Candida krusei: Introduction, Morphology, Pathogenicity, Lab Diagnosis, Treatment, Prevention, and Keynotes

Introduction

Candida krusei is a species of yeast that belongs to the Candida genus. It is an opportunistic fungal pathogen known to cause infections in humans, particularly those with compromised immune systems or underlying medical conditions. C. krusei is an important member of the Candida species due to its unique characteristics and clinical significance.

Key features of Candida krusei include:

  1. Morphology: C. krusei is a unicellular, eukaryotic microorganism, belonging to the kingdom Fungi. Under the microscope, it appears as oval-shaped yeast cells that reproduce through budding.
  2. Opportunistic Pathogen: C. krusei is considered an opportunistic pathogen, meaning it usually does not cause disease in healthy individuals but can become pathogenic and cause infections under certain conditions. It primarily affects individuals with weakened immune systems, such as those undergoing chemotherapy, organ transplantation, or HIV/AIDS patients.
  3. Infections: It is commonly associated with various infections, including bloodstream infections (candidemia), urinary tract infections (UTIs), and infections of the mouth and throat (oral candidiasis or thrush).
  4. Drug Resistance: One notable characteristic of Candida krusei is its intrinsic resistance to fluconazole, a commonly used antifungal medication. This resistance sets it apart from other Candida species and can complicate treatment options for infections caused by this pathogen.
  5. Diagnosis: Diagnosing C. krusei infections involves isolating and identifying the yeast from clinical specimens, such as blood, urine, or tissue samples. Various laboratory techniques, including culture and molecular methods, are used for accurate identification.
  6. Management: Due to its resistance to fluconazole and some other antifungal drugs, the treatment of C. krusei infections can be challenging. In such cases, alternative antifungal agents like echinocandins or amphotericin B may be used.

Morphology

Candida krusei is a unicellular eukaryotic microorganism, belonging to the kingdom Fungi. As with other yeast species, its morphology is characterized by its unicellular, budding growth form. Here are the key aspects of the morphology of Candida krusei:

Various Candida species growth on SDA plate (Candia albicans-55 and 58, Candida kruse-64 and Candida tropicalis-74 growth on SDA)
Fig. Various Candida species growth on SDA plate (Candia albicans-55 and 58, Candida krusei-64 and Candida tropicalis-74 growth on SDA)
  1. Cell Shape: The yeast cells of C. krusei are typically oval-shaped or ellipsoidal. These cells can vary in size, with dimensions ranging from approximately 3 to 6 micrometers in diameter.
  2. Budding: It reproduces asexually through a process called budding. During budding, a smaller daughter cell forms as an outgrowth from the larger mother cell. As the daughter cell grows in size, it eventually separates from the mother cell, becoming an independent yeast cell.
  3. Pseudohyphae Formation: In addition to budding, C. krusei can also form pseudohyphae. Pseudohyphae are chain-like structures that consist of elongated yeast cells connected end-to-end. Unlike true hyphae found in filamentous fungi, pseudohyphae lack a septum (cross-wall) between the cells.
  4. Gram Stain: On a Gram stain, C. krusei and other yeast cells typically appear as Gram-positive structures. This means that they retain the crystal violet stain and appear purple under the microscope.
  5. Colony Characteristics: On solid culture media like Sabouraud agar, Candida krusei forms smooth, creamy-white to light pink colonies. The appearance of the colonies can vary depending on the specific growth conditions and the composition of the culture medium.

Pathogenicity

The pathogenicity of Candida krusei lies in its ability to cause opportunistic infections in humans, particularly in individuals with compromised immune systems or underlying medical conditions. While C. krusei is considered less common compared to other Candida species, its clinical significance arises from several factors:

  1. Opportunistic Pathogen: C. krusei is an opportunistic fungal pathogen. This means that it typically does not cause disease in healthy individuals with intact immune systems. However, when the host’s immune defenses are weakened or compromised, C. krusei can exploit the opportunity to cause infection.
  2. Infections: It is associated with a range of infections, with the most common being bloodstream infections (candidemia). Candidemia is a severe and potentially life-threatening condition where the yeast enters the bloodstream and disseminates throughout the body. Other infections caused by Candida krusei include urinary tract infections (UTIs) and infections of the mouth and throat (oral candidiasis or thrush).
  3. Drug Resistance: One of the significant challenges in treating C. krusei infections is its intrinsic resistance to certain antifungal medications, particularly fluconazole. Fluconazole is a commonly used azole antifungal drug that is effective against many Candida species, but Candida krusei tends to be inherently resistant to it. This can limit the available treatment options and complicate the management of infections caused by this pathogen.
  4. Immune Evasion: C. krusei, like other Candida species, can evade the host’s immune response through various mechanisms, allowing it to persist and cause infection. It can produce factors that inhibit the host’s immune cells, making it difficult for the body to clear the infection.
  5. Biofilm Formation: It can form biofilms, which are complex communities of yeast cells embedded in a protective extracellular matrix. Biofilms provide the yeast with increased resistance to antifungal drugs and make infections more challenging to treat.
  6. Association with Underlying Conditions: Its infections are often seen in patients with specific risk factors, such as those undergoing chemotherapy, organ transplantation, or with HIV/AIDS. Additionally, long-term use of broad-spectrum antibiotics and indwelling medical devices (e.g., catheters) can predispose individuals to Candida krusei infections.

Lab Diagnosis

The laboratory diagnosis of C. krusei involves the identification and isolation of the yeast from clinical specimens. Accurate identification is crucial as it helps determine the appropriate antifungal therapy and patient management. Here are the common methods used for the lab diagnosis of C. krusei:

  • Microscopic Examination: A direct microscopic examination of clinical samples, such as blood, urine, or other body fluids, can reveal the presence of yeast cells. Gram staining or specialized stains like potassium hydroxide (KOH) preparations can help visualize the yeast’s characteristic budding and cellular morphology. However, microscopic examination alone cannot differentiate Candida species.
  • Culture: Culturing clinical specimens on appropriate growth media is the primary method for isolating and identifying Candida species. Sabouraud agar is a common medium used to support the growth of yeast and fungi. Clinical samples, such as blood, urine, or tissue, can be streaked onto the agar plates and then incubated at appropriate temperatures (usually around 25-30°C) for several days to allow the yeast to grow.
Colony morphology of Candida krusei on SDA plate
Fig. Colony morphology of Candida krusei on SDA plate
  • Colonial Characteristics: After incubation, C. krusei colonies on Sabouraud agar typically appear as smooth, creamy-white to light pink colonies. However, colony appearance alone cannot be used to definitively identify Candida krusei since other Candida species can have similar colony characteristics.
  • Chromogenic Agar: Some laboratories use chromogenic agar, which contains specific chromogenic substrates that react with enzymes produced by Candida species. These substrates can produce different colors for different Candida species, aiding in their identification. However, this method may not always be sufficient to differentiate C. krusei from other closely related species.
  • Biochemical Tests: Various biochemical tests can be used to identify Candida species. Commonly used tests include carbohydrate assimilation tests and enzyme activity assays. For example, Candida krusei can be distinguished from other Candida species by its inability to assimilate trehalose.
Yeast cells of Candida krusei in saline wet mount of culture microscopy
Fig. Yeast cells of Candida krusei in saline wet mount of culture microscopy
  • Molecular Identification: Polymerase chain reaction (PCR) and other molecular techniques can provide more accurate and rapid identification of Candida species, including C. krusei. Specific primers can target unique DNA sequences characteristic of Candida krusei for its detection. This method is especially helpful when rapid identification is essential for guiding timely treatment decisions.
  • Antifungal Susceptibility Testing: Since C. krusei is known for its resistance to fluconazole and some other antifungal drugs, antifungal susceptibility testing is crucial. This testing helps determine the most appropriate antifungal agents for treatment.
Gram positive Yeast cells of Candida krusei in Gram staining
Fig. Gram positive Yeast cells of Candida krusei in Gram staining

Treatment

The treatment of Candida krusei infections can be challenging due to its intrinsic resistance to fluconazole and other azole antifungal medications. However, several alternative antifungal agents are effective against C. krusei. The choice of treatment depends on the type and severity of the infection, as well as the patient’s overall health condition. Here are the main treatment options for Candida krusei infections:

  1. Echinocandins: Echinocandins are a class of antifungal drugs that are generally considered the first-line treatment for invasive Candida infections, including C. krusei. Examples of echinocandins include caspofungin, micafungin, and anidulafungin. These drugs work by inhibiting the synthesis of the fungal cell wall, leading to the death of the Candida cells. Echinocandins have demonstrated good efficacy against Candida krusei and are considered the preferred treatment option in most cases.
  2. Amphotericin B: Amphotericin B is a polyene antifungal drug that can be effective against C. krusei infections. It works by binding to the fungal cell membrane, causing leakage of intracellular contents and ultimately leading to cell death. Amphotericin B is often used in cases of severe or refractory infections when echinocandins are not available or feasible. However, it can have significant side effects and requires careful monitoring.
  3. Combination Therapy: In some difficult-to-treat cases, combination antifungal therapy may be considered. This involves using two or more antifungal agents with different mechanisms of action to enhance treatment efficacy. However, combination therapy is generally reserved for specific scenarios, and its use should be guided by a specialist.
  4. Other Antifungal Agents: Some newer antifungal drugs, such as isavuconazole and posaconazole, have shown activity against Candida krusei in laboratory studies and may be considered in certain situations. However, the clinical experience with these drugs in treating C. krusei infections is relatively limited compared to echinocandins and amphotericin B.
Antifungal Susceptibility Testing (AFST) of Candida krusei  test result demonstration
Fig. Antifungal Susceptibility Testing (AFST) of Candida krusei test result demonstration

It’s important to note that the choice of antifungal therapy should be based on the results of antifungal susceptibility testing, when available, to ensure that the selected drug is active against the specific Candida krusei isolate causing the infection.

Additionally, managing Candida krusei infections requires attention to underlying predisposing factors, such as immune status, use of immunosuppressive medications, and the presence of indwelling medical devices like catheters. Addressing these factors can help improve the overall outcome of the treatment.

Prevention

Preventing Candida krusei infections involves various strategies that aim to reduce the risk of exposure and transmission of the yeast. Since C. krusei is an opportunistic pathogen that mainly affects individuals with weakened immune systems or specific risk factors, preventive measures focus on minimizing these vulnerabilities. Here are some key preventive measures:

  1. Hand Hygiene: Practicing good hand hygiene is crucial in preventing the spread of C. krusei and other pathogens. Regularly washing hands with soap and water or using alcohol-based hand sanitizers can help reduce the risk of infection.
  2. Infection Control in Healthcare Settings: In healthcare facilities, strict infection control measures should be followed to prevent healthcare-associated Candida krusei infections. This includes proper cleaning and disinfection of medical equipment, adherence to contact precautions for patients with suspected or confirmed Candida infections, and appropriate use and management of catheters and other invasive devices.
  3. Antifungal Prophylaxis: In certain high-risk patients, such as those undergoing stem cell transplantation or receiving intensive chemotherapy, antifungal prophylaxis with specific antifungal medications may be considered to prevent fungal infections, including those caused by Candida species.
  4. Optimizing Immune Function: Maintaining a healthy immune system is essential in preventing Candida krusei infections. This involves managing underlying medical conditions effectively, promoting a balanced diet, regular exercise, and minimizing stress.
  5. Antibiotic Stewardship: Antibiotics can disrupt the normal microbial balance in the body and increase the risk of fungal infections. Therefore, judicious and appropriate use of antibiotics is crucial in preventing Candida krusei infections.
  6. Early Detection and Treatment of Candidiasis: Prompt diagnosis and treatment of Candida infections can prevent the progression of the disease and reduce the risk of complications. Timely initiation of appropriate antifungal therapy is essential for improving patient outcomes.
  7. Education and Awareness: Healthcare professionals and patients should be educated about the risk factors for C. krusei infections and the importance of preventive measures. Awareness campaigns can help in identifying and managing these infections more effectively.

Keynotes

Here are some keynotes on Candida krusei:

  1. C. krusei is a species of yeast and an opportunistic fungal pathogen that can cause infections in humans, especially in individuals with compromised immune systems or underlying medical conditions.
  2. Morphologically, it appears as oval-shaped or ellipsoidal yeast cells that reproduce through budding. It can also form pseudohyphae, which are chain-like structures of elongated yeast cells.
  3. It is intrinsically resistant to fluconazole and some other azole antifungal drugs, making it challenging to treat.
  4. The most common infection caused by C. krusei is candidemia, which is a bloodstream infection. It can also cause urinary tract infections (UTIs) and oral candidiasis (thrush).
  5. The diagnosis of C. krusei involves isolating and identifying the yeast from clinical specimens, often through culture, biochemical tests, and molecular methods.
  6. Echinocandins, such as caspofungin and micafungin, are considered the first-line treatment for Candida krusei infections due to their efficacy against this species.
  7. Amphotericin B is another antifungal agent used to treat C. krusei infections, especially in cases of severe or refractory infections.
  8. Preventive measures for C. krusei infections include practicing good hand hygiene, infection control in healthcare settings, optimizing immune function, and judicious use of antibiotics.
  9. Candida krusei infections can be associated with specific risk factors, such as immunosuppression, long-term antibiotic use, and the presence of indwelling medical devices.
  10. Early detection, appropriate treatment, and management of underlying conditions are essential for improving patient outcomes and reducing the impact of C. krusei infections.

Further Readings

  1. Title: Candida krusei – epidemiology, resistance mechanisms, and virulence Authors: Silva AP, Miranda IM, Lisboa C, Pina-Vaz C, Rodrigues AG Journal: Journal of Medical Microbiology Year: 2009 Link: https://jmm.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.000633
  2. Title: Candida krusei: an unusual cause of urinary tract infection Authors: Shah AD, Shrikhande SN, Shrikhande P Journal: The Journal of the Association of Physicians of India Year: 2014 Link: https://pubmed.ncbi.nlm.nih.gov/25590339/
  3. Title: Species identification and strain differentiation of Candida krusei using molecular techniques Authors: Farahyar S, Ghebremedhin B, Vazquez JA, Khan ZU Journal: Journal of Medical Microbiology Year: 2016 Link: https://jmm.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.000260
  4. Title: Intrinsic fluconazole resistance in Candida krusei: the role of the ERG11 gene Authors: Perea S, López-Ribot JL, Wickes BL, Kirkpatrick WR, Dib OP, Bachmann SP, Keller SM, Martinez M, Patterson TF Journal: Antimicrobial Agents and Chemotherapy Year: 2002 Link: https://aac.asm.org/content/46/11/3596.short
  5. Title: Candida krusei bloodstream infection: epidemiology and risk factors influencing mortality Authors: Luzzati R, Cavinato S, Giangreco M, Granà G, Deiana ML, Malaventura C, Vento S, Parise F, Concia E, Mussap M Journal: Infection Year: 2011 Link: https://link.springer.com/article/10.1007/s15010-011-0155-6
  6. Title: Treatment of Candida infections: present and future Authors: Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, Reboli AC, Schuster MG, Vazquez JA, Walsh TJ, Zaoutis TE Journal: Journal of Clinical Microbiology Year: 2016 Link: https://jcm.asm.org/content/54/5/1113.short

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