negative but infection is strongly suspected, particularly in cases where empirical anti-infective therapy yields unsatisfactory results. One limitation of this study is that the pathogen was not confirmed through anaerobic culture.