Metronidazole-resistant vaginal trichomoniasis--an emerging problem.
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Animals↗
Biomedical subjects
J D Sobel
Publications and source records attributed to J D Sobel.
Management of asymptomatic candiduria.
Candiduria is a common nosocomial infection, occurring predominantly in elderly debilitated subjects with frequent co-morbid pathology, especially diabetes mellitus. The majority of candiduric patients are catheterized or have been recently catheterized or instrumented. Physician surveys indicate considerable variation in attitude towards treatment of asymptomatic candiduria. Management of candiduria is seriously limited by lack of understanding of the natural history of this infection as well as reliable data of treatment efficacy based upon controlled studies. The recent availability of oral antifungal agents has strongly influenced physicians in adopting a more interventional role. Most therapeutic studies quoted in the literature compare active intervention with a variety of systemic or local measures. Reference is made to a recent placebo-controlled prospective study, in which fluconazole was significantly more effective than placebo in short-term eradication of asymptomatic candiduria. Nevertheless, follow-up of these asymptomatic patients revealed identical candiduria rates within 1 month of cessation of therapy. In most studies, evidence of clinical benefit in asymptomatic patients by the eradication of candiduria has not been evident. In conclusion, the majority of hospitalized patients, particularly those with continued catheterization, do not require local or systemic antifungal therapy for asymptomatic candiduria.
Amphotericin B↗
Comparative in vitro activity of antiseptics and disinfectants versus clinical isolates of Candida species.
OBJECTIVE: To evaluate the in vitro activity of antiseptics and detergents against Candida. DESIGN: One strain each of Candida albicans, Candida tropicalis, Candida lusitaniae, Candida parapsilosis, Candida kefyr, Candida glabrata, and an American Type Culture Collection strain of Escherichia coli (control) were studied. Clinical isolates were obtained from patients in a bone marrow unit of a large tertiary hospital. Antiseptic and disinfectant agents studied were used in the hospital where isolates were identified for cleaning of inanimate surfaces or hand washing. In vitro susceptibility was determined using a broth macrodilution method with exposure times to antiseptic or disinfectant agent of 15 seconds to 4 minutes and concentrations of agents that ranged from undiluted to 1:10,000 dilution. SETTING: A 900-bed teaching hospital. RESULTS: Of disinfectants tested, Vestal and Sparquat inhibited growth of all species at dilutions of < or = 1:100 at all contact times for all species. Clorox showed inhibition of growth at 1:100 dilution after 30 seconds of contact time for all isolates. Of antiseptics studied, Hibiclens inhibited growth of all species except C tropicalis at dilutions of < or = 1:100 at all contact times and for C tropicalis after 60 seconds. Clinidine inhibited growth of all species at dilutions of < or = 1:100 at all contact times for all species with the exception of Cglabrata and C tropicalis, which grew at the undiluted concentration. Ultradex failed to demonstrate killing of any species for any dilutions tested. CONCLUSIONS: The results of this study show varying degrees of in vitro inhibition of growth by a variety of antiseptics and disinfectants against clinical isolates of Candida species from hospitalized patients.
Anti-Infective Agents, Local↗
Evolution of vaginal Candida species recovered from human immunodeficiency virus-infected women receiving fluconazole prophylaxis: the emergence of Candida glabrata? Terry Beirn Community Programs for Clinical Research in AIDS (CPCRA).
The effect of fluconazole prophylaxis on the vaginal flora of 323 human immunodeficiency virus-infected women was evaluated in a multicenter, randomized, double-blind, placebo-controlled trial. Women with CD4 cell counts of < or = 300/mm3 received either 200 mg of fluconazole per week or placebo. Vaginal surveillance cultures were performed every 3 months. After a follow-up of 29 months, Candida albicans was recovered from 53% of patients receiving fluconazole and 68% of patients assigned placebo. Fluconazole was associated with a 50% reduction in the odds of being colonized with C. albicans but with higher rates for non-albicans Candida species. Candida glabrata was recovered from 40 women assigned fluconazole and 29 assigned placebo (relative odds, 1.96; 95% confidence interval, 0.98-3.94). Fluconazole had an early and persistent effect on the vaginal mycoflora, with the emergence of C. glabrata vaginal colonization within the first 6 months. The effect of fluconazole prophylaxis can be attributed to the reduction in vaginal C. albicans colonization; however, C. glabrata colonization rapidly supervened.
AIDS-Related Opportunistic Infections↗
A comparison of itraconazole versus fluconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. National Institute of Allergy and Infectious Diseases Mycoses Study Group.
This study was designed to compare the effectiveness of fluconazole vs. itraconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. HIV-infected patients who had been successfully treated (achieved negative culture of CSF) for a first episode of cryptococcal meningitis were randomized to receive fluconazole or itraconazole, both at 200 mg/d, for 12 months. The study was stopped prematurely on the recommendation of an independent Data Safety and Monitoring Board. At the time, 13 (23%) of 57 itraconazole recipients had experienced culture-positive relapse, compared with 2 relapses (4%) noted among 51 fluconazole recipients (P = .006). The factor best associated with relapse was the patient having not received flucytosine during the initial 2 weeks of primary treatment for cryptococcal disease (relative risk = 5.88; 95% confidence interval, 1.27-27.14; P = .04). Fluconazole remains the treatment of choice for maintenance therapy for AIDS-associated cryptococcal disease. Flucytosine may contribute to the prevention of relapse if used during the first 2 weeks of primary therapy.
AIDS-Related Opportunistic Infections↗
Involvement of calcium inhibitable binding to the cell wall in the fungicidal activity of CAN-296.
CAN-296 is a heat stable, complex carbohydrate (molecular mass 4300 Da) isolated from the cell wall of the filamentous fungus Mucor rouxii. It possesses potent in-vitro fungicidal activity against a wide spectrum of pathogenic yeasts, including azole-resistant isolates of Candida albicans and Candida glabrata. As a preliminary step in the study of the mode of action of this novel antifungal agent, we investigated the effect of various cations on the antifungal activity as well as the binding of CAN-296 to intact cells and cell-wall fractions of C. albicans. The antifungal activity of CAN-296 was inhibited by low concentrations of calcium, magnesium and lithium and by high concentrations of barium, cobalt and manganese, but not by potassium and copper. The calcium-mediated inhibition of the antifungal activity of CAN-296 was readily reversible by the removal of calcium by dialysis, and the fungicidal activity of the inhibited compound was fully restored. The uptake/binding of CAN-296 to intact cells and to the cell-wall fraction of C. albicans was time and concentration dependent. Maximum uptake/binding was obtained at 5 mg/L within 60 min and was associated with the aggregation of intact cells. Washing intact cells and the cell-wall fraction preincubated with radiolabelled CAN-296 with 150-fold excess of unlabelled compound failed to remove CAN-296 associated with the intact cells and the cell-wall fraction, suggesting that the binding of CAN-296 to C. albicans is tight. The uptake/binding of CAN-296 and the drug-mediated aggregation of intact cells were inhibited by calcium in a concentration-dependent manner. The fact that CAN-296 is a fungicidal agent that binds to intact cells and the cell-wall fraction of C. albicans very tightly, together with the observation that calcium was able to inhibit the fungicidal activity as well as the uptake/binding of CAN-296, suggests that the mode of action of this novel antifungal agent may involve interaction with the cell wall of C. albicans.
Antifungal Agents↗
Preventing intra-abdominal candidiasis in surgical patients.
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Abdomen↗
High-frequency, in vitro reversible switching of Candida lusitaniae clinical isolates from amphotericin B susceptibility to resistance.
Recent studies have revealed an increase in the incidence of serious infections caused by non-albicans Candida species. Candida lusitaniae is of special interest because of its sporadic resistance to amphotericin B (AmB). The present in vitro study demonstrated that, unlike other Candida species, C. lusitaniae isolates frequently generated AmB-resistant lineages form previously susceptible colonies. Cells switching from a resistant colony to a susceptible phenotype were also detected after treatment with either UV light, heat shock, or exposure to whole blood, all of which increased the frequency of switching. In some C. lusitaniae lineages, after a cell switched to a resistant phenotype, the resistant phenotype was stable; in other lineages, colonies were composed primarily of AmB-susceptible cells. Although resistant and susceptible lineages were identical in many aspects, their cellular morphologies were dramatically different. Switching mechanisms that involve exposure to antifungals may have an impact on antifungal therapeutic strategies as well as on standardized susceptibility testing of clinical yeast specimens.
Amphotericin B↗
Candida glabrata: review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans.
Until recently, Candida glabrata was considered a relatively nonpathogenic commensal fungal organism of human mucosal tissues. However, with the increased use of immunosuppressive agents, mucosal and systemic infections caused by C. glabrata have increased significantly, especially in the human immunodeficiency virus-infected population. A major obstacle in C. glabrata infections is their innate resistance to azole antimycotic therapy, which is very effective in treating infections caused by other Candida species. Candida glabrata, formerly known as Torulopsis glabrata, contrasts with other Candida species in its nondimorphic blastoconidial morphology and haploid genome. C. glabrata currently ranks second or third as the causative agent of superficial (oral, esophageal, vaginal, or urinary) or systemic candidal infections, which are often nosocomial. Currently, however, there are few recognized virulence factors of C. glabrata and little is known about the host defense mechanisms that protect against infection. Two established animal models (systemic and vaginal) have been established to study treatment, pathogenesis, and immunity. Treatment of C. glabrata infections can include azoles but often requires amphotericin B or flucytosine. This review summarizes all known clinical and experimental information about C. glabrata infections with comparisons to C. albicans as a means of contrasting the two species commonly observed and emphasizing the many recognized differences.
Animals↗
Oral lesions among women living with or at risk for HIV infection. HIV Epidemiology Research Study (HERS) Group.
PURPOSE: Our objectives were to compare the prevalence of oropharyngeal mucosal lesions among human immunodeficiency virus (HIV) seropositive and demographically similar seronegative women, and to determine the association of oral lesions with immunosuppression, substance abuse, use of medications, and utilization of dental services. POPULATION AND METHODS: Participants in a multicenter, longitudinal cohort study of HIV infection in women were evaluated at baseline by interview, physical examination, and laboratory studies. RESULTS: Oropharyngeal pathology was found in 40% of seropositive and 23% of seronegative women. Oral candidiasis was identified in 15% of seropositive and 3% of seronegative women. Among seropositive women, history of previous oral candidiasis, lower CD4 lymphocyte counts, and current antibiotic use were associated with oral candidiasis. Hairy leukoplakia was identified in 5% of seropositive women and was significantly associated with lower CD4 lymphocyte counts. Gingival erythema and ulcerative gingivitis were found in 23% of participants overall, but were unrelated to HIV serostatus or CD4 lymphocyte count. Substance abuse, lack of dental care, and African-American race were associated with gingival pathology. CONCLUSION: The high prevalence of oral lesions among HIV seropositive and at-risk seronegative women underscores the need for routine oral examination and targeted treatment of this population.
AIDS-Related Opportunistic Infections↗
Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations.
Although it is the second most common vaginal infection in North America, vulvovaginal candidiasis is a non-notifiable disease and has been excluded from the ranks of sexually transmitted diseases. Not surprisingly, vulvovaginal candidiasis has received scant attention by public health authorities, funding agencies, and researchers. Epidemiologic data on risk factors and pathogenic mechanisms remain inadequately studied. Most important, standards of care, including diagnosis and therapy, remain undefined. A conference was held in April 1996 to define and summarize what is known and supported by scientific data in the areas of epidemiology, diagnosis, and treatment of vulvovaginal candidiasis; but, more important, the conference aimed at defining what is not known, poorly studied, and controversial. Guidelines for the treatment and diagnosis of the different forms of vulvovaginal candidiasis are suggested.
Antifungal Agents↗
Vulvovaginitis. When Candida becomes a problem.
Problematic vaginitis due to Candida presents both a diagnostic and therapeutic challenge. An essential first step is confirmation of clinical diagnosis and avoidance of empiricism. Once correctly diagnosed, most episodes of vaginitis due to Candida are uncomplicated, responding to all forms of antifungal therapy. Unfortunately, increased numbers of complicated cases now occur requiring additional microbiological study and longer duration therapy with selected antifungal agents.
Antifungal Agents↗
Difficult-to-treat trichomoniasis: results with paromomycin cream.
Vaginal trichomoniasis poses a difficult therapeutic challenge when metronidazole is ineffective or contraindicated. We conducted a retrospective study of 6.25% paromomycin cream in the treatment of nine women referred with cases of vaginal trichomoniasis where metronidazole resistance or allergy was present. Results obtained immediately and 1 month after treatment were reviewed. The median age of the patients was 46 years; four women were nulliparous. The median symptom duration was 1 year. Five women were allergic to metronidazole. In four cases, resistance to high doses of metronidazole was demonstrated. Smears or cultures were positive immediately after treatment for three patients; a fourth relapsed 2 weeks later. Of these patients for whom treatment failed, one was cured with a 3-week course of paromomycin cream, and another was successfully treated with paromomycin cream and oral tinidazole. Three patients developed vaginal ulcerations that resolved spontaneously. Adverse effects may be a result of local formulation. Paromomycin cream was useful for treatment of cases of trichomonas infection where metronidazole resistance or allergy was encountered.
Adult↗
Mucosal candidal colonization and candidiasis in women with or at risk for human immunodeficiency virus infection. HIV Epidemiology Research Study (HERS) Group.
The epidemiology of mucosal candidal colonization and candidiasis was studied in a multicenter cohort of 871 human immunodeficiency virus (HIV)-seropositive and 439 demographically and behaviorally similar HIV-seronegative women. Cross-sectional analyses at baseline revealed that oropharyngeal colonization with Candida species was more prevalent among seropositive women and among women reporting recent cigarette smoking and injection drug use. Oropharyngeal candidiasis was also more prevalent among seropositive women. Both oropharyngeal colonization and candidiasis were significantly associated with a lower median CD4 lymphocyte count among seropositive women. Vaginal candidal colonization was more prevalent among seropositive women and among those reporting recent injection drug use and current insulin or oral antihyperglycemic therapy. Vaginal candidiasis was equally likely to be diagnosed in seropositive and seronegative women and was not significantly related to recent sexual contact. Neither vaginal colonization nor candidiasis was significantly related to a lower median CD4 lymphocyte count among seropositive women. Baseline evaluation indicated differences in the epidemiology of oropharyngeal and vaginal candidal colonization and candidiasis in HIV-seropositive women and suggested possible variation in pathogenesis of candidal infection at these two mucosal sites.
AIDS-Related Opportunistic Infections↗
Frequency and response to vaginal symptoms among white and African American women: results of a random digit dialing survey.
The prevalence of vaginal symptoms and response to those symptoms in a nonclinic setting has not been previously described. Two thousand women living throughout the United States identified by random digit dialing completed a computer-assisted telephone interview about history of vaginal symptoms and use of healthcare services in response to these symptoms. The analysis was limited to 1698 white (WA) and 144 African American (AA) women (n = 1842). An episode of vaginal symptoms of any severity during 1995 was reported by 7.5% of WA women and 18.1% of AA women. Fifty-five percent of WA women and 83% of AA women with symptoms consulted a healthcare professional about their most recent episode. The racial difference in prevalence and consultation was not explained by marital status, education, employment, or lifetime number of sex partners. Most women purchased an over-the-counter antifungal preparation to treat their symptoms, whether or not a physician was consulted. The racial differences in prevalence and use of health services in response to vaginal symptoms observed here should be confirmed, and the potential causes should be explored.
Black or African American↗
Vulvovaginitis due to Candida glabrata. An emerging problem.
A review is presented of the emerging problem of resistant and chronic vaginitis due to Candida glabrata. Although accurate numbers are lacking, several investigators report encountering increased numbers of women with vaginitis due to C. glabrata. Possible reasons for this apparent increase are discussed. Risk factors and clinical manifestations of symptomatic C. glabrata vaginitis differ from those of C. albicans, C. glabrata being less susceptible to fungistatic azole agents is more difficult to eradicate. Successful management of chronic C. glabrata vaginitis constitutes a major challenge with currently available therapeutic agents.
Candida↗
Nosocomial Candida glabrata colonization: an epidemiologic study.
Candida glabrata has emerged as an important nosocomial pathogen, yet little is known about its epidemiology. We prospectively followed 98 patients admitted to a medical intensive care unit and the bone marrow transplant unit of a university hospital. Samples from environmental surfaces and the hands of hospital personnel were also cultured. Patients with newly acquired C. glabrata strains were compared to controls who were culture negative for C. glabrata. C. glabrata was recovered from multiple sites from 24 patients and three environmental surfaces. Sixteen patients (17%) acquired C. glabrata after admission to the study units. Significant risk factors for the nosocomial acquisition of C. glabrata were prolonged duration of hospitalization in the unit and prior antimicrobial use. Strain delineation by restriction enzyme analysis revealed 28 different strains of C. glabrata; three strain types were common to nine patients. The environmental isolates were of the same strain type and common to five patients (four patients with newly acquired strains). These results suggest the possibility of exogenous nosocomial acquisition of C. glabrata, including the possible acquisition from the hospital environment. Transmission may be by indirect contact since identical strains of C. glabrata were recovered from patients who were geographically and temporally associated.
Adult↗
Stable phenotypic resistance of Candida species to amphotericin B conferred by preexposure to subinhibitory levels of azoles.
The fungicidal activity of amphotericin B (AmB) was quantitated for several Candida species. Candida albicans and C. tropicalis were consistently susceptible to AmB, with less than 1% survivors after 6 h of exposure to AmB. C. parapsilosis and variants of C. lusitaniae and C. guilliermondii were the most resistant, demonstrating 50 to 90% survivors in this time period and as high as 1% survival after a 24-h exposure time. All Candida species were killed (<1% survivors) after 24 h of exposure to AmB. In contrast, overnight exposure to either fluconazole or itraconazole resulted in pronounced increases in resistance to subsequent exposures to AmB. Most dramatically, C. albicans was able to grow in AmB cultures after azole preexposure. Several other Candida species did not grow in AmB but showed little or no reduction in viability after up to 24 h in AmB. Depending on the growth conditions, Candida cells preexposed to azoles may retain AmB resistance for days after the azoles have been removed. If this in vitro antagonism applies to the clinical setting, treatment of patients with certain antifungal combinations may not be beneficial. The ability of some Candida isolates to survive transient exposures to AmB was not reflected in the in vitro susceptibility changes as measured by standard MIC assays. This finding should be considered in studies attempting to correlate patient outcome with in vitro susceptibilities of clinical fungal isolates. Patients who fail to respond to AmB may be infected with isolates that are classified as susceptible by standard in vitro assays but that may be resistant to transient antifungal exposures which may be more relevant in the clinical setting.
Amphotericin B↗