Severe pneumonia due to infection with Candida krusei

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Severe pneumonia due to infection with Candida krusei: case report of a suspected Middle East Respiratory Syndrome and literature review

Running Title: a case report of Candida krusei pneumonia

Abstract

Introduction: Candida krusei (C. krusei) pneumonia is a rare infection and often associated with poor outcome. In this report, we present an unusual case of Candida krusei pneumonia who was initially suspicious of Middle East Respiratory Syndrome (MERS).

Case presentation: A 64-year-old Saudi Arabian male patient was admitted to our hospital with complaints of cough and Dyspnea for 6 days. He was hyperpyrexial (oral temperature of 38.5°) and slightly tachypneic (25 respirations/min). A chest computerized tomography showed unclear lung fields, diffuse pathological changes in both lungs and multiple lymphadenectasis in retrocaval and para-aortic arch area. He received 95-98% oxygen (6 L/min) for 24 h, Cefoperazone Sodium and Sulbactam Sodium for Injection (3.0 g) every 12 h, oral Oseltamivir capsule (75 mg) twice a day, Medaron injection (80 mg) and 750 mL fluid infusion, but died on day 3 of admission. The infection was documented by sputum smear and culture after he died.Sputum smear showed massive fungal infection and sputum culture grew C. krusei. Serum PCT concentrations were 4.73 μg/L and 7.23 μg/L days 3 and 4 of admission, respectively.

Conclusion: The diagnosis of Candida pneumonia should be strongly considered in the presence of growth of Candida from sputum culture and a suggestive CT image. Tumescent diaphragmatic lymph nodes may be an important symptom of candida pneumonia. Treatment should be started immediately to improve tissue oxygenation, restore cardiovascular function, and improve other organ functions.

Key words: Candida krusei, Candida pneumonia, PCT

Introduction

Pneumonia due to Candida, often associated with fatal outcome [1], is a rare infection, and it occurs predominantly in immunocompromised patients or who received broad-spectrum antibiotic therapy [2]. Candida pneumonia was first described by Rosen Von Rosenstein in 1771, and later reported by Castellani [3]. Since then, only scattered cases have been reported in the English literature [3]. Especially, C. krusei is less frequently encountered in clinical mycology than other species since its first public description in 2002 [1, 4]. Herein, we report a case of C. krusei pneumonia who was initially suspicious of Middle East Respiratory Syndrome (MERS).

Patient report

A 64-year-old Saudi Arabian male patient was admitted to our hospital on December 7th, 2014 with complaints of cough and Dyspnea for 6 days. The patient initially have abrupt onset of paroxysmal cough without obvious inducements, accompanied by chest tightness, tachypnea and slight fever, but with no expectoration, no chest pain and hemoptysis and no oliguresis, and he did not receive regular therapy. Within the 6 days after the onset of symptoms, cough and chest tightness became worse progressively. Recently, patient had complaints of edema of both lower limbs. Past medical history was significant for diabetes over the past 20 years which was treated with insulin, coronary heart disease 10 years ago and chronic diabetic kidney insufficiency over the last 4 years. Additionally, the patient admitted that chest tightness and tachypnea occurred soon after walking for 100 steps within the 10 years. Family history was unremarkable.

On admission, the patient was hyperpyrexial (oral temperature of 38.5°) and slightly tachypneic (25 respirations/min), with a heart rate (HR) of 60 beats/min, a pulse of 60/minand blood pressure (BP) of 180/90 mmHg. His oxygen saturation was 90% on air and he had cyanosis in oral lips. Cardiovascular examinations showed an irregular heart rhythm but no obvious pathological murmur at auscultatory valve areas as well as no distension of jugular vein at semireclining position. Crude breath sounds of bilateral lung were heard on chest auscultation, without obvious dry and moist rales. Other physical examinations included pot belly in the absence of tenderness and rebound, unsatisfactory palpation of liver and spleen, borborygmus of 4/min with negative shifting dullness, as well as mild edema of both lower limbs. Neurogenic examination showed no abnormalities. The admitting diagnosis was severe pneumonia (suspected Middle East Respiratory Syndrome [MERS]), respiratory and heart failure, acid base imbalance and electrolyte disturbances, diabetes, chronic kidney insufficiency and hypertension.

Laboratory examinations revealed hemoglobin, 96 g/L; white blood cells, 10.2 × 109/L (77.6% neutrophils, 13.7% lymphocytes and 8.7% monocytes); C-reactive protein (CRP) > 200 mg/dL. Blood gases were pH of 7.42, PO2 of 65.8 mmHg, PCO2 of 30.8 mmHg, base excess (BE) of 4 mmol/L, HCO3- of 19.8 mmol/L and lactic acid of 2.10 mmol/L. Biochemical analyses showed aspartate aminotransferase (AST), 85U/L; lactate dehydrogenase (LDH), 369 U/L; blood potassium, 5.01 mmol/L; blood sodium, 128 mmol/L; blood glucose, 16.89 mmol/L; creatinine, 224 umol/L; urea nitrogen, 20.62 mmol/L; troponin, weakly positive; and brain natriuretic peptide (BNP), 4567 pg/mL. Computerized tomography (CT) of the chest demonstrated unclear lung fields associated with diffuse pathological changes in both lungs, signs of severe pulmonary infection (Fig.1A), pleural effusionand multiple lymphadenectasis in retrocaval and para-aortic arch area (Fig.1B). Blood samples were obtained for detection of procalcitonin (PCT) and the absence of syphilis and Human immunoddficiency virus (HIV), and cultured for bacteria. Meanwhile, samples of blood, sputum and pharynx swab were collected and sent to Provincial Center for Disease Control to detect viruses or bacteria. On December 9th, antibody to syphilis and HIV in blood was negative. Patient’s serum PCT concentrations were 4.73 μg/L on December 9th and 7.23 μg/L on December 10th. All repeat blood culture sets did not yield any growth. Diagnosis of viruses by nucleic acid detection was also negative on December 9th, including Middle East Coronavirus (MERS-CoV), flu viruses type A and B, 2009 influenza A (H1N1), avian influenza A (H7N9), Mycoplasma pneumonia, Chlamydia pneumonia, Respiratory adenovirus, Respiratory Syncytial Viruses, various parainfluenza virus (types I, II and III). Sputum smear showed a preliminary result of massive fungal infection. Sputum culture repeated three times was finalized on December 11th as C. krusei. The galactomannan (GM) detection in blood was negative.

Initially the patient was isolated and received 95-98% oxygen at atmospheric pressure at a rate of 6 L/min through a nasal catheter for 24 h after he entered the hospital. He was started on Cefoperazone Sodium and Sulbactam Sodium for Injection (3.0 g) every 12 h for anti-bacterial infections. Oral administration of Oseltamivir capsule (75 mg) was given twice a day for anti-viruses infections. Medaron intravenously with a dose of 80 mg was started empirically for anti-inflammatory, as well as 750 mL fluid infusion. However, there was no significant improvement and the patient took a turn for the worse, with heart and respiratory arrest at 3:00 on day 2 of admission. Immediately, cardiopulmonary resuscitation (CPR) was performed and patient recovered weakly respiration with an assisted respirator. His BP at this time was 70/50 mmHg, which rised and stabilized at 110/80 mmHg after adjusting the speed of fluid infusion, monitoring central venous pressure (CVP) and minipump infusion (4-20 mL/h, adjusted according to BP) of vasoactive agents including noradrenaline (10 mg) and normal saline (50 mL). Meanwhile, he had a low HR of 30-40 beats/min and was given cardiotonic therapy consisting of adrenalin injection (10 mg) and normal saline (50 mL) at a minipump maintenance dose of 4-20 mL/h (adjusted according to BP and HR). Furthermore, his renal function was aggravated, with the appearance of oliguria and anuresis. In spite of continuing renal replacement therapy (CRRT), the patient unfortunately died one day after.

Discussion

Candida is an opportunistic pathogen of normal human microbial flora localized in skin, mucous membranes and digestive tract, and it could cause life-threatening invasive infections [5]. Despite not the most frequently isolated species in patients infected with candida, C. krusei invasive infection is of growing incidence [6]. Candida pneumonia, a scarce infection associated with high mortality, should always be considered in the presence of cough, expectoration of purulent secretions, occasional hemoptysis and invariably hypoxemia [3]. In the present report, consistently, the patient developed paroxysmal cough, accompanied by chest tightness, tachypnea and slight fever.

However, pulmonary infection due to C. krusei in this patient was difficult to be diagnosed and initially suspected as MERS. MERS was caused by novel MERS-CoV, a viral respiratory infection first reported in the Saudi Arabian peninsula in 2012 [7], and is characterized by acute respiratory infection, and developed into respiratory failure, cute respiratory distress syndrome (ARDS) and multiple organ failure (MODS), especially renal failure [8]. The common symptoms of MERS also include fever, cough and shortness of breath. Besides, most MERS patients had underlying comorbid medical disorders, including diabetes, hypertension, chronic cardiac disease and chronic renal disease [9]. Unfortunately, the present patient had most similar symptoms as above. However, MERS was excluded by negative virus’s nucleic acid detection.

Histopathological examination of tissue specimens obtained by invasive procedures is still considered as the gold standard for diagnosis of Candida pneumonia [10]. Considering the difficulty to perform biopsy,repeat blood and sputum culture were conducted. Isolation of C. krusei from the sputum is almost always considered to represent colonisation of the respiratory tract. But this diagnostic method is obviously with great hysteresis. Currently, PCT and GM tests are used as auxiliary examination for diagnosis of fungous infection. Serum PCT is detected at 0.1 μg/L in healthy individuals, and will be secreted under bacterial infection [11, 12]. In this case, the repeating high PCT concentrations support a diagnosis of C. krusei infection, although false-negative reactions have been noted in GM test, which was not considered because it was not conducted successionally and repeatedly.

Candida Invasive infection usually affects immunocompromised patients or who received broad-spectrum antibiotic therapy. As the few previous reports, solid organ transplant, haematological malignancies, oesophageal perforation and diabetes appear to facilitate C. krusei pneumonia and empyema [4]. Similarly, this patient had long term of medical history but not drug administration of hormone and antibiotics. The pathogenetic condition progressed severely and fast, which was inconsistent with common fungal pneumonia, and might result in misdiagnosis.

There are a few learning points from this case. The diagnosis of Candida pneumonia should be strongly considered in the presence of growth of Candida from sputum culture and a suggestive CT image. Tumescent diaphragmatic lymph nodes may be an important symptom of candida pneumonia. Treatment should be started immediately to improve tissue oxygenation, restore cardiovascular function, and improve other organ functions.

Acknowledgement

References

1.Petrocheilou‐Paschou, V., et al., Pneumonia due to Candida krusei. Clinical microbiology and infection, 2002. 8(12): p. 806-809.

2.Carvajal, C., J. Rello, and J. Lipman, Candida Pneumonia in Patients with Hematological Neoplasia, in Pulmonary Involvement in Patients with Hematological Malignancies. 2011, Springer. p. 349-356.

3.Mohsenifar, Z., et al., Candida pneumonia: experience with 20 patients. Western Journal of Medicine, 1979. 131(3): p. 196.

4.Imtiaz, T., et al., Candida krusei bronchopneumonia with nodular infiltrates in a patient with chronic renal failure on haemodialysis–case report and review of literature. Mycoses, 2011. 54(5): p. e611-e614.

5.Galván, B. and F. Mariscal, Epidemiología de la candidemia en UCI. Revista iberoamericana de micología, 2006. 23(1): p. 12-15.

6.Fidan, I., et al., Immunomodulatory Effects of Voriconazole and Caspofungin on Human Peripheral Blood Mononuclear Cells Stimulated by Candida albicans and Candida krusei. The American journal of the medical sciences, 2014. 348(3): p. 219-223.

7.Zaki, A.M., et al., Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. New England Journal of Medicine, 2012. 367(19): p. 1814-1820.

8.Group, W.M.-C.R., State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans. PLoS currents, 2013. 5.

9.Assiri, A., et al., Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. The Lancet infectious diseases, 2013. 13(9): p. 752-761.

10.Vélez, L., et al., Diagnostic accuracy of bronchoalveolar lavage samples in immunosuppressed patients with suspected pneumonia: analysis of a protocol. Respiratory medicine, 2007. 101(10): p. 2160-2167.

11.Groselj-Grenc, M., et al., Neutrophil and monocyte CD64 indexes, lipopolysaccharide-binding protein, procalcitonin and C-reactive protein in sepsis of critically ill neonates and children. Intensive care medicine, 2009. 35(11): p. 1950-1958.

12.Christ-Crain, M., et al., Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet, 2004. 363(9409): p. 600-607.

Figure Legend

Fig. 1 Computerized tomography (CT) scan of the chest indicated unclear lung fields associated with diffuse pathological changes in both lungs, signs of severe pulmonary infection (A), pleural effusion and multiple lymphadenectasis in retrocaval and para-aortic arch area (B).

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