Sex: M
Vaccine: PPV
Symptoms: Viral test negative, White blood cell count increased
Clinical narrative: Information has been received from authors of a published article. This literature marketed report was concerning a 63-year-old man with a history of chronic obstructive pulmonary disease (COPD) and multiple hospitalizations for recurrent pneumonias presented with a 2-week history of progressive shortness of breath associated with productive cough with yellow sputum, fevers, chills, anorexia, and a 12lb unintentional weight loss. His medical history was significant for COPD, prior pulmonary tuberculosis successfully treated in 2001, and multiple admissions for bacterial pneumonias that began increasing in frequency since 2015. The causative organisms in the prior pneumonias are unknown. During 2016, he had 4 hospital admissions for bacterial pneumonias, including Pseudomonas. He had been treated with a carbapenem during his most recent hospitalization, but experienced only slight improvement of his symptoms. His social history was significant for being a 35-pack-year smoker. There was no known family history of pulmonary conditions or immunologic disorders. He had no history of environmental or drug allergies. On physical examination, his temperature was 36.5 Celsius degree; heart rate 66 beats/min; respiratory rate 18 breaths/min; blood pressure 93/57 mm Hg; and oxygen saturation, of 98% on 3L via nasal cannula. He had moderate respiratory distress, speaking in 3- to 4-word sentences, and subsequently required bilevel positive airway pressure therapy. Physical examination was notable for severe cachexia with a weight of 40 kg (11.8 kg/m2), diffuse rales in the bilateral lung fields, and asymmetrical chest wall expansion and diminished breath sounds on the left side. Initial complete blood count demonstrated an elevated white blood cell count of 17,200/uL with 88% neutrophils, hemoglobin of 10.9 g/dL, and platelets of 414,000/uL. Computed tomography of the chest demonstrated extensive parenchymal disease with multiple cavities, a left lower lobe consolidation, and small right pleural effusion. Blood and respiratory bacterial cultures, Streptococcus pneumoniae and Legionella pneumophila urine antigens, Mycoplasma immunoglobulinM (IgM), galactomannan, Coccidioides complement fixation test, Histoplasma urine antigen, and Cryptococcus serum antigen were negative. A thoracentesis was performed, which revealed a transudative effusion with negative fungal and bacterial cultures. Bronchoalveolar lavage was performed, and fungal culture demonstrated Malbranchea species; bacterial, mycobacterial, and viral cultures were negative. Staining for Nocardia species and that for Pneumocystis jirovecii were both negative as well. Malbrancheawas confirmed based on its typical morphology microscopically. He was initially treated empirically with broad-spectrum antibiotics. Voriconazole was added because of concerns of a possible fungal pneumonia (275 mg intravenous once daily) and continued after the diagnosis of Malbranchea was confirmed. Malbranchea was found to be susceptible to all tested antifungal antibiotics, which included amphotericin B, anidulafungin, caspofungin, micafungin, itraconazole, posaconazole, voriconazole, and isavuconazole. Because of his significant pulmonary infection history and the growth of Malbranchea species, an immunodeficiency evaluation was commenced. A human immunodeficiency virus antigen/antibody test was negative. An initial total IgM level was less than 5 mg/dL, with all other antibodies within normal limits, including IgA of 308 mg/dL, IgG of 1270 mg/dL, and IgE of 10.5 mg/dL. Immunoglobulin G subclasses were normal, and IgG4 was 71 mg/dL, ruling out subclass deficiency and hyper-IgG4 disease. He had normal antibody titers to protein antigens with tetanus and diphtheria titers, both at 0.1 IU/mL. Antibody titers to carbohydrate antigens (pneumococcus) were low at baseline (roughly 50% of serotypes with levels <1.3 mg/dL). The patient's immunoglobulin G titers before vaccination was as following: Ig G serotype 1: 3.19 ug/ml; serotype 3: 0.44 ug/ml; serotype 4: 0.74ug/ml; serotype 5: 1.16 ug/ml; serotype 6B: 2.36 ug/ml; serotype 7F: 2.40 ug/ml; serotype 8: 0.46 ug/ml; serotype 9N: 15.12 ug/ml; serotype 9V:1.36 ug/ml; serotype 12F: 0.52 ug/ml; serotype 14G: 2.61 ug/ml; serotype 18C: 5.54 ug/ml; serotype 19F: 3.43 ug/ml; serotype 23F: 0.4 ug/ml. On an unknown date, Voriconazole was later changed to posaconazole (manufacturer unknown) extended-release tablet 300 mg daily, orally (lot# and expiration date were not reported for the Malbranchea infection (product use in unapproved indication), because of increased transaminases (alanine aminotransferase of 166 U/L and an aspartate aminotransferase of 164 U/L), as well as the development of visual disturbances. On an unknown date, the patient was vaccinated with pneumococcal Vaccine, Polyvalent (23-valent) (manufacturer unknown) (dose, route, lot# and expiration date were not reported) for prophylaxis. On an unknown date, after vaccination, the patient's immunoglobulin G titers as following: Ig G serotype 1: 3.02 ug/ml; serotype 3: 0.61 ug/ml; serotype 4: 0.67ug/ml; serotype 5: 0.75 ug/ml; serotype 6B: 3.92 ug/ml; serotype 7F: 2.78 ug/ml; serotype 8: 0.60 ug/ml; serotype 9N: 11.31 ug/ml; serotype 9V:0.79 ug/ml; serotype 12F: 0.26 ug/ml; serotype 14G: 3.28 ug/ml; serotype 18C: 4.40 ug/ml; serotype 19F: 4.04 ug/ml; serotype 23F: 0.5 ug/ml. It was also reported that a baseline level of 1.3 µg/mL was considered protective. If baseline levels were less than 1.3 µg/mL for a given serotype, a 2-fold rise in that serotype constituted an adequate response. If the baseline level was less than 1.3 µg/mL, then a 4-fold rise constituted an adequate response. It demonstrated virtually no rise in antibody titers in any of the serotypes. The event was considered as no therapeutic response. The outcome of the event was not reported. The reporter considered the event of no therapeutic response to be related to pneumococcal Vaccine, Polyvalent (23-valent) (manufacture unknown).