A 22-year-old Chinese male form Zhejiang province initially presented to the local community hospital. He complained of 10 days of intermittent fever with a temperature of up to 38.7 C and 3 days of progressive dyspnea and dry cough. He was given moxifloxacin at the local community hospital. However, he contracted chest thrush after using moxifloxacin, so this treatment was stopped and he was given ambroxol hydrochloride. Due to a history of male sexual partners and weight loss, an HIV test was obtained which returned positive. Then he came to our institution, the infectious disease department of the First Affiliated Hospital, School of Medicine, Zhejiang University, and hospitalized.
Upon presentation at our institution, he still had fever, dyspnea, fatigue, cough with a small amount of pale sputum, and occasionally pectoralgia and dyspnea during activity. Physical examination found a body temperature of 37.4 C, blood pressure of 113/50 mmHg, a pulse of 115 beats per minute, a respiration rate of 23 breaths per minute, and SpO2 93% using fingertip pulse oximetry. The bilateral lung presented moist rales. The patient did not have a skin rash. The laboratory results were as follows: white blood cell count 7.7 x 109/L, with a neutrophil ratio of 65.7%, hemoglobin 133 g/L, and platelet count 365 x 109/L; C-reactive protein (CRP) 8.5 mg/L; erythrocyte sedimentation rate (ESR) 5 mm/h; and procalcitonin 0.08 ng/mL. Blood biochemical index results showed that lactate dehydrogenase content increased to 401 U/L (reference range 150-250 U/L), and -hydroxybutyrate dehydrogenase content increased to 326 U/L (reference range 72-182 U/L). The 1,3-beta-D-glucan test (G test) result (251.64 pg/ml) was positive, while galactomannan test (GM test) (0.1 mug/L) and cryptococcus capsular antigen test results were negative. His CD4 count was 16 cells/muL. Arterial blood gas analysis (with O2 3 L/min via nasal catheter) showed pH 7.51; pCO2 27 mmHg; pO2 98 mmHg; HCO3 -21.9 mmol/L; SBE -0.8 mmol/L; lactate 0.8 mmol/L; and O2 saturation 99%. A chest computed tomography (CT) scan showed extensive ground-glass opacities in the bilateral lung with multiple thin-walled cavity lesions in the left upper lung (Figures 1A,B). The IgG and IgM antibodies of coronavirus disease 2019 (COVID-19) were negative. The nucleic acid detection of COVID-19 was negative. Nucleic acid detection of common respiratory pathogens (including Mycoplasma pneumoniae, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus, parainfluenza virus, and influenza A and B) was negative. The IgG antibodies of Epstein-Barr virus (EBV) and human cytomegalovirus (CMV) were positive, while the IgM antibodies of EBV and CMV were negative. The nucleic acid of CMV in the blood was reported at 1.86 x 104 copies/mL by quantitative PCR. Mycobacterium tuberculosis (MTB) was negative based on blood test with T-SPOT.TB as well as acid-fast staining of sputum smear and GeneXpert. The blood, sputum, and urine smear and culture of bacteria and fungi were negative. We also sent the sputum sample to perform Gomori-Grocott methenamine silver nitrate staining (GMS) for Pneumocystis jirovecii detection and obtained a negative result. Given the patient's hypoxia and demonstration of diffuse ground-glass opacities on CT of the chest, a clinical diagnosis of P. jirovecii pneumonia (PCP) was made. Oral trimethoprim-sulfamethoxazole (TMP-SMX, TMP 0.24 g /SMX 1.2 g, q8h), intravenous clindamycin (0.6 g, q12h), and methylprednisolone (40 mg daily) were administered, which resulted in the improvement of general conditions and abatement of fever and dyspnea in 3 days.
To verify pathogen-induced pneumonia, the patient underwent a bronchoscopy examination with a collection of BALF specimens on day 5 of admission. The BALF was sent to the laboratory for conventional tests and an NGS test [using the MGISeq 2000 platform (MGI Tec Co. Ltd, Shenzhen, China)]. The BALF Gram stain and acid-fast stain were negative. The G test and GM test of BALF were negative. In addition, a BALF culture of fungal and bacteria showed no organisms. Microbiological tests of BALF were negative for MTB by the smear and GeneXpert MTB/RIF assay. Two days later, the NGS results showed that P. jirovecii (1,000,078 reads) and CMV (4,192 reads) were found in the BALF. The other microorganisms detected by NGS were bacteria and are listed in Table 1, but they were not regarded as responsible for the invasive pulmonary infection. Based on the report, the diagnosis of multi-pathogenic pneumonia due to PCP and CMV was made in this patient, and intravenous ganciclovir (0.25, Q12H) was started.
After 2 weeks of hospitalization, his symptoms disappeared, general conditions returned to normal, and laboratory findings improved. The chest CT scan showed that lesions had been significantly absorbed except for a faint patchy opacity in the lateral segment and thin-walled cavity lesions in the left upper lung (Figures 1C,D). So, the patient began antiretroviral therapy with Truvada (emtricitabine and tenofovir disoproxil fumarate tablets, 500 mg QD) and dolutegravir (50 mg QD). He was discharged to complete 1 week of TMP-SMX and 2 weeks of oral ganciclovir (500 mg, three times daily) at home, and then switch to prophylactic doses of TMP-SMX until CD4 count recovery. At his 2-week follow-up visit, he had no symptoms. At his 2-month follow up, he appeared healthy with no symptoms and a chest CT scan exhibited no abnormal findings except for a faint patchy opacity in the left lateral segment (Figures 1E,F).