Editor's Note: Candidiasis presents with a wide range of clinical manifestations, among which invasive candidiasis poses significant risks, leading to longer hospital stays, increased healthcare costs, and higher mortality rates. Research indicates that early empirical treatment (before blood culture results) combined with source control can improve survival rates. At a recent academic conference, Dr. Baiyi Chen from the Department of Infectious Diseases at the First Hospital of China Medical University provided a systematic overview of the key elements in the early empirical treatment of invasive candidiasis, sharing his clinical insights on the early empirical diagnosis and treatment of candidiasis.
When to Initiate Early Empirical Treatment for Invasive Candidiasis?
The core of initiating early empirical treatment lies in clinical recognition. Patients susceptible to invasive candidiasis generally experience a loss or breach of three major barriers: prolonged use of broad-spectrum antibiotics leading to a loss of microbial barrier function (manifested by high-intensity colonization of Candida at multiple sites), disruption of anatomical barriers due to various diseases and treatments, and defects in cellular immune barriers.
In clinical practice, healthcare professionals must remain highly vigilant with high-risk patients who may develop invasive candidiasis. For such patients, early empirical treatment should be considered when there is persistent fever unresponsive to sufficient antibacterial treatment, high-intensity Candida colonization at multiple sites (actively assessed), significant barrier function loss, hemodynamic and organ function disorders, and when the severity of the illness leaves no room for trial and error.
Selection of Antifungal Drugs for Early Empirical Treatment
The latest guidelines for invasive candidiasis recommend echinocandins as the first-line treatment due to their broad antifungal spectrum, strong in vitro fungicidal activity, good biofilm penetration, and high safety profile. However, with the widespread use of echinocandins, resistance issues have emerged, and rigidly adhering to guidelines may lead to new problems. Therefore, while following guidelines, clinicians should also develop clinical reasoning skills in drug selection, considering factors such as pathogen and resistance assessment, the extent of infection, severity of the disease, and potential drug toxicities to devise individualized treatment plans that allow for diverse therapeutic approaches.
First, pathogen identification and assessment are crucial. Individualized judgment of the most likely pathogen should be based on regional epidemiological data and the patient’s underlying conditions and prior antifungal exposure. The China Hospital Invasive Fungal Infection Surveillance Network (CHIF-NET) study shows that although the proportion of invasive candidiasis caused by Candida albicans has decreased, it remains the most common species, accounting for 41.8%. Candida parapsilosis complex ranks second at 23.8%, followed by Candida tropicalis (17.6%) and Candida glabrata complex (12.3%).
Regarding resistance, developed countries like the United States and Europe are primarily concerned with Candida glabrata’s resistance to echinocandins. In China, there is an upward trend in resistance to azole drugs among Candida tropicalis, and the emergence of Candida auris marks the entry into a multi-drug resistant era, presenting a challenging trend. This highlights the need for a more individualized approach in antifungal drug selection. Only through individualized treatment can diversity be achieved, thereby reducing the development of antifungal resistance.
Second, drug selection should consider not only bloodstream infections but also potential infections at other sites, such as liver, spleen, kidney, lung, and eye, especially in cases of catheter-related bloodstream infections. Addressing both the primary infection site and metastatic sites is essential for successful treatment. The key is to optimize the pharmacokinetics/pharmacodynamics (PK/PD) of antifungal drugs, particularly focusing on tissue penetration and dose optimization.
Finally, clinical decisions should also consider the severity of the illness, drug toxicities, and cost-effectiveness.
When to Discontinue Early Empirical Treatment?
It is easy to start anti-infective treatment but difficult to stop it. Studies have shown that the positive predictive value of existing evaluation tools, including various predictive instruments, is limited. The 2016 IDSA guidelines recommend discontinuing treatment if, after 4-5 days, the patient shows no response, there is no subsequent evidence of invasive candidiasis (e.g., negative blood cultures), or non-culture diagnostic evaluations (such as G-test) remain persistently negative. Research indicates that timely discontinuation of early empirical treatment based on biomarkers does not affect prognosis.
Conclusion
Diagnosing invasive candidiasis poses many challenges, making early empirical treatment and source control critical to reducing mortality. For high-risk patients, healthcare providers must remain highly vigilant, comprehensively considering risk factors, clinical manifestations, and laboratory tests to promptly identify Candida infections and initiate empirical treatment. When devising treatment plans, it is important to account for prior antifungal exposure, infer pathogen characteristics and resistance, consider pharmacokinetic properties, and assess the severity of the illness to tailor an individualized treatment plan. After initiating treatment, close monitoring of treatment efficacy and further diagnostic evaluations is essential to determine the optimal time for discontinuation. By practicing “individualized” treatment in drug selection and dosage adjustment, diverse anti-infective therapies can be achieved, which not only saves lives but also effectively curbs the development and spread of resistance.
