Approximately half of the respondents are content with staying the course, while the other half chose to alter therapy.  I presume half believe that the patient is responding, while half believe that treatment is not producing an adequate response.  Generally, we use a combination of clinical, radiographic and microbiological evidence in determining response to therapy.  When all signals are pointing in the same direction, the decision is simple.  When the signals are mixed, as in this case, determining response is quite difficult. 

Clinical signs and symptoms are at best imprecise indicators of response. Radiography can provide some semi-quantitative data as to an increase or decrease in the 3-dimensional volume of the infiltrate.  The problem is that infiltrates can increase either due to greater pathogen burden or due to an increase in the host inflammatory response to the pathogen.  In this case, we are told that neutrophil recovery has occurred.  Earlier studies demonstrate that the natural history of Aspergillus pneumonia (that eventually gets better with antifungal therapy) is that the infiltrate worsens during the first week and only decreases after about two weeks^1,2.  Indeed, cavitation often occurs only at time of neutrophil recovery.  Immune reconstitution has been a well described cause of both clinical and radiographic worsening during treatment of a number of infectious syndromes, and this was recently noted in Aspergillosis². 

In this case, I believe immune reconstitution is the reason for the increase in the pulmonary infiltrate and continuing voriconazole is the most appropriate course of action.  The galactomannan test was positive when the infiltrate first appeared and repeating the test now is potentially useful in monitoring treatment response³.  The galactomannan assay converts to negativity in patients who respond, while remaining persistently positive in those who do not.  Such a surrogate marker can be enormously useful in determining if the fungal burden is coming under control.

Although this patient was responding to therapy, similar cases fail to respond.  There are several reasons for lack of response.  They include drug failure (resistance of the pathogen to the drug or inadequate dose), wrong diagnosis, superinfection or co-infection by another pathogen, or inability of the host to mount any protective defense.  How to evaluate these various possibilities is discussed with helpful suggestions in two articles now in press^4,5.