Authors: Lin Chen, Wang Shishou, An Ran, Feng Tao, Huang Shimei
Unit: Department of Respiratory and Critical Care Medicine, Shengli Oilfield Central Hospital, Dongying City, Shandong Province, and Department of Clinical Laboratory, Shengli Oilfield Central Hospital, Dongying City, Shandong Province
Cite this article: Lin Chen, Wang Shishou, An Ran, et al. A case of Nocardia carcardia complicated with Aspergillus infection in guinea pig otitis [J] . Chinese Journal of Tuberculosis and Respiration, 2024, 47(3): 237-240. DOI: 10.3760/cma.j.cn112147-20230714-00008.
summary
Nocardia is a rare opportunistic gram-positive bacillus with strong aggressiveness and disseminatence, mainly through traumatic invasion or inhalation, often leading to illness in immunocompromised people, and may be life-threatening in severe cases. Nocardia infection is a rare type of nocardia infection, and concomitant aspergillus infection is rarer. When two infections occur at the same time, a rapid and accurate diagnosis is essential for subsequent selection of appropriate anti-infective therapy. This article reports the diagnosis, treatment and treatment of a case of pulmonary guinea pig otitis with Nocardia complicated with Aspergillus infection. In this case, the patient had acute onset and rapid progression, and was diagnosed with pulmonary guinea pig otitis Nocardia complicated with Aspergillus infection by respiratory pathogen culture, bronchoscopy, and targeted next-generation sequencing (tNGS).
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The patient, a 68-year-old farmer, was admitted to the hospital on June 16, 2023 with "fever with cough, sputum production, and wheezing for 10 days". The patient had fever without obvious cause 10 days ago, with a maximum body temperature of 38.5 °C, accompanied by cough, sputum production, wheezing, and yellow sticky sputum. Self-administration of oral antipyretic drugs is not effective, and the body temperature does not drop to normal. Considering "lung infection", ceftazidime (2 g, intravenous infusion, 2 times/d) was given anti-infection treatment for 6 days, the body temperature did not improve, and the cough and sputum production were worse than before, the amount of sputum increased, and the breathing difficulty gradually appeared, so he was admitted to our department for further diagnosis and treatment. The patient had a smoking index of 300 and had not quit smoking. Physical examination on admission: body temperature 38 °C, pulse 80 times/min, respiration 20 times/min, blood pressure 150/81 mmHg (1 mmHg=0.133 kPa), poor general condition, acute wheezing, dry and wet rales in both lungs, no abnormalities in the physical examination of the heart and abdomen, and no edema in both lower limbs. After admission, blood gas analysis (FiO2 was 29%):p H value was 7.519, PaCO2 was 31.9 mmHg, PaO2 was 75.5 mmHg, oxygen saturation was 93%, oxygenation index was 260 mmHg, blood routine + CRP: white blood cells 13.82×109/L, neutrophil count 12.32×109/L, lymphocytes 1.01×109/L, hemoglobin 119 g/L, CRP 183.60 mg/ L, 0.14 μg/L for PCT, 51 U/L for ALT, 30.1 g/L for ALB, 15.06 mmol/L for glucose, and no abnormalities in the remaining indexes, Myocalcium triplet, BNP, four items of coagulation, D-dimer, lung tumor markers (carcinoembryonic antigen, neuron-specific enolase, cytokeratin 19 fragment, squamous cell carcinoma antigen), blood culture, 1,3-β-D dextran detection (G test), galactomannan antigen detection (GM test), There were no abnormalities in the T-spot and PPD tests. Pulmonary function showed moderate obstructive ventilatory dysfunction. The patient's blood glucose was significantly elevated, and the fasting blood glucose was 13~17 mmol/L, the blood glucose was 15~28 mmol/L 2 h after meals, and the glycosylated hemoglobin was 9.3%. On June 17, 2023, the enhanced CT of the chest (Fig. 1) showed that the mass of soft tissue density increase in the upper lobe of the right lung, about 7.9 cm × 5.3 cm, showed signs of lobulation, burr, pleural depression, inflatable bronchi, and spinous protrusions, and the posterior basal segment of the lower lobe of the left lung was partially solid soft tissue density increase shadow, about 4.2 cm × 3.3 cm, multiple nodular and patchy dense shadows were seen in both lungs, and multiple enlarged lymph nodes were found in the mediastinum and right hilar area. Preliminary diagnosis: (1) Mass lesions in the lungs: right upper lung cancer with metastasis of both lungs and mediastinal lymph nodes, lung infection, and (2) type I respiratory failure. (3) Chronic obstructive pulmonary disease. (4) Type 2 diabetes mellitus with poor glycemic control. After admission, cefminol combined with moxifloxacin was given anti-infection, phlegm and cough suppressant, antispasmodic and asthma and subcutaneous insulin injection to lower blood sugar, but the patient still had recurrent fever, body temperature of about 38 °C, chest tightness, breath-holding, cough, and sputum production did not improve. On 18 June 2023, sputum cultures showed Nocardia guinea pig otitidis and Aspergillus flavus (Figure 2). In order to further clarify the diagnosis, bronchoscopy was performed under general anesthesia on June 21, 2023, and the bronchial lumen of the left lingual, lower and right upper lobes was incompletely blocked by white secretions, and a small amount of white secretions were attached to the walls of the right middle and lower lobes. In the right upper lobe, normal saline alveolar lavage and brush examination were sent for etiology and cytopathology. On June 23, 2023, a large number of gram-positive mycobacterium filamentous were detected in the alveolar lavage fluid, suspected to be Nocardia, fungal hyphae were detected by microscopic examination of fungal fluorescence staining and fungal smear, and Nocardia cardia, and Aspergillus fumigatus were identified by MOLDI-TOF mass spectrometry (Fig. 4). Pathogen-targeted sequencing of alveolar lavage fluid was performed by tNGS to detect Aspergillus flavus, Aspergillus fumigatus (sequence number 189), and Nocardia guinea pig otitidis (sequence number 16858). Final diagnosis: Nocardia carcardia in pulmonary guinea pig otitidis combined with Aspergillus infection, cefminol was discontinued, and sulfamethoxazole/trimethoprim (1 200 mg, oral, 4 times/d), moxifloxacin (0.4 g, intravenous infusion, 1 time/d), voriconazole [200 mg, oral, 2 times/day (400 mg, 1 time/12 hours on the first day)] anti-infective therapy was given. After the above treatment, the patient's body temperature gradually dropped to normal, chest tightness and breath-holding were significantly reduced, and the blood oxygen saturation was maintained above 95% without oxygen inhalation. On June 30, 2023, the chest CT was re-examined (Fig. 5), and the mass shadows of the right upper lobe, the left lower lobe and the nodules of both lungs were significantly reduced compared with before, the cavitation in the left lower lung mass disappeared, and the enlarged lymph nodes in the mediastinum and right hilar area disappeared. The patient was discharged with oral medication and instructed to continue oral sulfamethoxazole/trimethoprim and voriconazole treatment outside the hospital. On September 9, 2023, the patient came to the hospital for follow-up and had no fever, his wheezing disappeared, and he occasionally coughed and produced sputum, and chest CT (Fig. 6) showed that the lesions in both lungs were further absorbed and improved compared with before.
Fig.1 On June 17, 2023, the chest CT with contrast showed the hyperdensity of the masses of the upper lobe of the right lung (Fig. 1A), the multiple patchy and nodular densities of both lungs (Fig. 1B), the mass of the left lower lung with cavitary formation (Fig. 1C), and the multiple swollen lymph nodes of the mediastinum and the right hilum (Fig. 1D)
Fig.2 On June 18, 2023, 48 hours after sputum culture inoculation of Colombian blood plate, white raised, granular or petal-like colonies were seen, agar philotropic, and depressed growth (Fig. 2A), and fungal hyphae, septated, 45° branched, and antler-like were seen on sputum smear Gram staining (Fig. 2B)
Fig.3 On June 21, 2023, bronchoscopy showed that the left lingual, lower and right upper lobe bronchial lumen were incompletely blocked by white secretions
Fig.4 Gram-positive mycobacterium filamentous with uneven coloration was seen on HE staining of alveolar lavage fluid on June 23, 2023 (Fig. 4A, high magnification), fluorescent staining of alveolar lavage fluid showed suspected Aspergillus hyphae, mycobacterium filaria, suspected Nocardia (Fig. 4B), alveolar lavage fluid inoculated with Sapaul's medium for 48 h, Aspergillus fumigatus growth was seen, and the center of the colony was delicate blue-green powder (Fig. 4C)
Fig.5 On June 30, 2023, chest CT showed that the mass soft tissue shadow of the upper lobe of the right lung was absorbed more than anterior (Fig. 5A), the multiple patchy and nodular shadows of both lungs were absorbed anteriorly (Fig. 5B), the mass of the left lower lung was reduced compared with the anterior and its internal cavity disappeared (Fig. 5C), and the lymph nodes of mediastinum and right hilar enlargement disappeared (Fig. 5D)
Fig.6 On September 9, 2023, chest CT showed that the lesions in both lungs were further absorbed, and no enlarged lymph nodes were found in the mediastinum and right hilum
discuss
Nocardia is an aerobic, gram-positive corynebacterium belonging to the order Actinomycetes, which is less acid-tolerant and widely found in soil, air, dust, freshwater, seawater, and decaying plants [1]. It is an opportunistic pathogen that infects immunocompromised or compromised individuals, with a small number (approximately 10 percent) of infections occurring in immunocompetent patients with structural lung diseases, such as chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis [2, 3]. Nocardia bacteria are transmitted into the human body by inhalation or contact, and there are three main forms of primary cutaneous, lung, and systemic disseminated infection, with pulmonary infection being the most common [4]. Imaging of Nocardia infection in the lungs is common with single or multiple pulmonary nodules, lobar consolidation, and pleural effusions, sometimes infiltrative lesions, necrotizing granulomas, and cavitation in immunocompromised patients [5]. Clinical diagnosis of nocardia infection is difficult due to the lack of specificity of symptoms, signs, and imaging findings, and pathogenic testing is often relied upon. Among the clinically confirmed patients with Nocardia infection, Nocardia guinea pig otitidis is rare, accounting for about 3%~5% of all Nocardia infections [6], and Aspergillus infection is even rarer. Aspergillus and Nocardia infections lack specificity on imaging, and both can manifest as small or large patches of pulmonary infiltrates, accompanied by single or multiple nodular hyperdense shadows, and some patients may have cavitation, which may be accompanied by mediastinal or hilar lymphadenopathy, which is difficult to distinguish from lung cancer, lung abscess, tuberculosis and other diseases, so they are often missed or misdiagnosed or mistreated clinically [7]. Pathogen testing is the only way to confirm the diagnosis of Nocardia and Aspergillus. Sputum, pus, pleural effusion, puncture fluid, alveolar lavage, or abscess drainage fluid can be used as aetiological specimens [8]. Nocardia is an aerobic bacterium that increases the positive rate with the correct medium, extended incubation times, and multiple iterations [9]. In this case, the patient initially developed symptoms such as fever and wheezing, and lung cancer was considered to have a high possibility of metastasis in combination with imaging, but no new organisms were found in bronchoscopy, so we reconsidered the possibility of infectious diseases. The patient is a farmer with a previously normal immune function, and his living environment has a chance of exposure to decaying plants, and inhalation is the most likely route of infection. Patients with chronic smoking and pulmonary function tests are considered to have chronic obstructive pulmonary disease. Patients with structural lung disease have increased susceptibility to opportunistic pathogens, which may be related to changes in bronchial structure, alteration of ciliary movement by lower airway colonizing bacteria that cause epithelial damage, damage to alveolar macrophages by inhaled corticosteroids, and frequent antibiotic therapy [10]. Combined with the patient's living environment and the patient's structural lung disease and diabetes, we consider him to be a high-risk group for infection with specific pathogens. The rapid improvement of the condition of this case after targeted anti-infective therapy is considered to be related to the timely diagnosis and treatment and the normal autoimmune function of the patient. Treatment of Nocardia includes specific antibiotics, incision and drainage, surgical resection of the lesion, and improvement of host immune function [11]. Treatment depends on a variety of factors, including host immune status, severity of disease, location of lesions, and toxicity of the drug to organs. Sulfonamides are the best choice for the treatment of Nocardia [12] and have the advantages of high oral bioavailability, strong permeability, and good aggregation in the lungs and central nervous system. Patients who are allergic to or intolerant of sulfonamides may be replaced with amoxicillin-clavulanate potassium or minocycline. In addition to these agents, Nocardia is susceptible to quinolones, amikacin, ceftriaxone, and imipenem [13]. Treatment with sulfonamides alone is very effective in patients with pulmonary or cutaneous Nocardiosis infection, but in patients with severe immunosuppression, such as those with organ transplantation or disseminated Nocardiosis infection, a combination of antimicrobials such as imipenem plus third-generation cephalosporin or amikacin is recommended. The treatment course of pulmonary nocardia infection is relatively long, usually 3~6 months, and for immunocompromised people, it takes up to 6~12 months [14]. For the treatment of pulmonary aspergillosis, guidelines [15] recommend intravenous infusion or oral voriconazole (400 mg once every 12 hours on the first day and 200 mg once every 12 hours thereafter) for approximately three months. For invasive pulmonary aspergillosis that occurs in immunocompromised patients, treatment is prolonged. The results of sputum culture, alveolar lavage fluid culture and tNGS were all Nocardia guinea pig otitidis and Aspergillus. Since the pathogen was isolated from the lower respiratory tract, both were considered to be pathogenic bacteria, and after more than 10 days of treatment with sulfamethoxazole/trimethoprim combined with voriconazole, chest CT showed nodular shadows, cavitary shadows and mediastinal enlarged lymph nodes in both lungs. Fungal infections are often difficult to achieve significant improvement on imaging with short-term treatment, so this manifestation is more in line with the characteristics of nocardia treatment response, so it is considered that this case is mainly based on nocardia guinea pig otitidis infection. The overall case fatality rate of nocardia infection is high, and the prognosis is closely related to diagnosis, duration of treatment, severity of the patient's underlying disease, and whether bloodstream infection has occurred. Early and frequent use of glucocorticoids and systemic infection are important factors in poor prognosis [16]. Early isolation and identification of Nocardia strains and timely and effective treatment with sulfonamides can help reduce the mortality rate.
In summary, both Nocardia and Aspergillus are exogenous and opportunistic pathogens, and infections are common in immunocompromised people. Due to the lack of specificity in the clinical manifestations and imaging of the two, they are easily misdiagnosed and missed, and accurate etiological detection needs to be relied upon. Co-infection is rare, and early diagnosis and timely treatment are of great significance to reduce the mortality rate.
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