Pneumococcal pneumonia complicated by <i>Aspergillus fumigatus</i> and <i>Pseudomonas aeruginosa</i> lung abscesses

A 5-year-old boy presented with a 4-day history of fever and respiratory distress. He had a medical history of severe neonatal asphyxia and gastroesophageal reflux, that were treated with Nissen fundoplication. His current medications included triclofos sodium, eperisone hydrochloride, and phenobarbital. His vaccination history included 13-valent pneumococcal conjugated vaccines (PCV) four times. On admission, body temperature was 36.3°C, heart rate was 134 beats/min, respiratory rate was 50 breaths/min, blood pressure was 82/62 mmHg, SpO2 was 88% (ambient air), and Glasgow coma scale was E1V1M1. Physical examination revealed retraction and paradoxical breathing, rhonchi, and peripheral cyanosis. The blood test results showed leukopenia (white blood cell count: 1200/μL) and elevated C-reactive protein (9.82 mg/dL). Chest radiography revealed bilateral lung infiltration. Intensive care management was initiated, including mechanical ventilation and vasoactive agents, and intravenous cefepime (CFPM) was initiated. Gram-positive diplococcus was found in the blood cultures taken on Day 1 of admission, and intravenous vancomycin was administered. The blood culture and susceptibility test results revealed penicillin-sensitive Streptococcus pneumoniae serotype 35 B infection (Day 3) and treatment was switched to ampicillin. On Day 4, his fever resolved, and his general condition and laboratory results improved. On Day 7, the patient developed fever, and his sputum culture was positive for Pseudomonas aeruginosa. The antibacterial agent was replaced with CFPM; however, his condition did not improve. On Day 11, contrast-enhanced chest computed tomography (CT) showed a cavitary lesion in the right upper lobe with infiltration and air bronchograms (Figure 1A,B). Aspergillus fumigatus was found in the sputum culture obtained on Day 8 (Figure 2), and treatment with voriconazole was commenced (Day 12). P. aeruginosa was considered a carrier, and sulbactam/ampicillin was prescribed. The patient's symptoms and laboratory findings did not improve, and chest CT showed fluid formation in the lung abscess (Figure 1C,D). Surgical intervention was planned. Fistula formation between the abscess cavity and bronchus was suspected. P. aeruginosa was detected in the abscess cavity specimen, and the antimicrobial agent was changed to CFPM (Day 23). On Day 27, chest CT showed that the abscess had shrunk but persisted, and antimicrobial therapy was continued. The clinical symptoms and laboratory findings normalized on Day 30. It was difficult to extubate the patient because of long-term intubation management. A tracheostomy was performed on Day 33. Contrast-enhanced chest CT (Day 79) showed a reduction in the cavity lesion with a small amount of fluid retention (Figure 1E,F). The patient was discharged without home oxygen therapy (Day 84). One month after discharge, immunodeficiency screening, including immunoglobulin, complement, neutrophil function test, and lymphocyte subset analysis revealed no abnormalities. Outpatient chest CT revealed that the cavitary lesion in the right upper lobe had almost completely disappeared. Antimicrobial therapy was completed after 18 weeks. In this case, a cavitary lesion formed after pneumococcal pneumonia and subsequently developed into a lung abscess caused by A. fumigatus and P. aeruginosa. S. pneumoniae commonly causes community-acquired pneumonia in children, although its frequency has decreased with the introduction of PCV.1 While pneumococcal pneumonia typically does not cause lung tissue destruction, lung abscesses may occur in cases of mixed infections involving Staphylococcus aureus and anaerobes.2 In this case, only S. pneumoniae was detected, and due to the lack of consecutive sputum cultures it was unclear whether the patient had polymicrobial infections. The prevalence of S. pneumoniae-associated lung abscesses has decreased with the introduction of PCV, but complications caused by nonvaccine serotypes still occur.2 Aspergillus spp. are widespread in the environment and rarely cause disease in healthy individuals; however, they can infect immunocompromised individuals, resulting in risk factors including neutropenia, neutrophil dysfunction, and the presence of lesions that destroy alveolar structures.3 Our patient had cerebral palsy from neonatal asphyxia but showed no obvious structural lung abnormalities on chest radiography. The cavitary lesions were attributed to pneumococcal pneumonia and Aspergillus spp.-produced mycotoxins and proteases promoted the formation of lung abscesses.3, 4 P. aeruginosa, a Gram-negative bacterium, is commonly associated with nosocomial, ventilator-associated pneumonia, and previous use of broad-spectrum antimicrobial agents and can lead to lung abscesses as a complication of bacterial pneumonia.5 This case developed during the management of pneumococcal pneumonia with mechanical ventilation and long-term antimicrobial administration. The occurrence of consecutive complications, such as lung abscesses caused by P. aeruginosa or A. fumigatus as a complication of pneumococcal pneumonia, are scarce. The host immune response to S. pneumoniae, P. aeruginosa, and Aspergillus spp. involves the role of neutrophils and humoral immunity factors such as complement proteins and immunoglobulins.2, 3, 5 Structural lung abnormalities increase the risk of both A. fumigatus and P. aeruginosa infections by facilitating transmission from the environment to the respiratory tract.3, 5 Immunological screening tests were performed in this case, but no abnormalities were found. Lung structure abnormalities may result from these complications, despite their absence during regular outpatient visits. In conclusion, pneumococcal pneumonia leading to a lung abscess caused by A. fumigatus and P. aeruginosa is a rare occurrence. Physicians should be aware of these complications, especially in the presence of risk factors such as lung structure destruction. It is essential to investigate the presence of abscess lesions and determine the cause using imaging and microbiological identification when clinical symptoms relapse during antimicrobial therapy. Pneumococcal pneumonia is rarely associated with tissue destruction of the lungs in cases where host immunity is preserved. In this case study, a child with no previous immunodeficiency developed cavitary lesions after the onset of invasive pneumococcal pneumonia, followed by a lung abscess caused by A. fumigatus. During antimicrobial administration and artificial ventilation, the cavitary lesion caused microbial substitution, and a lung abscess was caused by P. aeruginosa. Eighteen-week antimicrobial therapy and a tracheostomy were required. Immunological screening detected no abnormalities, and local immune compromise due to pneumococcal pneumonia was ascertained as the cause. When clinical symptoms relapse during antimicrobial therapy, it is important to consider imaging techniques to assess whether abscess lesions are present and identify microbial infections using the appropriate specimens. Aika Matsushima and Shinsuke Mizuno conceptualized the study; collected, analyzed, and interpreted the data; drafted the initial manuscript; and critically reviewed and revised it. Shogo Minamikawa, Yasuo Nakagishi, and Masashi Kasai collected the data, drafted the initial manuscript, and reviewed and revised it. All the authors have read and approved the final version of the manuscript. The authors declare no conflict of interest. The authors confirm that written informed consent for publication of this report was obtained from the patient's parents. This study was approved by our institutional review board (no. R5-99).