Case report 1
The first patient was a 55-year-old man who had a history of smoking for more than 10 years. The patient underwent mitral valve replacement in 2012. On 24th of December 2017, he was admitted into the First Affiliated Hospital of Sun Yat-Sen University because of aggravated shortness of breath for one month and edema of both lower extremities for 3 days. The initial blood count showed hemoglobin level of 100 g/L, WBC count of 5.28 × 109 cells/L (46.6% neutrophils, 36.2% lymphocytes), raised Erythrocyte sedimentation rate (ESR) (74 mm/h) and C-reactive protein (10.60 mg/L). The PCT, troponin T and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) all increased (Table S1). Bed-side chest radiograph showed inflammation of both lungs and enlarged heart shadow in the supine position. Transthoracic echocardiography (TTE) showed two vegetations on prosthetic mitral valve, accelerated velocity of the prosthetic mitral valve and the effective orifice area was 1.8 cm2(Fig. 1), which revealed infectious endocarditis after MVR. TTE also found moderate tricuspid regurgitation and mild pulmonary artery hypertension. The LVEF was approximately normal (56%) and diastolic function was reduced. The ECG indicated atrial flutter (2–3: 1 conduction) with rapid ventricular rate. The (1,3) -β-D glucan was 93.99 pg / mL and Candida parapsilosis sensu stricto was identified in the blood culture by Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI TOF-MS®) (Flucytosine minimal inhibitory concentration (MIC) 4 ug/mL, amphotericin B MIC 0.5 ug/mL, voriconazole MIC 0.06 ug/mL, itraconazole MIC 0.125 ug/mL, fluconazole MIC 1 ug/mL). Repeat blood cultures continued to grow Candida parapsilosis sensu stricto. The patient was initiated on vancomycin 1 g iv three times a day and voriconazole 200 mg iv twice a day after admission. Then, combination antifungal therapy with vancomycin 1 g iv three times a day and caspofungin iv 50 mg once a day was initiated on Dec 29. Because of high vancomycin blood concentration, the therapy changed to vancomycin 1 g iv twice a day and caspofungin 50 mg iv once a day on Dec 30 and lasted until discharging. Besides, Rocephin was administrated from Dec 30 of 2017 to Jan 3 of 2018 to fight lung infections. After a series of anti-infective treatment, the patient's condition improved. However, the blood cultures continued to grow Candida parapsilosis sensu stricto and the patient refused the surgical treatment despite of the indications of operation. The patient went back to local hospital and was recommended to continue the combination antifungal therapy according to the drug sensitivity.
Case report 2
The second patient was a 71-year-old man with a history of hypertension for 3 years and smoking for 30 years. He was admitted into the First Affiliated Hospital of Sun Yat-Sen University on April 26 of 2019 for repeated chest tightness and palpitations for more than 10 years, aggravating by 1 year. TTE showed that posterior mitral valve tendon cord was ruptured, which resulted posterior mitral valve prolapse and severe mitral valve regurgitation. At the same time, TEE found mild aortic valve stenosis and mild-moderate regurgitation, anterior tricuspid valve prolapse and medium regurgitation, severe pulmonary artery hypertension. The aorta root, the left atrium and left ventricle were significantly enlarged. The right atrium was slightly larger. And LVEF was about 70%. On May 5, the patient underwent aortic valve and mitral valve bioprosthesis replacement, tricuspid valvuloplasty, aortic annuloplasty and temporary cardiac pacemaker implantation. The patient was given sulperazone 3 g iv three times a day from May 5 to May 17, imipenem cilastatin sodium iv 1 g once a day from May 20 to May 28 and sulperazone 3 g iv three times a day from May 28 to May 31. On May 24, the blood culture grew yeast-like fungus (Flucytosine minimal inhibitory concentration (MIC) 4 ug/mL, amphotericin B MIC 0.5 ug/mL, voriconazole MIC 0.06 ug/mL, itraconazole MIC 0.125 ug/mL, fluconazole MIC 1 ug/mL) and the patient was administrated caspofungin (50 mg iv once day) to fight fungal infection. On June 13, the blood culture still grew yeast-like fungus and the patient continued to use caspofungin (50 mg iv once day). On June 24, the patient had a fever of 39.2℃ and the blood culture still grew yeast-like fungus. Then the patient was given voriconazole (200 mg oral twice a day) instead of caspofungin. The blood culture became negative after 1 month using voriconazole. The patient continued to use voriconazole (200 mg oral once a day) for 2 weeks after discharging.
Six months later, the patient was readmitted into the First Affiliated Hospital of Sun Yat-Sen University on November 4 due to fever for 20 days and shortness of breath for 3 days after activity. The initial blood count showed WBC count of 3.76 × 109 cells/L (78.8% neutrophils, 10.3% lymphocytes). The (1,3) -β-D glucan was 144.85 pg/mL and the blood culture grew Candida parapsilosis sensu stricto which was identified by MALDI TOF-MS (Flucytosine minimal inhibitory concentration (MIC) 4 ug/mL, amphotericin B MIC 0.5 ug/mL, voriconazole MIC 0.06 ug/mL, itraconazole MIC 0.125 ug/mL, fluconazole MIC 1 ug/mL). (Table 1 and Table S1). Transesophageal echocardiography (TEE) showed a dehiscence about 10mm × 0 mm and severe perivalvular leakage from the medial part of the prosthetic mitral valve. TEE also found a small strip fluttering a lot from left atrium side of the medial prosthetic ring, suggesting infective endocarditis (Fig. 2). The patient was administrated voriconazole 200 mg iv twice a day from November 4 to 21, caspofungin 50 mg iv twice a day from November 21 to December 4 and amphotericin B 1 mg iv once a day from November 26 to December 4. Besides, the patient was administrated tazocin 4.5 g iv three times a day from Nov 4 to Nov 6, vancomycin 0.5 g iv once a day from Nov 17 to Nov 21 and tienam iv 1 g once a day from from Nov 21 to Dec 4. The patient's body temperature was relieved, fluctuating around 37.5 ℃. Then the patient was discharged and recommended antifungal treatment in local hospital with imipenem and cilastatin sodium for injection 1000 mg three times a day, caspofungin 50 mg once a week and amphotericin B 30 mg once a week.
Table 1. Clinical characteristics of the patients
|
Case 1
|
Case 2
|
Case 3
|
Case 4
|
Age(years)
|
55
|
71
|
70
|
64
|
Gender
|
Male
|
Male
|
Male
|
Male
|
Type of surgery
|
Mitral valve replacement
|
Aortic and mitral valve replacement
|
Aortic valve replacement
|
Aortic and mitral valve replacement
|
Type of valve replacement
|
/
|
Medtronic Hanko Ⅱ 27# (mitral valve); Medtronic HankoⅡ 21# (aortic valve)
|
/
|
Edward 25# (mitral valve); Edward 21# (aortic valve).
|
Possible
predisposing
factor for infective
endocarditis
|
Smoking
|
Fungemia Hypertension Smoking
|
/
|
Hepatitis B
|
Symptoms on
admission
|
Aggravated shortness of breath for one month and edema of both lower extremities for 3 days.
|
Fever for 20 days and shortness of breath for 3 days after activity
|
Repeated fever for more than 50 days and acute bloating for 12 days.
|
Repeated fever for nearly 2 months
|
Infection site
|
Mitral valve
|
Mitral valve
|
Aortic valve
|
Mitral valve
|
Time post
implantation
|
Five years
|
Six months
|
Four years
|
Three years
|
Pathogen (isolated
from blood)
|
Candida parapsilosis sensu stricto
|
Candida parapsilosis sensu stricto
|
Candida parapsilosis sensu stricto
|
Candida metapsilosis
|
MIC (ug/mL)
|
|
|
|
|
Flucytosine
|
4
|
4
|
4
|
4
|
Amphotericin B
|
0.5
|
0.5
|
0.5
|
0.5
|
Voriconazole
|
0.06
|
0.06
|
0.06
|
0.06
|
Itraconazole
|
0.125
|
0.125
|
0.125
|
0.125
|
Fluconazole
|
1
|
1
|
1
|
2
|
Choice of
antifungal drugs
|
Voriconazole, caspofungin
|
Voriconazole, caspofungin, amphotericin B
|
Voriconazole, fluconazole
|
Fluconazole, caspofungin
|
Outcome
|
Successful medical therapy
|
Successful medical therapy
|
Death
|
Death
|
MIC: minimal inhibitory concentration