Candidiasis: Practice Essentials, Background, Pathophysiology (original) (raw)

Practice Essentials

Candidiasis is a fungal infection caused by yeasts from the genus Candida. Candida albicans is the predominant cause of the disease. [1, 2]

Soreness and cracks at the lateral angles of the mouth (angular cheilitis) are a frequent expression of candidiasis in elderly individuals. Courtesy of Matthew C. Lambiase, DO.

Signs and symptoms

Chronic mucocutaneous candidiasis

Findings reveal disfiguring lesions of the face, scalp, hands, and nails. Chronic mucocutaneous candidiasis occasionally is associated with oral thrush and vitiligo. [3]

Oropharyngeal candidiasis

Individuals with oropharyngeal candidiasis (OPC) usually have a history of HIV infection, wear dentures, have diabetes mellitus, or have been exposed to broad-spectrum antibiotics or inhaled steroids. [4, 5] Although patients frequently are asymptomatic, when symptoms do occur, they can include the following:

• Sore and painful mouth
• Burning mouth or tongue
• Dysphagia
• Thick, whitish patches on the oral mucosa

Physical examination reveals a diffuse erythema and white patches that appear on the surfaces of the buccal mucosa, throat, tongue, and gums.

The following are the 5 types of OPC:

• Membranous candidiasis - One of the most common types; characterized by creamy-white, curdlike patches on the mucosal surfaces
• Chronic atrophic candidiasis (denture stomatitis) - Also thought to be one of the most common forms of the disease; presenting signs and symptoms include chronic erythema and edema of the portion of the palate that comes into contact with dentures
• Erythematous candidiasis - Associated with an erythematous patch on the hard and soft palates
• Angular cheilitis - Inflammatory reaction characterized by soreness, erythema, and fissuring at the corners of the mouth
• Mixed - A combination of any of the above types is possible

Esophageal candidiasis

Patients with esophageal candidiasis may be asymptomatic or may have 1 or more of the following symptoms:

• Normal oral mucosa (>50% of patients)
• Dysphagia
• Odynophagia
• Retrosternal pain
• Epigastric pain
• Nausea and vomiting

Physical examination almost always reveals oral candidiasis.

Nonesophageal gastrointestinal candidiasis

The following symptoms may be present:

• Epigastric pain
• Nausea and vomiting
• Abdominal pain
• Fever and chills
• Abdominal mass (in some cases)

Genitourinary tract candidiasis

The types of genitourinary tract candidiasis are as follows:

• Vulvovaginal candidiasis (VVC) - Erythematous vagina and labia; a thick, curdlike discharge; and a normal cervix upon speculum examination [6]
• Candida balanitis - Penile pruritus and whitish patches on the penis
• Candida cystitis - Many patients are asymptomatic, but bladder invasion may result in frequency, urgency, dysuria, hematuria, and suprapubic pain
• Asymptomatic candiduria - Most catheterized patients with persistent candiduria are asymptomatic
• Ascending pyelonephritis - Flank pain, abdominal cramps, nausea, vomiting, fever, chills and hematuria
• Fungal balls - Intermittent urinary tract obstruction with subsequent anuria and ensuing renal insufficiency

See Clinical Presentation for more detail.

Diagnosis

Diagnostic tests for candidiasis include the following:

• Mucocutaneous candidiasis - For a wet mount, scrapings or smears obtained from skin, nails, or oral or vaginal mucosa are examined under the microscope; a potassium hydroxide smear, Gram stain, or methylene blue is useful for direct demonstration of fungal cells
• Cutaneous candidiasis - Using a wet mount, scrapings or smears obtained from skin or nails can be examined under the microscope; potassium hydroxide smears are also useful
• Genitourinary candidiasis - A urinalysis should be performed; evidence of white blood cells (WBCs), red blood cells (RBCs), protein, and yeast cells is common; urine fungal cultures are useful
• Gastrointestinal candidiasis - Endoscopy with or without biopsy

See Workup for more detail.

Management

Management of candidiasis includes the following:

• Cutaneous candidiasis - Most localized cutaneous candidiasis infections can be treated with any number of topical antifungal agents (eg, clotrimazole, econazole, ciclopirox, miconazole, ketoconazole, nystatin) [7]
• Chronic mucocutaneous candidiasis - This condition is generally treated with oral azoles
• Oropharyngeal candidiasis - This can be treated with either topical antifungal agents or systemic oral azoles [4, 5]
• Esophageal candidiasis - Treatment requires systemic therapy with oral azoles, such as fluconazole, itraconazole, and voriconazole [8, 9]
• VVC - Topical antifungal agents or oral fluconazole can be used [10]
• Candida cystitis - In noncatheterized patients, Candida cystitis should be treated with fluconazole; in catheterized patients, the Foley catheter should be removed or replaced; if the candiduria persists after the catheter change, then patients can be treated with fluconazole

See Treatment and Medication for more detail.

Background

Candidiasis is caused by infection with species of the genus Candida, predominantly with Candida albicans. Candida species are ubiquitous fungi that represent the most common fungal pathogens that affect humans. The growing problem of mucosal and systemic candidiasis reflects the enormous increase in the number of patients at risk and the increased opportunity that exists for Candida species to invade tissues normally resistant to invasion. Candida species are true opportunistic pathogens that exploit recent technological advances to gain access to the circulation and deep tissues. [11]

The increased prevalence of local and systemic disease caused by Candida species has resulted in numerous new clinical syndromes, the expression of which depends primarily on the immune status of the host. Candida species produce a wide spectrum of diseases, ranging from superficial mucocutaneous disease to invasive illnesses, such as hepatosplenic candidiasis, Candida peritonitis, and systemic candidiasis. The management of serious and life-threatening invasive candidiasis remains severely hampered by delays in diagnosis and the lack of reliable diagnostic methods that prevent the early identification of candidemia and invasive candidiasis. [1, 12, 13]

The growing significance of fungal infections has prompted the publication of a fungal pririty pathogens list by WHO (WHO PPPL), analog to a previous bacterial pathogens priority list. The list classifies organisms as critical, high or medium, considering both research and development needs and perceived public health importance. Both C albicans and C auris are in the critical priority group_._ [2, 14]

Advances in medical technology, chemotherapeutics, cancer therapy, and organ transplantation have greatly reduced the morbidity and mortality of life-threatening disease. Patients who are critically ill and in medical and surgical ICUs have been the prime targets for opportunistic nosocomial fungal infections, primarily due to Candida species. Studies suggest that the problem is not under control and, in fact, show it is worsening. On a daily basis, virtually all physicians are confronted with a positive Candida isolate obtained from one or more various anatomic sites. High-risk areas for Candida infection include neonatal, pediatric, and adult ICUs, both medical and surgical. [15, 16] Candida infections can involve any anatomic structure.

Pathophysiology

Candida species are yeastlike fungi that can form true hyphae and pseudohyphae. For the most part, Candida species are confined to human and animal reservoirs; however, they are frequently recovered from the hospital environment, including on foods, countertops, air-conditioning vents, floors, respirators, and medical personnel. They are found as commensals of diseased skin and normal mucosal membranes of the gastrointestinal, genitourinary, and respiratory tracts, since early in life.

Candida species also contain their own set of well-recognized but poorly characterized virulence mechanisms that contribute to their ability to cause infection. [17, 18, 19] The main virulence factors include the following:

• Surface molecules that permit adherence of the organism to other structures (eg, human cells, extracellular matrix, prosthetic devices)
• Acid proteases and phospholipases that involve penetration and damage of cell envelopes
• Ability to convert to a hyphal form (phenotypic switching)
• Upregulation of alternative carbon utilization pathways (metabolic adaptation)
• Induction of differential stress resistance responses (superoxidedismutases)
• Masking of cell wall components for immune evasion

As with most fungal infections, host defects play a significant role in the development of candidal infections. [2] Host defense mechanisms against Candida infection and their associated defects that allow infection are as follows:

• Intact mucocutaneous barriers - Wounds, intravenous catheters, burns, ulcerations
• Polymorphonuclear leukocytes - Chronic granulomatous disease
• Cell-mediated immunity - Chronic mucocutaneous candidiasis, diabetes mellitus, cyclosporin A, corticosteroids, HIV infection
• Mucocutaneous protective bacterial flora - Broad-spectrum antibiotics

Risk factors associated with mucocutaneous, invasive or systemic candidiasis include the following [12, 18, 20, 21, 22, 23, 13] :

• Granulocytopenia
• Bone marrow transplantation
• Solid organ transplantation (liver, kidney)
• Parenteral hyperalimentation
• Hematologic malignancies
• Foley catheters
• Solid neoplasms
• Recent chemotherapy or radiation therapy
• Corticosteroids, TNF-α inhibitors, tocilizumab (IL-6 inibitor, elevated risk of candidemia during the COVID-19 pandemic), IL-17A- and IL-23-targeted biologics (secukinumab, ustekinumab)
• Clostridioides difficile infection
• Broad-spectrum antibiotics
• Burns
• Prolonged hospitalization
• Recent bacterial infection
• Recent surgery
• Gastrointestinal tract surgery
• Central intravascular access devices
• Premature birth
• Hemodialysis
• Acute and chronic renal failure
• Mechanical ventilation for longer than 3 days

The first step in the development of a candidal infection is colonization of the mucocutaneous surfaces, followed by proliferation of yeast blastospores and hyphae formation with activation of fungal virulence factors. [24]

All of the conditions outlined above are associated with increased colonization rates. The routes of candidal invasion include (1) disruption of a colonized surface (skin or mucosa), allowing the organisms access to the bloodstream, and (2) persorption via the gastrointestinal wall, which may occur following massive colonization with large numbers of organisms that pass directly into the bloodstream.

Frequency

United States

Candida species are the most common cause of fungal infection in immunocompromised persons. [1, 2] Oropharyngeal colonization is found in 30-55% of healthy young adults, and Candida species may be detected in 40-65% of normal fecal flora. [4, 5]

Three of every 4 women experience at least 1 bout of vulvovaginal candidiasis (VVC) during their lifetime.

More than 90% of persons infected with HIV who are not receiving highly active antiretroviral therapy (HAART) eventually develop oropharyngeal candidiasis (OPC), and 10% eventually develop at least 1 episode of esophageal candidiasis. [4, 5]

In persons with systemic infections, Candida species have been found as the fourth most commonly isolated pathogens from blood cultures. [25]

Clinical and autopsy studies have confirmed the marked increase in the incidence of disseminated candidiasis, reflecting a parallel increase in the frequency of candidemia. This increase is multifactorial in origin and reflects increased recognition of the fungus, a growing population of patients at risk (eg, patients undergoing complex surgical procedures, patients with indwelling vascular devices), and the improved survival rates among patients with underlying neoplasms or collagen-vascular disease and patients who are immunosuppressed.

International

Similar rates of mucocutaneous and systemic candidiasis/candidemia have been observed worldwide. [26, 27] In fact, throughout the world, Candida species have replaced Cryptococcus species as the most common fungal pathogens affecting immunocompromised hosts. The frequency of non-albicans Candida causing candidemia and invasive candidiasis has grown, an observation also found in the United States. [28, 13] As for the most recent years (last 10 years), it is unclear whether there is a continued increase, as variable trends are reported from different countries. COVID-19 pandemic did show an association with increased risk of candidemia, probably related to increased use of CVCs. [29]

Mortality/Morbidity

Mucocutaneous candidiasis: Most candidal infections are mucocutaneous and, as such, do not cause mortality. However, in patients with advanced immunodeficiency due to HIV infection, these mucosal infections can become refractory to antifungal therapy and may lead to severe oropharyngeal and esophageal candidiasis that initiates a vicious cycle of poor oral intake, malnutrition, wasting, and early death. [4, 5]

Candidemia and disseminated candidiasis: Mortality rates associated with these infections have not improved markedly and remain in the range of 30-40%. Systemic candidiasis causes more case fatalities than any other systemic mycosis. [12] More than a decade ago, investigators reported the enormous economic impact of systemic candidiasis in hospitalized patients. Candidemia is associated with considerable prolongation in hospital stays (70 d vs 40 d in comparable patients without fungemia). Although mucocutaneous fungal infections, such as oral thrush and Candidaesophagitis, are extremely common in patients with AIDS, candidemia and disseminated candidiasis are uncommon.

Sex

Neither sex is predisposed to candidal colonization; however, VVC is the second most common cause of vaginitis in women.

Age

Persons at the extremes of age (neonates and adults >65 y) are most susceptible to candidal colonization. Mucocutaneous candidiasis is also more prevalent in neonates and older adults. Very-low-birth-weight and extremely-low-birth-weight infants are at high risk for blood culture–proven late-onset candidiasis (defined as sepsis that develops after age 72 h). [30]

1. Vergidis P. Fungi. Porter RE. The Merck Manual of Diagnosis and Therapy. Rahway, NJ: Merck & Co Inc; Reviewed/Revised September 2023. [Full Text].
2. Vergidis P. Fungi. Porter RE. The Merck Manual of Diagnosis and Therapy. Rahway, NJ: Merck & Co Inc; Reviewed/Revised September 2023. [Full Text].
3. Aaron DM. Fungal Skin Infections. Porter RE. The Merck Manual of Diagnosis and Therapy. Rahway, NJ: Merck & Co Inc; Reviewed/Revised September 2023. [Full Text].
4. de Repentigny L, Lewandowski D, Jolicoeur P. Immunopathogenesis of oropharyngeal candidiasis in human immunodeficiency virus infection. Clin Microbiol Rev. 2004 Oct. 17(4):729-59, table of contents. [QxMD MEDLINE Link].
5. Skiest DJ, Vazquez JA, Anstead GM, et al. Posaconazole for the treatment of azole-refractory oropharyngeal and esophageal candidiasis in subjects with HIV infection. Clin Infect Dis. 2007 Feb 15. 44(4):607-14. [QxMD MEDLINE Link].
6. Sobel JD. Vulvovaginal candidosis. Lancet. 2007 Jun 9. 369(9577):1961-71. [QxMD MEDLINE Link].
7. Giglio M, Caggiano G, Dalfino L, Brienza N, Alicino I, Sgobio A, et al. Oral nystatin prophylaxis in surgical/trauma ICU patients: a randomised clinical trial. Crit Care. 2012 Apr 10. 16(2):R57. [QxMD MEDLINE Link].
8. Husain S, Paterson DL, Studer S, et al. Voriconazole prophylaxis in lung transplant recipients. Am J Transplant. 2006 Dec. 6(12):3008-16. [QxMD MEDLINE Link].
9. Ostrosky-Zeichner L, Oude Lashof AM, Kullberg BJ, et al. Voriconazole salvage treatment of invasive candidiasis. Eur J Clin Microbiol Infect Dis. 2003 Nov. 22(11):651-5. [QxMD MEDLINE Link].
10. Nurbhai M, Grimshaw J, Watson M, et al. Oral versus intra-vaginal imidazole and triazole anti-fungal treatment of uncomplicated vulvovaginal candidiasis (thrush). Cochrane Database Syst Rev. 2007 Oct 17. CD002845. [QxMD MEDLINE Link].
11. Kim JS, Cha H, Bahn YS. Comprehensive Overview of Candida auris: An Emerging Multidrug-Resistant Fungal Pathogen. J Microbiol Biotechnol. 2024 Jul 28. 34 (7):1365-1375. [QxMD MEDLINE Link].
12. Leleu G, Aegerter P, Guidet B. Systemic candidiasis in intensive care units: a multicenter, matched-cohort study. J Crit Care. 2002 Sep. 17(3):168-75. [QxMD MEDLINE Link].
13. Pfaller MA, Pappas PG, Wingard JR. Invasive fungal pathogens: current epidemiological trends. Clin Infect Dis. Aug 1 2006. 43 (Suppl 1):S3-S14. [Full Text].
14. World Health Organization. WHO fungal priority pathogens list to guide research, development and public health action. Geneva. 2022. Available at https://www.who.int/publications/i/item/9789240060241.
15. Pappas PG, Rex JH, Lee J, et al. A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis. 2003 Sep 1. 37(5):634-43. [QxMD MEDLINE Link].
16. Zaoutis TE, Heydon K, Localio R, et al. Outcomes attributable to neonatal candidiasis. Clin Infect Dis. 2007 May 1. 44(9):1187-93. [QxMD MEDLINE Link].
17. Yang YL. Virulence factors of Candida species. J Microbiol Immunol Infect. 2003 Dec. 36(4):223-8. [QxMD MEDLINE Link].
18. Lopes JP, Lionakis MS. Pathogenesis and virulence of Candida albicans. Virulence. 2022 Dec. 13 (1):89-121. [QxMD MEDLINE Link].
19. Gómez-Gaviria M, Ramírez-Sotelo U, Mora-Montes HM. Non-albicans Candida Species: Immune Response, Evasion Mechanisms, and New Plant-Derived Alternative Therapies. J Fungi (Basel). 2022 Dec 21. 9 (1):[QxMD MEDLINE Link].
20. Pappas PG. Invasive candidiasis. Infect Dis Clin North Am. 2006 Sep. 20(3):485-506. [QxMD MEDLINE Link].
21. Feng Y, Zhou B, Wang Z, Xu G, Wang L, Zhang T, et al. Risk of Candida Infection and Serious Infections in Patients with Moderate-to-Severe Psoriasis Receiving Biologics: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Int J Clin Pract. 2022. 2022:2442603. [QxMD MEDLINE Link].
22. Tsay S, Williams SR, Benedict K, Beldavs Z, Farley M, Harrison L, et al. A Tale of Two Healthcare-associated Infections: Clostridium difficile Coinfection Among Patients With Candidemia. Clin Infect Dis. 2019 Feb 1. 68 (4):676-679. [QxMD MEDLINE Link].
23. Khan S, Bilal H, Khan MN, Fang W, Chang W, Yin B, et al. Interleukin inhibitors and the associated risk of candidiasis. Front Immunol. 2024. 15:1372693. [QxMD MEDLINE Link].
24. Sobel JD, Vempati YS. Bacterial Vaginosis and Vulvovaginal Candidiasis Pathophysiologic Interrelationship. Microorganisms. 2024 Jan 5. 12 (1):[QxMD MEDLINE Link].
25. Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007 Jan. 20(1):133-63. [QxMD MEDLINE Link].
26. Morgan J. Global trends in candidemia: review of reports from 1995-2005. Curr Infect Dis Rep. 2005 Nov. 7(6):429-39. [QxMD MEDLINE Link].
27. Colombo AL, Nucci M, Park BJ, et al. Epidemiology of candidemia in Brazil: a nationwide sentinel surveillance of candidemia in eleven medical centers. J Clin Microbiol. 2006 Aug. 44(8):2816-23. [QxMD MEDLINE Link].
28. Vannini M, Emery S, Lieutier-Colas F, Legueult K, Mondain V, Retur N, et al. Epidemiology of candidemia in NICE area, France: A five-year study of antifungal susceptibility and mortality. J Mycol Med. 2022 Mar. 32 (1):101210. [QxMD MEDLINE Link].
29. Soriano-Martín A, Muñoz P, García-Rodríguez J, Cantón R, Vena A, Bassetti M, et al. Unresolved issues in the diagnosis of catheter related candidemia: A position paper. Rev Esp Quimioter. 2024 Feb. 37 (1):1-16. [QxMD MEDLINE Link].
30. Maródi L, Johnston RB Jr. Invasive Candida species disease in infants and children: occurrence, risk factors, management, and innate host defense mechanisms. Curr Opin Pediatr. 2007 Dec. 19(6):693-7. [QxMD MEDLINE Link].
31. Fernandez J. Immunodeficiency Disorders. Porter RE. The Merck Manual of Diagnosis and Therapy. Rahway, NJ: Merck & Co Inc; Reviewed/Revised January 2023. [Full Text].
32. Malani AN, Kauffman CA. Candida urinary tract infections: treatment options. Expert Rev Anti Infect Ther. 2007 Apr. 5(2):277-84. [QxMD MEDLINE Link].
33. Dias V. Candida species in the urinary tract: is it a fungal infection or not?. Future Microbiol. 2020 Jan. 15:81-83. [QxMD MEDLINE Link].
34. Guery BP, Arendrup MC, Auzinger G, Azoulay E, Borges Sá M, Johnson EM, et al. Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis. Intensive Care Med. 2009 Jan. 35(1):55-62. [QxMD MEDLINE Link].
35. Picazo JJ, González-Romo F, Candel FJ. Candidemia in the critically ill patient. Int J Antimicrob Agents. 2008 Nov. 32 Suppl 2:S83-5. [QxMD MEDLINE Link].
36. Pappas PG, Lionakis MS, Arendrup MC, Ostrosky-Zeichner L, Kullberg BJ. Invasive candidiasis. Nat Rev Dis Primers. 2018 May 11. 4:18026. [QxMD MEDLINE Link].
37. Falcone M, Barzaghi N, Carosi G, Grossi P, Minoli L, Ravasio V, et al. Candida infective endocarditis: report of 15 cases from a prospective multicenter study. Medicine (Baltimore). 2009 May. 88(3):160-8. [QxMD MEDLINE Link].
38. Shah CP, McKey J, Spirn MJ, et al. Ocular candidiasis: a review. Br J Ophthalmol. 2008 Apr. 92(4):466-8. [QxMD MEDLINE Link].
39. Adelhoefer SJ, Gonzalez MR, Bedi A, Kienzle A, Bäcker HC, Andronic O, et al. Candida spondylodiscitis: a systematic review and meta-analysis of seventy two studies. Int Orthop. 2024 Jan. 48 (1):5-20. [QxMD MEDLINE Link].
40. Blot SI, Vandewoude KH, De Waele JJ. Candida peritonitis. Curr Opin Crit Care. 2007 Apr. 13(2):195-9. [QxMD MEDLINE Link].
41. Vazquez JA, Sobel JD. Candidiasis. Clinical Mycology, Dismukes WE, Pappas PG, and Sobel JD, eds. Oxford Univers. 2003. 143-87.
42. Borman AM, Johnson EM. Name Changes for Fungi of Medical Importance, 2018 to 2019. J Clin Microbiol. 2021 Jan 21. 59 (2):[QxMD MEDLINE Link].
43. de Hoog S, Walsh TJ, Ahmed SA, Alastruey-Izquierdo A, Alexander BD, et al. A conceptual framework for nomenclatural stability and validity of medically important fungi: a proposed global consensus guideline for fungal name changes supported by ABP, ASM, CLSI, ECMM, ESCMID-EFISG, EUCAST-AFST, FDLC, IDSA, ISHAM, MMSA, and MSGERC. J Clin Microbiol. 2023 Nov 21. 61 (11):e0087323. [QxMD MEDLINE Link].
44. Eiland EH, Hassoun A, English T. Points of concern related to the micafungin versus caspofungin trial. Clin Infect Dis. 2008 Feb 15. 46(4):640-1; author reply 641. [QxMD MEDLINE Link].
45. Jones CR, Neill C, Borman AM, Budd EL, Cummins M, Fry C, et al. The laboratory investigation, management, and infection prevention and control of Candida auris: a narrative review to inform the 2024 national guidance update in England. J Med Microbiol. 2024 May. 73 (5):[QxMD MEDLINE Link].
46. Watkins RR, Gowen R, Lionakis MS, Ghannoum M. Update on the Pathogenesis, Virulence, and Treatment of Candida auris. Pathog Immun. 2022. 7 (2):46-65. [QxMD MEDLINE Link].
47. CDC. Candida auris. US Centers for Disease Control and Prevention. Available at https://www.cdc.gov/candida-auris/index.html. Accessed: September 27, 2024.
48. Ostrowsky B, Greenko J, Adams E, et al. Candida auris Isolates Resistant to Three Classes of Antifungal Medications — New York, 2019. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/candida-auris/. Accessed: September 26, 2024.
49. Françoise U, Desnos-Ollivier M, Le Govic Y, Sitbon K, Valentino R, Peugny S, et al. Candida haemulonii complex, an emerging threat from tropical regions?. PLoS Negl Trop Dis. 2023 Jul. 17 (7):e0011453. [QxMD MEDLINE Link].
50. FDA. FDA allows marketing of the first test to identify five yeast pathogens directly from a blood sample [news release.] September 22, 2014. US Food and Drug Administration. Available at https://www.fda.gov/news-events/press-announcements/fda-allows-marketing-test-identify-organisms-cause-bloodstream-infections-and-provide-antibiotic. February 23, 2017; Accessed: September 26, 2024.
51. Brooks M. FDA clears rapid blood test for sepsis-causing pathogens. Medscape Medical News. September 23, 2014. [Full Text].
52. Odabasi Z, Mattiuzzi G, Estey E, et al. Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis. 2004 Jul 15. 39(2):199-205. [QxMD MEDLINE Link].
53. Alexander BD, Pfaller MA. Contemporary tools for the diagnosis and management of invasive mycoses. Clin Infect Dis. 2006. 43:S15-S27.
54. Shepard JR, Addison RM, Alexander BD, et al. Multicenter evaluation of the Candida albicans/Candida glabrata peptide nucleic acid fluorescent in situ hybridization method for simultaneous dual-color identification of C. albicans and C. glabrata directly from blood culture bottles. J Clin Microbiol. 2008 Jan. 46(1):50-5. [QxMD MEDLINE Link].
55. Alves J, Alonso-Tarrés C, Rello J. How to Identify Invasive Candidemia in ICU-A Narrative Review. Antibiotics (Basel). 2022 Dec 12. 11 (12):[QxMD MEDLINE Link].
56. Delavy M, Dos Santos AR, Heiman CM, Coste AT. Investigating Antifungal Susceptibility in Candida Species With MALDI-TOF MS-Based Assays. Front Cell Infect Microbiol. 2019. 9:19. [QxMD MEDLINE Link].
57. Tang BHE, Bay JW, Yeong FM, Samuel M. Efficacy and safety of echinocandin monotherapy and combination therapy for immunocompromised patients with systemic candidiasis: A systematic review and meta-analysis. J Mycol Med. 2023 Feb 16. 33 (2):101362. [QxMD MEDLINE Link].
58. Lewis R. Candida: New Rapid Blood Test Could Cut Mortality. Medscape Medical News. Apr 25 2013. Medscape. Available at https://www.medscape.com/viewarticle/803135. April 25, 2013; Accessed: September 27, 2024.
59. Neely LA, Audeh M, Phung NA, Min M, Suchocki A, Plourde D, et al. T2 magnetic resonance enables nanoparticle-mediated rapid detection of candidemia in whole blood. Sci Transl Med. 2013 Apr 24. 5(182):182ra54. [QxMD MEDLINE Link].
60. [Guideline] Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Feb 15. 62 (4):e1-50. [QxMD MEDLINE Link]. [Full Text].
61. Chandrasekar PH, Sobel JD. Micafungin: a new echinocandin. Clin Infect Dis. 2006 Apr 15. 42(8):1171-8. [QxMD MEDLINE Link].
62. Vazquez JA, Sobel JD. Anidulafungin: a novel echinocandin. Clin Infect Dis. 2006 Jul 15. 43(2):215-22. [QxMD MEDLINE Link].
63. Thompson GR, Soriano A, Skoutelis A, Vazquez JA, Honore PM, Horcajada JP, et al. Rezafungin Versus Caspofungin in a Phase 2, Randomized, Double-blind Study for the Treatment of Candidemia and Invasive Candidiasis: The STRIVE Trial. Clin Infect Dis. 2021 Dec 6. 73 (11):e3647-e3655. [QxMD MEDLINE Link].
64. Colombo RE, Vazquez JA. An evaluation of ibrexafungerp for the treatment of invasive candidiasis: the evidence to date. Expert Opin Pharmacother. 2021 May. 22 (7):797-807. [QxMD MEDLINE Link].
65. El Ayoubi LW, Allaw F, Moussa E, Kanj SS. Ibrexafungerp: A narrative overview. Curr Res Microb Sci. 2024. 6:100245. [QxMD MEDLINE Link].
66. Kett DH, Shorr AF, Reboli AC, et al. Anidulafungin compared with fluconazole in severely ill patients with candidemia and other forms of invasive candidiasis: Support for the 2009 IDSA treatment guidelines for candidiasis. Crit Care. 2011 Oct 25. 15(5):R253. [QxMD MEDLINE Link].
67. Brooks M. Micafungin Sodium (Mycamine) Gets Pediatric Indication. Medscape [serial online]. Available at https://www.medscape.com/viewarticle/807188. Accessed: September 27, 2024.
68. van Burik JA, Ratanatharathorn V, Stepan DE, et al. Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis. 2004 Nov 15. 39(10):1407-16. [QxMD MEDLINE Link].
69. Andes DR, Safdar N, Baddley JW, Playford G, Reboli AC, Rex JH, et al. Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials. Clin Infect Dis. 2012 Apr. 54(8):1110-22. [QxMD MEDLINE Link].
70. Clancy CJ, Nguyen MH. The end of an era in defining the optimal treatment of invasive candidiasis. Clin Infect Dis. 2012 Apr. 54(8):1123-5. [QxMD MEDLINE Link].
71. FDA. FDA limits usage of Nizoral (ketoconazole) oral tablets due to potentially fatal liver injury and risk of drug interactions and adrenal gland problems. US Food and Drug Administration. Available at https://www.fda.gov/Drugs/DrugSafety/ucm362415.htm. Accessed: September 27, 2024.
72. Lowes R. FDA, EMA Come Down Hard on Oral Ketoconazole. Medscape Medical News. Available at https://www.medscape.com/viewarticle/808484. Accessed: September 27, 2024.
73. Ordaya EE, Clement J, Vergidis P. The Role of Novel Antifungals in the Management of Candidiasis: A Clinical Perspective. Mycopathologia. 2023 Dec. 188 (6):937-948. [QxMD MEDLINE Link].
74. Jaijakul S, Vazquez JA, Swanson RN, Ostrosky-Zeichner L. (1,3)-ß-D-Glucan (BG) as a Prognostic Marker of Treatment Response in Invasive Candidiasis. Clin Infect Dis. 2012 May 9. [QxMD MEDLINE Link].
75. Pasternak B, Wintzell V, Furu K, Engeland A, Neovius M, Stephansson O. Oral Fluconazole in Pregnancy and Risk of Stillbirth and Neonatal Death. JAMA. 2018 Jun 12. 319 (22):2333-2335. [QxMD MEDLINE Link].
76. Brexafemme (ibrexafungerp) [package insert]. Jersey City, NJ: https://www.accessdata.fda.gov/drugsatfda\_docs/label/2021/214900s000lbl.pdf. June 2021. Available at [[Full Text]](https://SCYNEXIS, Inc).
77. Phillips NA, Rocktashel M, Merjanian L. Ibrexafungerp for the Treatment of Vulvovaginal Candidiasis: Design, Development and Place in Therapy. Drug Des Devel Ther. 2023. 17:363-367. [QxMD MEDLINE Link].
78. Charlier C, Hart E, Lefort A, et al. Fluconazole for the management of invasive candidiasis: where do we stand after 15 years?. J Antimicrob Chemother. 2006 Mar. 57(3):384-410. [QxMD MEDLINE Link].
79. Sobel JD, Revankar SG. Echinocandins--first-choice or first-line therapy for invasive candidiasis?. N Engl J Med. 2007 Jun 14. 356(24):2525-6. [QxMD MEDLINE Link].
80. Reboli AC, Rotstein C, Pappas PG, et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med. 2007 Jun 14. 356(24):2472-82. [QxMD MEDLINE Link].
81. Kuse ER, Chetchotisakd P, da Cunha CA, et al. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet. 2007 May 5. 369(9572):1519-27. [QxMD MEDLINE Link].
82. Locke JB, Pillar CM, Castanheira M, Carvalhaes CG, Andes D, Aram JA, et al. Outcomes by Candida spp. in the ReSTORE Phase 3 trial of rezafungin versus caspofungin for candidemia and/or invasive candidiasis. Antimicrob Agents Chemother. 2024 May 2. 68 (5):e0158423. [QxMD MEDLINE Link].
83. Thompson GR 3rd, Soriano A, Cornely OA, and the, ReSTORE trial investigators. Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial. Lancet. 2023 Jan 7. 401 (10370):49-59. [QxMD MEDLINE Link].
84. Espinel-Ingroff A, Wiederhold NP. A Mini-Review of In Vitro Data for Candida Species, Including C. auris, Isolated during Clinical Trials of Three New Antifungals: Fosmanogepix, Ibrexafungerp, and Rezafungin. J Fungi (Basel). 2024 May 20. 10 (5):[QxMD MEDLINE Link].
85. Kriegl L, Egger M, Boyer J, Hoenigl M, Krause R. New treatment options for critically important WHO fungal priority pathogens. Clin Microbiol Infect. 2024 Mar 9. [QxMD MEDLINE Link].
86. Sharma D, Vazquez JA. An evaluation of Rezafungin: the latest treatment option for adults with candidemia and invasive candidiasis. Expert Opin Pharmacother. 2024 Mar. 25 (4):339-347. [QxMD MEDLINE Link].
87. Kullberg BJ, Sobel JD, Ruhnke M, et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial. Lancet. 2005 Oct 22-28. 366(9495):1435-42. [QxMD MEDLINE Link].
88. Schuster MG, Edwards JE Jr, Sobel JD, Darouiche RO, Karchmer AW, Hadley S, et al. Empirical fluconazole versus placebo for intensive care unit patients: a randomized trial. Ann Intern Med. 2008 Jul 15. 149(2):83-90. [QxMD MEDLINE Link].
89. Ullmann AJ, Cornely OA. Antifungal prophylaxis for invasive mycoses in high risk patients. Curr Opin Infect Dis. 2006 Dec. 19(6):571-6. [QxMD MEDLINE Link].
90. Maseda E, Martín-Loeches I, Zaragoza R, Pemán J, Fortún J, Grau S, et al. Critical appraisal beyond clinical guidelines for intraabdominal candidiasis. Crit Care. 2023 Oct 3. 27 (1):382. [QxMD MEDLINE Link].
91. Thompson GR 3rd, Jenks JD, Baddley JW, Lewis JS 2nd, Egger M, Schwartz IS, et al. Fungal Endocarditis: Pathophysiology, Epidemiology, Clinical Presentation, Diagnosis, and Management. Clin Microbiol Rev. 2023 Sep 21. 36 (3):e0001923. [QxMD MEDLINE Link].
92. Cornely OA, Lasso M, Betts R, et al. Caspofungin for the treatment of less common forms of invasive candidiasis. J Antimicrob Chemother. 2007 Aug. 60(2):363-9. [QxMD MEDLINE Link].
93. Pachl J, Svoboda P, Jacobs F, et al. A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis. Clin Infect Dis. 2006 May 15. 42(10):1404-13. [QxMD MEDLINE Link].
94. Jamil Y, Akinleye A, Mirzaei M, Lempel M, Farhat K, Pan S. Candida endocarditis: Update on management considerations. World J Cardiol. 2023 Oct 26. 15 (10):469-478. [QxMD MEDLINE Link].
95. Khan FA, Slain D, Khakoo RA. Candida endophthalmitis: focus on current and future antifungal treatment options. Pharmacotherapy. 2007 Dec. 27(12):1711-21. [QxMD MEDLINE Link].
96. Kauffman CA. Clinical efficacy of new antifungal agents. Curr Opin Microbiol. 2006 Oct. 9(5):483-8. [QxMD MEDLINE Link].
97. Sable CA, Strohmaier KM, Chodakewitz JA. Advances in antifungal therapy. Annu Rev Med. 2008. 59:361-79. [QxMD MEDLINE Link].

Author

Jose A Hidalgo, MD Assistant Professor, Universidad Nacional Mayor de San Marcos; Attending Physician, Department of Internal Medicine, Division of Infectious Diseases, Guillermo Almenara Hospital, Peru

Jose A Hidalgo, MD is a member of the following medical societies: HIV Medicine Association, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

Jose A Vazquez, MD, FACP, FIDSA Chief, Professor, Department of Medicine, Division of Infectious Diseases, Medical College of Georgia at Augusta University

Jose A Vazquez, MD, FACP, FIDSA is a member of the following medical societies: American Society for Microbiology, HIV Medicine Association, Immunocompromised Host Society, Infectious Diseases Society of America, International AIDS Society, International Immunocompromised Host Society, International Society for Human and Animal Mycology, International Society for Infectious Diseases, Medical Mycological Society of the Americas, Mycological Society of America, National Foundation for Infectious Diseases

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cidara; Amplyx; F2G; Melinta;
Serve(d) as a speaker or a member of a speakers bureau for: Allergan; Astellas;Melinta.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

David Hall Shepp, MD Program Director, Fellowship in Infectious Diseases, Department of Medicine, North Shore University Hospital; Associate Professor, New York University School of Medicine

David Hall Shepp, MD is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Received salary from Gilead Sciences for management position.