Treating Invasive Candidiasis: Sooner (Much Sooner) is Better

Abstract & Commentary

By Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.

Synopsis: Mortality was significantly lower in post-surgical patients with invasive candidiasis who received preemptive therapy when compared to historical controls with later initiation of antifungal therapy.

Source: Shan YS, et al. Early Presumptive Therapy with Fluconazole for Occult Candida Infection After Gastrointestinal Surgery. World J Surg. 2006;30:119-126.

Shan and colleagues examined outcomes of 18 gastrointestinal surgery patients with invasive candidiasis who were treated preemptively based on clinical criteria from 1999 through 2002, and compared them to outcomes of 18 patients treated only on the basis of positive blood cultures or other unequivocal evidence of deep infection from 1995 through 1998. Almost 90% in each group were infected with Candida albicans. The clinical criteria used for initiation of preemptive therapy were: persistent fever with prolonged post-operative ileus, absence of other cause of fever, and receipt of broad spectrum antibacterial agents. They excluded patients with hyperalimentation-related candidemia, as well as patients whose fever subsided after removal of a central venous catheter, even if blood cultures were positive.

During 1995-1998, 11 patients were treated with fluconazole or amphotericin B (doses unstated), while 7 received no antifungal therapy; 14 (77.7%) of the 18 died. All patients were initially treated with fluconazole 400 mg daily. In contrast, only 2 (11.1%) of the 18 patients treated preemptively during 1999-2002 died, one with disseminated Candida albicans infection. Each of these 18 initially received fluconazole 400 mg daily.

Four patients in each group, most with persistent ileus, had breakthrough candidemia. Two in the preemptive group had therapy changed to amphotericin B, but after proving intolerant to this drug, they were treated with fluconazole in doses as high as 16 mg/kg daily. While no susceptibility data is provided, Shan et al mention lower susceptibility as the cause of 2 cases of breakthrough candidemia. Multivariate analysis identified early preemptive therapy as the only independent predictor of lower mortality (OR, 0.025; 95% CI, 0.003-0.182; P < 0.001).

Commentary

The results of this analysis, which relies on an historical control group, can only be taken as suggestive that early preemptive therapy improves outcomes in patients with candidiasis. The results, nonetheless, are consistent with another retrospective study of 134 patients with candidemia that found that initiation of antifungal therapy within 12 hours of the phlebotomy that yielded the first positive blood culture was associated with a significantly improved survival when compared to later times of initiation.l Thus, waiting for a positive blood culture may be too late, especially since as many as one-half of patients with nvasive candidiasis, even with dissemination, may have negative blood cultures. A variety of scoring systems have been utilized, but their accuracy is uncertain. Whether the commercial availability of a test that detects fungal -glucan in serum2 will help the clinician remains uncertain. In general, empiric antifungal therapy in a critical care patient, especially one who has undergone abdominal surgery, should be considered when the patient remains persistently febrile in the face of broad spectrum antibiotic therapy and is colonized with Candida spp.

Once having decided to initiate antifungal therapy, a choice must be made among the available agents. This choice is conditioned by the spectrum of activity against various Candida spp., whether the agent is fungicidal or fungistatic against these organisms, potential toxicity and drug interactions, and cost. Recommendations may be gleaned from the guidelines of the Infectious Disease Society of America,3 as well as in a more recently published paper.4 In the latter, it is recommended that empiric therapy with fluconazole should not be used if the patient is hemodynamically unstable or is neutropenic and/or if Candida glabrata or Candida krusei are likely causes. In such cases, a polyene, an echinocandin or, possibly, voriconazole are preferred.

References

  1. Morrell M, et al. Delaying the Empiric Treatment of Candida Bloodstream Infection Until Positive Blood Culture Results Are Obtained: A Potential Risk Factor for Hospital Mortality. Antimicrob Agents Chemother. 2005;49:3640-3645.
  2. Ostrosky-Zeichner L, et al. Multicenter Clinical Evaluation of the (1-->3) Beta-D-Glucan Assay As An Aid to Diagnosis of Fungal Infections in Humans. Clin Infect Dis. 2005;41:654-659.
  3. Pappas PG, et al. Guidelines for Treatment of Candidiasis. Clin Infect Dis. 2004;38:161-189.
  4. Spellberg BJ, et al. Current Treatment Strategies for Disseminated Candidiasis. Clin Infect Dis. 2006;42:244-251.