Pharmacy OneSource Blog

An Update on the Candidiasis Infection Guidelines

Posted on 03/24/16

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The Infectious Diseases Society of America (IDSA) recently updated the 2009 clinical practice guideline for the management of candidiasis, a major cause of morbidity and mortality in the healthcare environment. The 2016 update reflects “new data pertaining to diagnosis, prevention, and treatment for proven or suspected invasive candidiasis” and recommendations to address the emergence of resistant Candida species. The new guidelines are endorsed by the American Academy of Pediatrics (AAP), the Pediatric Infectious Diseases Society (PIDS) and the Mycoses Study Group (MSG).1

These guidelines acknowledge the limitations of blood cultures for diagnosing candidiasis and describe emerging adjunct tests that may provide early detection, potentially shortening the time to diagnosis and intervention. The guidelines do not address the use of peptide nucleic acid fluorescent in situ hybridization (PNA FISH) or matrix-assisted laser desorption-ionization time-of flight mass spectrometry (MALDI-TOF).

The following information summarizes major updates to the IDSA guidelines. This information is not all inclusive; please refer to the guideline for further details.

Patient Population: Candidemia in non-neutropenic patients

First Line Agent

2009 IDSA Guidelines

  • Fluconazole or an echinocandin
  • Echinocandin is preferred if (1) severe illness (2) recent azole exposure
  • Amphotericin B deoxycholate or lipid amphotericin B is an alternative in intolerance, limited availability of other antifungals

2016 IDSA Guidelines

  • Echinocandin
  • Fluconazole is an alternative if (1) not critically ill (2) lack of fluconazole-resistant Candida
  • Lipid amphotericin B is an alternative in intolerance, limited availability, or resistance to other antifungals
  • Transition from amphotericin B to fluconazole in 5 -7 days if susceptible, clinically stable, and repeat cultures are negative

Azole susceptibility

2009 IDSA Guidelines

  • Transition from an echinocandin to fluconazole is recommended

2016 IDSA Guidelines

  • Testing is recommended

Candida glabrata infection

2009 IDSA Guidelines

  • Echinocandin is preferred.
  • Fluconazole or voriconazole as step down oral therapy, if susceptible

2016 IDSA Guidelines

  • High dose fluconazole or voriconazole should only be considered in confirmed susceptible isolates

Patient Population: Candidemia in neutropenic patients

First Line Agent

2009 IDSA Guidelines

  • An echinocandin or lipid amphotericin

2016 IDSA Guidelines

  • An echinocandin
  • Lipid amphotericin B is an effective, but less attractive alternative
  • Fluconazole or voriconazole and as a step-down therapy if susceptible with bloodstream clearance

 

An echinocandin agent is the recommended first-line therapy for both neutropenic and nonneutropenic candidemia. Pooled analysis of neutropenic candidemia clinical trials suggest a survival advantage with initial echinocandin; in nonneutropenic patients, an echinocandin is preferred due to its fungicidal properties and safety profile.1,3

The guidelines emphasize susceptibility testing and transitioning to azole-susceptible agents if the patient is clinically stable with documented bloodstream clearance. In nonneutropenic patients, azole susceptibility is recommended for all Candida isolates and echinocandin susceptibility should be considered in patients with prior echinocandin treatment or current C.glabrata or C.parapsilosis infection. Patients with candidemia are at increased risk for sight-threatening endophthalmitis and should receive a dilated ophthalmological exam within a week of diagnosis if nonneutropenic.1,4 The guidelines endorse early removal in suspected central venous catheter-related candidemia if it is a feasibly safe option.1,3

An echinocandin is the preferred agent for empiric treatment for suspected invasive candidiasis in nonneutropenic patients in an intensive care setting. The new guidelines specified a two-week duration of empiric therapy in patients who improve and describe an approach to de-escalation in patients with no clinical response after 4-5 days of therapy, no evidence of invasive candidiasis, or a negative non-culture based diagnostic assay with a high negative predictive value. Prophylaxis should be considered in adult intensive care units (ICUs) with a high rate (greater than 5%) of invasive candidiasis. Options include first-line fluconazle, an echinocandin, and daily bathing of ICU patients with chlorhexidne.5,6,7

Other additions to the guidelines include1,8:

  • Further guidance on neonatal infections, including neonatal central nervous system infection
  • Expansion on Candida endophthalmitis treatments, including treatment for chorioretinitis with and without vitritis
  • Additional recommendations for treating urinary tract infections and vulvovaginal candidiasis
  • A new section specifically addressing intra-abdominal infections

The guidelines stressed the need for more data on less common Candida infections, including osteomyelitis, endophthalmitis, and infective endocarditis in order to provide optimal therapeutic recommendations.1

These updated guidelines reflect the emergence of azole-resistant Candida species. Azole recommendations are stipulated with susceptibility confirmation and echinocandins are now preferred agents for most candidiasis infections. Safe, antifungal options for treating candidiasis are declining and the recent emergence of multidrug-resistant Candida species further limits treatment options.1 The trend in antifungal resistance calls for an increase in antifungal stewardship and infection prevention efforts.9

References

  1. Pappas PG, Kauffman CA, Andes D et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 62(4): e1-e50.
  2. Wheat LJ. Approach to the diagnosis of invasive aspergillosis and candidiasis. Clin Chest Med 2009; 30(2):367–77.
  3. Andes DR, Safdar N, Baddley JW, 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; 54(8):1110–22
  4. Vinikoor MJ, Zoghby J, Cohen KL, Tucker JD. Do all candidemic patients need an ophthalmic examination? Int J Infect Dis 2013; 17(3):e146–8.
  5. Garbino J, Lew DP, Romand JA, Hugonnet S, Auckenthaler R, Pittet D. Prevention of severe Candida infections in nonneutropenic, high-risk, critically ill patients: a randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination. Intensive Care Med 2002; 28(12):1708–17.
  6. Pelz RK, Hendrix CW, Swoboda SM, et al. Double-blind placebo-controlled trial of fluconazole to prevent candidal infections in critically ill surgical patients. Ann Surg 2001; 233(4):542–8.
  7. O’Horo JC, Silva GL, Munoz-Price LS, Safdar N. The efficacy of daily bathing with chlorhexidine for reducing healthcare-associated bloodstream infections: a meta-analysis. Infect Control Hosp Epidemiol 2012; 33(3):257–67.
  8. Pappas PG, Kauffman CA, Andes D et al. Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48(5): 503-535.
  9. Center for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013.S. Department of Health and Human Services. http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf. Accessed March 16, 2016.

Topics: Antimicrobial Stewardship

About the Author

Tam Le, PharmD is a current PGY-1 Pharmacy Practice Resident at Woman’s Hospital in Baton Rouge, Louisiana. She graduated from the University of Texas at Austin with a Bachelor of Science in Biochemistry. She then joined the United States Air Force as a Communications Officer and was stationed at Warner Robins, Georgia. After her military service, Dr. Le obtained her Doctorate of Pharmacy degree from the University of Louisiana at Monroe. Dr. Le is currently on a distance-learning clinical decision support and informatics rotation with Justin Clark, PharmD, Clinical Program Manager and Director of the Fellowship Program for Wolters Kluwer - Pharmacy OneSource. This rotation is a collaborative effort and learning experience for Dr. Le to work with Wolters Kluwer clinicians to optimize the use of Sentri7® for clinical activities.