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Candidiasis

Updated : February 6, 2024





Background

Candidiasis is a fungal infection caused by Candida species naturally present in the human body. Candida auris, identified in 2009, is a notable species due to its capacity for severe infections and resistance to multiple antifungal drugs. It has spread globally in healthcare settings, posing challenges for detection and control. Its resistance complicates treatment, and strict infection control measures are essential. While Candida auris is a concern, other Candida species, like Candida albicans, can also cause infections, emphasizing the need for comprehensive prevention and control strategies.

Candidiasis is most commonly seen as a secondary infection in immunocompromised patients. Thrush is the common name for candidiasis of the mouth. It appears as white patches on the throat, tongue, and other mouth areas. Other symptoms of thrush include soreness and difficulty swallowing. They only become pathogenic when favorable conditions exist. It can affect the vagina, mouth, penis, and other body areas.

 

Epidemiology

Candidiasis, a fungal infection caused by various Candida species, is primarily attributed to Candida albicans. However, other species such as C. auris, C. tropicalis, C. glabrata, C. parapsilosis, and C. krusei are also recognized as causative agents. Of particular concern is Candida auris, an emerging multi-drug-resistant fungus spreading rapidly on a global scale, identified as a contributor to hospital-associated infections.

The incidence of candidiasis exhibits geographical and patient population variations. A comprehensive review in the Journal of Intensive Care delves into the global spread of C. auris, covering clinical and microbiological aspects, virulence mechanisms, antifungal resistance, and the effectiveness of control, preventive, and therapeutic strategies. Another review in Mycoses addresses the epidemiology of invasive candidiasis, discussing Candida species distribution worldwide, changing aetiology, and the emergence of antifungal resistance. The Centers for Disease Control and Prevention (CDC) offers statistics detailing the proportion of Candida species causing infections in the United States.

Candidiasis is prevalent in infancy and old age. Thrush affects approximately 37% of newborns in the United States. Oral candidiasis is common in children with a history of inhaled steroids. It is common in women during pregnancy. Thrush could be the first sign of HIV infection. Thrush is widespread and more common in undernourished populations and affects both men and women equally. Even though Candida albicans is the predominant cause of candidiasis, non-Candida species have risen in recent years.

It is critical to understand non-albicans species because treatment varies according to species. Fluconazole resistance may exist in Candida species other than Albicans. Invasive and disseminative candidiasis is becoming more common worldwide, and individuals with compromised immune systems are particularly vulnerable.

Anatomy

Pathophysiology

Candidiasis is a fungal infection caused by various Candida species. Candida auris is an emerging multidrug-resistant yeast, persisting on surfaces in healthcare settings and causing invasive infections with a high mortality rate. It adheres to medical devices, produces biofilms, and can lead to outbreaks. Candida albicans, a common cause of mucosal and systemic infections, switches between yeast and hyphal forms, invading tissues. Other Candida species share similar mechanisms. Immune response, risk factors (e.g., prolonged antibiotic use), and clinical manifestations vary.

Candida enters the bloodstream via three routes:

  • The most common is through the gastrointestinal tract mucosal barrier, followed by an intravascular catheter and a localized infection.
  • Candida can enter the bloodstream of both neutropenic and intensive care unit patients.
  • They are also a normal part of the gut microflora, and a person immunocompromised status can lead to bloodstream candidiasis.

Candida growth in indwelling catheters, particularly central lines, can occur at either the implantation site or the hub, leading to the subsequent Candida infection. Candida albicans typically colonize thrush in neonates during the passage via the infected vagina, with an active vaginal yeast infection, the neonate’s chances of developing thrush increase.

Management involves antifungal medications, with preventive measures crucial for reducing outbreaks, especially with drug-resistant species like Candida auris. The use of local or systemic antimicrobial therapy may precipitate vulvovaginal candidiasis, and it may also polymerize frequent episodes of disease. Bloodstream invasion from a localized infection is uncommon, but it is common with ascending Candida urinary tract infections associated with either innate obstruction or external compression.

Etiology

Candida albicans cause mucosal candidiasis when present in an immunocompromised host. Patients with leukemia or lymphoma who have been administered corticosteroids or cytotoxic drugs have deteriorated immunity, which leads to candidal infection. Antibiotic use is frequently linked to candidiasis.

Cancer cytotoxic chemotherapy can cause Candida albicans fungemia, which develops from fungal translocation via vulnerable mucosal barriers. Due to changes in intrinsic bacterial composition or population and the host environment, fungi in the upper and lower GI tract can develop opportunistic pathogens.

Pregnancy, diabetes mellitus, and oral contraceptives increase vaginal colonization. Oral candidiasis is strongly linked to HIV patients. Candida infection affects more than 90% of HIV patients.

Myxedema, tuberculosis, hypoparathyroidism, nutritional deficiency, Addison’s disease, smoking, IV tubes, poorly maintained dentures, catheters, heart valves, infancy, pregnancy, and old age are all risk factors for candidiasis. Because of the lack of protective antifungal proteins, histatin, and calprotectin, xerostomia is also a risk factor.

Candida auris is an emerging multidrug-resistant yeast species prevalent in healthcare settings, known for surface persistence and resistance to common disinfectants. Infections occur in individuals with underlying health conditions, recent surgeries, or weakened immune systems. Candida auris exhibits resistance to multiple antifungal drugs, making treatment challenging, and necessitating stringent infection control measures.

Other Candida species, like Candida glabrata, may also cause candidiasis with varying etiology, risk factors, and antifungal susceptibility. Management involves tailored antifungal therapy based on the specific Candida species, considering susceptibility. Addressing underlying risk factors and implementing infection control measures are essential, especially in healthcare settings, to prevent and manage candidiasis effectively.

Genetics

Prognostic Factors

Untreated Candida infections can spread to other organs and cause a systemic infection. The long-term prognosis of systemic candidiasis is determined by the severity and site of the Candida infection, the infected person’s overall health, and the timeframe of diagnosis and treatment.

Almost one-third of candidemia patients develop septic shock due to host factors such as age and source of infection rather than intrinsic virulence variables of organisms.

Clinical History

Physical Examination

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

The treatment paradigm for candidiasis involves antifungal medications and may vary based on the specific Candida species, the severity of infection, and patient factors.

Antifungal Medications:

  • Azoles (e.g., fluconazole, voriconazole): These are commonly employed for Candida albicans infections, with fluconazole often prescribed for mucosal and superficial infections.
  • Echinocandins (e.g., caspofungin, micafungin, anidulafungin): Widely used for invasive candidiasis, echinocandins demonstrate effectiveness against a diverse range of Candida species.
  • Polyenes (amphotericin B): This antifungal medication is suitable for severe or systemic infections. Lipid formulations of amphotericin B are often favored due to reduced toxicity.

For Candida albicans:

  • Localized or superficial infections: Topical antifungal agents such as clotrimazole, miconazole, or nystatin may be employed.
  • Recurrent or persistent infections: Extended courses of oral azoles might be considered in the treatment plan.

Candida auris-Specific Considerations:

  • Resistance to multiple antifungal drugs: Management involves a combination of antifungal medications and rigorous infection control measures.
  • Choice of antifungal agents: Susceptibility testing guides the selection, and in certain instances, higher doses or combination therapies may be contemplated.

Infection Control Measures:

  • Outbreak potential: Given Candida auris’s propensity to cause outbreaks in healthcare settings, strict infection control measures are indispensable. This includes meticulous hand hygiene, isolation of affected patients, and thorough cleaning and disinfection of the environment.

Management of Underlying Conditions:

  • Identification and addressing: Recognizing and managing underlying conditions or predisposing factors contributing to candidiasis development is crucial. This may involve interventions like immunosuppression management, diabetes control, or addressing other systemic health issues.

Follow-Up and Monitoring:

  • Regular assessment: Consistent monitoring of the patient’s response to treatment is vital. This involves clinical evaluations, laboratory tests, and, if necessary, imaging studies. Adjustments to the treatment plan may be made based on the patient’s progress.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Nonpharmacological treatment

Candidiasis, caused by Candida species, often involves Candida albicans, but multidrug-resistant Candida auris is a growing concern. Non-pharmacological measures complement antifungal medications:

Hygiene:

Emphasize personal hygiene, especially in healthcare settings.
Regular handwashing with soap and water is crucial to prevent infection spread.

Environmental Control:

Implement strict infection control in healthcare settings.
Thoroughly clean and disinfect surfaces and medical equipment to curb Candida transmission.

Proper Nutrition:

Support the immune system and overall health with a balanced diet to aid natural defenses against fungal infections.

Probiotics:

Consider probiotics to restore microbial balance, particularly in the gut where Candida overgrowth may occur.

Antifungal Diet:

Explore reducing sugar and refined carbs to discourage yeast overgrowth, although scientific evidence is inconclusive.

Avoiding Irritants:

For mucosal infections, such as oral or genital candidiasis, avoid irritants like douches or harsh soaps to promote healing.

Stress Management:

Manage chronic stress through techniques like meditation or exercise to bolster the immune system.

Alternative Therapies:

Exercise caution with alternative therapies like herbal supplements or essential oils, as their efficacy and safety are not well-established.

Medication

 

fluconazole 

Oesophageal candidiasis
200mg orally on day 1, then 100mg every day

Oropharyngeal candidiasis
200mg orally on day 1, then 100mg every day

Prophylaxis of candidiasis with bone marrow transplantation
400mg orally every day



fluconazole 

Indicated for candida UTI/peritonitis:

50-200mg orally every day



butoconazole 

5g of the cream (1 applicatorful of cream) administered intravaginally as a single dose
Extend the dose for 6 days only in the second and third trimesters of pregnancy (Not recommended in the first trimester)



micafungin 

Esophageal Candidiasis
150mg/day intravenous administration for 10 to 30 days

Candida Infections in HSCT Recipients Prophylaxis
50mg/day intravenous administration for 6 to 51 days

Treatment of acute disseminated candidiasis, candidemia, abscesses, and candida peritonitis
100mg/day intravenous administration for 10 to 47 days



flucytosine 

50-150 mg/kg orally each day divided every 6 hours
Take the dose with a plenty glass full of water
In the case of renal impairment, adjust the dose
If more than one capsule is taken, keep a gap of 15 minutes between each swallow to prevent vomiting and nausea



 

fluconazole 

Oropharyngeal candidiasis
6mg/kg orally on day 1, then 3mg/kg daily
Do not exceed 600mg/day

Oesophageal candidiasis
6mg/kg orally on day 1, then 3mg/kg daily
Do not exceed 600mg/day

Systemic candida infections
6-12mg/kg/day orally or intravenously. Do not exceed 600mg/day



micafungin 

Four months and older
Esophageal Candidiasis
>30 kgs: 2.5 mg/kg intravenous every day. Do not exceed 150mg/day
≤30 kgs: 3 mg/kg intravenous every day

Candida Infections in HSCT Recipients Prophylaxis
1 mg/kg intravenous every day. Do not exceed 50mg/day

Treatment of acute disseminated candidiasis, candidemia, abscesses, and candida peritonitis
2 mg/kg intravenous every day. Do not exceed 100mg/day

younger than four months old
4mg/kg intravenous everyday



flucytosine 

For children- 50-150 mg/kg orally each day divided every 6 hours
For neonates (less than 28 years old)- 80-160 mg/kg orally each day divided every 6 hours
In the case of renal impairment, adjust the dose



 

Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK560624/

Candidiasis

Updated : February 6, 2024




Candidiasis is a fungal infection caused by Candida species naturally present in the human body. Candida auris, identified in 2009, is a notable species due to its capacity for severe infections and resistance to multiple antifungal drugs. It has spread globally in healthcare settings, posing challenges for detection and control. Its resistance complicates treatment, and strict infection control measures are essential. While Candida auris is a concern, other Candida species, like Candida albicans, can also cause infections, emphasizing the need for comprehensive prevention and control strategies.

Candidiasis is most commonly seen as a secondary infection in immunocompromised patients. Thrush is the common name for candidiasis of the mouth. It appears as white patches on the throat, tongue, and other mouth areas. Other symptoms of thrush include soreness and difficulty swallowing. They only become pathogenic when favorable conditions exist. It can affect the vagina, mouth, penis, and other body areas.

 

Candidiasis, a fungal infection caused by various Candida species, is primarily attributed to Candida albicans. However, other species such as C. auris, C. tropicalis, C. glabrata, C. parapsilosis, and C. krusei are also recognized as causative agents. Of particular concern is Candida auris, an emerging multi-drug-resistant fungus spreading rapidly on a global scale, identified as a contributor to hospital-associated infections.

The incidence of candidiasis exhibits geographical and patient population variations. A comprehensive review in the Journal of Intensive Care delves into the global spread of C. auris, covering clinical and microbiological aspects, virulence mechanisms, antifungal resistance, and the effectiveness of control, preventive, and therapeutic strategies. Another review in Mycoses addresses the epidemiology of invasive candidiasis, discussing Candida species distribution worldwide, changing aetiology, and the emergence of antifungal resistance. The Centers for Disease Control and Prevention (CDC) offers statistics detailing the proportion of Candida species causing infections in the United States.

Candidiasis is prevalent in infancy and old age. Thrush affects approximately 37% of newborns in the United States. Oral candidiasis is common in children with a history of inhaled steroids. It is common in women during pregnancy. Thrush could be the first sign of HIV infection. Thrush is widespread and more common in undernourished populations and affects both men and women equally. Even though Candida albicans is the predominant cause of candidiasis, non-Candida species have risen in recent years.

It is critical to understand non-albicans species because treatment varies according to species. Fluconazole resistance may exist in Candida species other than Albicans. Invasive and disseminative candidiasis is becoming more common worldwide, and individuals with compromised immune systems are particularly vulnerable.

Candidiasis is a fungal infection caused by various Candida species. Candida auris is an emerging multidrug-resistant yeast, persisting on surfaces in healthcare settings and causing invasive infections with a high mortality rate. It adheres to medical devices, produces biofilms, and can lead to outbreaks. Candida albicans, a common cause of mucosal and systemic infections, switches between yeast and hyphal forms, invading tissues. Other Candida species share similar mechanisms. Immune response, risk factors (e.g., prolonged antibiotic use), and clinical manifestations vary.

Candida enters the bloodstream via three routes:

  • The most common is through the gastrointestinal tract mucosal barrier, followed by an intravascular catheter and a localized infection.
  • Candida can enter the bloodstream of both neutropenic and intensive care unit patients.
  • They are also a normal part of the gut microflora, and a person immunocompromised status can lead to bloodstream candidiasis.

Candida growth in indwelling catheters, particularly central lines, can occur at either the implantation site or the hub, leading to the subsequent Candida infection. Candida albicans typically colonize thrush in neonates during the passage via the infected vagina, with an active vaginal yeast infection, the neonate’s chances of developing thrush increase.

Management involves antifungal medications, with preventive measures crucial for reducing outbreaks, especially with drug-resistant species like Candida auris. The use of local or systemic antimicrobial therapy may precipitate vulvovaginal candidiasis, and it may also polymerize frequent episodes of disease. Bloodstream invasion from a localized infection is uncommon, but it is common with ascending Candida urinary tract infections associated with either innate obstruction or external compression.

Candida albicans cause mucosal candidiasis when present in an immunocompromised host. Patients with leukemia or lymphoma who have been administered corticosteroids or cytotoxic drugs have deteriorated immunity, which leads to candidal infection. Antibiotic use is frequently linked to candidiasis.

Cancer cytotoxic chemotherapy can cause Candida albicans fungemia, which develops from fungal translocation via vulnerable mucosal barriers. Due to changes in intrinsic bacterial composition or population and the host environment, fungi in the upper and lower GI tract can develop opportunistic pathogens.

Pregnancy, diabetes mellitus, and oral contraceptives increase vaginal colonization. Oral candidiasis is strongly linked to HIV patients. Candida infection affects more than 90% of HIV patients.

Myxedema, tuberculosis, hypoparathyroidism, nutritional deficiency, Addison’s disease, smoking, IV tubes, poorly maintained dentures, catheters, heart valves, infancy, pregnancy, and old age are all risk factors for candidiasis. Because of the lack of protective antifungal proteins, histatin, and calprotectin, xerostomia is also a risk factor.

Candida auris is an emerging multidrug-resistant yeast species prevalent in healthcare settings, known for surface persistence and resistance to common disinfectants. Infections occur in individuals with underlying health conditions, recent surgeries, or weakened immune systems. Candida auris exhibits resistance to multiple antifungal drugs, making treatment challenging, and necessitating stringent infection control measures.

Other Candida species, like Candida glabrata, may also cause candidiasis with varying etiology, risk factors, and antifungal susceptibility. Management involves tailored antifungal therapy based on the specific Candida species, considering susceptibility. Addressing underlying risk factors and implementing infection control measures are essential, especially in healthcare settings, to prevent and manage candidiasis effectively.

Untreated Candida infections can spread to other organs and cause a systemic infection. The long-term prognosis of systemic candidiasis is determined by the severity and site of the Candida infection, the infected person’s overall health, and the timeframe of diagnosis and treatment.

Almost one-third of candidemia patients develop septic shock due to host factors such as age and source of infection rather than intrinsic virulence variables of organisms.

The treatment paradigm for candidiasis involves antifungal medications and may vary based on the specific Candida species, the severity of infection, and patient factors.

Antifungal Medications:

  • Azoles (e.g., fluconazole, voriconazole): These are commonly employed for Candida albicans infections, with fluconazole often prescribed for mucosal and superficial infections.
  • Echinocandins (e.g., caspofungin, micafungin, anidulafungin): Widely used for invasive candidiasis, echinocandins demonstrate effectiveness against a diverse range of Candida species.
  • Polyenes (amphotericin B): This antifungal medication is suitable for severe or systemic infections. Lipid formulations of amphotericin B are often favored due to reduced toxicity.

For Candida albicans:

  • Localized or superficial infections: Topical antifungal agents such as clotrimazole, miconazole, or nystatin may be employed.
  • Recurrent or persistent infections: Extended courses of oral azoles might be considered in the treatment plan.

Candida auris-Specific Considerations:

  • Resistance to multiple antifungal drugs: Management involves a combination of antifungal medications and rigorous infection control measures.
  • Choice of antifungal agents: Susceptibility testing guides the selection, and in certain instances, higher doses or combination therapies may be contemplated.

Infection Control Measures:

  • Outbreak potential: Given Candida auris’s propensity to cause outbreaks in healthcare settings, strict infection control measures are indispensable. This includes meticulous hand hygiene, isolation of affected patients, and thorough cleaning and disinfection of the environment.

Management of Underlying Conditions:

  • Identification and addressing: Recognizing and managing underlying conditions or predisposing factors contributing to candidiasis development is crucial. This may involve interventions like immunosuppression management, diabetes control, or addressing other systemic health issues.

Follow-Up and Monitoring:

  • Regular assessment: Consistent monitoring of the patient’s response to treatment is vital. This involves clinical evaluations, laboratory tests, and, if necessary, imaging studies. Adjustments to the treatment plan may be made based on the patient’s progress.

Candidiasis, caused by Candida species, often involves Candida albicans, but multidrug-resistant Candida auris is a growing concern. Non-pharmacological measures complement antifungal medications:

Hygiene:

Emphasize personal hygiene, especially in healthcare settings.
Regular handwashing with soap and water is crucial to prevent infection spread.

Environmental Control:

Implement strict infection control in healthcare settings.
Thoroughly clean and disinfect surfaces and medical equipment to curb Candida transmission.

Proper Nutrition:

Support the immune system and overall health with a balanced diet to aid natural defenses against fungal infections.

Probiotics:

Consider probiotics to restore microbial balance, particularly in the gut where Candida overgrowth may occur.

Antifungal Diet:

Explore reducing sugar and refined carbs to discourage yeast overgrowth, although scientific evidence is inconclusive.

Avoiding Irritants:

For mucosal infections, such as oral or genital candidiasis, avoid irritants like douches or harsh soaps to promote healing.

Stress Management:

Manage chronic stress through techniques like meditation or exercise to bolster the immune system.

Alternative Therapies:

Exercise caution with alternative therapies like herbal supplements or essential oils, as their efficacy and safety are not well-established.

fluconazole 

Oesophageal candidiasis
200mg orally on day 1, then 100mg every day

Oropharyngeal candidiasis
200mg orally on day 1, then 100mg every day

Prophylaxis of candidiasis with bone marrow transplantation
400mg orally every day



fluconazole 

Indicated for candida UTI/peritonitis:

50-200mg orally every day



butoconazole 

5g of the cream (1 applicatorful of cream) administered intravaginally as a single dose
Extend the dose for 6 days only in the second and third trimesters of pregnancy (Not recommended in the first trimester)



micafungin 

Esophageal Candidiasis
150mg/day intravenous administration for 10 to 30 days

Candida Infections in HSCT Recipients Prophylaxis
50mg/day intravenous administration for 6 to 51 days

Treatment of acute disseminated candidiasis, candidemia, abscesses, and candida peritonitis
100mg/day intravenous administration for 10 to 47 days



flucytosine 

50-150 mg/kg orally each day divided every 6 hours
Take the dose with a plenty glass full of water
In the case of renal impairment, adjust the dose
If more than one capsule is taken, keep a gap of 15 minutes between each swallow to prevent vomiting and nausea



fluconazole 

Oropharyngeal candidiasis
6mg/kg orally on day 1, then 3mg/kg daily
Do not exceed 600mg/day

Oesophageal candidiasis
6mg/kg orally on day 1, then 3mg/kg daily
Do not exceed 600mg/day

Systemic candida infections
6-12mg/kg/day orally or intravenously. Do not exceed 600mg/day



micafungin 

Four months and older
Esophageal Candidiasis
>30 kgs: 2.5 mg/kg intravenous every day. Do not exceed 150mg/day
≤30 kgs: 3 mg/kg intravenous every day

Candida Infections in HSCT Recipients Prophylaxis
1 mg/kg intravenous every day. Do not exceed 50mg/day

Treatment of acute disseminated candidiasis, candidemia, abscesses, and candida peritonitis
2 mg/kg intravenous every day. Do not exceed 100mg/day

younger than four months old
4mg/kg intravenous everyday



flucytosine 

For children- 50-150 mg/kg orally each day divided every 6 hours
For neonates (less than 28 years old)- 80-160 mg/kg orally each day divided every 6 hours
In the case of renal impairment, adjust the dose



https://www.ncbi.nlm.nih.gov/books/NBK560624/