Fluconazole resistance in cryptococcal disease: emerging or intrinsic?

With the widespread use of long-term fluconazole prophylaxis and suppressive treatment, the potential development of fluconazole resistance poses a threat to the management of cryptococcal disease. Interpretive breakpoints for the in vitro antifungal susceptibility testing of C. neoformans have not been established and it is unclear whether the fluconazole minimum inhibitory concentration (MIC) is clinically relevant. To gain insight into the management of patients with cryptococcosis who fail fluconazole therapy, we conducted a PubMed literature search for cases of fluconazole-resistant cryptococcosis reported from 1991 to 2011. A total of 20 such cases were identified in which most patients had AIDS and 30% had never had prior exposure to fluconazole. Fluconazole failure in patients with cryptococcal disease cannot be fully attributed to emerging resistance of the etiologic agent and heteroresistance is a potential alternative mechanism. There is a need to refine the definition of fluconazole-resistant cryptococcosis and additional studies of such patients will improve treatment strategies and outcomes.

Aspergillus endocarditis 2003-2009.

A retrospective study of 35 case reports of Aspergillus endocarditis published between 2003 and 2009 was carried out. Fifteen percent of cases presented with a new cardiac murmur, 38% with an embolus. Eighty percent of cases involved the aortic or mitral valves. Seventy-four percent of cases involved patients with a history of prior surgery, 48% of these involved a heart valve, 20% had other cardiac surgery and 32% had non-cardiac surgery. Galactomannan testing was helpful diagnostically in four out of nine cases, but PCR testing was positive in six out of six cases. Overall mortality was 68%, all eight survivors had heart valve surgery apart from one - an 8-month-old child. Seven out of eight survivors received liposomal amphotericin B, three of these in combination with other antifungals. We need to think more about the possibility of Aspergillus endocarditis, particularly in immunocompromised patients with recent surgery. Galactomannan and PCR testing may be used more vigorously. Valve replacement, or at least vegetectomy, should be carried out in all patients. Liposomal amphotericin B, 3-5mg/kg/day, for at least 4 weeks is the treatment of choice. Oral voriconazole should be used for at least 2 years. Posaconazole may be an alternative, however there have been no prior cases reported to suggest its efficacy. The value of combination antifungal therapy is uncertain, but consideration should be given to the use of a second agent in addition to liposomal amphotericin. While further case reports on this condition will be helpful, more definitive management guidelines will depend on a prospective study.

Three cases of Q fever osteomyelitis in children and a review of the literature.

Q fever is a common zoonosis worldwide. Awareness of the disease and newer diagnostic modalities have resulted in increasing recognition of unusual manifestations. We report 3 cases of Q fever osteomyelitis in children and review the literature on 11 other reported cases. The cases demonstrate that Coxiella burnetii can cause granulomatous osteomyelitis that presents without systemic symptoms and frequently results in a chronic, relapsing, multifocal clinical course. Optimal selection and duration of antimicrobial therapy and methods of monitoring therapy are currently uncertain.