Recognizing therapeutic failure

Cases are presented that raise the issue of how to recognize treatment failure, including radiologic, serologic, and/or clinical definitions with special attention to assessment when available information is conflicting or ambiguous. Just as the diagnosis of invasive aspergillus (IA) remains difficult to secure for many patients, so too is the assessment of a patient for possible treatment failure. Specifically the absence of a sensitive surrogate marker to monitor response leaves clinicians with several insensitive, non-specific and often conflicting pieces of information. For example, CT evidence of response is well-described to lag at least a week behind patient improvement and so this modality cannot be relied upon to assess daily or even weekly patient response. The clinical assessment of the patient is complicated by the presence or absence of neutropenia since patients may appear to worsen as their neutropenia recovers; conversely, patients with advanced infection may exhibit only subtle signs of IA if profoundly immunosuppressed. Finally, IA does not respond to any antifungal quickly; thus the clinician must patiently wait longer than is typical for a bacterial infection to determine whether the response is slow or simply not present. Assessment of a patient with IA for treatment failure is a complicated determination that requires the clinician to synthesize incomplete and often conflicting information. Further adding to the difficulty are the morbidity and mortality of the disease and the relative lack of effectiveness of the available antifungal agents.