Table 2. Responses to antifungal therapy in patients with candidemia and other forms of invasive candidiasis.
| Outcome, response | Criteria |
|---|---|
| Success | |
| Complete response | Survival and resolution of all attributable symptoms and signs of disease; plus |
| Documented clearance of pathogen from the blood in cases of candidemia; plus | |
| Documented clearance of infected sites that are accessible to repeated sampling (e.g., CSF) | |
| If additional cultures are not feasible (e.g., in cases of candidiasis involving visceral organs), survival and resolution of all attributable symptoms and signs of disease and radiological resolution can be equated with a complete response | |
| Partial response | Survival and improvement of attributable symptoms and signs of diseasea; plus |
| Documented clearance of blood in cases of candidemia; plus | |
| Documented clearance of infected sites that are accessible to repeated sampling (e.g., CSF). | |
| If additional cultures are not feasible, survival and resolution of attributable symptoms and signs of disease and radiological improvement or stabilization can be equated with a partial responseb | |
| Failure | |
| Stable response | Survival and minor or no improvement in attributable symptoms and signs of disease; plus |
| Persistent isolation of Candida species from blood specimens or specimens from other sterile sites; or | |
| If additional cultures are not feasible, radiological stabilization can be equated with a stable responseb | |
| Progression of disease | Persistent isolation of Candida species from blood specimens or specimens from other sterile sites in association with worsening clinical symptoms or signs of disease (e.g., septic shock, progression of hematogenous cutaneous candidiasis); or |
| New sites of disease or worsening of preexisting lesions radiologically (e.g., those observed in chronic disseminated candidiasis) in association with clinical deterioration | |
| Death | Death during the prespecified period of evaluation regardless of attribution |
NOTE. The minimum period of observation is 4 weeks after start of therapy. The rationale for this minimum period of evaluation is to detect relapses of disease. Relapse generally requires a positive result of a culture of a specimen of blood or of another sterile site and not simply recurrence of symptoms or signs (e.g., fever) that are generally nonspecific. In the specific cases of visceral organ involvement (e.g., endocarditis, meningitis, retinitis, or chronic disseminated candidiasis), we suggest a period of observation of at least 12 weeks after start of therapy.
Fever without localizing symptoms or other abnormal physical examination findings is the most common manifestation of candidemia. However, because fever can result from multiple causes unrelated to candidemia, we suggest that more weight be given to documented clearance of pathogens from the blood than to resolution of fever in the global assessment of response to therapy. Thus, the scenario of persistent or recurrent fever despite clearance of blood should be assessed as at least a partial response and, therefore, equated with a successful response.
In visceral candidiasis (e.g., hepatosplenic candidiasis) with negative blood culture results at baseline, persistent fever may be the only attributable clinical sign of candidiasis, and radiological abnormalities can persist for prolonged periods. In such situations, resolution of fever and stable radiological disease may be equated with a partial response. Laboratory markers, such as PCR and the (1→3)-β-d-glucan assay, have not been adequately validated as markers of response to therapy for invasive candidiasis.