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Practice guidelines for the treatment of candidiasis. Infectious Diseases Society of America.

Infections due to Candida species are the most common of the fungal infections. Candida species produce a broad range of infections, ranging from nonlife-threatening mucocutaneous illnesses to invasive process that may involve virtually any organ. Such a broad range of infections requires an equally broad range of diagnostic and therapeutic strategies. This document summarizes current knowledge about treatment of multiple forms of candidiasis and is the guideline of the Infectious Diseases Society of America (IDSA) for the treatment of candidiasis. Throughout this document, treatment recommendations are scored according to the standard scoring scheme used in other IDSA guidelines to illustrate the strength of the underlying data. The document covers 4 major topical areas. The role of the microbiology laboratory. To a greater extent than for other fungi, treatment of candidiasis can now be guided by in vitro susceptibility testing. The guidelines review the available information supporting current testing procedures and interpretive breakpoints and place these data into clinical context. Susceptibility testing is most helpful in dealing with infection due to non-albicans species of Candida. In this setting, especially if the patient has been treated previously with an azole antifungal agent, the possibility of microbiological resistance must be considered. Treatment of invasive candidiasis. In addition to acute hematogenous candidiasis, the guidelines review strategies for treatment of 15 other forms of invasive candidiasis. Extensive data from randomized trials are really available only for therapy of acute hematogenous candidiasis in the nonneutropenic adult. Choice of therapy for other forms of candidiasis is based on case series and anecdotal reports. In general, both amphotericin B and the azoles have a role to play in treatment. Choice of therapy is guided by weighing the greater activity of amphotericin B for some non-albicans species (e.g., Candida krusei) against the lesser toxicity and ease of administration of the azole antifungal agents. Flucytosine has activity against many isolates of Candida but is not often used. Treatment of mucocutaneous candidiasis. Therapy for mucosal infections is dominated by the azole antifungal agents. These drugs may be used topically or systemically and have been proven safe and efficacious. A significant problem with mucosal disease is the propensity for a small proportion of patients to suffer repeated relapses. In some situations, the explanation for such a relapse is obvious (e.g., relapsing oropharyngeal candidiasis in an individual with advanced and uncontrolled HIV infection), but in other patients the cause is cryptic (e.g., relapsing vaginitis in a healthy woman). Rational strategies for these situations are discussed in the guidelines and must consider the possibility of induction of resistance over time. Prevention of invasive candidiasis. Prophylactic strategies are useful if the risk of a target disease is sharply elevated in a readily identified group of patients. Selected patient groups undergoing therapy that produces prolonged neutropenia (e.g., some bone-marrow transplant recipients) or who receive a solid-organ transplant (e.g., some liver transplant recipients) have a sufficient risk of invasive candidiasis to warrant prophylaxis.

Adult↗

Caspofungin in the treatment of azole-refractory esophageal candidiasis in kidney transplant recipients.

BACKGROUND: Infection is a common cause of morbidity and mortality in kidney transplant recipients. The incidence of esophageal and urogenital candidiasis in kidney and kidney-pancreas transplant recipients has not been well documented. Azoles are safe, effective agents to treat esophageal candidiasis. However, resistance to azoles is now becoming common. This study reports the use of caspofungin for the treatment of azole-resistant esophageal and urogenital candidiasis in kidney transplant recipients. PATIENTS AND METHODS: The incidence of esophageal and urogenital candidiasis was evaluated among 140 kidney transplantations and four combined kidney-pancreas transplants performed over a 2-year period. RESULTS: Twenty-two patients (15.7%) presented with esophageal candidiasis, while seven patients (5%) showed urogenital candidiasis. Thirteen patients with esophageal candidiasis (59%) and four patients (57%) with urogenital candidiasis did not improve after a week of azole treatment. A regimen of caspofungin was started in these patients, who tolerated the treatment. Urogenital candidiasis recurred in two patients 2 and 3 months after the treatment. One patient with esophageal candidiasis did not improve with caspofungin and was switched to amphotericin B therapy. There were no other recurrences of candidiasis among patients treated with caspofungin for a median follow-up of 8 months. CONCLUSIONS: Renal transplant patients remain at high risk for fungal infections. Although the number of patients was limited, the results of this study indicated that caspofungin is an effective, well-tolerated alternative for difficult-to-treat, azole-resistant candida infections in kidney and pancreas transplant recipients. The high costs of the drug limit the use of caspofungin as first-line antifungal therapy, reserving its use to recipients who had undergone unsuccessful azole therapy.

Adult↗

Longitudinal study of mucosal Candida species colonization and candidiasis among human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women.

Acquisition and loss rates and estimates of duration of oral and vaginal Candida species colonization and candidiasis were examined among 868 human immunodeficiency virus (HIV)-seropositive and 437 at-risk HIV-seronegative women monitored prospectively during 1993-1999. Colonization and candidiasis acquisition rates, both oral and vaginal, were significantly higher among HIV-seropositive women; the magnitude of increase in candidiasis outcomes for HIV-seropositive women was greater for oral candidiasis than for vaginal candidiasis. Loss rates and estimates of duration of incident outcomes indicated that persistent mucosal colonization was more likely among HIV-seropositive women. However, results did not suggest persistent mucosal candidiasis. Higher HIV loads were significantly associated with increased odds of incident or persistent oral and vaginal colonization and candidiasis, an effect significantly reduced by highly active antiretroviral therapy for the incident outcomes of oral candidiasis and vaginal colonization. Cell-mediated immunodeficiency (CD4(+) lymphocyte count <500 cells/mm(3)) was significantly associated with increased odds of oral colonization or candidiasis, but not with vaginal colonization or candidiasis. In HIV-seropositive women, mucosal candidiasis is the consequence of multiple interacting factors.

AIDS-Related Opportunistic Infections↗

Clinical, endoscopic, immunologic, and therapeutic aspects of oropharyngeal and esophageal candidiasis in HIV-infected patients: a survey of 114 cases.

The medical records of 114 consecutive HIV-infected patients with oropharyngeal and esophageal candidiasis, in whom esophagoscopy was performed, were reviewed. Esophageal candidiasis and isolated oral candidiasis were found in 75% and 25% of patients, respectively. Esophageal candidiasis was the AIDS-defining illness in 65 patients and dysphagia was the commonest symptom, but asymptomatic Candida esophagitis was observed in 43% of them. Symptoms were present in six patients with oropharyngeal candidiasis; three of them had a normal esophagoscopy and the other three had acute nonfungal esophagitis. Invasive fungal esophagitis was confirmed by biopsy in 47/74 patients (64%). The patients with esophageal candidiasis had lower CD4+ cell counts (129/microliter) and CD4:CD8 ratios (0.23) than those with oropharyngeal candidiasis (CD4 179/microliter; CD4:CD8 0.35). Thirty-six patients with esophageal candidiasis were treated with fluconazole, 100 mg/daily, for 28 days, and another 34 patients received the same dose for 10 days. A similar efficacy was seen in both regimens, but a higher incidence of oropharyngeal fungal colonization and liver dysfunction was observed in the longer therapy (p < 0.001). We conclude that asymptomatic C. esophagitis is common in HIV-infected patients. Patients with oropharyngeal candidiasis may complain of esophageal symptoms; it could be due to superficial C. infection or another not-identified opportunistic infection. More severe immunologic impairment was required to develop esophageal candidiasis than oropharyngeal candidiasis. A short course of 10 days of fluconazole therapy could be the standard regimen for the treatment of C. esophagitis in AIDS.

Biopsy↗

Quantitative urine cultures do not reliably detect renal candidiasis in rabbits.

The significance of quantitative urine cultures in patients at risk for hematogenous disseminated candidiasis is controversial. While various concentrations of Candida spp. in urine have been suggested as critical cutoff points in the diagnosis of renal candidiasis, other investigators consider quantitative cultures less critical in diagnosing upper tract infections. To determine the significance of quantitative urine cultures in renal candidiasis, we studied serial quantitative urinary cultures of Candida albicans in a rabbit model of hematogenous infection. Of 197 urine samples from 34 infected animals, 144 were culture positive, with a sensitivity of 73.1% for urine cultures and a lower limit of detection of 10 CFU/ml. The yield of urine cultures varied according to severity and duration of infection. The mean renal and urinary concentrations of C. albicans from rabbits with subacute candidiasis differed significantly from those from rabbits with acute candidiasis (P = 0.013 and P < or = 0.001, respectively). During the first 4 days of subacute renal candidiasis, more than one-half of all urine cultures were negative for C. albicans. Only 12 (8.1%) of 148 urine cultures in animals with subacute renal candidiasis had concentrations of > 10(3) CFU/ml, 2.7% had concentrations of > 10(4) CFU/ml, and none were > or = 10(5) CFU/ml. By comparison, all urine cultures from the animals with lethal acute renal candidiasis had higher concentrations of C. albicans and were positive throughout the course of infection. Urinary concentrations of C. albicans were not predictive of the amount of Candida in the kidney (r < or = 0.49) and did not correlate with survival (r = 0.0232). However, the renal concentration of C. albicans (in CFU/gram) inversely correlated with the duration of survival (in days) of rabbits with renal candidiasis (r = 0.76; P < 0.001). These findings indicate that a negative urine culture in rabbits does not preclude the presence of renal candidiasis. The interpretation of a urine culture positive at any concentration, on the other hand, must involve an analysis of the risk factors for renal candidiasis, for any urinary concentration of C. albicans may reflect kidney infection.

Animals↗

Interventions for treating oral candidiasis for patients with cancer receiving treatment.

BACKGROUND: Treatment of cancer is increasingly effective but is associated with short and long-term side effects. Oral side effects, including oral candidiasis, remain a major source of illness despite the use of a variety of agents to treat them. OBJECTIVES: To assess the effectiveness of interventions for the treatment of oral candidiasis for patients with cancer receiving chemotherapy and or radiotherapy. SEARCH STRATEGY: Computerised searches of Cochrane Oral Health Group Specialised Register, CCTR, MEDLINE and EMBASE were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information. Date of the most recent searches May 2001: (CCTR 2001, issue 3) SELECTION CRITERIA: All randomised controlled trials comparing agents prescribed to treat oral candidiasis in people receiving chemotherapy or radiotherapy for cancer. The outcomes were eradication of oral candidiasis, dysphagia, systemic infection, amount of analgesia, length of hospitalisation, cost and patient quality of life. DATA COLLECTION AND ANALYSIS: Data were independently extracted, in duplicate, by two reviewers. Authors were contacted for details of randomisation and withdrawals and a quality assessment was carried out. The Cochrane Oral Health Group statistical guidelines were followed and relative risk values calculated using random effects models where significant heterogeneity was detected (P<0.1). MAIN RESULTS: Eight trials involving 418 patients, satisfied the inclusion criteria and are included in this review. Only two agents, each in single trials, were found to be effective for eradicating oral candidiasis. A drug absorbed from the gastrointestinal tract, ketoconazole, was more beneficial than placebo in eradicating oral candidiasis (RR=0.35 95%CI 0.20 to 0.61) and clotrimazole, at a higher dose of 50mg was more effective than a lower 10mg dose in eradicating oral candidiasis, when assessed mycologically (RR=0.47 95%CI 0.25 to 0.89). Another trial demonstrated no difference between a 10mg dose of the partially absorbed drug, clotrimazole, and placebo. No differences were found when comparing different absorbed drugs; and comparing absorbed drugs with drugs which are not absorbed. REVIEWER'S CONCLUSIONS: There is weak and unreliable evidence that the absorbed drug, ketoconazole, may eradicate oral candidiasis and that a higher dose of the partially absorbed drug, clotrimazole, may give greater benefit than a lower 10mg dose, however, researchers may wish to prevent rather than treat oral candidiasis. Further well designed, placebo-controlled trials assessing the effectiveness of old and new interventions for treating oral candidiasis are needed.

Antifungal Agents↗

Interventions for treating oral candidiasis for patients with cancer receiving treatment.

BACKGROUND: Treatment of cancer is increasingly effective but is associated with short and long-term side effects. Oral side effects, including oral candidiasis, remain a major source of illness despite the use of a variety of agents to treat them. OBJECTIVES: To assess the effectiveness of interventions for the treatment of oral candidiasis for patients with cancer receiving chemotherapy and or radiotherapy. SEARCH STRATEGY: Computerised searches of Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE and EMBASE were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information.Date of the most recent searches: August 2003: (CENTRAL) (The Cochrane Library Issue 3, 2003). SELECTION CRITERIA: All randomised controlled trials comparing agents prescribed to treat oral candidiasis in people receiving chemotherapy or radiotherapy for cancer. The outcomes were eradication of oral candidiasis, dysphagia, systemic infection, amount of analgesia, length of hospitalisation, cost and patient quality of life. DATA COLLECTION AND ANALYSIS: Data were independently extracted, in duplicate, by two reviewers. Authors were contacted for details of randomisation and withdrawals and a quality assessment was carried out. The Cochrane Oral Health Group statistical guidelines were followed and relative risk values calculated using random effects models where significant heterogeneity was detected (P < 0.1). MAIN RESULTS: Eight trials involving 418 patients, satisfied the inclusion criteria and are included in this review. Only two agents, each in single trials, were found to be effective for eradicating oral candidiasis. A drug absorbed from the gastrointestinal tract, ketoconazole, was more beneficial than placebo in eradicating oral candidiasis (relative risk (RR) = 0.35, 95% confidence interval (CI) 0.20 to 0.61) and clotrimazole, at a higher dose of 50 mg was more effective than a lower 10 mg dose in eradicating oral candidiasis, when assessed mycologically (RR = 0.47, 95% CI 0.25 to 0.89). Another trial demonstrated no statistically significant difference between a 10 mg dose of the partially absorbed drug, clotrimazole, and placebo. No differences were found when comparing different absorbed drugs; and comparing absorbed drugs with drugs which are not absorbed. REVIEWER'S CONCLUSIONS: There is weak and unreliable evidence that the absorbed drug, ketoconazole, may eradicate oral candidiasis and that a higher dose of the partially absorbed drug, clotrimazole, may give greater benefit than a lower 10 mg dose, however, researchers may wish to prevent rather than treat oral candidiasis. Further well designed, placebo-controlled trials assessing the effectiveness of old and new interventions for treating oral candidiasis are needed.

Antifungal Agents↗

Esophageal candidiasis in human immunodeficiency virus-infected pediatric patients after the introduction of highly active antiretroviral therapy.

OBJECTIVE: To investigate epidemiologic trends, clinical features and outcome of esophageal candidiasis in the era of highly active antiretroviral therapy in a prospectively monitored population of HIV-infected children and adolescents followed at the National Cancer Institute. PATIENTS AND METHODS: The records of all HIV-infected pediatric patients (n = 266) followed between 1995 and 2000 were reviewed for a history of esophageal candidiasis. Proven esophageal candidiasis was defined as clinical plus radiographic and/or endoscopic findings of esophageal candidiasis. Probable esophageal candidiasis was defined as esophageal symptoms that responded promptly to appropriate antifungal therapy. The medical records of all patients fulfilling these criteria were reviewed for demographic, clinical and laboratory features at presentation, as well as therapeutic interventions and outcome. RESULTS: Of the 266 patients 9 (3.4%) had 18 documented episodes of proven (n = 16) or probable (n = 2) esophageal candidiasis. A history of prior mucosal candidiasis was present in 94% of all episodes. The median CD4+ count at the time of diagnosis was 7/microl (range, 0 to 550), and the median viral load was 98000 copies/ml (range, 22916 to 1278933). Concurrent oropharyngeal candidiasis was the most common clinical presentation (72%) followed by fever (55%), odynophagia (50%) and nausea or vomiting (39%). Treatment consisted of antifungal triazoles (61%) or amphotericin B (39%). Clinical cure was achieved in 15 cases, including all patients receiving triazoles. CONCLUSION: Esophageal candidiasis persists in the subgroup of patients not responding to highly active antiretroviral therapy and in that setting may present without concomitant oropharyngeal candidiasis or typical clinical symptoms, thus underscoring the need for a high index of suspicion in children with very low CD4+ counts.

Adolescent↗

Immunity in vaginal candidiasis.

PURPOSE OF REVIEW: Vulvovaginal candidiasis and recurrent vulvovaginal candidiasis remain a significant problem in women of child-bearing age. While host defense mechanisms against infection are poorly understood, the most recent studies continue to challenge dogma relative to anti-Candida immunity at other mucosal sites that is normally associated with T helper 1-type CD4 T cells. RECENT FINDINGS: Four studies comprise the latest findings in host defense against vulvovaginal candidiasis. The first from an animal model provided the most definitive data to date for the lack of involvement by systemic or local T-cell-mediated immunity. The second study confirmed a limited role for antibodies in vaginal candidiasis; similar to past studies, systemic and local Candida-specific antibodies in women with vulvovaginal candidiasis were either similar or elevated compared with controls. The third study from a cohort of adolescents provided evidence for some form of local protective immunity based on high asymptomatic vaginal fungal burden with low incidence rate of vulvovaginal candidiasis. This was addressed more specifically through a natural history protocol involving an intravaginal challenge with live Candida. Results showed a strong correlation between infiltration of polymorphonuclear neutrophils and symptomatic vulvovaginal candidiasis, with no evidence of an inflammatory response in those protected against infection. SUMMARY: Instead of vulvovaginal candidiasis being caused by defective or dysfunctional CD4 T helper 1-type cell-mediated immune reactivity, data suggest that symptomatic vulvovaginal candidiasis is associated with an aggressive response by polymorphonuclear neutrophils, whereas protection appears to be innate and noninflammatory. The role for innate immunity in both protection against, and promotion of, symptomatic vulvovaginal candidiasis is paradigm changing.

Adult↗

Risk factors for recurrent vulvovaginal candidiasis in women receiving maintenance antifungal therapy: results of a prospective cohort study.

OBJECTIVE: The purpose of this study was to examine risk factors for symptomatic vulvovaginal candidiasis episodes among women with recurrent vulvovaginal candidiasis (defined as >/=4 vulvovaginal candidiasis episodes in 1 year) who were receiving maintenance antifungal therapy. STUDY DESIGN: A prospective study of 65 women aged >/=18 years with recurrent vulvovaginal candidiasis who attended vaginitis clinics in Detroit, Mich, and Philadelphia, Pa. RESULTS: The 9-month risk of vulvovaginal candidiasis recurrence was 41.8%. Almost two fifths of the women reported activity limitations because of vulvovaginal candidiasis episodes, most or all of the time. Younger women and those women with a history of bacterial vaginosis were at increased risk of vulvovaginal candidiasis episodes. Behavioral factors that were associated significantly with increasing vulvovaginal candidiasis recurrence >/=2- fold included wearing pantyliners or pantyhose and consuming cranberry juice or acidophilus-containing products. CONCLUSION: The use of pantyliners or pantyhose, consumption of cranberry juice or acidophil-containing products, a history of bacterial vaginosis, and age <40 years were positively associated with a symptomatic vulvovaginal candidiasis episode.

Adult↗

Incident and persistent vulvovaginal candidiasis among human immunodeficiency virus-infected women: Risk factors and severity.

OBJECTIVE: To examine risk factors for vulvovaginal candidiasis among women with or at risk for human immunodeficiency virus (HIV) infection. METHODS: Data were from 856 HIV-infected women and 421 at-risk uninfected women observed semiannually at four study sites from April 1993 through February 1999. At enrollment women were 15-55 years old and had no acquired immunodeficiency syndrome-defining conditions. Three definitions for vulvovaginal candidiasis of differing severity were constructed using data from vaginal Candida culture and Gram stains scored for yeast and three signs on pelvic examination (vulvovaginal edema, erythema, or discharge): 1) culture or Gram stain positivity plus at least one clinical sign, 2) culture or Gram stain positivity plus at least two clinical signs, and 3) visible yeast on Gram stain plus at least one clinical sign. RESULTS: The prevalence and cumulative incidence of each definition of vulvovaginal candidiasis were greater among HIV-infected women than among women not infected with HIV (P <.01 for all comparisons). Stratified by status at the preceding visit, vulvovaginal candidiasis was most likely among women with prior vulvovaginal candidiasis, least likely among women without earlier Candida colonization, and intermediately likely among women with preceding subclinical Candida colonization. Among HIV-infected women, lower CD4 count and higher HIV viral load were associated with vulvovaginal candidiasis. Several other factors were independently associated with vulvovaginal candidiasis, with strong associations for diabetes mellitus and pregnancy in particular. Vulvovaginal candidiasis was not more severe among HIV-infected women. CONCLUSION: Vulvovaginal candidiasis occurred with higher incidence and greater persistence, but not greater severity, among HIV-infected women.

Adolescent↗

Recurrent vaginal candidiasis and allergic rhinitis: a common association.

BACKGROUND: In a recent series of studies, it has been shown that hypersensitivity is an important factor in recurrent vaginal candidiasis and several referring gynecologists have been asking for our support in the evaluation of women with regard to the possibility of local vaginal hypersensitivity. This study was instituted because, since the first anamnesis, a high incidence of perennial allergic rhinitis, as well as family allergies have been observed in these patients. OBJECTIVE: To study the association between recurrent vaginal candidiasis and perennial allergic rhinitis, and to explore the allergic characteristics of the patients and of the disease. METHODS: For 28 months, we have prospectively studied 95 patients with recurrent vaginal candidiasis referred by gynecologists to a private allergy practice. All of them were unresponsive to all other modalities of therapy, and had no diabetes or immunodeficiency diseases. As a control group, we studied 100 women, who came to the allergy office for other reasons, and had no recurrent vaginal candidiasis. All of these 195 women were submitted to a standard allergy medical history, a complete physical examination, and immediate skin tests with a standard battery of inhalant allergens and Candida albicans. The incidence of allergic diseases in the two groups was compared. RESULTS: Sixty-four patients with recurrent vaginal candidiasis also had allergic rhinitis (71%), while in the control group the incidence of this pathology was 42%. The difference was considered statistically significant, according to the software Epi info (P < .0001). The study (1) did not show an association between recurrent vaginal candidiasis and asthma and (2) indicated that patients with recurrent vaginal candidiasis have a high incidence of skin tests positive to inhalant allergens (50%), to Candida albicans (55%), and a high incidence of family history of allergies (73%). In control women, the incidence of skin test positive to inhalant allergens was 72% and to Candida albicans, 10%. There was a family history of allergies in 61% of women. CONCLUSIONS: The data demonstrate that recurrent vaginal candidiasis is statistically associated with perennial allergic rhinitis and that many of these women with recurrent vaginal candidiasis tend to be atopic.

Adolescent↗

Oroesophageal candidiasis is lethal for transgenic mice with combined natural killer and T-cell defects.

Germfree transgenic epsilon 26 (Tgepsilon26) mice, which express the full-length human CD3epsilon gene, have combined defects in natural killer (NK) cells and T cells were found to be extremely susceptible to oroesophageal (palate, tongue, esophagus) and gastric (cardia-antrum section) candidiasis. The gnotobiotic Tgepsilon26 mice die, apparently from severe oroesophageal candidiasis, within 2-4 weeks after their alimentary tracts are colonized with Candida albicans. The Tgepsilon26 mice manifest resistance to acute systemic candidiasis (intravenous injection) and to systemic candidiasis of endogenous origin for the first 2 weeks after their alimentary tracts are colonized with C. albicans. Granulocyte depletion data suggest that granulocytes, in the absence of functional NK cells and T cells, can protect Tgepsilon26 mice from acute systemic candidiasis and from systemic candidiasis of endogenous origin, for at least 14 days after alimentary tract colonization. Granulocytes and macrophages, in the absence of NK cells and T cells, are unable to protect Tgepsilon26 mice from lethal oroesophageal candidiasis and systemic candidiasis of endogenous origin which was evident in moribund Tgepsilon26 mice 2-4 weeks after colonization. Thus, non-T cells (i.e., NK cells) and T cells play important roles in resistance to oroesophageal and systemic (acute and of endogenous origin) candidiasis.

Animals↗

Second-line therapy with caspofungin for mucosal or invasive candidiasis: results from the caspofungin compassionate-use study.

OBJECTIVES: To prospectively assess the efficacy and safety of caspofungin as second-line therapy for mucosal or invasive candidiasis in patients enrolled in the caspofungin compassionate-use study. MATERIALS AND METHODS: Thirty-seven patients with mucosal or invasive candida infections (17 oesophageal, four oropharyngeal and 16 invasive candidiasis) were enrolled in the caspofungin compassionate-use study. All patients were refractory to or intolerant of intravenous amphotericin B or lipid amphotericin formulation(s). Efficacy was assessed at the end of intravenous caspofungin therapy based on clinical (and, where appropriate, microbiological) response. RESULTS: HIV was the most common (91%) risk factor in patients with mucosal candidiasis; patients with invasive candidiasis commonly had acute leukaemia/lymphoma (50%) or diabetes mellitus (31%). Most patients with mucosal candidiasis (91%) and invasive candidiasis (94%) were refractory to >/=1 antifungal agent(s). A favourable response was noted in 82% (14/17) with oesophageal candidiasis, 100% (4/4) with oropharyngeal candidiasis and 87% (13/15) with invasive candidiasis. Caspofungin was generally well tolerated; one serious drug-related adverse event was reported. CONCLUSION: In this study, caspofungin was an effective alternative for patients with refractory candida infections.

Adolescent↗

Self-care intervention to reduce oral candidiasis recurrences in HIV-seropositive persons: a pilot study.

OBJECTIVES: This single-blind randomized controlled pilot study evaluated the efficacy of a behavioral intervention program, PRO-SELF: Candidiasis, to reduce time to recurrence of oral candidiasis over 6 months in susceptible HIV-seropositive persons. The intervention involved instruction by dentists on improving oral hygiene, minimizing sugar intake, and self-diagnosing candidiasis. METHODS: Participants were adults with oral candidiasis responsive to antifungals who presented to the UCSF Stomatology Clinic between 1997 and 2000. At 2-3 weeks of follow-up visits, a dentist "examiner", masked to group assignment, quizzed participants as to the presence of candidiasis, and assessed candidiasis status. A second, unmasked dentist "instructor" then delivered the program to intervention participants. Participants recorded dietary and oral hygiene practices in 24-h recall diaries: intervention participants at each visit and controls at initial and final visits. RESULTS: At randomization, CD4+ cell counts (cells/mm(3)) were 298 +/- 188 among 18 intervention participants and 396 +/- 228 among 17 controls. The candidiasis recurrence rates at 6 months were 78% among intervention compared with 88% among control participants (hazard ratio 0.72; 95% CI 0.35-1.50). Performing oral hygiene after meals/snacks showed the largest relative improvement: intervention-control difference in proportion of meals/snacks affected was 24% (95% CI -1 to 48%). Self-diagnoses of candidiasis were inaccurate, possibly because of mild episodes. CONCLUSIONS: The results weakly indicate that regular instruction from healthcare professionals helps patients delay candidiasis recurrence by improving oral hygiene. Among HIV-seropositive persons, those with poor oral hygiene, and high-sugar diets are most likely to benefit.

Adult↗

Gastro-oesophageal candidiasis.

A prospective search for gastro-oesophageal candidiasis was made by histological examination of all the biopsies taken from 465 patients endoscoped consecutively during a 12 month period. The criterion for diagnosis was the demonstration of infiltration of tissue or ulcer slough by yeasts and hyphae. Nineteen cases of candidiasis were found giving an overall incidence of 4%. There were 12 cases with oesophageal candidiasis, two with both oesophageal and gastric candidiasis, and five with gastric candidiasis. In none of the patients was candidiasis suspected before endoscopy. Symptoms referable to the candidiasis were uncommon and radiology was not helpful in diagnosis. There was associated local pathology (particularly peptic ulceration and carcinoma of the stomach or oesophagus) in all except two patients, which suggests that the candidiasis is usually secondary to mucosal damage. In the series, candidiasis was present in 27% of patients with oesophageal cancer, 20% of patients with gastric cancer, 16% of patients with benign gastric ulcers, and 15% of patients with oesophagitis.

Aged↗

Relative risk of vaginal candidiasis after use of antibiotics compared with antidepressants in women: postmarketing surveillance data in England.

BACKGROUND: Vaginal candidiasis is a common infection in women. The microflora of the vagina are influenced by a number of factors, including pregnancy, oral contraceptive use, menses and diabetes mellitus. Previous antibiotic use is generally accepted to be a risk factor for vaginal candidiasis but the published evidence to support this is limited. AIM: To determine the relative risk of vaginal candidiasis following the use of antibiotics compared with antidepressants in prescription-event monitoring (PEM) studies. METHODS: Using data from postmarketing surveillance studies of six antibiotics and six antidepressants, conducted using the observational cohort technique of PEM, the number of reports of vaginal candidiasis was determined in women aged > or =16 years, in each of the first 7 weeks following a prescription for one of these drugs. The relative risks for vaginal candidiasis following the use of these antibiotics and for each of the individual antibiotics compared with antidepressants were calculated for each week and for the overall 7-week period. Women treated with antidepressants were the most suitable comparator group from the PEM database, as they were of a similar age range and the studies were conducted at a similar time period to those of the antibiotics. Also, there was no pharmacological plausibility for vaginal candidiasis being associated with antidepressants. RESULTS: There were 188 reports of vaginal candidiasis in 31 588 women, aged > or =16 years, treated with antibiotics and 70 in the 45 492 treated with antidepressants. The relative risk for vaginal candidiasis (antibiotic/antidepressants), was highest in the second week, 10.70 (95% CI 4.86-23.55) but was also significantly greater in the first and third weeks after the start of treatment. The risk was also higher in each of the 3 weeks after starting the course for five of the antibiotics, compared individually to the group treated with antidepressants, the exception being fosfomycin, which had a much smaller cohort. CONCLUSION: This study shows a significant increase in the risk of developing vaginal candidiasis following the use of the antibiotics studied (ciprofloxacin, ofloxacin, norfloxacin, cefixime, azithromycin and fosfomycin) compared with that after taking the antidepressants fluvoxamine, fluoxetine, paroxetine, sertraline, venlafaxine and nefazodine in these PEM studies.

Adult↗

[Esophageal candidiasis as complication of inhaled steroid therapy].

UNLABELLED: Gastrointestinal endoscopy was performed in two bronchial asthma patients using inhaled corticosteroid who complained of odynophagia. The endoscopic finding was high grade with white moss (Grade III) in both patients. Esophageal candidiasis is often recognized in bronchial asthmatic patients receiving long-term fluticasone propionate (FP) dry powder (Diskhaler) inhalation. We therefore examined the complicated context of esophageal candidiasis in patients with long-term FP inhalation. Out of 20 bronchial asthmatic patients who had been using FP inhalation long-term, seven showed signs of esophageal candidiasis. Three patients had mild grade (Grade I), one middle grade (Grade II) and three high grade (Grade III) candidiasis, with a frequency of 35%. This rate is higher than the usual spontaneous occurrence rate of esophageal candidiasis, and it is suggested that inhalation of corticosteroid medication can penetrate into the esophagus after deep inhalation. We tested this hypothesis in two studies. 1) To measure the esophageal concentration of FP, four healthy adults inhaled 200 microg FP once. Right after inhalation, FP concentration in the esophageal washing fluid was 3.3 microg. On another day, 30 minutes after the same dose of inhaled FP, one FP concentration in the esophageal washing fluid was 0.67 microg (immediately laydown), and another was 0.11 microg (remained standing). This indicates that even though FP dissipates quickly, it remains in the esophagus 30 minutes after inhalation. 2) We observed the process in one patient with high grade (Grade III) esophageal candidiasis. The time of inhalation was changed from just after getting up and just before going to bed to before breakfast and before dinner. Under this regimen, the signs of esophageal candidiasis improved from high to middle grade. CONCLUSION: If asthmatic patients do not go to sleep immediately after FP inhalation, the remaining FP in the esophagus decreases rapidly, thereby decreasing the risk of esophageal candidiasis. In addition, by changing the FP inhalation times to before breakfast and dinner, the remaining FP in the esophagus is washed away and does not remain in the esophagus. Therefore, this study, which avoided inhalation before going to bed, provides useful information for the prevention and improvement of esophageal candidiasis.

Administration, Inhalation↗