Seminars in respiratory and critical care medicine
-
Resistance to the azole antifungals itraconazole, voriconazole, and posaconazole in Aspergillus species is a growing concern. This is especially alarming for A. fumigatus, where acquired resistance has been documented in patients with invasive disease caused by this species that were exposed to these agents, as well as in azole-naive individuals. The primary mechanisms of resistance that have been described in clinical strains include different point mutations in the CYP51A gene, which encodes the enzyme responsible for converting lanosterol to ergosterol via demethylation. ⋯ These mutations, including TR34/L98H and TR46/Y121F/T289A have also been found in the environment in several areas of the world and have been demonstrated to cause resistance to azole fungicides used in agriculture, thus raising the concern of environmental spread of resistance. Treatment options are limited in patients with infections caused by azole-resistant isolates and include amphotericin B formulations or combination therapy involving an echinocandin. However, there are few clinical data available to help guide therapy, and infections caused by resistant A. fumigatus isolates have been reported to have high mortality rates.
-
Semin Respir Crit Care Med · Oct 2015
ReviewPulmonary Sporotrichosis: An Evolving Clinical Paradigm.
In recent decades, sporotrichosis, caused by thermally dimorphic fungi Sporothrix schenckii complex, has become an emerging infection in many parts of the world. Pulmonary infection with S. schenckii still remains relatively uncommon, possibly due to underrecognition. ⋯ However, this changing knowledge has not yet been fully translated into a better understanding of the clinical aspects of pulmonary sporotrichosis, as such current management guidelines remain unsupported by high-level clinical evidence. This article examines recent advances in the knowledge of sporotrichosis and its application to the difficult challenges of managing pulmonary sporotrichosis.
-
Semin Respir Crit Care Med · Oct 2015
ReviewVoriconazole: How to Use This Antifungal Agent and What to Expect.
Voriconazole is an important agent in the antifungal armamentarium. It is the treatment of choice for invasive aspergillosis, other hyaline molds, and many brown-black molds. It is also effective for infections caused by Candida species, including those that are fluconazole resistant, and for infections caused by the endemic mycoses, including those that occur in the central nervous system. ⋯ Some of the adverse effects seen with voriconazole are related to high serum concentrations, and, as a result, therapeutic drug monitoring is essential when using this agent. Drug-drug interactions are common, and possible interactions must be sought before voriconazole is prescribed. With prolonged use, newly described adverse effects, including periostitis, alopecia, and development of skin cancers, have been noted.
-
Semin Respir Crit Care Med · Oct 2015
ReviewComplications of Candidemia in ICU Patients: Endophthalmitis, Osteomyelitis, Endocarditis.
Bloodstream infection with Candida species is not uncommon in the intensive care unit setting and has the potential to distribute organisms to many different organ systems causing secondary infections, such as endophthalmitis, osteomyelitis, and endocarditis. In some patients, these types of infections become manifested shortly after the episode of candidemia. In others, especially vertebral osteomyelitis, weeks pass before the diagnosis is entertained. ⋯ In patients who manifest symptoms or signs suggesting these infections, magnetic resonance imaging and transesophageal echocardiography, respectively, are extremely helpful diagnostic tests. Newer approaches to the treatment of these infections allow the use of better tolerated, safer antifungal agents. Endophthalmitis is often treated with fluconazole or voriconazole, and the echinocandins are increasingly used, instead of amphotericin B, as initial therapy for osteomyelitis and endocarditis before step-down therapy to oral azole agents.
-
Semin Respir Crit Care Med · Oct 2015
ReviewInvasive Aspergillosis: Epidemiology, Clinical Aspects, and Treatment.
Invasive aspergillosis remains an often fatal, difficult-to treat infection in immunocompromised patients. Patients not classically defined as immunocompromised, especially those in an intensive care unit setting, also develop invasive aspergillosis. ⋯ Voriconazole has supplanted amphotericin B, with its various toxicities, as primary treatment for invasive aspergillosis. Combination therapy with voriconazole and an echinocandin for initial therapy, based on results from a recent controlled clinical trial, could become the standard of care in high-risk patients.