A 44-year-old man with AML-M3 for two months was admitted to our hospital with fever and neutropenia (absolute neutrophil count = 400 cells/mm3) starting seven days after chemotherapy. At the time of admission, the patient presented with an oral temperature of 38 C; physical examination was otherwise normal. Specimens were obtained for blood culture (B/C), urine analysis (U/A), and urine culture (U/C). Meropenem was started subsequently. Chest X-ray showed patchy consolidation in both upper lung lobes, and the patient had a provisional diagnosis of health care associated pneumonia. Parenteral vancomycin and ciprofloxacin were added to meropenem; however, P. jiroveci was also probable according to CXR. High resolution computed tomography scan (HRCT) of the lungs was performed and revealed bilateral symmetrical peribronchovascular infiltration in both upper lobes and superior segment of lower lobes in favor of P. jiroveci (Figure 1). Co-trimoxazole and hydrocortisone (due to hypoxemia, with arterial oxygen pressure of 50 mm Hg while breathing room air) were administered.
First B/C and U/C were negative. Due to continuous fever, B/C, U/C and CXR were repeated; serum galactomannan was measured; and amphotericin B deoxycholate was started empirically. However, after the administration of amphotericin B, the patient developed severe chills and rigors. Thus, amphotericin B was changed to caspofungin. On day nine, he complained of shortness of breath and dyspnea; he remained febrile but leukocyte count increased to 4300/mm3 with a normal differential. Due to poor response to initial treatment for P. jiroveci, we changed co-trimoxazole to primaquine and clindamycin. One day later, a serum galactomannan index (GMI) of 1.7 was reported (GMI>=0.5 is regarded as positive). Therefore, a probable diagnosis of invasive pulmonary aspergillosis (IPA) was made, and consequently caspofungin was replaced with voriconazole. Bronchoscopy, bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) were performed; specimens were sent for tuberculosis polymerase chain reaction (PCR), P. jiroveci PCR, cytomegalovirus (CMV) PCR, herpes simplex virus PCR, galactomannan, cytology and bacterial and fungal culture. All of the above tests were negative except for the BAL sample for CMV PCR (quantitative PCR=1404 copies/mL). Because of this result and the clinical deterioration of the patient, we decided to add ganciclovir to his treatment protocol. On day 13, the fungal culture of BAL revealed Penicillium SP. This specimen was sent to the Reference Mycology Research Center and cultured on Sabouraud glucose agar (SGA), which revealed green-blue color and velvety appearance. Slide culture and lacto phenol staining were done. Penicillium notatum was identified based on slide culture morphology and colony shape (Figure 2 A,B).
On the other hand, TBLB (methylene blue staining of lung section) revealed severe interstitial inflammatory cells, fibrin deposition and reactive pneumocytes (Figure 3A) and intra alveolar eosinophilic material (Figure 3B) suggestive of P. jiroveci; accordingly, primaquine and clindamycin were continued for 14 days. In addition, the pathology report showed angioinvasion of fungal organism.
After eight days of receiving voriconazole, the patient's fever subsided and his dyspnea improved. This course of treatment was continued during the next 12 weeks. He is currently asymptomatic and repeated CXR revealed a regression of infiltration.