Fungemia Candidiasis


Article Author:
Andres Mora Carpio


Article Editor:
Antonette Climaco


Editors In Chief:
Venkat Minnaganti
John Brusch
Janak Koirala


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
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Saad Nazir
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Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
6/3/2019 3:06:53 PM

Introduction

Candidemia is defined as the presence of Candida species in the blood. It is the most common fungal bloodstream infection in hospitalized patients[1]. Mortality is very high. It reaches almost 50% in some studies[2]. Although Candida albicans is still the most common Candida species causing candidemia, in recent years there has been an increase in nonalbicans Candida species, which may represent a therapeutic challenge given the different antibiotic susceptibility profile of different Candida species[1]. This new trend is likely caused by the process of natural selection of resistant species to the most common antifungals used.

Etiology

Candida albicans is the most common cause of candidemia, representing 35% to 60% of isolates. Candida parapsilosisCandida tropicalisCandida glabrata and Candida krusei, are the most common nonalbicans Candida species identified in cultures[3][4][5]. C. glabrata and C. krusei are frequently resistant to the azole antifungals.[6]

C. albicans, C. tropicalis, and C. glabrata are the more virulent species, and infections with them represent a higher risk of mortality.

Epidemiology

Candidemia is the most common fungal bloodstream infection, and possibly the fourth most common all-type bloodstream infection seen in the intensive care unit setting[1].

The incidence of Candida bloodstream infection is bimodal, with the elderly and very young having the highest risk of any population for suffering from this disease[1].

Most common risk factors include critical illness and prolonged intensive care unit stay. The presence of a central venous catheter, antibiotic exposure, abdominal surgery (especially if repeated laparotomies or anastomotic leakage is present), malignancy (solid organ and hematologic), acute necrotizing pancreatitis, organ transplant recipients, and total parenteral nutrition are other major risk factors.[3][4][7]

Pathophysiology

Candida species are part of the normal gastrointestinal microbiome. The most common mechanism causing Candida bloodstream infection is thought to be by translocation through the intestinal mucosa after some insult. This is the reason that abdominal surgeries, anastomotic leakage, antibiotic exposure, and pancreatitis increase the risk of infection. Access via an intravenous catheter, especially in patients with central venous lines, is also a common mechanism of infection. This is especially true in the case of patients receiving total parenteral nutrition (TPN) as lipid emulsions have been shown to increase Candida biofilm production and morphology, possibly increasing its virulence. It is also hypothesized that recipients of TPN have altered the gut function to Candida, making it easier for translocation to occur.[8][9]

Another less frequent mechanism of infection is the direct introduction of Candida from a sterile site, such as in ascending renal candidiasis. Although candidemia is the most common manifestation of invasive candidiasis, culture-negative deep-tissue infection after hematogenous seeding can occur[1]. It is likely that some genetic factors are linked to susceptibility for developing candidemia. This is currently an avid area of research.

History and Physical

Clinical manifestations of candidemia are nonspecific. It presents like any other bloodstream infection with a clinical spectrum that goes from chills, shivering, and fever to severe sepsis and septic shock with signs of end-organ damage. Physical findings can vary from a normal exam to findings specific to localized deep-seated tissue infections, for example, endophthalmitis skin lesions, candiduria, and central nervous system findings.[10]

Evaluation

The gold standard for diagnosis of candidemia is based on direct fungal detection in blood cultures. The advantage of cultures is the ability to do susceptibility testing. However, sensitivity is low, reaching only 21% to 71% in some studies. Cultures have the further disadvantage of taking a long time to grow and being negative in cases where candidemia has subsided but has caused a persistent deep-seated tissue infection without bloodstream infection.

  • In patients with localized findings, a biopsy should be done and sent for culture and gram staining.
  • Other markers of infection like Candida mannan antigen and anti-mannan antibodies and B-d-glucan have the advantage of resulting faster but can have a high false-positive rate.[11]
  • New polymerase chain reaction tests are being developed and evaluated in clinical trials. They show promising results. Currently available is the T2Candida test.
  • When evaluating a patient with suspicion for invasive candidiasis, consideration should be made to order blood both cultures and one non-culture method like B-d-glucan.[12]

Treatment / Management

Early empiric antifungal therapy should be strongly considered in critically ill patients with risk factors for invasive candidiasis in whom the disease is suspected, as some studies have shown reduced mortality with this strategy. The decision to start therapy should be based on clinical suspicion, risk factors, and surrogate markers of candidemia (e.g., B-d-glucan). Empiric therapy should start with an echinocandin (caspofungin, micafungin, anidulafungin) as first choice therapy. Fluconazole may be considered in certain patients who are not critically ill and in whom susceptibility to fluconazole is likely. Amphotericin B can be given to patients with intolerance or contraindications to other treatments.[12]

When blood cultures have confirmed candidemia, treatment with an echinocandin and central venous catheter removal should be the first step to take[2][12][1]. Transition to fluconazole is recommended for stable patients in whom cultures have resulted in sensitive Candida species, such as C. albicans. Repeated blood cultures should show clearance of the bloodstream infection. Amphotericin B is given in the case of azole- and echinocandin-resistant fungi.

Initial treatment with an azole should be considered in a patient with concomitant meningitis, endophthalmitis, urinary tract infections (due to low penetrance of echinocandins to this areas), as well as in patients with prior exposure to echinocandins.[12]

Recommended duration of therapy is at least two weeks after documented clearance of the infection and longer (i.e., four weeks) for complicated infections, such as endophthalmitis, endocarditis or osteomyelitis.[12][1]

Some species of Candida have particular susceptibility profiles. For example, C. parapsilosis is less susceptible to echinocandins. This should be taken into consideration when starting therapy and when titrating to culture results. Emergent resistance to different antifungals is more commonly caused by selection of species with intrinsic resistance when using certain drugs as opposed to developing resistance in a previously susceptible isolate (although this too has been reported).

Pearls and Other Issues

There is no role for routine prophylaxis for candidemia. Prophylaxis should be considered in the ICU for selected patients at high risk of candidemia as in those individuals with recurrent gastrointestinal perforations, anastomotic leakage, and small bowel or pancreas transplant. Prophylaxis, when indicated, is done with fluconazole.

All patients with candidemia should undergo an ophthalmologic evaluation to rule out endophthalmitis.

Enhancing Healthcare Team Outcomes

Candidemia is a life threatening infection with very high mortality. The infection is best managed by a multidisciplinary team that includes an infectious disease expert, intensivist, microbiologist, laboratory specialist and an internist. These patients should be monitored by ICU nurses. The key is to reverse the state of immunosuppression. Most patients have involvement of multiple organs and the prognosis is poor, despite optimal treatment.[13][14]


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Fungemia Candidiasis - Questions

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A 25-year-old man with no significant past medical history was hospitalized after a gun shot wound to the abdomen. He had a complicated postoperative course requiring multiple re-interventions for anastomotic leakage. After 8 days in the intensive care unit, the patient started to develop fever. Urinalysis and chest x-ray show no clear focus of infection. Which of the following is the best initial test to perform?



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A 17-year-old female with no significant past medical history was hospitalized after a gunshot wound to the abdomen. She had a complicated postoperative course requiring multiple re-interventions for anastomotic leakage. She is receiving total parenteral nutrition via a central venous catheter and is on broad-spectrum antibiotics for the bowel perforation. After 8 days in the intensive care unit, the patient became febrile and hypotensive. Urinalysis and chest x-ray show no clear focus of infection. Blood cultures are pending. Beta-d-glucan is positive for candida of unknown species. What is the best initial therapy?



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2 days after obtaining cultures from a blood specimen from an ICU patient, the lab calls saying that cultures are growing yeast consistent with Candida. What is the most likely candida species growing in the cultures?



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72 year old male in the ICU for respiratory failure is receiving total parenteral nutrition (TPN) has been developing fever and signs of sepsis. This patient has multiple risk factors for fungemia including age, ICU stay, central venous catheter, and recipient of TPN. Apart from the regular studies for sepsis as urinalysis, chest x-ray, blood and urine cultures, which other tests will help you identify the presence of candidemia?



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39 year old male with history of alcoholism and poorly controlled asthma on high dose inhaled corticosteroids comes to emergency department complaining of 72 hours of severe abdominal pain nausea and vomiting. Exam showed right lower quadrant rebound. The patient was taken emergently to the operating room where a severely infected and ruptured appendix was resected. The postoperative course was complicated with multiple re-operations. On day 17 of his admission patient developed fever and cultures grew Candida albicans. Which of the following factors most predisposes the patient to develop candidemia?



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A 72-year-old male in the intensive care unit (ICU) for respiratory failure is receiving total parenteral nutrition (TPN) and has signs of sepsis. He has multiple risk factors for fungemia including age, ICU stay, central venous catheter, and TPN. Cultures are positive for Candida and treatment is started with caspofungin. The central line is removed and he responds well to the caspofungin. What other intervention should be considered?



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Fungemia Candidiasis - References

References

Epidemiology and Microbiologic Characterization of Nosocomial Candidemia from a Brazilian National Surveillance Program., Doi AM,Pignatari AC,Edmond MB,Marra AR,Camargo LF,Siqueira RA,da Mota VP,Colombo AL,, PloS one, 2016     [PubMed]
Invasive Candidiasis., Kullberg BJ,Arendrup MC,, The New England journal of medicine, 2015 Oct 8     [PubMed]
Epidemiology, risk factor, species distribution, antifungal resistance and outcome of Candidemia at a single French hospital: a 7-year study., Tadec L,Talarmin JP,Gastinne T,Bretonnière C,Miegeville M,Le Pape P,Morio F,, Mycoses, 2016 May     [PubMed]
Significance of yeasts in bloodstream infection: Epidemiology and predisposing factors of Candidaemia in adult patients at a university hospital (2010-2014)., Pongrácz J,Juhász E,Iván M,Kristóf K,, Acta microbiologica et immunologica Hungarica, 2015 Sep     [PubMed]
Epidemiology of invasive candidiasis in a surgical intensive care unit: an observational study., Aguilar G,Delgado C,Corrales I,Izquierdo A,Gracia E,Moreno T,Romero E,Ferrando C,Carbonell JA,Borrás R,Navarro D,Belda FJ,, BMC research notes, 2015 Sep 29     [PubMed]
Nosocomial Bloodstream Infection Due to Candida spp. in China: Species Distribution, Clinical Features, and Outcomes., Li Y,Du M,Chen LA,Liu Y,Liang Z,, Mycopathologia, 2016 Mar 19     [PubMed]
[Analysis of clinical characteristics in 122 adult patients with candidemia]., Zhan L,Huang L,Qu J,Zhong C,Lü X,, Zhonghua yi xue za zhi, 2015 Sep 1     [PubMed]
Specificity of mannan antigen and anti-mannan antibody screening in patients with haematological malignancies at risk for fungal infection., Duettmann W,Koidl C,Krause R,Lackner G,Woelfler A,Hoenigl M,, Mycoses, 2016 Jun     [PubMed]
Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America., Pappas PG,Kauffman CA,Andes DR,Clancy CJ,Marr KA,Ostrosky-Zeichner L,Reboli AC,Schuster MG,Vazquez JA,Walsh TJ,Zaoutis TE,Sobel JD,, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2016 Feb 15     [PubMed]
Candida sepsis during total parenteral nutrition: An endogenous infection indicating the severity of patients' disease state., Carmon M,Rimon B,Freund HR,, Clinical nutrition (Edinburgh, Scotland), 1992 Aug     [PubMed]
Altered gut barrier function to Candida during parenteral nutrition., Pappo I,Polacheck I,Zmora O,Feigin E,Freund HR,, Nutrition (Burbank, Los Angeles County, Calif.), 1994 Mar-Apr     [PubMed]
Parenteral lipid emulsion induces germination of Candida albicans and increases biofilm formation on medical catheter surfaces., Swindell K,Lattif AA,Chandra J,Mukherjee PK,Ghannoum MA,, The Journal of infectious diseases, 2009 Aug 1     [PubMed]
Dudoignon E,Alanio A,Anstey J,Depret F,Coutrot M,Fratani A,Jully M,Cupaciu A,Chaussard M,Oueslati H,Ferry A,Benyamina M,de Tymowski C,Boccara D,Serror K,Chaouat M,Mimoun M,Lafaurie M,Denis B,Gits-Muselli M,Bretagne S,Mebazaa A,Legrand M,Soussi S, Outcome and potentially modifiable risk factors for candidemia in critically ill burns patients: A matched cohort study. Mycoses. 2019 Mar;     [PubMed]
Jia X,Li C,Cao J,Wu X,Zhang L, Clinical characteristics and predictors of mortality in patients with candidemia: a six-year retrospective study. European journal of clinical microbiology     [PubMed]

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