Mechanisms of Acquired In Vivo and In Vitro Resistance to Voriconazole by Candida krusei following Exposure to Suboptimal Drug Concentration.

Five Candida krusei isolates (susceptible and resistant) recovered from the urine of a kidney transplant patient treated with voriconazole (VRC) 200 mg twice daily for 20 days were studied. Eight unrelated clinical isolates of C. krusei were exposed in vitro to VRC 0.001 µg/ml for 30 days. Development of VRC transient resistance occurred in vivo, and induction of permanent resistance occurred in vitro Mostly, ABC1 and ERG11 genes were overexpressed, and a homozygous T418C mutation in the ERG11 gene was found.

New Insights Regarding Yeast Survival following Exposure to Liposomal Amphotericin B.

In vitro resistance to amphotericin B is an extremely rare event among pathogenic yeasts. However, in vivo response is sometimes reduced, resulting in an unfavorable outcome. Such adverse outcomes might be related to subfungicidal plasma concentrations. We aimed to clarify the mechanisms of liposomal amphotericin B (AMB-L; AmBisome)-induced lesions and the mechanisms responsible for yeast cell recovery following exposure at plasma concentrations. The physiological statuses developing following exposure to AMB-L at simulated plasma concentrations (20 to 0.1 mg/liter) and at a constant concentration (3 mg/liter) were assessed in a 24-h time course assay. Time-kill experiments also were carried out under the same AMB-L treatment conditions. Our results suggest that yeast cells develop compensatory responses related to membrane polarization, metabolic activity, and reactive oxygen species (ROS) production after exposure to high plasma concentrations (20 to 5 mg/liter) during the first 6 h; in the remaining 18 h, when exposed to lower concentrations, cells reveal almost full recovery with no evidence of fungicidal activity. In contrast, whenever cells are exposed to a constant concentration above the MIC, despite initially exhibiting compensatory stress responses, soon afterwards they exhibit membrane depolarization, a decrease of metabolic activity, increasing ROS production, and lastly, programmed cell death and necrosis, resulting in succumbing to AMB-L fungicidal effects. This study may represent a step forward in the support of AMB-L use for clinical treatment of invasive fungal infections, since it demonstrates the importance of maintaining levels of AMB-L above the MIC in plasma and tissues to ensure it produces its fungicidal effects.

In vivo and in vitro acquisition of resistance to voriconazole by Candida krusei.

Candida krusei is an important agent of opportunistic infections that often displays resistance to several antifungals. We describe here the in vivo acquisition of resistance to voriconazole (VRC) by C. krusei isolates recovered from a leukemia patient during a long period of VRC therapy. In order to mimic the in vivo development of VRC resistance, a susceptible C. krusei isolate was exposed daily to 1 µg/ml of VRC in vitro. Interestingly, after 5 days of exposure to VRC, a MIC of 4 µg/ml was achieved; this value remained constant after 25 additional days of treatment with VRC and also after 30 consecutive days of incubation in VRC-free medium. Our objective was to determine the associated molecular resistance mechanisms, such as expression of efflux pump genes and ERG11 gene mutations, among the resistant strains. Synergistic effects between the efflux blocker tacrolimus (FK506) and VRC were found in all of the resistant strains. Moreover, ABC1 gene expression increased over time in both the in vivo- and in vitro-induced resistant strains, in contrast to the ABC2 and ERG11 genes, whose expression was invariably lower and constant. ERG11 gene sequencing showed two different types of mutations, i.e., heterozygosity at T1389T/C, corresponding to synonymous mutations, in C. krusei strains and a missense mutation at position T418C, resulting in a change from Tyr to His, among resistant C. krusei clinical isolates. This study highlights the relevance of ATP-dependent efflux pump (namely, Abc1p) activity in VRC resistance and describes new mutations in the ERG11 gene among resistant C. krusei clinical isolates.

Evaluation of Giardia duodenalis viability after metronidazole treatment by flow cytometry.

Giardia duodenalis (syn. lamblia; syn. intestinalis) susceptibility testing is not routinely performed because the classical culture methods are very time-consuming and laborious. We developed a novel flow cytometry (FC) assay to evaluate the susceptibility of G. duodenalis trophozoites to metronidazole (MTZ). Different concentrations of MTZ were added to cultures of trophozoites (10 5 /mL) and the cultures were incubated for different periods. The 50% inhibitory concentration was calculated and propidium iodide (PI) was used to quantify the number of dead cells. After treatment, PI-positive trophozoites increased with increasing drug concentration and exposure time. An excellent correlation was found between FC and the classical method. A novel, accurate and reliable method is now available to evaluate G. duodenalis viability.

Genital Warts in Women Vaccinated against HPV in Childhood: A Systematic Review.

Human papillomavirus (HPV) is the most prevalent sexually transmitted infection among young women. Notably, more than ten years after the introduction of HPV vaccination programs in Europe, it is essential to review the real-world evidence of the incidence of anogenital warts (GWs) among women vaccinated during childhood. In this systematic review, three databases were searched for studies published between January 2008 and September 2023. Nine cohort studies were included. A total of 890,320 HPV-vaccinated women and 1,922,033 unvaccinated women were evaluated. All the studies but one investigated the 4vHPV vaccine. The incidence rate of GWs in vaccinated women ranged from 0.0 to 1650 per 100,000 person-years. The highest incidence rates were found in women vaccinated with one dose at the age of 17-19 years old and in fully vaccinated women only after 19 years of age. Similar incidence values were reported among unvaccinated women. The incidence of GWs was lower when the age at first dose was 9-11 years old. This systematic review reveals that the incidence of GWs among HPV-vaccinated women is related to the age of vaccination and the number of vaccine doses received. In the post-vaccination era, epidemiological surveillance of the incidence of GWs and their genotypes is crucial.

Reducing Blood Loss in a Burn Care Unit: A Review of Its Key Determinants.

Patients with a major burn injury differ considerably from the typical critical ill and trauma population. Very often, burn patients suffer from anemia throughout their hospital stay. This is caused both by combination of persistent blood loss with decreased erythropoiesis. Therefore, burn patients do have major transfusion requirements. However, transfusion is not devoid of risks or costs. We hereby review the best surgical techniques and medical approaches, aiming to reduce blood loss in a burn patient and optimize red cell production, so that we can reduce the need of RBC transfusion. The implementation of a combination of surgical techniques aiming to reduce blood loss and medical care approaches to prevent anemia, rather than single attitudes, should be adopted in burn care. There is an urgent need for clear guidelines that can easily be accepted, applied, and spread across different burn units to methodically implement measures to reduce blood loss and transfusion needs, and ultimately improve burn patients' outcome and the health care financial status.

Does repeated exposure to hydrogen peroxide induce Candida auris resistance?

BACKGROUND: To minimize environmental colonization by microorganisms that may persist and thrive in healthcare settings, thus reducing healthcare-associated infections (HAIs), new insights over already known biocides are certainly of relevance. Although the efficacy of hydrogen peroxide (H2O2) against the emergent yeast Candida auris is moderately documented, concerns over the potential induction of resistance after repeated exposure do persist. The main objective of the present study was to evaluate the hypothetical induction of Candida auris resistance following 30 days of consecutive exposure to lethal and sublethal concentrations of H2O2. Furthermore, the authors aimed to elucidate about the rank of efficacy of H2O2 against C. auris comparing to other Candida species and whether different strains of C. auris may display different susceptibilities to H2O2. METHODS: During the induction of resistance assays, both type strains and clinical isolates of Candida auris, Candida albicans and Candida parapsilosis were exposed repeatedly to defined concentrations of H2O2, for 30 days. RESULTS: After that period, no significant differences were found when comparing the minimal inhibitory concentration values of H2O2 in case of the induced strains versus each respective positive control. Moreover, H2O2 displayed similar effectiveness against all the tested Candida species and no differences were demonstrated among the distinct strains of C. auris. CONCLUSIONS: The adoption of H2O2 solutions in routine protocols in order to promote disinfection standards against Candida auris, improving patient safety and reducing healthcare costs, is certainly welcomed.

Impact of Human Papillomavirus Vaccination on Male Disease: A Systematic Review.

Human papillomavirus (HPV)-related diseases are highly prevalent in men worldwide, comprising external anogenital condyloma, anal intraepithelial neoplasia (AIN), penile intraepithelial neoplasia (PIN), and anogenital and oropharyngeal cancers. There is exceptionally low vaccine coverage in the male population. Only 4% of men were fully vaccinated, worldwide, as of 2019. The aim of this review is to assess the impact of HPV vaccination on male disease. Three databases (MEDLINE, Web of Science, Scopus) and Clinical Trials.gov were searched. We included thirteen studies, eight randomized controlled trials (RCTs), and five cohorts, comprising a total of 14,239 participants. Regarding anal disease, seven studies reported HPV vaccine efficacy ranging from 91.1% to 93.1% against AIN1, and ranging from 89.6% to 91.7% against AIN2|3 and anal cancer. Five studies showed an efficacy against genital condyloma of 89.9% in HPV-naïve males, varying between 66.7% and 67.2% in intention-to-treat populations. Studies reporting no efficacy have included older participants. These results support vaccination of young men previously infected, beyond HPV-naïve males. The evidence quality was moderate to low for most outcomes, namely genital diseases. RCTs are needed to assess the efficacy of HPV vaccination on male oropharyngeal cancer.

Mpox Person-to-Person Transmission-Where Have We Got So Far? A Systematic Review.

The recent multi-country outbreak of Mpox (Monkeypox disease) constituted a public health emergency. Although animal-to-human transmission is known to be the primary way of transmission, an increasing number of cases transmitted by person-to-person contact have been reported. During the recent Mpox outbreak sexual or intimate contact has been considered the most important way of transmission. However, other routes of transmission must not be ignored. The knowledge of how the Monkeypox Virus (MPXV) spreads is crucial to implement adequate measures to contain the spread of the disease. Therefore, this systematic review aimed to collect scientific data published concerning other implicated sources of infection beyond sexual interaction, such as the involvement of respiratory particles, contact with contaminated surfaces and skin-to-skin contact. The current study was performed using the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Publications analyzing contacts of Mpox index cases and their outcome after contact were included. A total of 7319 person-to-person contacts were surveyed and 273 of them became positive cases. Positive secondary transmission of MPXV was verified after contact with people cohabiting in the same household, with family members, with healthcare workers, or within healthcare facilities, and sexual contact or contact with contaminated surfaces. Using the same cup, sharing the same dishes, and sleeping in the same room or bed were also positively associated with transmission. Five studies showed no evidence of transmission despite contact with surfaces, skin-to-skin contact, or through airway particles within healthcare facilities where containment measures were taken. These records support the case for person-to-person transmission and suggest that other types of contact beyond sexual contact pose a significant risk of acquiring the infection. Further investigation is crucial to elucidate MPXV transmission dynamics, and to implement adequate measures to contain the spread of the infection.

Microbiota of Urine, Glans and Prostate Biopsies in Patients with Prostate Cancer Reveals a Dysbiosis in the Genitourinary System.

Prostate cancer (PCa) is the most common malignant neoplasm with the highest worldwide incidence in men aged 50 years and older. Emerging evidence suggests that the microbial dysbiosis may promote chronic inflammation linked to the development of PCa. Therefore, this study aims to compare the microbiota composition and diversity in urine, glans swabs, and prostate biopsies between men with PCa and non-PCa men. Microbial communities profiling was assessed through 16S rRNA sequencing. The results indicated that α-diversity (number and abundance of genera) was lower in prostate and glans, and higher in urine from patients with PCa, compared to non-PCa patients. The different genera of the bacterial community found in urine was significantly different in PCa patients compared to non-PCa patients, but they did not differ in glans and prostate. Moreover, comparing the bacterial communities present in the three different samples, urine and glans show a similar genus composition. Linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed significantly higher levels of the genera Streptococcus, Prevotella, Peptoniphilus, Negativicoccus, Actinomyces, Propionimicrobium, and Facklamia in urine of PCa patients, whereas Methylobacterium/Methylorubrum, Faecalibacterium, and Blautia were more abundant in the non-PCa patients. In glans, the genus Stenotrophomonas was enriched in PCa subjects, while Peptococcus was more abundant in non-PCa subjects. In prostate, Alishewanella, Paracoccus, Klebsiella, and Rothia were the overrepresented genera in the PCa group, while Actinomyces, Parabacteroides, Muribaculaceae sp., and Prevotella were overrepresented in the non-PCa group. These findings provide a strong background for the development of potential biomarkers with clinical interest.

Microbiome in Male Genital Mucosa (Prepuce, Glans, and Coronal Sulcus): A Systematic Review.

The human body represents a complex and diverse reservoir of microorganisms. Although the human microbiome remains poorly characterized and understood, it should not be underestimated, since recent studies have highlighted its importance in health. This is especially evident when considering microbiota in the male reproductive system, responsible for men's fertility and sexual behavior. Therefore, the aim of this systematic review is to provide an overview of the microbial communities of the healthy male genital mucosa and its role in disease. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was limited to the English language and studies published until August 2022 that included culture-independent techniques for microbiome characterization in male genital mucosa. Ten articles were included. The bacterial composition of the male genital mucosa consists of several genera including Prevotella, Finegoldia, Peptoniphilus, Staphylococcus, Corynebacterium, and Anaerococcus, suggesting that the male genital microbiome composition shows similarities with the adjacent anatomical sites and is related with sexual intercourse. Moreover, male circumcision appears to influence the penile microbiome. Despite the lack of knowledge on the male genital mucosa microbiome in disease, it was reported that Staphylococcus warneri and Prevotella bivia were associated with balanoposthitis, whereas Enterobacteriaceae, Prevotella, and Fusobacterium were more abundant in male genital lichen sclerosus. The limited data and paucity of prospective controlled studies highlight the need for additional studies and established criteria for sampling methods and the microbiome assay procedure. Such a consensus would foster the knowledge about the composition of the genital microbiome of healthy males and its role in disease.

Genetic relatedness and antifungal susceptibility profile of Candida albicans isolates from fungaemia patients.

A prospective study to assess fungaemia was conducted for 12 months at a Portuguese University Hospital. A total of 35 Candida albicans isolates obtained from 12 patients with fungaemia were compared by a multiplex PCR system using four microsatellite loci. Blood isolates were evaluated against concomitant isolates from urine, lower respiratory secretions and central venous catheters, as well as with successive isolates recovered from recurrent episodes of fungaemia. The data analyzed included the department of admission, underlying diseases and antifungal therapy. The susceptibility phenotypes of all isolates to amphotericin B, fluconazole, itraconazole, voriconazole and caspofungin were determined according to the CLSI M27-A3 protocol. We observed a high degree of similarity between successive blood isolates and between blood and concomitant isolates from other sites of the same patient. This is suggestive of the recurrence of fungaemia and was due to the same strain, possibly as a result of the failure of antifungal therapy. The genetic similarity observed between some strains isolated from different patients suggested the likelihood that they were hospital acquired. Distinct patients were infected by the same strain at different time periods, and an increase in antifungal resistance was observed over time for some of these strains. Hospital-acquired exogenous nosocomial infections can be associated with higher risks of antifungal resistance and need to be closely monitored. Particular attention should also be given to endogenous non-blood Candida isolates which can be critical in high risk patients, as they often can become invasive in immunodeficient individuals.

Animal model of implant capsular contracture: effects of chitosan.

BACKGROUND: The mechanism(s) responsible for breast capsular contracture (CC) remain unknown, but inflammatory pathways play a role. Various molecules have been attached to implant shells in the hope of modifying or preventing CC. The intrinsic antibacterial and antifungal activities of chitosan and related oligochitosan molecules lend themselves well to the study of the infectious hypothesis; chitosan's ability to bind to growth factors, its hemostatic action, and its ability to activate macrophages, cause cytokine stimulation, and increase the production of transforming growth factor (TGF)-ß1 allow study of the hypertrophic scar hypothesis. OBJECTIVE: The authors perform a comprehensive evaluation, in a rabbit model, of the relationship between CC and histological, microbiological, and immunological characteristics in the presence of a chitooligosaccharide (COS) mixture and a low molecular weight chitosan (LMWC). METHODS: Eleven adult New Zealand rabbits were each implanted with three silicone implants: a control implant, one impregnated with COS, and one impregnated with LMWC. At four-week sacrifice, microdialysates were obtained in the capsule-implant interfaces for tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8) level assessment. Histological and microbiological analyses were performed. RESULTS: Baker grade III/IV contractures were observed in the LMWC group, with thick capsules, dense connective tissue, and decreased IL-8 levels (p < .05) compared to control and COS groups. Capsule tissue bacterial types and microdialysate TNF-α levels were similar among all groups. CONCLUSIONS: Chitosan-associated silicone implantation in a rabbit model resulted in Baker grade III/IV CC. This preclinical study may provide a model to test various mechanistic hypotheses of breast capsule formation and subsequent CC.

Direct impression on agar surface as a diagnostic sampling procedure for candida balanitis.

BACKGROUND: The diagnosis of candida balanitis should be based upon both clinical and mycological data. The procedure of material collection is a critical issue to confirm or rule out the clinical diagnosis of candida balanitis. OBJECTIVE: To compare direct impression of the glans on the agar surface of solid culture media with the collection of genital exudates with cotton swab for the diagnosis of candida balanitis. METHODS: A prospective cross-sectional study was carried out during a 36-month period. Sexually transmitted disease clinic attendees with balanitis and asymptomatic men were included. Specimens for yeast culture were collected from the glans penis and inner preputial layer using the direct impression on CHROMagar candida medium and by swabbing with a sterile cotton swab. RESULTS: Among 478 men enrolled, 189 had balanitis. The prevalence of candida balanitis was 17.8% (85/478) confirmed after culture by direct impression; the swab method detected only 54/85 (63.5%) of these men. Of the 289 asymptomatic men, 36 (12.5%) yielded Candida spp; the swab method detected only 38.9% of these men. The risk of having candida balanitis is 8.9 (IC 95% 2.48 to 32.04) whenever the number of candida colonies recovered by direct impression was greater than 10. CONCLUSIONS: Direct impression on CHROMagar candida medium resulted in the highest Candida spp recovery rate. More than 10 colonies yielded by impression culture were statistically associated with candida balanitis. This method shows the ideal profile for sampling the male genital area for yeasts and should be included in the management of balanitis.

FKS1 mutation associated with decreased echinocandin susceptibility of Aspergillus fumigatus following anidulafungin exposure.

Invasive aspergillosis (IA) is a potentially lethal infection that affects mostly immunocompromised patients caused by Aspergillus fumigatus. Echinocandins are a second-line therapy against IA, used as a salvage therapy as well as for empirical or prophylactic therapy. Although they cause lysis of growing hyphal tips, they are considered fungistatic against molds. In vivo echinocandins resistance is uncommon; however, its wide clinical use could shortly lead to the emergence of A. fumigatus resistance. The aims of the present work was to assess the development of reduced echinocandins susceptibility phenotype by a A. fumigatus strain and to unveil the molecular mechanism underlying such phenotype. We induced in vitro cross-resistance to echinocandins following exposure of A. fumigatus to anidulafungin. Stability of the resistant phenotype was confirmed after removal of anidulafungin pressure. The FKS1 gene was partially sequenced and a E671Q mutation was found. A computational approach suggests that it can play an important role in echinocandin resistance. Given the emerging importance of this mechanism for clinical resistance in pathogenic fungi, it would be prudent to be alert to the potential evolution of this resistant mechanism in Aspergillus spp infecting patients under echinocandins therapeutics.

Dynamics of in vitro acquisition of resistance by Candida parapsilosis to different azoles.

Candida parapsilosis is a common isolate from clinical fungal infectious episodes. Resistance of C. parapsilosis to azoles has been increasingly reported. To analyse the development of resistance in C. parapsilosis, four azole-susceptible clinical strains and one American Type Culture Collection type strain were cultured in the presence of fluconazole, voriconazole and posaconazole at different concentrations. The isolates developed variable degrees of azole resistance according to the antifungal used. Fluconazole was the fastest inducer while posaconazole was the slowest. Fluconazole and voriconazole induced resistance to themselves and each other, but not to posaconazole. Posaconazole induced resistance to all azoles. Developed resistance was stable; it could be confirmed after 30 days of subculture in drug-free medium. Azole-resistant isolates revealed a homogeneous population structure; the role of azole transporter efflux pumps was minor after evaluation by microdilution and cytometric assays with efflux pump blockers (verapamil, ibuprofen and carbonyl cyanide 3-chloro-phenylhydrazone). We conclude that the rapid development of azole resistance occurs by a mechanism that might involve mutation of genes responsible for ergosterol biosynthesis pathway, stressed by exposure to antifungals.

Ibuprofen reverts antifungal resistance on Candida albicans showing overexpression of CDR genes.

Several mechanisms may be associated with Candida albicans resistance to azoles. Ibuprofen was described as being able to revert resistance related to efflux activity in Candida. The aim of this study was to uncover the molecular base of antifungal resistance in C. albicans clinical strains that could be reverted by ibuprofen. Sixty-two clinical isolates and five control strains of C. albicans were studied: the azole susceptibility phenotype was determined according to the Clinical Laboratory for Standards Institute, M27-A2 protocol and minimal inhibitory concentration values were recalculated with ibuprofen (100 microg mL(-1)); synergistic studies between fluconazole and FK506, a Cdr1p inhibitor, were performed using an agar disk diffusion assay and were compared with ibuprofen results. Gene expression was quantified by real-time PCR, with and without ibuprofen, regarding CDR1, CDR2, MDR1, encoding for efflux pumps, and ERG11, encoding for azole target protein. A correlation between susceptibility phenotype and resistance gene expression profiles was determined. Ibuprofen and FK506 showed a clear synergistic effect when combined with fluconazole. Resistant isolates reverting to susceptible after incubation with ibuprofen showed CDR1 and CDR2 overexpression especially of the latter. Conversely, strains that did not revert displayed a remarkable increase in ERG11 expression along with CDR genes. Ibuprofen did not alter resistance gene expression significantly (P>0.05), probably acting as a Cdrp blocker.

Epidemiology and susceptibility profile to classic antifungals and over-the-counter products of Malassezia clinical isolates from a Portuguese University Hospital: a prospective study.

PURPOSE: Clinical epidemiological data about the distinct Malassezia species remain scarce. The recurrence of Malassezia-related skin diseases, despite long-term use of antifungals, raises concern about the hypothetical emergence of antifungal resistance. We aimed to assess the distribution of Malassezia species among patients from a University Hospital with pityriasis versicolor, seborrheic dermatitis and healthy volunteers, and to evaluate the susceptibility profile to classic antifungals and over-the-counter compounds, searching for clinical associations. METHODOLOGY: The enrollment of volunteers was conducted at the Dermatology Department of a University Hospital over a 3 year period. Malassezia culture isolates were identified to the species-level by sequencing. The drug susceptibility profile was assessed according to a broth microdilution assay, as recommended by the Clinical Laboratory Standards Institute. RESULTS: A total of 86 Malassezia isolates were recovered from 182 volunteers. Malassezia sympodialis was the most frequent isolated species. We found high MIC values and a wide MIC range in the case of tested azoles, and very low terbinafine MIC values against most isolates. Previous topical corticosteroid therapy was associated with a significant increase of MIC values of fluconazole and of terbinafine. CONCLUSION: Conversely to other European studies, M. sympodialis was the most common isolated species, which might be related to geographic reasons. The impact of previous topical corticotherapy upon the antifungal susceptibility profile was hereby demonstrated. In vitro susceptibility test results suggest that terbinafine might be a valid alternative for Malassezia-related skin diseases nonresponsive to azoles.

Propofol lipidic infusion promotes resistance to antifungals by reducing drug input into the fungal cell.

BACKGROUND: The administration of non-antifungal drugs during patient hospitalization might be responsible for discrepancies between in vitro and in vivo susceptibility to antifungals. Propofol is often administered to intensive care units as a sedative. The purpose of this study was to evaluate the effect of propofol lipidic infusion upon the growth and susceptibility profile of pathogenic fungi. Candida and Aspergillus were studied regarding the ability to grow and its susceptibility profile to antifungals in the presence of propofol infusion (Fresenius(R)) (1.25, 2.5 and 5 mg.ml-1) and its lipidic vehicle. The intensity of fluorescence after staining with FUN1, in the presence and absence of propofol infusion, was determined by flow cytometry. Radioactivity assays were also performed in order to quantify the input of [3H]- itraconazole into the fungal cell in the presence of propofol. Assays were repeated after addition of sodium azide, in order to block efflux pumps. RESULTS: Propofol infusion promoted budding of Candida and the germination of Aspergillus, latter forming a lipid layer around the hypha. An increase of minimal fungicidal concentrations regarding both Candida and Aspergillus strains was found for all antifungals when incubated simultaneously with propofol infusion. A decrease of the intensity of fluorescence of Candida cells was systematically observed, as well as a significant reduced intracellular uptake of [3H] itraconazole in cells treated with propofol infusion, even after the blockade of efflux pumps. The results obtained when testing with the lipid vehicle were similar. CONCLUSION: Propofol infusion, due to its lipidic vehicle, increased the fungal germination and promoted resistance to antifungals. This effect seems to be related to the reduced access and/or permeabilization to fungal cells by antifungals.

Fungal infections after haematology unit renovation: evidence of clinical, environmental and economical impact.

OBJECTIVE AND METHODS: The Haemato-Oncology Unit, Hospital S. Joao, suffered extensive refurbishing intervention in order to adapt for autotransplant patients. Eight new individual rooms with central HEPA filtration system were built. All patients admitted in the department during 14 months prior to and 14 months after renovation works were enrolled. A total of 403 admissions were considered and a detailed analysis of all patients with fungal infections, air quality and antifungal consumption were evaluated in order to study clinical, environmental and economical impact after unit renovation. RESULTS: Patients with acute myeloid leukaemia submitted to induction treatment were the most susceptible to acquisition of fungal infections. Fungal infections were reduced after installation of HEPA filters in individual rooms, particularly proven and probable fungal infections. No patients were diagnosed with proven or probable mould infection in the period after the unit renovation and no deaths were registered among patients with the diagnosis of possible fungal infection. Considering the group of patients diagnosed with fungal infection, the average of hospitalization was reduced 3 d in the latter period. The new high-protected rooms showed a reduction of 50% and 95% of airborne fungi, respectively in the first week and after the second week. The consumption of voriconazole and caspofungin was reduced, respectively, 66% and 59% and the final cost with antifungal therapy was reduced by 17.4%. CONCLUSIONS: Autotransplant patients may be under higher risk of infection, however, the installation of high-protective measures may efficiently prevent fungal infections in these patients. Renovation of haematology unit resulted in major clinical, environmental and economical improvements. The definition of reference values for airborne agents in hospital facilities remains urgent.