Candida Case File

Candida Case File

Eugene C.Toy, MD, Cynthia Debord, PHD, Audrey Wanger, PHD, Gilbert Castro, PHD, James D. Kettering, PHD, Donald Briscoe, MD

CASE 41

A 28-year-old woman presents complaining of 2-days of itchy vaginal discharge. One week ago you saw and treated her for a urinary tract infection (UTI) with sulfamethoxazole and trimethoprim (SMX-TMP). She completed her medication as ordered and developed the vaginal discharge shortly thereafter.

She denies abdominal pain, and her dysuria has resolved. She is not currently taking any medications. On examination, she is comfortable appearing and has normal vital signs. Her general physical examination is normal. A pelvic examination reveals a thick, curd-like, white discharge in her vagina that is adherent to the vaginal sidewalls. There is no cervical discharge or cervical motion tenderness, and bimanual examination of the uterus and adnexa is normal.

◆ What is the most likely cause of these symptoms?

◆ What are the most likely reservoirs of this organism in this patient?

ANSWERS TO CASE 41: Candida

Summary: A 28-year-old woman who recently took antibiotics now presents with a vaginal discharge consistent with candidiasis.

◆ Most likely etiologic organism: Candida albicans

◆ Most likely reservoirs of infection: Gastrointestinal (GI) and vaginal colonization

CLINICAL CORRELATION

Most Candida infections come from the host’s endogenous flora. Both humoral and cell-mediated immune functions play a role in defense against Candida infections. Those with impaired or suppressed immunity are predisposed to more severe or diffuse disease. Neutropenic persons, such as those on chemotherapy or posttransplant patients, are at risk for severe disease, which disseminates in the blood stream. In contrast, AIDS patients often develop oral, pharyngeal, or esophageal candidiasis but rarely disseminated disease. Intact skin also plays a key role in preventing cutaneous infections, because breaks in the skin of even healthy hosts may result in Candida skin infections. The use of antibiotics is probably the most significant predisposing factor for the development of Candida infections. Antibiotics that suppress the growth of the normal host bacterial flora can allow Candida to proliferate. This is a frequent contributing cause of the development of vaginal candidiasis in women and Candida diaper dermatitis in infants.

Candida is the cause of a wide range of infections from oral lesions (thrush) to disseminated disease including endocarditis and meningitis. Candida albicans is the most common cause of vaginitis. Predisposing factors include diabetes, previous antimicrobial use, pregnancy, and use of oral contraceptives. Although the pathogenesis and the virulence mechanisms of Candida infection is unclear, the presence of pseudohyphae seems to indicate active disease versus colonization. Pseudohyphae are able to adhere to epithelial cells, then the blastoconidia.

APPROACH TO THE SUSPECTED Candida PATIENT

Objectives

1. Know the morphology, reservoirs, and reproduction of Candida species.
2. Know the clinical syndromes, risk factors, and routes of transmission of diseases associated with Candida infection.

Definitions

Neutropenia: A decrease in the number of neutrophils circulating in the blood to less than 2.0 × 109/L, with significant neutropenia being less than 0.5 × 109/L.

Thrush: Form of oral candidiasis in which a membrane forms in the oral cavity consisting of Candida, desquamated cells and white blood cells and debris. The appearance is of a creamy white, curd-like exudative plaque on the tongue and in the mouth.

DISCUSSION

Characteristics of Candida

Candida are yeasts that exist as both sexual and asexual forms, reproduce by budding and form blastospores, which are small, thin-walled ovoid cells. Blastospores, pseudohyphae may be seen on examination of clinical specimens. There are over 150 species of Candida, 9 of which appear to cause disease in humans. Candida albicans is the most common cause of human candidiasis. It can be found in soil and on inanimate objects and foods. It is also found in the normal flora of the human GI tract, vagina, and skin.

Diagnosis

Diagnosis of vaginitis is made by a combination of physical examination and testing the vaginal exudate. Ruling out other causes of vaginitis may be aided by determining the pH of the exudates as well as stain and culture of the material. Yeast cells are larger than bacteria and can be visualized easily by direct wet preparation of the exudates with KOH. Candida will grow with 24–48 hours on most routine laboratory media; however, Sabouraud dextrose agar can be used to inhibit the normal flora bacteria in cultures for mucosal candidiasis. Candida colonies are smooth and creamy, although some species may be dry and can be identified as yeast by a wet preparation. Candida species produce round or oval blastoconidia, and some species also produce pseudohyphae (chains of elongated blastoconidia), as in Figure 41-1. Preliminary differentiation of Candida albicans from the other Candida species can be made by observation of the presence of a germ tube. Candida albicans will make a germ tube after several hours incubation in the presence of serum. Candida albicans can also be differentiated from other yeast based on their microscopic morphology on corn meal agar. Candida albicans produce chlamydospores, large rounded structures in the middle of the pseudohyphae. Yeasts that are germ tube-negative can be further identified by assimilation of different substrates. Several commercial kits are available that identify Candida to the species level.

Figure 41-1. Candida albicans. Pseudohyphae noted on microscopy. (Reproduced, with permission, Brooks G, Butel J, Morse S. Jawetz, Melnick, & Adelberg’s medical microbiology, 23rd ed. New York: McGraw-Hill, 2004:646.)

Treatment and Prevention

Therapy for Candida vaginitis is usually topical antifungal agent such as nystatin or clotrimazole. It is not uncommon for patients to remain or be recurrently colonized with vaginal yeast after appropriate therapy. This may or may not lead to a symptomatic recurrence. Oral or intravenous therapy with either an azole antifungal such as fluconazole, amphotericin B, or the new agent, caspofungin, are used for treatment of disseminated infections with Candida. The agent of choice is dependent on the species of Candida isolated and the susceptibility of the isolate to the antifungal. Prophylaxis for Candida infections is not routinely recommended because of the selection of strains of Candida that are resistant to antifungal agents. The only population in which some benefit has been seen with prophylaxis is in bone marrow transplant patients. Partly as a result of the increased use of fluconazole, the incidence of Candida species not albicans, or the species more likely to be fluconazole resistant have also increased.

COMPREHENSION QUESTIONS

[41.1] Candida albicans can be differentiated from other Candida species on cornmeal agar by its unique ability to form which of the following?

A. Arthrospores

B. Aseptate hyphae

C. Chlamydospores

D. Germ tubes

E. Tuberculate macroconidia

[41.2] A young man in his mid-twenties presented with mucosal lesions in his mouth. Based on his CD4 cell count and other signs during the past few months, he was diagnosed as having AIDS. Which of the following is the most likely etiology of the oral lesions?

A. Aspergillus

B. Candida

C. Cryptococcus

D. Mucor

E. Rhizopus

[41.3] Which of the following morphologic structures is not associated with Candida albicans?

A. Chlamydospore

B. Hyphae

C. Pseudohyphae

D. Sporangium

E. Yeast

[41.4] Which of the following is the main reason that individuals taking tetracycline often develop candidiasis?

A. Candida albicans is capable of degrading the antibiotic.

B. The action of the antibiotic is neutralized by the protein of C. albicans.

C. The antibiotic damages the host mucous membrane.

D. The antibiotic is nutritionally favorable for the growth of C. albicans.

E. The normal bacterial flora is drastically altered by tetracycline.

Answers

[41.1] C. Although multiple Candida species may cause disease in humans, C. albicans is the most frequent species identified. Chlamydospores (chlamydoconidia) are round, thick-walled spores formed directly from the differentiation of hyphae in which there is a concentration of protoplasm and nutrient material. They may be intercalary (within the hyphae) or terminal (end of hyphae). Germ tubes appear as hyphal-like extensions of yeast cells, usually without a constriction at the point of origin from the cell. Approximately 75 percent of the yeasts recovered from clinical specimens are C. albicans, and the germ-tube test can usually provide identification within 3 hours. The morphologic features of yeasts on cornmeal agar containing Tween 80 allow for the differentiation of C. albicans from five other Candida species.

[41.2] B. The risk factors for cutaneous and mucosal candidiasis include AIDS, pregnancy, diabetes, young or old age, birth control pills, and trauma. Oral thrush can occur on the tongue, lips, gums, or palate. It may be patchy to confluent, and it forms whitish lesions composed of epithelial cells, yeasts, and pseudohyphae. Oral thrush commonly occurs in AIDS patients. Although the other genera listed may be opportunistic, only Candida routinely presents with mucosal lesions.

[41.3] D. A sporangium is a sac enclosing spores, seen in certain fungi, but not Candida species. Spores produced within a sporangium, usually located at the tip of a long hyphal stalk are released by rupture of the sporangial wall. All other options (chlamydospore, hyphae, pseudohyphae, and yeasts) are routinely observed in C. albicans cultures, depending on conditions of growth.

[41.4] E. Patients with compromised host defenses are susceptible to ubiquitous fungi to which healthy people are exposed but usually resistant. Candida and related yeasts are part of the normal microbial flora, but are kept at low numbers by faster-growing normal flora bacteria. If broad-spectrum antimicrobials are used, much of the usual flora bacteria may be eliminated. No longer held in check, the opportunist yeast may become more predominant and opportunistic. Discontinuation of use of the broad-spectrum antibiotic is an important first step in patient management, allowing for reestablishment of the normal or usual flora and control of the yeast species.

MICROBIOLOGY PEARLS ❖ Candida albicans is a germ tube—positive yeast that is the most common cause of vaginitis. ❖ Candida albicans can be distinguished from the other Candida species by formation of a germ tube after incubation in serum. ❖ The incidence of Candida species other than albicans has increased because of the increased use of azoles and their propensity to develop resistance to those antifungal agents.

REFERENCES

Edwards JE. Candida species. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 6th ed. Philadelphia, PA: Churchill Livingstone, 2005:2938–57. 

Murray PR, Rosenthal KS, Pfaller MA. Opportunistic mycoses. In: Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology, 5th ed. St. Louis, MO: Mosby, 2005:779–800.

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