Table 3 Summary of 38 cryptococcosis cases since 2000

[23]

UK

M

HIV infection

Fever, ulcerated lesion over left loin, dry mucous membranes, headache, vomiting; 14 days

Intravenous AmB (1 mg/kg per day) and flucytosine (100 mg/kg per day) for 2 weeks; fluconazole (400 mg/day) for 10 weeks

No neurological complications and no further episodes of opportunistic infections at 12-month follow-up

[24]

USA

M

HIV-infection (CD4 count less than 20 cells/µl), intermittent asthma, migraines

Altered mental state, weight loss, neck pain, cough, fever, nausea, vomiting, photophobia; 7 days

AmB and flucytosine; placement of a lumbar drain

Clinical improvement and was discharged on oral fluconazole

[25]

Australia

M

Autosomal dominant polycystic kidney disease, renal transplant, direct contact with cockatiel bird

Pruritic and painless rash; 1 month

LAmB and flucytosine 6 weeks; then oral fluconazole consolidation

Improvement in lower leg cellulitis, renal allograft function is stable

[26]

China

M

Uremia, kidney transplant

Headache, dizziness, vomiting, dyspnea, fever; 2 days

ABLC, flucytosine and voriconazole for the first 11 days; ABLC and flucytosine for 8 weeks; fluconazole for maintenance

Asymptomatic at 3-week follow-up

[27]

Iran

F

Relapsing remitting multiple sclerosis, two times

Headache, fever, weakness, and progressive loss of consciousness, neck stiffness with Kernig and Brudzinski signs, bilateral pupil mydriasis and papilledema

LAmB 300 mg/day and fluconazole 800 mg/day for 2 weeks; LAmB 300 mg/day and fluconazole 400 mg/day for 4 weeks; fluconazole 200 mg/day

Discharge without any major complaints after 6-week hospitalization

[28]

Spain

M

Diabetes, worked in public works water and sewer maintenance

5 kg weight loss and 24 h fever, 6-month history of mechanical lumbar pain

Single dose of LAmB (10 mg/kg, 870 mg) infused over 3 h, oral fluconazole (800 mg/day); fluconazole (800 mg/day for 14 days, then 400 mg/day for 1 year

No symptoms at 12-month follow-up

[29]

Cameroon

F

HIV-infection, gastric Kaposi’s sarcoma

Subacute occipital headaches associated with photophobia, blurred vision, phonophobia, projectile vomiting; 4 weeks

Fluconazole 1200 mg/day and flucytosine 1500 mg × 4/day

Died on day 6 of this treatment

[30]

USA

M

Renal transplantation recipient, diabetes, coronary artery disease, hypertension, and hyperlipidemia

Dizziness, generalized weakness, hypotension; 28 days

AmB and flucytosine for 4 days LAmB and fluconazole for 2 weeks; then oral fluconazole 400 mg/day for 8 weeks

Admitted for delirium 7 weeks after discharge and died at a 3-week hospital course due to sepsis

[22]

Vietnam

M

Myasthenia gravis, thymus gland removal, diabetes, HCV hepatitis, TB pneumonia, had been breeding birds

Recurrent and progressive skin lesions, mild fever, painful and persistent skin lesions with painful and swollen left knee, headache

AmB 1 mg/kg per day and fluconazole 800 mg/day for 4 weeks; fluconazole (1000 mg) for 12 months

Ulcer regression over 11 days with no exudates; discharged on day 32

[31]

Côte d’Ivoire

M

HIV infection

Confused, incoherent, vomiting, headache

Patient received high oral dose of fluconazole (1200 mg/day)

Died 17 days after treatment initiation

[32]

Japan

M

Renal transplantation recipient

Pain, high fever, erythema, ecchymosis, vesicle formation, and erosion

Lipid AmB and flucytosine

Suffered from immune reconstruction inflammatory syndrome and died

[33]

Sri Lanka

M

Renal transplantation recipient

Headache, low grade fever, alert, neck stiffness, bilateral symmetrical near complete ophthalmoplegia

Intravenous AmB 1 mg/kg per day for 6 weeks; then oral fluconazole 400 mg for 10 weeks

Regained full range of eye movements after 6 weeks

[34]

Saudi Arabia

M

Liver transplantation, cirrhosis developed severe hyponatremia, diabetes

Dizziness, confusion, ataxia, abnormal muscle movements, and leg pain, fever, drowsy, unable to follow commands

AmB for 6 weeks; then fluconazole for 1 year

Serum sodium level returned to normal baseline 3 weeks after starting AmB treatment

[35]

Japan

M

Ischemic heart disease 4 years prior, ICD implantation, diabetes, chronic hepatitis B

Non-productive cough and respiratory discomfort

LAmB 250 mg/day, oral flucytosine 6000 mg/day, and daptomycin 350 mg/day for 25 days

Died 54 days after initial hospital admission, an autopsy was declined by his family

[36]

China

M

Nephrotic syndrome

Massive shallow ulcers of both lower extremities, fever of 39 °C, severe pain

Intravenous fluconazole (400 mg/day) for 8 days; intravenous antibiotic therapy

Died 8 days after initial hospital admission

[37]

Germany

F

Rheumatoid arthritis

Skin ulceration, swelling, erythema and severe pain

Intravenous fluconazole (400 mg/day) for 10 days; then fluconazole (400 mg/day) for 4 weeks

The skin defect was successfully closed with a mesh graft

[38]

USA

M

Cardiac transplantation with mild rejection

Fever, back pain, severe left lower extremity pain

Oral fluconazole and intravenous AmB; Due to fluconazole resistance, switched to oral voriconazole and intravenous AmB

There were no fungal organisms present after treatment

[39]

China

M

No significant past medical history; no noted exposure to bird droppings

Progressive multiple abscesses, fever, lower extremity weakness, urinary retention; 7 months

LAmB, itraconazole, flucytosine, and fluconazole for 4 months

Afebrile, with no new-onset abscess, could walk slowly at 18-month follow-up

[40]

Thailand

M

With a 5-year history of primary myelofibrosis, hypertension, asthma, and osteoporosis presented

Erythematous swollen left leg for 7 days; fever, dyspnea on exertion, and orthopnea for 6 days; multiple ulcers on right foot for 10 days

AmB 50 mg/day and oral fluconazole 800 mg/day; switched to LAmB 180 mg/day and fluconazole 800 mg/day for 28 days; then oral fluconazole 400 mg/day

Developed septic shock and died 48 days after hospital admission

[41]

Japan

M

Hepatitis type B virus infection, hepatic failure, hypertension

Headache, vomiting, gait disturbance; 1 month

LAmB and fluconazole

Developed renal failure and ultimately died 25 days after admission

[42]

China

M

Hepatitis type B virus infection

Aphasia and left hemiparesis; 3 days

Intravenous fluconazole 400 mg/day; switched to intravenous AmB (0.6 mg/kg per day) and voriconazole (400 mg/kg per day) and oral flucytosine (100 mg/kg per day, 4 equal parts) for 2 weeks; then oral voriconazole for 11 months

Neurological recovery was complete and no recurrence was recorded at 6-month follow-up

[43]

Canada

F

Diabetes, seizure disorder with remote left temporal lobectomy

Fever up to 38.4 °C

Posaconazole 300 mg/day for 12 months

Antigen titers were negative at 1-year follow-up

[44]

Argentina

F

Smoking, arterial hypertension, breast cancer, nephroangiosclerosis, kidney graft

Fever, headache episodes, weight loss

Intravenous AmB and oral fluconazole

Infection resolved after antifungal treatment

[45]

Norway

M

Hypertension, migraine

Influenza-like symptoms, palpitations, activity-related presyncope

Intravenous fluconazole (800 mg); switched to AmB (200 mg/day) and flucytosine (1500 mg/ day) twice daily for 1 month; then flucytosine (1500 mg × 2) and fluconazole (400–800 mg/day) for 1 month; then fluconazole (400 mg/day) for 11 months

There was no evidence of infection recurrence during 2 years of follow-up

[46]

Brazil

M

Pulmonary tuberculosis, HIV infection

Difficulty performing basic daily life activities, anorexia, fever, profuse sweating, vomiting episodes preceded by nausea

AmB (1 mg/kg per day) and intravenous fluconazole (800 mg/day) for 7 days; then fluconazole (1200 mg/day) for 7 days; fluconazole (800 mg/day) for 8 weeks

CSF cultures for fungi were negative at 1 and 2 weeks following treatment initiation

[47]

Netherlands

M

HIV-negative patient with low MBL and low naïve CD4 count, chronic relapsing meningoencephali-tis with relatively mild symptoms for approximately 2 years

Relapsing diffuse headaches lasting several days; 3.5 months

LAmB (3 mg/kg per day) and flucytosine (100 mg/kg per day) for 2 weeks; fluconazole (400–800 mg/day) for 8 weeks; then fluconazole maintenance therapy for 12 weeks

Mild headaches

[48]

USA

M

Renal transplantation, diabetes

General weakness, altered mental status, hypoxemia, mild hyponatremia, hypochloremia

AmB and flucytosine

After an initial improvement, the patient became suddenly hypotensive, and died soon after

[49]

China

M

Unremarkable

Apathetic, uncommunicative and slow to move, unresponsive and bed ridden, consciousness level continued to decline during admission

Intravenous AmB 25 mg/day was given initially and then gradually increased to 50 mg/day, with oral flucytosine 6 g/day

Coma began 1 week after treatment onset; treatment was stopped according to the circumstances, and the patient died

[50]

Germany

F

Relapse remitting multiple sclerosis, owned a birdhouse

Cephalgia, fever, confusion, coughing and generalized weakness

Intravenous LAmB and oral fluconazole, replaced by flucytosine

Remained clinically stable

[51]

China

M

Chronic hepatitis B

Dry cough; more than 6 months

Fluconazole 400 mg/day for 6 months

Two pulmonary cryptococcal nodules disappeared

[52]

–

M

HIV-negative; alcoholic liver cirrhosis

Fever, seizure

Flucytosine

Multi-system organ failure leading to death

[53]

China

M

HIV infection

Multiple skin lesions, intermittent headache

AmB and fluconazole

Died 3 days after adding fluconazole

[53]

China

F

HIV infection, diabetes

Mild fever, productive cough, dyspnea on exertion, swelling in both lower limbs

Oral fluconazole 100 mg for 3 days; then AmB (1 mg/kg per day) for 3 days followed by fluconazole 400 mg/day

Became afebrile after 72 h of treatment with considerable improvement of other comorbidities; discharged with continuing oral antifungal therapy

[54]

China

M

Advanced stage non-small cell lung cancer, smoking, severe underlying chronic obstructive pulmonary disease

Non-anginal anterior chest pain, progressive dyspnea

Fluconazole 400 mg/day

Progressive clinical improvements at 10 month follow-up, the patient passed away from malignancy

[55]

China

F

With a 2-month history of elevated serum CA19-9 levels (50.05 IU/ml)

No symptoms

Fluconazole 400 mg/day for 3 months; fluconazole 200 mg/day for 3 months

After 6 months of treatment, serum CA19-9 levels regressed to the normal range