"Bayis Ilh Tus - a strong breath" a community-based research project to estimate the prevalence of chronic obstructive pulmonary disease in remote and rural first nations communities in Canada: research protocol.

BACKGROUND: Respiratory health conditions appear to be more common among First Nations people versus non-First Nations people in Canada. However, the prevalence of chronic obstructive pulmonary disease (COPD) and its associated risk factors in First Nations communities are unknown. This project aims to estimate the prevalence of COPD in several First Nations communities in British Columbia, Canada and to characterize respiratory symptoms, COPD risk factors, and healthcare utilization. METHODS: This project is approved by both the University of British Columbia and Carrier Sekani Family Services Research Ethics Boards. We will randomly sample 220 adults, 30 years and older, from 11 participating First Nations. Each participant will complete pre- and post-bronchodilator spirometry tests and the adapted American Thoracic Society Epidemiological Questionnaire with items about smoking history, respiratory symptoms, co-morbidities, and exposures, in order to identify the presence of COPD and its associated individual, occupational, and community risk factors. Homes will be assessed for air quality measures including particulate matter, carbon monoxide and carbon dioxide, and humidity. Health care utilization will be abstracted from the electronic medical record. DISCUSSION: This is the first project in Canada to estimate the prevalence of COPD in First Nations communities using a random-sampling approach to recruitment. Additionally, although this study will collect detailed information on smoking history, we will also characterize past and current risk factors beyond cigarette smoking. Finally, our methodology ensures that the benefits to the communities are realized during the study period. Individual results will be shared with individuals and health providers to facilitate care. Air quality results will be sent to each Nation's governing council to facilitate remediation where necessary. TRIAL REGISTRATION: The study has been retrospectively registered at clinicaltrials.gov ( NCT04105088 ).

Noise exposure among teachers in technology educational shops in selected British Columbia, Canada, high schools.

Teachers in technology education shops (TESs) in high schools are at risk from exposure to occupational hazards, including physical work demands and chemicals, particulate matter and noise, as well as non-optimal working conditions negatively affected by temperature, humidity, and lighting. This study evaluated the exposure to noise of 17 TES teachers working in 17 wood-working, metal-working, and automotive shops in selected high schools in British Columbia, Canada, and examined the quality of the acoustical teaching environments due to background noise. This study characterized noise control measures in the sampled TESs and observed the safety practices of teachers during TES classes. The results of this investigation indicated that almost 60% of the participating teachers were exposed to unacceptable levels of noise during teaching and working in TESs. It also showed that TES acoustical environmental quality was adversely affected by high background noise levels due to poor room designs and settings. Practical recommendations were provided to reduce and control the exposure to noise in TESs and to enhance the quality of health, safety, and quality of teaching environment in these TESs.

Climate Classification System-Based Determination of Temperate Climate Detection of Cryptococcus gattii sensu lato.

We compared 2 climate classification systems describing georeferenced environmental Cryptococcus gattii sensu lato isolations occurring during 1989-2016. Each system suggests the fungus was isolated in temperate climates before the 1999 outbreak on Vancouver Island, British Columbia, Canada. However, the Köppen-Geiger system is more precise and should be used to define climates where pathogens are detected.

Searching for clues for eighteen years: Deciphering the ecological determinants of Cryptococcus gattii on Vancouver Island, British Columbia.

Cryptococcus gattii emerged on Vancouver Island in 1999 for unknown reasons, causing human and animal fatalities and illness. The apparent emergence of this fungus in another temperate area, this time in the Pacific Northwest, suggests the fungus may have expanded its ecological niche. Yet studies that directly examine the potential roles of climatic and land use changes on C. gattii are still lacking. We aim to summarize the existing global literature on the ecology of C. gattii, with particular focus on the gap in knowledge surrounding the potential effects of climatic and land use changes. We systematically reviewed English peer-reviewed literature on the ecological determinants of C. gattii. We included studies published from January 1970 through June 2016 and identified 56 relevant studies for our review. We identified environmental isolations of C. gattii from 18 countries, spanning 72 separate regions across six continents. Fifty-three tree species were associated with C. gattii, spanning 10 climate classifications and 36 terrestrial ecoregions. No studies directly tested the potential effects of climatic changes (including climatic oscillations and global climate change) on C. gattii, while only one study directly assessed those of land use change. To improve model predictions of current and future distributions of C. gattii, more focus is needed on the potential effects of climatic and land use changes to help decrease the public health risk. The apparent emergence of C. gattii in British Columbia is also an opportunity to explore the factors behind emerging infectious diseases in Canada and elsewhere.

Climatic Influences on Cryptococcus gattii [corrected] Populations, Vancouver Island, Canada, 2002-2004.

Vancouver Island, Canada, reports the world's highest incidence of Cryptococcus gattii infection among humans and animals. To identify key biophysical factors modulating environmental concentrations, we evaluated monthly concentrations of C. gatti in air, soil, and trees over a 3-year period. The 2 study datasets were repeatedly measured plots and newly sampled plots. We used hierarchical generalized linear and mixed effect models to determine associations. Climate systematically influenced C. gattii concentrations in all environmental media tested; in soil and on trees, concentrations decreased when temperatures were warmer. Wind may be a key process that transferred C. gattii from soil into air and onto trees. C. gattii results for tree and air samples were more likely to be positive during periods of higher solar radiation. These results improve the understanding of the places and periods with the greatest C. gattii colonization. Refined risk projections may help susceptible persons avoid activities that disturb the topsoil during relatively cool summer days.

Novel oral amphotericin B formulation (iCo-010) remains highly effective against murine systemic candidiasis following exposure to tropical temperature.

PURPOSE: To evaluate the antifungal activity of amphotericin B (AmB) in a mouse model of systemic candidiasis following administration of a novel oral AmB formulation (iCo-010) that has been pre-exposed to tropical temperatures. METHODS: Amphotericin B (AmB) was prepared as a 5 mg/mL dispersion in a mixture of Peceol, Gelucire 44/14 and VitE-TPGS 2,3 (iCo-010). The formulation was protected from light and incubated in a sealed container at 43 °C for 60 days. Mice infected with Candida albicans were treated with either iCo-010 formulation pre-incubated at 43 °C for 60 days or freshly prepared iCo-010 formulation at doses of 5, 10 and 20 mg/kg once daily for five consecutive days. Single intravenous 5 mg/kg dose of AmBisome® was used as a positive control group. Seven days following the last dose, the kidney, liver, spleen, lung, heart and brain were removed and the number of colony forming units (CFUs) was determined as a measure of tissue fungal load. In addition, the concentration of AmB within each tissue was determined using high performance liquid chromatography (HPLC). RESULTS: There were no significant differences in the reduction of CFUs and the concentration of AmB recovered in all organs at all iCo-010 doses tested between the freshly prepared iCo-010 formulation compared to the formulation that was incubated at 43 °C for 60 days. CONCLUSIONS: A novel oral AmB formulation, iCo-010, incubated at 43 °C for 60 days to simulate the exposure of the formulation to tropical temperatures remained highly effective against murine systemic candidiasis.

Prevalence of indoor air pollutants from First Nation homes in North Central British Columbia, Canada.

Poor indoor air quality poses significant health risks. This study addresses the gap in knowledge regarding the prevalence of indoor air pollutants in remote and rural First Nation communities in north-central British Columbia, Canada. Dust samples from 75 homes were collected and analysed for house dust mites, pet allergens, mould antigens, and bacterial endotoxins. Indoor air quality parameters, including carbon monoxide, carbon dioxide, particulate matter, temperature, and humidity, were measured. A detailed questionnaire on household characteristics and potential pollutant sources was administered. Homes exhibited exposure to multiple pollutants, with wood stove smoke identified as a primary source. Felis domesticus (cat allergen) and Canis familiaris (dog allergen) were prevalent, with detectable levels in 64% and 60% of homes, respectively. Bacterial endotoxins were present in all households. One-third of homes exceeded recommended thresholds for 3 or more pollutants. This study provides critical insights into the prevalence and magnitude of indoor air pollutants, contributing to a broader initiative to characterise respiratory health in First Nations communities. While many homes in First Nations communities had acceptable air quality, one-third of homes exceeded thresholds for 3 or more pollutants. The results can guide ongoing community efforts to address housing concerns and advocate for increased federal funding.

Efficacy of an oral and tropically stable lipid-based formulation of Amphotericin B (iCo-010) in an experimental mouse model of systemic candidiasis.

OBJECTIVE: An oral lipid based formulation that exhibits tropical stability (iCo-010) was developed to enhance the absorption of orally administered amphotericin B (AmB). iCo-010 has previously shown high efficacy in an acute model of systemic candidiasis in rats, directing the focus of this study to be its efficacy in a chronic model of systemic candidiasis in mice. METHODS: Mice were infected with 0.6 to 1×108 CFUs of Candida albicans ATCC 18804 strain by tail vein injection and were left for three days to develop the infection after which time treatment was initiated. The infected animals were assigned to the following treatment groups: no treatment (control) or iCo-010 at 5, 10 and 20 mg/kg administered by oral gavage once daily (QD) for 5 consecutive days. The animals were sacrificed 7 days after the last dose and the concentration of AmB and the fungal burden were assessed within the liver, kidneys, heart, lungs, spleen and brain. RESULTS: Although the infection was relatively low (~ 60-100 CFUs/ 1 ml tissue homogenate) in the liver, lungs and heart, the infection level was very high (70 000 CFUs / 1 ml tissue homogenate) in the kidney tissues for the control group. The highest concentrations of AmB were recovered in the kidneys and the spleen. The fungal burden in the tissues was lowered by 69-96% in the treatment groups when compared to the control group. CONCLUSION: Oral iCo-010 is an effective treatment of systemic candidiasis in the mouse model.

Detection of Cryptococcus gattii in selected urban parks of the Willamette Valley, Oregon.

Human and animal infections of the fungus Cryptococcus gattii have been recognized in Oregon since 2006. Transmission is primarily via airborne environmental spores and now thought to be locally acquired due to infection in non-migratory animals and humans with no travel history. Previous published efforts to detect C. gattii from tree swabs and soil samples in Oregon have been unsuccessful. This study was conducted to determine the presence of C. gattii in selected urban parks of Oregon cities within the Willamette Valley where both human and animal cases of C. gattii have been diagnosed. Urban parks were sampled due to spatial and temporal overlap of humans, companion animals and wildlife. Two of 64 parks had positive samples for C. gattii. One park had a positive tree and the other park, 60 miles away, had positive bark mulch samples from a walkway. Genotypic subtypes identified included C. gattii VGIIa and VGIIc, both considered highly virulent in murine host models.

A decade of experience: Cryptococcus gattii in British Columbia.

It has been over a decade since Cryptococcus gattii was first recognized as the causative organism of an outbreak of cryptococcosis on Vancouver Island, British Columbia. A number of novel observations have been associated with the study of this emergent pathogen. A novel genotype of C. gattii, VGIIa was described as the major genotype associated with clinical disease. Minor genotypes, VGIIb and VGI, are also responsible for disease in British Columbians, in both human and animal populations. The clinical major genotype VGIIa and minor genotype VGIIb are identical to C. gattii isolated from the environment of Vancouver Island. There is more heterogeneity in VGI, and a clear association with the environment is not apparent. Between 1999 and 2010, there have been 281 cases of C. gattii cryptococcosis. Risk factors for infection are reported to be age greater than 50 years, history of smoking, corticosteroid use, HIV infection, and history of cancer or chronic lung disease. The major C. gattii genotype VGIIa is as virulent in mice as the model Cryptococcus, H99 C. neoformans, although the outbreak strain produces a less protective inflammatory response in C57BL/6 mice. The minor genotype VGIIb is significantly less virulent in mouse models. Cryptococcus gattii is found associated with native trees and soil on Vancouver Island. Transiently positive isolations have been made from air and water. An ecological niche for this organism is associated within a limited biogeoclimatic zone characterized by daily average winter temperatures above freezing.

Surveillance for Cryptococcus gattii in horses of Vancouver Island, British Columbia, Canada.

In the last decade Cryptococcus gattii has emerged as an important human and animal pathogen in southwestern British Columbia (BC), Canada. When the disease initially emerged it was identified in humans and multiple animal species on the east coast of Vancouver Island. From fall 2003 until summer 2004, active surveillance was initiated to look for horses exposed to or infected with the organism by performing nasal cultures and serum antigen testing in horses residing within 10 km of known areas of environmental reservoirs of the fungus. Surveillance efforts were facilitated by local equine practitioners who were also encouraged to report clinical cases. Nasal colonization was identified in four of the 260 horses tested but none had a serum cryptococcal antigen titer. All positive horses were from the same geographic area near Duncan, BC. During the study period, a single horse was diagnosed with systemic cryptococcosis and euthanized; clinical and post mortem information is described. As this organism continues to disseminate in the Pacific Northwest it is important for veterinarians to be familiar with the disease as early diagnosis may enable more effective treatment.

In vitro cytotoxicity of two novel oral formulations of Amphotericin B (iCo-009 and iCo-010) against Candida albicans, human monocytic and kidney cell lines.

BACKGROUND: Invasive fungal infections such as candidiasis constitute an increasingly important medical problem. Drugs currently used for the treatment of candidiasis include polyenes (such as Amphotericin B) and azoles. Amphotericin B (AmpB) presents several limitations such as its nephrotoxicity and limited solubility. We have developed two novel lipid-based AmpB formulations which in vivo show less nephrotoxicity and enhanced solubility compared to Fungizone™ a commercial AmpB formulation. The purpose of this study was to determine the cytotoxicity of Fungizone™, Ambisome™ and two novel AmpB formulations (iCo-009 and iCo-010) against Candida albicans, human kidney (293T) cells and monocytic (THP1) cells. METHODS: Cell cytotoxicity to the AmpB formulations was evaluated by MTS and LDH assays. In vitro anti-Candida albicans activity was assessed after a 48 h drug incubation. RESULTS: None of the AmpB formulations tested showed cytotoxicity against 293T cells. In the case of THP1 cells only Fungizone™ and Ambisome™ showed cytotoxicity at 500 µg/L (n = 4-10, p < 0.05).The calculated EC50 to Candida albicans for the different formulations was as follows: 26.8 ± 2.9 for iCo-010, 74.6 ± 8.9 for iCo-009, 109 ± 31 for Ambisome™ and 87.1 ± 22 for Fungizone™ (µg of AmpB/L, n = 6-12, p < 0.05). CONCLUSIONS: The AmpB formulations analyzed were not cytotoxic to 293T cells. Cytotoxicity in THP1 cells was observed for Fungizone™ and Ambisome™, but not with the novel AmpB formulations. iCo-010 had higher efficacy compared to other three AmpB formulations in the Candida albicans model.The absence of cytotoxicity as well as its higher efficacy for the Candida model compared to Fungizone™ and Ambisome™ suggest that iCo-010 has potential in treating candidiasis.

Respiratory health of two cohorts of terminal grain elevator workers studied 30 years apart.

INTRODUCTION: We evaluated the respiratory health of two cohorts of grain terminal elevator workers who participated in one of either respiratory health surveys undertaken in 1978 and 2008. METHODS: Questionnaire and spirometry data from 584 workers from the 1978 survey and 215 workers from the 2008 survey were compared using logistic regression and general linear modeling. RESULTS: The geometric means of area samples of grain dust averaged 8.28 mg/m(3) in 1978 and 2.06 mg/m(3) in 2008. Workers in the 1978 survey had a significantly higher prevalence of respiratory symptoms (with the largest adjusted odds ratio of 3.78, 95% CI 2.07-7.25, for shortness of breath), a lower prevalence of atopic conditions and lower mean lung function. CONCLUSION: Current grain workers had a lower risk of respiratory health consequences and a greater prevalence of atopic conditions than workers surveyed 30 years prior, most likely associated with reduced exposure to grain dust in the terminal elevator environment.

Ambient concentrations of airborne endotoxin in two cities in the interior of British Columbia, Canada.

This study measured and analyzed the outdoor airborne endotoxin concentration, on particulate matter (PM²·5 and PM¹°), for two cities in the interior of British Columbia, Canada. Samples were collected throughout one seasonal cycle, from October 2005 to September 2006. It was found that concentrations were generally highest in the summer and fall, and lowest in the winter and spring. Temperature and relative humidity were found to be most influential, with highest endotoxin concentrations recorded during warm periods and moderate relative humidity (35 to 75 percent). No clear association of concentration with wind direction was observed. Results were comparable between the two cities considered in this study, and concentrations were similar to or slightly higher than those reported by other studies considering urban locations. Endotoxin concentration was also found to be positively associated with agricultural dust sources identified by a source apportionment study conducted at one of the sampling locations.

In vitro antifungal susceptibilities and amplified fragment length polymorphism genotyping of a worldwide collection of 350 clinical, veterinary, and environmental Cryptococcus gattii isolates.

The in vitro susceptibilities of a worldwide collection of 350 Cryptococcus gattii isolates to seven antifungal drugs, including the new triazole isavuconazole, were tested. With amplified fragment length polymorphism (AFLP) fingerprinting, human, veterinary, and environmental C. gattii isolates were subdivided into seven AFLP genotypes, including the interspecies hybrids AFLP8 and AFLP9. The majority of clinical isolates (n = 215) comprised genotypes AFLP4 (n = 76) and AFLP6 (n = 103). The clinical AFLP6 isolates had significantly higher geometric mean MICs for flucytosine and fluconazole than the clinical AFLP4 isolates. Of the seven antifungal compounds examined in this study, isavuconazole had the lowest MIC(90) (0.125 µg/ml) for all C. gattii isolates, followed by a 1 log(2) dilution step increase (MIC(90), 0.25 µg/ml) for itraconazole, voriconazole, and posaconazole. Amphotericin B had an acceptable MIC(90) of 0.5 µg/ml, but fluconazole and flucytosine had relatively high MIC(90)s of 8 µg/ml.

Spread of Cryptococcus gattii into Pacific Northwest region of the United States.

Cryptococcus gattii has emerged as a human and animal pathogen in the Pacific Northwest. First recognized on Vancouver Island, British Columbia, Canada, it now involves mainland British Columbia, and Washington and Oregon in the United States. In Canada, the incidence of disease has been one of the highest worldwide. In the United States, lack of cryptococcal species identification and case surveillance limit our knowledge of C. gattii epidemiology. Infections in the Pacific Northwest are caused by multiple genotypes, but the major strain is genetically novel and may have emerged recently in association with unique mating or environmental changes. C. gattii disease affects immunocompromised and immunocompetent persons, causing substantial illness and death. Successful management requires an aggressive medical and surgical approach and consideration of potentially variable antifungal drug susceptibilities. We summarize the study results of a group of investigators and review current knowledge with the goal of increasing awareness and highlighting areas where further knowledge is required.

Biomarkers of airway acidity and oxidative stress in exhaled breath condensate from grain workers.

RATIONALE: Grain workers report adverse respiratory symptoms due to exposures to grain dust and endotoxin. Studies have shown that biomarkers in exhaled breath condensate (EBC) vary with the severity of airway inflammation. OBJECTIVES: The purpose of the study was to evaluate biomarkers of airway acidity (pH and ammonium [NH(4)(+)]) and oxidative stress (8-isoprostane) in the EBC of grain workers. METHODS: A total of 75 workers from 5 terminal elevators participated. In addition to EBC sampling, exposure monitoring for inhalable grain dust and endotoxin was performed; spirometry, allergy testing, and a respiratory questionnaire derived from that of the American Thoracic Society were administered. MEASUREMENTS AND MAIN RESULTS: Dust and endotoxin levels ranged from 0.010 to 13 mg/m(3) (median, 1.0) and 8.1 to 11,000 endotoxin units/m(3) (median, 610) respectively. EBC pH values varied from 4.3 to 8.2 (median, 7.9); NH(4)(+) values from 22 to 2,400 microM (median, 420); and 8-isoprostane values from 1.3 to 45 pg/ml (median, 11). Univariate and multivariable analyses revealed a consistent effect of cumulative smoking and obesity with decreased pH and NH(4)(+), and intensity of grain dust and endotoxin with increased 8-isoprostane. Duration of work on the test day was associated with decreased pH and NH(4)(+), whereas duration of employment in the industry was associated with decreased 8-isoprostane. CONCLUSIONS: Chronic exposures are associated with airway acidity, whereas acute exposures are more closely associated with oxidative stress. These results suggest that the collection of EBC may contribute to predicting the pathological state of the airways of workers exposed to acute and chronic factors.

Within- and between-person variability of exhaled breath condensate pH and NH4+ in never and current smokers.

Recent studies have suggested that the collection of exhaled breath condensate (EBC) may be a viable method in occupational field studies to sample secretions of the lower airway because it is simple to perform and non-invasive. However, there are unresolved questions about whether certain laboratory conditions may influence the analysis of EBC biomarker measurements. A total of 12 subjects performed 116 EBC tests. The effect of short and long-term sample storage and sample volume on two biomarkers of acid stress, pH and NH4+, in EBC were investigated and did not significantly influence either marker measurement after argon deaeration. We also investigated the variability and the effect of smoking on the biomarkers by collecting six samples each from five adult never smokers and five adult current smokers over a period of 1 month (n=60 total). For pH, the within-person and between-person variability was larger in current smokers compared to never smokers. Similar results were found for NH4+. Cigarette packs smoked per day now was also associated with both pH (p=0.01) and NH4+ (p=0.04) using mixed effects regression analysis. The variability and smoking results suggest that repeated measurements of EBC pH and NH4+ from the same individual may accurately predict the biological state of the airways of current smokers when compared to never smokers.

Communicating the risks of a new, emerging pathogen: the case of Cryptococcus gattii.

The news media are an important channel for communicating public health messages, providing important information about geographic extent, symptoms, and precautionary measures. This function may be particularly important in the case of new and emerging infectious diseases, which are unfamiliar to both the public and health professionals. We conducted a content analysis of the coverage in six Canadian newspapers of two emerging infectious pathogens in British Columbia (BC), West Nile virus and Cryptococcus gattii (C. gattii), between 2001 and 2006. C. gattii was first identified in the Canadian Pacific Northwest in 1999, having previously been restricted to tropical and subtropical areas. By summer 2006, C. gattii had killed at least eight people and was responsible for over 150 hospitalizations in the province of BC, as well as significant morbidity and mortality among companion animals. West Nile virus reached Canada in 2001 and has since caused significant morbidity and mortality. It has not, to date, reached BC. Despite the much higher incidence of disease and death caused by C. gattii in BC, West Nile virus received five times more news coverage in the British Columbian and national newspapers examined. Surprisingly, the local newspaper closest to the center of the British Columbia C. gattii outbreak had a much lower proportion of coverage of the disease than other papers in the province. The article discusses possible explanations for these findings, and the implications for public health communication.

Assessing the antifungal activity, pharmacokinetics, and tissue distribution of amphotericin B following the administration of Abelcet and AmBisome in combination with caspofungin to rats infected with Aspergillus fumigatus.

The purpose of this study was to assess the antifungal activity, pharmacokinetics, and tissue distribution of amphotericin B (AmpB) following the administration of Abelcet and AmBisome alone and in combination with Caspofungin to rats infected with Aspergillus fumigatus. Aspergillus fumigatus inoculum (2.1-2.5 x 10(7) colony forming units [CFU]) was injected via the jugular vein; 48 h later male albino Sprague-Dawley rats (350-400 g) were administered either a single intravenous (i.v.) dose of Abelcet (5 mg AmpB/kg; n = 6), AmBisome (5 mg AmpB/kg; n = 6), Caspofungin (3 mg/kg; n = 5), Abelcet (5 mg AmpB/kg) plus Caspofungin (3 mg/kg) (n = 6), AmBisome (5 mg AmpB/kg) plus Caspofungin (3 mg/kg) (n = 7), or physiologic saline (non-treated controls; n = 6) once daily for 4 days. Antifungal activity was assessed by organ CFU concentrations and plasma galactomannan levels. Plasma and tissue samples were taken from each animal for AmpB pharmacokinetic analysis and tissue distribution determinations. Abelcet treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 73% compared to non-treated controls. Ambisome treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 69% compared to non-treated controls. Caspofungin treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 80% compared to non-treated controls. Abelcet plus Caspofungin treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 81% compared to non-treated controls. Ambisome plus Caspofungin treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 98% compared to non-treated controls. Abelcet treatment significantly decreased plasma galactomannan levels by 50 and 75% 96 h following the initiation of treatment in the absence and presence of Caspofungin co-therapy, respectively. AmBisome treatment significantly decreased plasma galactomannan levels by 73 and 78% 96 h following the initiation of treatment in the absence and presence of Caspofungin co-therapy, respectively. Co-administration of Caspofungin with Abelcet and AmBisome did not significantly alter the plasma concentration-time profile, pharmacokinetic parameters, and tissue distribution of AmpB. Taken together, our findings suggest that an alternative mechanism, possibly at the cellular level rather than altered AmpB disposition, may be an explanation for the differences in organ CFU concentrations following Abelcet plus Caspofungin versus AmBisome plus Caspofungin administration.