Candida parapsilosis: Symptoms, Diagnosis, and Effective Antifungal Treatments

Table of Contents

• What is Candida parapsilosis?
• Habitat
• Morphology
• Cultural characteristics
• Pathogenesis
• Virulence factors
• Clinical Features
• Lab Diagnosis
• Treatment
• Prevention and control
• References

What is Candida parapsilosis?

Candida parapsilosis, a pathogenic yeast species, has recently gained recognition as an emerging pathogen responsible for invasive candidal diseases. 

• Initially discovered in Puerto Rico by Ashford in 1928, Candida parapsilosis was isolated from diarrheal stool samples and later identified as a causative agent of sepsis in intravenous drug users.
• Originally named Monilia parapsilosis, it was subsequently renamed Candida parapsilosis.
• This yeast strain is notable for causing sepsis, wound infections, and tissue infections, particularly in immunocompromised patients such as neonates and those in intensive care units.
• Candida parapsilosis is often associated with infections related to artificial feeding solutions, prosthetic devices, and indwelling medical devices. Transmission can occur through contact between healthcare workers and hospitalized patients via contaminated hands.
• Its virulence is attributed to factors like the secretion of hydrolytic enzymes, the presence of adhesins, and the formation of biofilms.

Habitat of Candida parapsilosis

• Candida parapsilosis typically resides as a commensal organism on the human skin, and its potential to cause disease is typically limited when the skin is intact.
• C. parapsilosis possesses the capability to thrive in total parenteral nutrition (a method of directly feeding patients) and form biofilms on catheters and other implanted medical devices. This facilitates its spread within healthcare settings through hand transmission and its persistence in hospital environments.
• The proliferation of C. parapsilosis is not limited to human hosts; it can also thrive in various non-human environments such as animals, insects, soil, and marine settings.
• Additionally, this microorganism is considered a part of the normal microbial flora in humans and can be found in the gastrointestinal and respiratory tracts, as well as on the skin, including the hands.

Morphology of Candida parapsilosis

• Candida parapsilosis cells exhibit various shapes, including oval, round, or cylindrical.
• These cells can assume multiple morphological forms.
• C. parapsilosis lacks the ability to form true hyphae and primarily exists in either a yeast phase or a pseudohyphal form.
• The transformation between yeast and pseudohyphal forms has been associated with the production of specific amino acids, such as citrulline, which contribute to changes in cellular and colony morphology.
• When grown on suitable media, yeast colonies appear smooth, whereas pseudohyphal colonies exhibit a wrinkled or concentric appearance.

Cultural characteristics of Candida parapsilosis

• On Sabouraud dextrose agar, Candida parapsilosis typically forms colonies that are white, creamy, and exhibit a shiny surface, with variations in texture, appearing either smooth or wrinkled.
• Cornmeal agar is employed as a diagnostic tool to detect pseudohyphae in Candida parapsilosis.
• Candida parapsilosis colonies appear pink in color when grown on Hicrome agar.

Pathogenesis of Candida parapsilosis

• Candida parapsilosis displays its adaptability by existing in either a yeast or pseudohyphal form, allowing it to thrive in diverse environments.
• Moreover, C. parapsilosis exhibits robust growth in environments rich in glucose, making it particularly well-suited for rapid proliferation in parenteral nutrition or hyperalimentation solutions administered to patients, as these solutions typically have high glucose concentrations.
• These characteristics significantly contribute to the fungus's potential for risk, transmission, and virulence when causing diseases in the human host.

Risk factors of Candida parapsilosis infections

• Individuals with compromised immune systems, notably those with HIV/AIDS.
• Patients who have undergone gastrointestinal surgery.
• Those who require extended periods of central venous catheter or indwelling device usage, such as cancer patients.
• Neonates who receive hyperalimentation solutions for nourishment.
• Recipients of organ transplants.
• Individuals diagnosed with diabetes.
• Patients undergoing surgical procedures.

Transmission of Candida parapsilosis

Candida parapsilosis, a yeast fungus responsible for invasive fungal infections, is primarily transmitted within healthcare settings through various routes, including:

• Medical devices that have become contaminated.
• Fluids, specifically hyperalimentation solutions, that have been contaminated.
• The hands of healthcare workers carrying the fungus.
• Prosthetic devices.
• Catheters that are used invasively.

Virulence factors of Candida parapsilosis

Adherence

• This fungus has the ability to attach itself to implanted medical devices, leading to the creation of a biofilm that facilitates harm to host cells.
• The fungus possesses a hydrophobic quality that aids in its adhesion to device surfaces and the development of a slimy substance that adheres to plastic catheters.

Biofilm formation

• A biofilm refers to a community of microorganisms that develop on surfaces, typically characterized by an extracellular matrix. It represents a mode of microbial growth on these surfaces.
• Candida parapsilosis, in particular, generates biofilms composed of pseudohyphal filaments that firmly attach to the surfaces of medical devices.
• During the process of biofilm formation, these fungi can undergo morphological changes, facilitating their growth and proliferation on medical devices.
• Biofilm development can also occur on skin or membrane surfaces, and when medical devices are inserted, the fungi gain entry through these routes.
• Furthermore, biofilms can establish themselves on bodily tissues, thereby enhancing the spread of disease.
• Importantly, biofilm formation plays a role in the fungi's resistance to antifungal treatments.

Secretion of hydrolytic enzymes

• Candida parapsilosis is known to secrete hydrolytic enzymes such as aspartic proteinases (Saps), phospholipases, and lipases. 
• These enzymatic substances have been associated with the pathogenicity of the fungus.

Clinical Features of Candida parapsilosis

Fungemia

• This is candidemia, a condition resulting from the invasion of Candida parapsilosis into the bloodstream.
• It primarily impacts individuals who are hospitalized, particularly those who have undergone surgeries, especially gastrointestinal procedures, which can create openings through which the normally harmless Candida enters the bloodstream.
• Candidemia also poses a threat to patients with underlying medical conditions like cancer, those who have received organ transplants, and individuals with diabetes.
• Additionally, it is a prevalent cause of candidemia in neonates, patients with intravenous lines or vascular catheters, especially those with a history of prior antifungal treatment, and individuals receiving parenteral nutrition.
• Candida parapsilosis is responsible for approximately 19% of all cases of candidemia.
• This infection is typically characterized by symptoms such as fever, septic shock, and kidney dysfunction.

Fungal endocarditis

• Candida parapsilosis is responsible for 17% of fungal endocarditis cases among patients who have undergone heart surgery.
• Common predisposing factors for Candida spp. infections include the use of transesophageal ultrasound and increased reliance on medical therapies.
• Candida parapsilosis-specific risk factors encompass prosthetic heart valves, intravenous drug use, parenteral nutrition via intravenous infusion, abdominal surgery, compromised immune function, treatment with broad-spectrum antibiotics, and prior valvular disease, as supported by research.
• Endocarditis primarily develops as a consequence of fungemia resulting from tissue infection.
• This condition typically affects various cardiac structures, including the aortic valves, mitral valves, tricuspid valves, ventricular walls, and pulmonary valves.

Meningitis

• Typical symptoms of candidal meningitis include headache, sensitivity to light (photophobia), stiffness in the neck (nuchal rigidity), fever, and confusion (delirium).
• Candida parapsilosis is responsible for acute neutropenic meningitis.
• This type of infection is commonly transmitted within hospital environments and primarily afflicts neonates who receive hyperalimentation solutions, as well as patients with prolonged hospital stays, such as transplant recipients.
• It represents a progressive infection resulting from invasive candidiasis.
• Nevertheless, instances of this condition are infrequent and uncommon.

Peritonitis

• Among patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis, this condition is notably prevalent.
• A primary contributing factor is the prolonged use of antibiotics targeting bacteria, which creates an environment conducive to fungal growth and overgrowth.
• Peritonitis caused by Candida parapsilosis is characterized by elevated levels of polymorphonuclear cells in the bloodstream, abdominal pain, fever, abscess formation, and bowel obstruction.
• Research findings suggest that Candida parapsilosis stands out as the leading cause of fungal peritonitis.

Ocular infection

• Candida parapsilosis is responsible for invasive ocular conditions, including endophthalmitis following surgical procedures and keratitis.
• While endogenous fungal endophthalmitis is infrequent, it is not an unusual occurrence.
• Candida parapsilosis can lead to keratitis, which is characterized by symptoms like redness, sensitivity to light (photophobia), pain, reduced vision, and the presence of a yellow-white infiltrate with dry, elevated slough and feathery margins. In severe cases, it can result in moist, necrotic stromal inflammation resembling other microbial keratitis infections.

Arthritis

• Fungal arthritis stemming from Candida parapsilosis is an infrequent yet not unheard-of condition.
• It tends to impact individuals with compromised immune systems (such as those with HIV/AIDS), the elderly following arthrocentesis procedures, individuals receiving joint injections, and patients with implanted prostheses.
• Transplant recipients can also be susceptible to this condition.
• The hallmark symptoms include knee swelling, tenderness, and reduced joint mobility.

Vulvovaginitis

• Vulvovaginitis caused by Candida parapsilosis is a rare occurrence, mainly because Candida albicans is responsible for 99% of these infections in women.
• The remaining 1% of cases are attributed to other Candida species, including C. parapsilosis, which typically coexists harmlessly in the genitourinary tract.
• This condition is more commonly found in pregnant women, diabetic patients, and individuals who have been on prolonged courses of antibacterial medications.
• Symptoms associated with it encompass redness, itching, painful urination, a burning sensation, dyspareunia (pain during intercourse), and the presence of white discharge with an odor.

Otomycosis

• This refers to an infection caused by Candida parapsilosis in the middle or outer ear, resulting in otitis and inflammation.
• Typical indicators of this condition include persistent discharge from the ear, which can be white or colorless, along with a perforation of the tympanic membrane. Other symptoms encompass swelling and redness of the residual tympanic membrane, ear pain, progressive hearing loss, and the presence of whitish, cotton-like, or greasy debris in the external auditory canal, on the tympanic membrane, or in the residual space due to the removal of cholesteatoma.
• It is commonly observed in immunocompetent individuals with chronic hyperplastic inflammation, which predisposes them to invasive fungi like Candida parapsilosis.
• The infection leads to an increased production of mucus and accumulation, creating conditions favorable for the colonization of pathogenic fungi.
• Otomycosis has also been associated with the aggressive use of antifungal and antibacterial treatments, increasing the susceptibility of individuals to Candida parapsilosis infections.

Onychomycosis

• This is a prevalent nail infection typically caused by fungi, primarily Candida parapsilosis.
• It tends to affect elderly individuals aged 50 and above, especially those with thickened nail plates and slower nail growth, which makes them more susceptible to fungal infections.
• This condition can also manifest in neonates.
• Predisposing factors include prior traumatic nail damage and exposure to soil during gardening activities.
• The infection is characterized by various symptoms, including complete dystrophic onychomycosis in individuals with chronic mucocutaneous candidiasis, nail deformities, hyperkeratosis of nail plates, groove formation along nail ridges, discoloration of nail margins, and onycholysis.

Urinary Tract Infection

• Candida parapsilosis is not a common causative agent of urinary tract infections (UTIs), unlike Candida albicans, which is responsible for the majority of fungal UTIs.
• However, the remaining 1% of UTIs can be attributed to C. parapsilosis and other Candida species.
• In women, infections caused by C. parapsilosis are often asymptomatic.

Lab Diagnosis of Candida parapsilosis

• Specimens collected: Nail scrapings, urine, tissue biopsies, centrifuged spinal fluid, and blood.
• Microscopic examination:
• 10% KOH wet mount and calcofluor white staining used to visualize fungal pseudohyphae under the microscope.
• Culture examination:
• Grown on Sabouraud Dextrose Agar (SDA), colonies appear white, creamy, shiny, and smooth or wrinkled with small blastospores on a mycelial stalk.
• Cornmeal Agar is primarily used to observe pseudohyphae formation.
• On Potato Dextrose Agar (PDA), colonies are also white, creamy, shiny, and smooth or wrinkled, but with larger blastospores.
• Incubation typically at room temperature for 24 hours.
• Biochemical tests:
• Used to detect urease production and secretion of hydrolytic enzymes such as phospholipases.
• Molecular assays:
• PCR used for the identification and detection of the fungal genome.
• Genomic sequencing employed to differentiate between various Candida species from clinical samples.

Treatment of Candida parapsilosis infections

• Fungal endocarditis:
• Treated with Amphotericin B.
• Recurrent cases may require combination therapy with Amphotericin B and low-dose fluconazole.
• Surgical intervention is often recommended.
• Fungal peritonitis:
• Removal of catheters is crucial to reduce biofilm formation.
• Intensive antifungal therapy with fluconazole and Amphotericin B is commonly used.
• Fungal arthritis:
• Managed with both systemic and local Amphotericin B.
• Oral flucytosine and fluconazole are also effective.
• Long-term treatment may include both oral and IV administration of fluconazole and flucytosine.
• Combination of Amphotericin B with ketoconazole has shown some effectiveness.
• Endophthalmitis:
• Treatment may involve cataract removal, intraocular lens implantation, and corticosteroid eye drops.
• Intraocular and topical Amphotericin B is used for endogenous or recurrent infections.
• Subtenonian and topical steroids may be included as supportive therapy.
• Otomycosis:
• Managed by cleaning the ears followed by topical application of clotrimazole.
• Urinary tract infections and vulvovaginitis:
• Respond well to antifungals such as fluconazole, buconazole, miconazole, and boric acid.
• Other antifungal options:
• Echinocandins (caspofungin, micafungin, anidulafungin) represent a newer class of antifungals.
• These drugs inhibit (1,3)-β-D-glucan synthase, an enzyme vital for fungal cell wall synthesis.
• Caspofungin has strong antifungal activity and is less toxic compared to Amphotericin B.

Prevention and control of Candida parapsilosis

• Ensure proper sanitation and maintenance of intravenous devices used in hospitalized patients.
• Timely removal of catheters to minimize the risk of infection and biofilm formation.
• Strict adherence to hand hygiene protocols by healthcare workers to prevent cross-contamination and transmission to patients.

References:

• Clinical Microbiology Reviews: Candida parapsilosis and its clinical significance. Available at: cmr.asm.org
• Case study on native valve endocarditis caused by Candida parapsilosis in an adult. Available at: thefreelibrary.com
• Overview of fungal endophthalmitis. Source: ScienceDirect
• Clinical aspects of fungal peritonitis. Source: ScienceDirect
• Diagnostic techniques for fungal arthritis. Source: ScienceDirect
• Introduction to echinocandins, a new antifungal drug class. Source: KnowTheCause
• General background on Candida parapsilosis. Available at: Wikipedia
• Full text: Clinical Microbiology Reviews article on C. parapsilosis. Available at: cmr.asm.org
• Study on C. parapsilosis bloodstream infections. Source: BMC Infectious Diseases
• Management guidelines for candidemia and invasive candidiasis. Source: UpToDate
• Introduction to Candida and related infections. Source: The Candida Diet
• Clinical signs and symptoms of Candida meningitis. Source: Symptoma
• Pharmacological information on fluconazole. Source: ScienceDirect
• Case studies of fungal infections and treatment options. Source: ScienceDirect
• Discussion on Candida parapsilosis as a potential vaginal pathogen. Source: ResearchGate
• NHS overview on endocarditis and its causes. Available at: NHS
• Clinical research on fungal virulence and resistance. Source: PubMed
• Invasive candidiasis in immunocompromised hosts. Source: PubMed
• Article on emerging fungal pathogens. Source: PMC
• Analysis of Candida biofilms. Source: PMC
• Signal transduction in fungal pathogens. Source: Science Signaling
• Biofilm structures in diabetic foot ulcers. Source: MicroGenDX
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• Characteristics of fungi. Source: Lumen Learning