Background
It has been axiomatic that echinocandins (e.g., caspofungin) are ineffective against mucormycosis. However, on the basis of preclinical data, we recently began treating rhino-orbital-cerebral mucormycosis (ROCM) with combination polyene-caspofungin therapy.
Methods
To determine the impact of polyene-caspofungin therapy, ROCM cases identified by an International Classification of Diseases, Ninth Revision search were retrospectively reviewed to gather data on demographic characteristics, clinical history, and outcomes. The predefined primary end point was success (i.e., the patients was alive and not in hospice care) at 30 days after hospital discharge.
Results
Forty-one patients with biopsy-proven ROCM were identified over 12 years; 23 (56%) of these patients were Hispanic, and 34 (83%) were diabetic. Patients treated with polyene-caspofungin therapy (6 evaluable patients) had superior success (100% vs. 45%; P = .02) and Kaplan-Meier survival time (P = .02), compared with patients treated with polyene monotherapy. Patients treated with amphotericin B lipid complex had inferior success (37% vs. 72%; P = .03) and a higher clinical failure rate (45% vs. 21%; P = .04), compared with patients who received other polyenes. However, patients treated with amphotericin B lipid complex plus caspofungin had superior success (100% vs. 20%; P = .009) and survival time (P = .01), compared with patients who received amphotericin B lipid complex alone. The benefit of combination therapy, compared with monotherapy, was most pronounced in patients with cerebral involvement (success rate, 100% vs. 25%; P = .01). In multivariate analysis, only receipt of combination therapy was significantly associated with improved outcomes (odds ratio, 10.9; 95% confidence interval, 1.3–∞; P = .02).
Conclusions
Combination polyene-caspofungin therapy represents a promising potential alternative to polyene monotherapy for patients with ROCM. Randomized, prospective investigation of these findings is warranted.
Effective management of TB requires attention to potential structural, metabolic, vascular, and infectious complications. In some instances, individualizing treatment regimens may be necessary. Imunosuppression and other host factors predispose to complications; others occur despite adequate treatment. Public health TB programs and health systems require additional resources to provide comprehensive TB and post-TB care.
Arthropod-borne viruses (arboviruses) threaten the health of humans, livestock, and wildlife. West Nile virus (WNV), the world’s most widespread arbovirus, invaded the United States in 1999 and rapidly spread across the county. Although the ecology of vectors and hosts are key determinants of WNV prevalence across landscapes, the factors shaping local vector and host populations remain unclear. Here, we used spatially-explicit models to evaluate how three land-use types (orchards, vegetable/forage crops, natural) and two climatic variables (temperature, precipitation) influence the prevalence of WNV infections and vector/host distributions at landscape and local spatial scales. Across landscapes, we show that orchard habitats were associated with greater prevalence of WNV infections in reservoirs (birds) and incidental hosts (horses), while increased precipitation was associated with fewer infections. At local scales, orchard habitats increased the prevalence of WNV infections in vectors (mosquitoes) and the abundance of mosquitoes and two key reservoir species, the American robin and the house sparrow. Thus, orchard habitats benefitted WNV vectors and reservoir hosts locally, creating focal points for the transmission of WNV at landscape scales in the presence of suitable climatic conditions.
Multidrug-resistant tuberculosis (MDR-TB) is on the rise, and is difficult to treat. The approval of two new drugs, bedaquiline and delamanid, and growing evidence for the use of linezolid, offer renewed hope for addressing MDR-TB. However, access to these medicines remains a significant challenge. These drugs have not been registered for TB in most settings; barriers to preapproval access persist; and high pricing and intellectual property restrictions limit access. Many unanswered research questions about optimal use of these drugs also limit access, particularly for vulnerable populations. This review outlines challenges in accessing drugs encountered from the perspective of clinicians, patients and affected communities, and offers potential solutions.
There are many promising new agents in development for the treatment of HIV type 1 (HIV-1). The targets of antiretroviral drugs include the three major HIV-1 enzymes (reverse transcriptase, protease, and integrase), final packaging and export of mature virions, and entry mediated by the CD4 receptor and the CCR5 and CXCR4 coreceptors. Drugs in development in existing classes are primarily designed to provide new options for those with resistance to existing agents. Novel agents such as those targeting integrase, entry inhibitors, and those targeting viral processing likely will be useful the treatment of antiretroviral-experienced patients. Depending on safety, efficacy, tolerability, and convenience of dosing, new agents may also alter the current treatment paradigms for first-line therapy. This review summarizes data on several drugs that could move forward into the clinical arena and affect the lives of those infected with HIV-1.
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