Efficacy and safety of posaconazole for chronic pulmonary aspergillosis.
BACKGROUND
Chronic pulmonary aspergillosis (CPA) is a severe, progressive respiratory infection characterized by multiple pulmonary cavities and increased levels of antibodies to Aspergillus species. We report the first use of posaconazole in patients with CPA.


METHODS
A retrospective study was performed. A composite clinical and radiological evaluation was used to assess response to posaconazole therapy. The rates of clinical response and failure after 6 and 12 months of therapy were determined. Kaplan-Meier survival models were developed to describe the time to clinical response and failure. The underlying diagnosis, the type of therapy (primary or salvage), Aspergillus antibody titer, and posaconazole serum concentrations were assessed as covariates. Aspergillus species were identified and minimum inhibitory concentrations (MICs) of triazoles were determined using standard techniques.


RESULTS
There were 79 patients that initially received posaconazole 400 mg twice per day. The median age of patients was 61 years, and 57% were male. Response to posaconazole was observed in 61% of patients at 6 months and in 46% at 12 months. Kaplan-Meier plots showed that the first response to posaconazole was observed in some patients only after approximately 1 year of therapy. Covariates were not significant. Adverse reactions were observed in 12 patients (15%) (nausea in 5, rash in 5, headache in 1, and lethargy in 1), leading to withdrawal of treatment for 9 patients. Aspergillus species were recovered from 22 patients. A posaconazole MIC of >8 mg/L was found in 4 isolates; in 1 of these isolates, this emerged during therapy. Treatment failed in all 4 patients from whom these 4 isolates had been recovered.


CONCLUSIONS
Posaconazole is a safe and partially effective treatment for CPA. Prospective comparative studies are now required.
Respiratory Research Group, Faculty of Medicine and the Human Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom. timothy.felton@manchester.ac.uk
Timothy W
TW
Felton
Caroline
C
Baxter
Caroline B
CB
Moore
Stephen A
SA
Roberts
William W
WW
Hope
David W
DW
Denning
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000908:Antibodies, Fungal / Q000097:blood; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology; D001230:Aspergillus / Q000187:drug effects / Q000302:isolation & purification; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D055732:Pulmonary Aspergillosis / Q000188:drug therapy* / Q000473:pathology; D013902:Radiography, Thoracic; D012189:Retrospective Studies; D044967:Serum / Q000737:chemistry / Q000276:immunology; D017211:Treatment Failure; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology
D000908:Antibodies, Fungal; D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole