The frequency of fungal infections has increased in recent years, largely due to the increasing size of the at risk population, which includes transplant recipients, cancer patients and other patients who receive immunosuppressive therapy. Additionally they are not uncommon in critically ill patients and are associated with considerable morbidity and mortality.
Invasive intra-abdominal candidiasis is associated with high mortality, especially in intensive-care units (ICUs). Both rapid initiation of appropriate antifungal therapy and efficient source control are essential for their treatment and have been shown to reduce mortality.
The epidemiological role of Candida species in intra-abdominal infections (IAIs) has not yet been conclusively defined, however it is well known that intra-abdominal candidiasis is associated with poor outcomes.
Intra-abdominal candidiasis refers to a heterogeneous group of infections that includes peritonitis, abdominal abscess, and purulent or necrotic infection in patients having recent abdominal surgery or intra-abdominal events complicated by gastrointestinal perforation or anastomotic leak. Intra-abdominal candidiasis is generally a nosocomial infection typical of critically ill patients receiving prolonged antibiotic treatment and having recent gastrointestinal surgery.
Prompt and accurate diagnosis of intra-abdominal fungal infection is crucial so that appropriate antifungal agents can be started rapidly. However, early diagnosis is not always easy.
Unfortunately diagnosis is hampered by the lack of specific clinical signs and symptoms. The definition of microbiologically demonstrated infection is restrictive and cannot be used to guide antifungal empirical reeatment in clinical practice. Thus, early empirical treatment of invasive candidiasis currently relies on the positive predictive value of risk assessment strategies, such as, candida scores and predictive rules based on combinations of risk factors such as candida colonization, previous broad-spectrum antibiotics and abdominal surgery.
The role of Candida risk scores in intra-abdominal candidiasis has not been established. There are limited data on the utility of using β-D-glucan in post-surgical patients with suspected intra-abdominal candidiasis.
Recently, the 2016 IDSA clinical practice guidelines for the management of candidiasis were developed and explicitly addressed candidal peritonitis. Clinical evidence for the use of antifungal therapy for patients with suspected intra-abdominal invasive candidiasis is limited. Most studies are small and uncontrolled, single-center, or performed in specific patient cohorts. IDSA guidelines suggested considering empiric antifungal therapy for patients with clinical evidence of intra-abdominal infection and significant risk factors for candidiasis, including recent abdominal surgery, anastomotic leaks, or necrotizing pancreatitis, who are doing poorly despite treatment for bacterial infections.
A laboratory report of yeast isolated from an abdominal specimen should be considered to distinguish between colonization, and invasive infection. Specimens taken from intra-abdominal catheters that have been in place for >24 hours do not provide useful information about intra-abdominal candidiasis.
Preferred empiric therapy in critically ill patients or those previously exposed to an azole is an echinocandin (caspofungin: loading dose of 70 mg, then 50 mg daily; micafungin:100 mg daily; anidulafungin: loading dose of 200 mg, then 100 mg daily). However, fluconazole, 800-mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily, should be still considered first-line, in hemodynamically stable patients with azole susceptible Candida species or who have no prior exposure to azoles. A role for echinocandin in the management of critically ill patients is confirmed by the increasing incidence of fluconazole-resistant and susceptible-dose dependent strains that should be taken into account when selecting empiric therapy in patients with sepsis or septic shock.
The duration of therapy should be determined by adequacy of source control and clinical response. Source control with adequate drainage is an important part of therapy of intra-abdominal candidiasis.
Several meta-analyses of antifungal prophylaxis in high-risk surgical ICU patients have yielded conflicting results. Antifungal prophylaxis may be effective to prevent candidemia only in high-risk patients or in patients hospitalized in ICUs showing very high rates of invasive candidiasis. Antifungal prophylaxis, however, should not be given indiscriminately to all ICU patients.
Some species of Candida are naturally resistant to certain antifungals. Other species may be normally susceptible to an antifungal, but may develop resistance over time by mutating existing genes. Fortunately, unlike bacteria, there are no described drug resistance plasmids or transposons to amplify antifungal resistance. However pre-exposure to triazoles or echinocandin drugs is associated with an increased risk of being infected with a Candida species with decreased drug susceptibility. This can seriously impact the outcomes of patients with invasive candidiasis. The problem will likely continue to evolve unless greater attention will be done to actions that can be used to prevent and control it.
References
Montravers P, Mira JP, Gangneux JP, Leroy O, Lortholary O. AmarCand study group. A multicentre study of antifungal strategies and outcome of Candida spp. peritonitis in intensive-care units. Clin Microbiol Infect. 2011;17:1061–1067.
Pappas PG, Kauffman CA, Andes D, Benjamin DK, Calandra TF, Edwards JE, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;48:503–535.
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