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As onychomycosis is unsightly, this study clinically evaluated whether the antifungal efficacy of amorolfine 5% nail lacquer ( NL) was affected by a masking, natural-coloured, cosmetic nail varnish applied 24 h later; in vitro investigations were also performed. Subjects with mild-to-moderate distal subungual toenail onychomycosis were randomised to receive amorolfine 5% NL once weekly with or without cosmetic nail varnish applied 24 h later. After 12-week treatment, antifungal activity of affected toenail clippings was assessed by measurement of zones of inhibition (ZOIs) on Trichophyton mentagrophytes seeded agar plates. Mean diameters were 53.5 mm for the amorolfine 5% NL-alone group ( n = 23) and 53.6 mm for amorolfine 5% NL plus cosmetic nail varnish group ( n = 25). Also, mycological cultures of subungual debris at week 12 were negative for all subjects in both groups. Most subjects (88%) reported that cosmetic nail varnish masked their infected toenails. Additionally, cadaver human nails coated in vitro with or without cosmetic nail varnish 10 min or 24 h post amorolfine NL application all gave ZOIs on Trichophyton rubrum agar plates representing potent antifungal activity. In conclusion, cosmetic nail varnish applied post amorolfine had no effect on the subungual antifungal activity of amorolfine 5% NL or its penetration through toenails. [ABSTRACT FROM AUTHOR]

Different concentrations (25, 30, 35 and 40%) of Nerium oleander L. leaf extracts were tested against the red grain beetle adults Tribolium castaneum (Herbst). Results showed that the percentage mortality ranged from 16.7% in the powder treatment increased to 70% in the alcohol extract at 40% concentration. Highest mortality rate was 49.2% in the alcohol extract, followed by 43.4% in the aqueous extract, while the least (30.9%) was recorded for the dry powder of N. oleander leaves. The results also showed an attraction and repellent effects of the extracts on the pest adults and there was a positive correlation between high mortality rate of the tested products and repellent effects on the adults, while a negative correlation was recorded between mortality rate and attractiveness. [ABSTRACT FROM AUTHOR]

Background Approval of topical onychomycosis drugs by regulatory agencies may be negatively impacted by an overly stringent definition of complete cure, which includes nail clearing plus mycological cure. Objectives In this position paper, we discuss interpretation of mycological outcome and clinical trial length. Methods We reviewed data from seven international onychomycosis trials that enrolled subjects with positive KOH and dermatophyte-positive culture at screening followed by 48 weeks of treatment. Further, we examined 94 KOH-positive/culture-negative week 52 follow-up samples for morphological hyphal damage. Results From 3054 samples collected at week 52 follow-up visits, 2360 were culture-negative. However, a significant percentage (78·7%) of these subungual samples ( n = 1857) remained KOH-positive. From the subset of follow-up samples examined for morphological changes, we identified hyphal breakage or distortion in 56 direct smears (60%), which may indicate nonviability. Conclusions Reassessment of the definition of onychomycosis cure is critical. For clinical trials of topical agents, length of treatment should be re-examined. Further, in our experience, a high rate of subungual debris samples remained direct smear-positive while converting to negative culture. Evidence of morphological hyphal damage suggests that late-visit microscopic results may be false-positives. Therefore, the absence of clinical signs following an adequate washout period, coupled with a negative culture, with or without negative microscopy, should be considered the definition of onychomycosis cure. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) infections can be serious in severely immunocompromised patients. Use of a targeted infection control program (TICP) has been shown to reduce RSV nosocomial transmission. We evaluated the impact of an enhanced seasonal infection control program (ESICP) vs standard TICP in a hematology-oncology ward. TICP was applied from 1999 to 2001 and ESICP applied from 2001 to 2003. ESICP consisted of strict isolation for all patients admitted on the ward during the RSV season. We prospectively evaluated the incidence, related morbidity and mortality of nosocomial RSV in both field interventions. A total of 40 hospitalized RSV infections were documented. The cumulative incidence of nosocomial RSV during TICP and ESICP was respectively of 42.8 and 3.9 cases/1000 admissions (relative risk=0.09). ESICP needed to be implemented on 26 admitted patients on our ward to prevent one RSV nosocomial case. Furthermore, implementation of ESICP prevented four pneumonias and two deaths per RSV season. We conclude that ESICP is significantly more efficient than TICP to reduce the occurrence of nosocomial RSV infections and its related morbidity and mortality in patients with hematological malignancy and recipients of hematopoietic SCT. [ABSTRACT FROM AUTHOR]

Miconazole (MICON) has long been used for the topical treatment of mucosal candidiasis. However, the preponderance of MICON susceptibility data was generated before standard methodology was established, and prior to the emergence of fluconazole (FLU)-resistant strains. The objective of this study was to determine the antifungal activity of MICON and comparators against recent clinical isolates of Candida spp. using standard Clinical and Laboratory Standards Institute methodology. One hundred and fifty isolates, consisting of 25 strains each of Candida albicans, C. krusei, C. glabrata, C. tropicalis, C. parapsilosis and C. dubliniensis, were tested. Of these, twenty-two strains were known to be FLU-resistant. Minimum inhibitory concentrations (MICs) were determined for MICON, amphotericin B (AM), caspofungin (CAS), clotrimazole (CLOT), FLU, itraconazole (ITRA), nystatin (NYS) and voriconazole (VOR). MICON demonstrated potent inhibitory activity against all of the strains tested. The MIC90 for MICON was 0.12 μg ml−1 against FLU-susceptible strains, which was comparable to that of AM, CAS, CLOT, ITRA and VOR. The MICON MIC90 against FLU-resistant strains was 0.5 μg ml−1, which was 12-fold lower than the FLU MIC90. Our study showed that MICON possesses potent activity against all of the Candida isolates tested, including those with known FLU resistance . This indicates that recent clinical isolates remain susceptible to this antifungal and that MICON could be used as first-line treatment for oropharyngeal candidiasis. [ABSTRACT FROM AUTHOR]

Recent studies suggest that differences in antifungal activity among echinocandins may exist. In this study, the activities of three echinocandins (anidulafungin, caspofungin, and micafungin) against Candida parapsilosis isolates from burn unit patients, healthcare workers and the hospital environment were determined. Additionally, the effect of these echinocandins on the cell morphology of caspofungin-susceptible and caspofungin-non-susceptible isolates was assessed using scanning electron microscopy (SEM). The C. parapsilosis isolates obtained from patients were susceptible to anidulafungin, but were less so to caspofungin and micafungin. Isolates obtained from healthcare workers or environmental sources were susceptible to all antifungals. SEM data demonstrated that although anidulafungin and caspofungin were equally active against a caspofungin-susceptible C. parapsilosis strain, they differed in their ability to damage a caspofungin-non-susceptible strain, for which lower concentrations of anidulafungin (1 mg/L) than of caspofungin (16 mg/L) were needed to induce cellular damage and distortion of the cellular morphology. To determine whether the difference in the antifungal susceptibility of C. parapsilosis isolates to anidulafungin as compared to the other two echinocandins could be due to different mutations in the FKS1 gene, the sequences of the 493-bp region of this gene associated with echinocandin resistance were compared. No differences in the corresponding amino acid sequences were observed, indicating that differences in activity between anidulafungin and the other echinocandins are not related to mutations in this region. The results of this study provide evidence that differences exist between the activities of anidulafungin and the other echinocandins. [ABSTRACT FROM AUTHOR]

Dear Editor, I Trichophyton rubrum i is the most common organism causing cutaneous fungal infections of the skin, hair and nails. Repeat testing for I T. rubrum i susceptibility revealed resistance to fluconazole (MIC > 16 µg mL SP -1 sp ), itraconazole (MIC > 8 µg mL SP -1 sp ) and terbinafine (MIC > 0-5 µg mL SP -1 sp ). Given that our patient was resistant to itraconazole, posaconazole - an antifungal typically reserved to treat invasive fungal infection in immunocompromised patients - was chosen as the subsequent therapy. [Extracted from the article]

Invasive fungal infections are major medical complications in immunocompromised patients. The recent rise in the incidence of cancer and the increased use of newer medical treatment modalities, including organ transplantations, have resulted in growing numbers of highly immunosuppressed individuals. Although aspergillosis and candidiasis are among the most common invasive mycoses in such patients, there is evidence that the incidence of infectious diseases caused by Zygomycetes has risen significantly over the past decade. Patients with diabetes, malignancies, solid organ or bone marrow transplants, or iron overload and those receiving immunosuppressive agents, deferoxamine therapy, or broad-spectrum antimicrobial drugs are at highest risk for zygomycosis. This review details the emergence and importance of zygomycosis in current clinical practice and its manifestations and management. The etiologic species, pathogenesis and risk factors for zygomycosis are reviewed and updated. The clinical spectrum of zygomycosis is now broader, and it can be difficult to distinguish between mucormycosis and enthomophthoramycosis, both of which can manifest as disease ranging from a superficial infection to an angioinvasive infection with high mortality. Finally, the three-part treatment strategy (antifungal drugs, surgery, control of underlying diseases) is reviewed. Lipid formulations of amphotericin B are the antifungal agents of choice for treatment of zygomycosis. A novel antifungal triazole, posaconazole, has been developed and may become approved for treatment of zygomycosis. The clinical experience with adjunctive treatments like colony-stimulating factors, interferon-gamma, and hyperbaric oxygen therapy is still limited. [ABSTRACT FROM AUTHOR]

Summary:The incidence of invasive fungal infection (IFIs) in hematopoietic stem cell transplantation (HSCT) recipients ranges from 10 to 25% with an overall case fatality rate of up to 70-90%. Candida and Aspergillus genera remain the two most common pathogens. Although fluconazole prophylaxis in this population has been moderately effective in reducing mortality due to invasive candidiasis, this agent does not have activity against invasive aspergillosis (IA) and other mould. Several new agents such as voriconazole and caspofungin have enhanced potency and broad-spectrum antifungal activity and show promising results against yeasts and filamentous fungi when given as therapy and as chemoprophylaxis. Further, new diagnostic tools to detect circulating fungal antigens in biological fluids and PCR-based methods to detect species or genus-specific DNA or RNA have been developed. Incorporating these techniques along with clinical criteria appear to improve the accuracy of preclinical diagnosis of IFIs. Such approaches may alter the current treatment strategy from prophylaxis to pre-emptive therapy, thereby potentially decreasing cost and toxicity in high-risk patients.Bone Marrow Transplantation (2004) 34, 377-389. doi:10.1038/sj.bmt.1704603 Published online 12 July 2004 [ABSTRACT FROM AUTHOR]

Wheat Stem Sawfly (WSS) Cephus pygmaeus Linnaeus is one of the main insect pests that invades both barley and wheat in many regions of the world. Larvae feed on the contents of the host stem, resulting in empty or small-seed spikes. Natural enemiesare one of the important integrated pest management components used to control this insect. A survey was conducted in some wheat fields in the Northern Iraq to determine the most common parasitoid species associated with this pest. Two hymenopterous species of parasitoids were recorded associated with the pest as new parasitoids in Iraq; Collyria coxator, Villers (Ichnoumonidae) and Bracon terebella, Wesmal (Braconidae). The overall ratio of parasitism reached 15%. The highest percentage was found in C. coxator by 8.2%, followed by 6.8%. with B. terebella. [ABSTRACT FROM AUTHOR]

Oropharyngeal candidiasis (OPC) is a common infection among the immuno-compromised population. Treatments include both systemic azoles, most commonly fluconazole (FLU), and topical agents such as miconazole (MICON). However, resistance to FLU has been reported with a greater frequency. The aim of this study was to determine the potential for development of resistance following repeated exposure of Candida spp. to MICON. Two clinical isolates each of Candida albicans, C. glabrata, and C. tropicalis were tested. Fifteen passages of each strain were performed in concentrations of MICON at 0.5 minimum inhibitory concentration (MIC), 1 MIC, 2 MIC and 4 MIC, with MIC determinations performed on growth obtained following each passage. There was no increase in the MIC of four of the six strains following fifteen passages in MICON. One C. albicans strain demonstrated a four-five dilution increase in MICON MIC at all concentrations and one C. glabrata strain showed a fivefold MICON MIC increase when exposed to 4 MIC. Although an increase in MIC was noted in these two isolates, the MICON MIC was still very low (0.5 μg ml). In general, there was no increase in MIC demonstrated by repeated exposure to MICON in this study. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the antifungal activity of terbinafine (TERB) with that of lanoconazole (LAN). Test isolates, which were clinical isolates of Japanese origin, included 10 strains each of Trichophyton rubrum, T. mentagrophytes and Epidermophyton floccosum. The minimum inhibitory concentration (MIC) of TERB and LAN against each dermatophyte isolate was determined according to the Clinical and Laboratory Standards Institute microbroth methodology, M38-A2. Minimum fungicidal concentrations were determined by subculturing the contents of each visibly clear well from the MIC assay for colony count. All LAN MICs were ≤0.008 μg ml−1, while the TERB range was 0.008–0.03 μg ml−1. Moreover, by standard definition, LAN was fungistatic against most strains, whereas TERB was fungicidal. Both LAN and TERB demonstrated potent antifungal activity against dermatophytes; however, the lack of fungicidal activity by LAN needs to be evaluated in terms of potential clinical efficacy. [ABSTRACT FROM AUTHOR]

Background Our group, in collaboration with seven other laboratories, has recently developed a method to determine the susceptibility of dermatophytes. Objectives The objective of this study was to determine the terbinafine susceptibility profile of dermatophyte isolates obtained from patients with tinea capitis enrolled in two large worldwide clinical trials and to investigate whether these susceptibilities differ by geographical location. Methods Susceptibilities were determined according to the Clinical and Laboratory Standards Institute M38-A2 standard. Results From a total of 978 baseline dermatophyte isolates, we selected 301 isolates at random. These included: Trichophyton tonsurans ( n = 125) , Microsporum canis ( n = 94), T. violaceum ( n = 63) and M. audouinii ( n = 19) . The terbinafine minimum inhibitory concentration (MIC) range was 0·001–0·25 μg mL−1, while MIC50 and MIC90 ranged between 0·002 and 0·125 μg mL−1 and 0·03 and 0·25 μg mL−1, respectively, for all species tested. MIC50 and MIC90 varied by individual species; however, there was no difference in terbinafine MIC among the different species isolated from U.S. and non-U.S. sites. Conclusion Terbinafine demonstrates potent antifungal activity against dermatophyte isolates obtained from patients with tinea capitis worldwide. [ABSTRACT FROM AUTHOR]

The Oral HIV/ AIDS Research Alliance ( OHARA) was established in 2006 to provide the capacity to investigate the oral complications associated with HIV/ AIDS within the ACTG infrastructure. Its goals were to explore the effects of potent antiretroviral therapy ( ART) on the development of opportunistic infections, and variation and resistance of opportunistic pathogens in the context of immune suppression and long-term ART. The objectives of this talk, presented as part of a plenary session at the 7th World Workshop on Oral Health and Disease in AIDS, were to (i) provide an overview of OHARA's most recent research agenda, and how it evolved since OHARA's inception; (ii) describe OHARA's main accomplishments, including examples of research protocols completed and their key findings; and (iii) describe spin-off projects derived from OHARA, lessons learned, and future directions. OHARA has met its central goal and made key contributions to the field in several ways: (i) by developing/updating diagnostic criteria for oral disease endpoints commonly measured in OHARA protocols and in HIV/ AIDS research in general and has creating standardized training modules, both for measuring these oral disease endpoints across clinical specialties, and for collecting oral fluid specimens; (ii) by implementing a total of nine protocols, six of which are completed. Three protocols involved domestic research sites, while three involved international research sites (in Africa, India, and South America); (iii) and by developing and validating a number of laboratory assays used in its protocols and in the field of oral HIV/ AIDS research. [ABSTRACT FROM AUTHOR]

Background. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments (ECTR) in poisoning and the results are presented here for acetaminophen (APAP). Methods. After a systematic review of the literature, a subgroup selected and reviewed the articles and summarized clinical and toxicokinetic data in order to propose structured voting statements following a pre-determined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Following discussion, a second vote determined the final recommendations. Results. Twenty-four articles (1 randomized controlled trial, 1 observational study, 2 pharmacokinetic studies, and 20 case reports or case series) were identified, yielding an overall very low quality of evidence for all recommendations. Clinical data on 135 patients and toxicokinetic data on 54 patients were analyzed. Twenty-three fatalities were reviewed. The workgroup agreed that N-acetylcysteine (NAC) is the mainstay of treatment, and that ECTR is not warranted in most cases of APAP poisoning. However, given that APAP is dialyzable, the workgroup agreed that ECTR is suggested in patients with excessively large overdoses who display features of mitochondrial dysfunction. This is reflected by early development of altered mental status and severe metabolic acidosis prior to the onset of hepatic failure. Specific recommendations for ECTR include an APAP concentration over 1000 mg/L if NAC is not administered (1D), signs of mitochondrial dysfunction and an APAP concentration over 700 mg/L (4630 mmol/L) if NAC is not administered (1D) and signs of mitochondrial dysfunction and an APAP concentration over 900 mg/L (5960 mmol/L) if NAC is administered (1D). Intermittent hemodialysis (HD) is the preferred ECTR modality in APAP poisoning (1D). Conclusion. APAP is amenable to extracorporeal removal. Due to the efficacy of NAC, ECTR is reserved for rare situations when the efficacy of NAC has not been definitively demonstrated. [ABSTRACT FROM AUTHOR]

Gentian violet (GV) is recommended for initial treatment of oral candidiasis in HIV-infected patients in resource-limited settings. Currently GV is not used because of its staining effects. In this study, we investigated the staining capacity of three different concentrations of GV to determine a concentration that does not cause staining. The selected concentration that did not cause staining was evaluated for its physical stability and antifungal activity. Fifteen healthy participants were randomized to rinse twice daily for 14 days with one of three GV concentrations: 0.1%, 0.0085%, or 0.00165%. Oral examination and intra-oral photographs were performed at baseline and at the end of therapy. Participants responded to a questionnaire to assess adverse events. Antifungal activity was evaluated using the Clinical and Laboratory Standard Institute methodology. GV at a concentration of 0.00165% did not stain the oral mucosa and was well tolerated. GV at a concentration of 0.00165% was stable and possessed antifungal activity when stored at certain temperatures for different time periods. Gentian violet solution at the concentration of 0.00165% does not stain the oral mucosa, is stable and possesses potent antifungal activity. [ABSTRACT FROM AUTHOR]

The Oral HIV/AIDS Research Alliance (OHARA) is part of the AIDS Clinical Trials Group (ACTG), the largest HIV clinical trials organization in the world. Its main objective is to investigate oral complications associated with HIV/AIDS as the epidemic is evolving, in particular, the effects of antiretrovirals on oral mucosal lesion development and associated fungal and viral pathogens. The OHARA infrastructure comprises: the Epidemiologic Research Unit (at the University of California San Francisco), the Medical Mycology Unit (at Case Western Reserve University) and the Virology/Specimen Banking Unit (at the University of North Carolina). The team includes dentists, physicians, virologists, mycologists, immunologists, epidemiologists and statisticians. Observational studies and clinical trials are being implemented at ACTG-affiliated sites in the US and resource-poor countries. Many studies have shared end-points, which include oral diseases known to be associated with HIV/AIDS measured by trained and calibrated ACTG study nurses. In preparation for future protocols, we have updated existing diagnostic criteria of the oral manifestations of HIV published in 1992 and 1993. The proposed case definitions are designed to be used in large-scale epidemiologic studies and clinical trials, in both US and resource-poor settings, where diagnoses may be made by non-dental healthcare providers. The objective of this article is to present updated case definitions for HIV-related oral diseases that will be used to measure standardized clinical end-points in OHARA studies, and that can be used by any investigator outside of OHARA/ACTG conducting clinical research that pertains to these end-points. [ABSTRACT FROM AUTHOR]

Onychomycosis is a common fungal disease infecting up to 20% of the population over age 40. The major causative agent of onychomycosis is Trichophyton rubrum. Uncontrolled infection may eventually lead to penetration of the newly forming nail plate. In spite of the encouraging cure rate with recent antifungal agents such as the allylamines (terbinafine) and azoles (itraconazole and fluconazole) some patients inevitably fail therapy. In this investigation, a group of patients from a multi-center study designed to assess the efficacy of terbinafine with known cases of onychomycosis were selected for evaluation. Nail samples from this patient group were colonized with T. rubrum throughout the terbinafine therapy. Antifungal susceptibility testing was performed on these T. rubrum isolates to detect change in MIC values. Strain relatedness was examined using random amplified polymorphic DNA (RAPD) technique. Our results revealed failure of patients to clear T. rubrum is not related to the development of resistance to the drug. While species determination was possible, we were not able to identify differences that would indicate reinfection with a new strain. Analysis of patient dentographic data revealed that 70% of patients were over 45 years old, 56.6% were previously treated with antifungals, 60% came from family history with onychomycosis and 13% were diabetic. In conclusion, our data indicate that patients' failure to clear onycchomycosis was not associated with resistant development. Failure of terbinafine therapy may be dependent on host-related factors. [ABSTRACT FROM AUTHOR]