Immunological and virological response to initial antiretroviral therapy among older people living with HIV in the Canadian Observational Cohort (CANOC).

OBJECTIVES: The aim of this study was to assess the adequacy of immunological recovery and virological suppression in response to antiretroviral therapy (ART) in the growing population of older people living with HIV (PLWH), as treatment regimens become more effective and tolerable. METHODS: An interprovincial Canadian cohort of treatment-naïve PLWH who initiated ART after 1 January 2000 was used and age assessed in decades. Longitudinal absolute CD4 count response to treatment was modelled using generalized estimating equations. Cumulative incidence functions and proportional hazards models with a competing risk of death were used to estimate time to: (1) CD4 ≥ 200 cells/µL, (2) CD4 ≥ 500 cells/µL, (3) virological suppression (≤ 50 copies/mL), and (4) virological failure (> 200 copies/mL). RESULTS: In all, 12 489 individuals starting ART between 2000 and 2016 with one or more post-treatment CD4 count or viral load were included in the analysis. Age > 60 years was associated with lower absolute CD4 recovery (adjusted ß = -31 cells/µL) compared with age ≤ 30 years when pre-treatment CD4 count and other covariates were accounted for. Older age groups were less likely to achieve a CD4 ≥ 500 cells/µL, with the greatest effect in the > 60 group [adjusted hazard ratio (aHR) = 0.69, 95% confidence interval (CI): 0.57-0.84 vs. age ≤ 30). Older age groups were more likely to achieve viral suppression (age > 60, aHR = 1.20, 95% CI: 1.05-1.37) and less likely to have virological failure (age > 60, aHR = 0.46, 95% CI: 0.3-0.71) compared with those aged ≤ 30 years. CONCLUSIONS: Older adults have robust virological responses to ART; however, individuals over the age 60 are more likely to experience blunted CD4 recovery.

Contraceptive options for HIV-positive women: making evidence-based, patient-centred decisions.

OBJECTIVES: Women of reproductive age represent a large proportion of the global population living with HIV/AIDS. With improvements in morbidity and mortality since the advent of combination antiretroviral therapy, contraception and pregnancy planning are an increasingly important issue for women living with HIV. This review aims to outline the key considerations when choosing contraceptive methods in HIV-positive women and provides a review of the literature to inform decision-making. METHODS: Pubmed was searched using the terms 'HIV', 'contraception', 'HIV progression', 'HIV acquisition', 'HIV transmission' and the combination of 'antiretroviral' and 'contraception'. Abstracts were reviewed and relevant articles were retrieved. Reference lists were also reviewed for pertinent citations. RESULTS: HIV and contraceptive methods can interact in several clinically meaningful ways. Concomitant use may result in altered contraceptive efficacy, drug-drug interactions, or increased toxicity. Hormonal contraceptives have not been shown to affect HIV progression. Notably, the impact of hormonal contraceptives on HIV transmission and acquisition remains unclear, particularly for injectable forms. Data are lacking on several newer methods of contraception including contraceptive rings, patches and intrauterine systems. CONCLUSIONS: Effective, reliable contraception is important for HIV-positive women. Efficacy, toxicity, drug interactions, and potential impacts on HIV disease progression, transmission, and acquisition must be assessed when making clinical decisions.

Switch to raltegravir decreases soluble CD14 in virologically suppressed overweight women: the Women, Integrase and Fat Accumulation Trial.

OBJECTIVES: Soluble CD14 (sCD14) is a monocyte activation marker associated with increased mortality in HIV infection. We assessed 48-week changes in sCD14 and other inflammatory biomarkers in virologically suppressed, HIV-infected women switching to raltegravir (RAL) from a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI). METHODS: HIV-infected women with central adiposity and HIV-1 RNA < 50 HIV-1 RNA copies/mL continued their thymidine-sparing nucleoside reverse transcriptase inhibitor (NRTI) backbone and were randomized to switch to open-label RAL at week 0 (immediate) or 24 (delayed). In an exploratory analysis, inflammatory biomarkers were measured on stored fasting plasma. RESULTS: Of the 37 evaluable subjects, 78% were non-White; the median age was 43 years, the median body mass index (BMI) was 32 kg/m(2) and the median CD4 count was 558 cells/µL. At baseline, biomarker values were similar between groups. After 24 weeks, median sCD14 significantly declined in subjects switching to RAL [-21% (P < 0.001) vs. PI/NNRTI -5% (P = 0.49); between-group P < 0.01]. After 48 weeks, immediate-switch subjects maintained this decline and delayed-switch subjects experienced a similar decline following the switch to RAL (-10%; within-group P < 0.01). Immediate-switch subjects also experienced an initial increase in tumour necrosis factor (TNF)-α that was neither maintained after 48 weeks nor seen in delayed-switch subjects. After adjustment for multiple testing, only declines in sCD14 remained significant. CONCLUSIONS: In this randomized trial of women with central adiposity, a switch to RAL from a PI or NNRTI was associated with a statistically significant decline in sCD14. Further studies are needed to determine whether integrase inhibitors have improved monocyte activation profiles compared with PIs and/or NNRTIs, and whether measured differences between antiretroviral agents translate to demonstrable clinical benefit.

Assay of HIV gp41 amino acid sequence to identify baseline variation and mutation development in patients with virologic failure on enfuvirtide.

In this study, we retrospectively assessed a gp41 genotypic assay in 404 enfuvirtide-naïve individuals (340 clade B, 64 non-B clade) to determine the prevalence of baseline polymorphisms and in 41 patients virologically failing enfuvirtide to determine correlates of resistance to this agent. Conserved and polymorphic regions of gp41 were identified in clade B isolates, with 127 of 328 codons (38.7%) being highly conserved (<1.0% variation) and 74 of 328 codons (22.6%) being partially conserved (1.0-5.0% variation). Polymorphisms were observed throughout gp41 in non-B clade virus sequences compared to the clade B reference strain, ranging from 53 natural substitutions in clade D to 76 in clade A. Insertions were common at positions 3, 105, 215 and 276. In the patients failing enfuvirtide, mutations were detected in the 10 amino acid region at positions 36-45 in all plasma virus sequences. Six additional mutations were selected outside of the common region which may be clinically significant at positions 33, 73, 75, 126, and 138. Two or three mutations at positions 36-45 were observed in the majority of plasma virus sequences from patients with virologic failure following the use of enfuvirtide. Further study is required to determine the clinical relevance of the clade related polymorphisms and the new mutations identified in the patients with virologic failure.

Non-nucleoside reverse transcriptase inhibitor failure impairs HIV-RNA responses to efavirenz-containing salvage antiretroviral therapy.

In a retrospective cohort study of salvage antiretroviral combination therapy including efavirenz, 60% of 51 patients were able to suppress HIV RNA by at least 1 log10 or to less than 50 copies/ml. A lack of the previous use of non-nucleoside reverse transcriptase inhibitors was the only factor predictive of response on multivariate analysis. No patient with a viral isolate with an increased IC50 to efavirenz by virtual phenotype had a virological response

Oxidative stress and thiol depletion in plasma and peripheral blood lymphocytes from HIV-infected patients: toxicological and pathological implications.

OBJECTIVES: To determine, first, whether the plasma and lymphocytes of HIV-positive individuals and AIDS patients have alterations in the major thiols glutathione and cysteine, and/or their oxidative disulphide and mixed disulphide products; and, secondly, whether thiol/disulphide status differs in patients with sulphonamide drug hypersensitivity reactions. DESIGN: Thiols provide critical cellular defence against toxic drug reactive intermediates and endogenous oxidative stress, and may modulate HIV replication. Glutathione is reported to be low in HIV-positive individuals and AIDS patients, but this is controversial and the mechanism responsible is unknown. Also unknown is whether altered thiol/disulphide status determines the predisposition of HIV-positive and AIDS patients to drug reactions. METHODS: Thiols and disulphides were measured by high-performance liquid chromatography. RESULTS: Both plasma thiols were decreased by approximately 58% in HIV-positive individuals and AIDS patients compared with uninfected controls (P < 0.05), with increases of up to threefold in oxidized products (P < 0.05). Similarly, in lymphocytes, thiols were decreased by 30-35% (P < 0.05), with apparent increases in oxidized products. For both glutathione and cysteine, the thiol/disulphide ratios also were decreased (P < 0.05). The plasma and lymphocyte glutathione thiol/disulphide ratios were highly correlated (r = 0.7661; P = 0.0001) among all subjects. No parameters differed in patients with drug reactions, or with antiretroviral therapy. CONCLUSIONS: The enhanced thiol oxidation in HIV-positive individuals and AIDS patients indicates oxidative stress, which also contributes to thiol depletion, and may enhance damage to macromolecular targets. These mechanisms may contribute to enhanced viral replication and other pathological outcomes. HIV-positive individuals' and AIDS patients' predisposition to drug hypersensitivity reactions appears to be unrelated to thiol/disulphide status.

Effects of vitamin E and C supplementation on oxidative stress and viral load in HIV-infected subjects.

OBJECTIVES: The HIV-infected population is known to be oxidatively stressed and deficient in antioxidant micronutrients. Since in vitro replication of HIV is increased with oxidative stress, this study assessed the effect of antioxidant vitamin supplementation on lipid peroxidation, a measure of oxidative stress, and viral load in humans. DESIGN: A randomized placebo-controlled, double-blind study. METHODS: Forty-nine HIV-positive patients were randomized to receive supplements of both DL-alpha-tocopherol acetate (800 IU daily) and vitamin C (1000 mg daily), or matched placebo, for 3 months. Plasma antioxidant micronutrient status, breath pentane output, plasma lipid peroxides, malondialdehyde and viral load were measured at baseline and at 3 months. New or recurrent infections for the 6-month period after study entry were also recorded. RESULTS: The vitamin group (n = 26) had an increase in plasma concentrations of alpha-tocopherol (P < 0.0005) and vitamin C (P < 0.005) and a reduction in lipid peroxidation measured by breath pentane (P < 0.025), plasma lipid peroxides (P < 0.01) and malondialdehyde (P < 0.0005) when compared with controls (n = 23). There was also a trend towards a reduction in viral load (mean +/- SD changes over 3 months, -0.45 +/- 0.39 versus +0.50 +/- 0.40 log10 copies/ml; P = 0.1; 95% confidence interval, -0.21 to -2.14). The number of infections reported was nine in the vitamin group and seven in the placebo group. CONCLUSION: Supplements of vitamin E and C reduce oxidative stress in HIV and produce a trend towards a reduction in viral load. This is worthy of larger clinical trials, especially in HIV-infected persons who cannot afford new combination therapies.

Predictors of virological response in HIV-infected patients to salvage antiretroviral therapy that includes nelfinavir.

Different salvage strategies have been used to regain control in patients with HIV who have virological failure on combination antiretroviral therapy. We conducted a cohort study of 63 extensively antiretroviral pretreated patients who initiated nelfinavir as part of salvage therapy, to determine predictors of virological response. The maximum HIV RNA response was >0.5 log10 copies/ml reduction in 43 patients (68%), including 21 patients (33%) who had suppression to <500 copies/ml. Corresponding response rates at 24 weeks were 41 and 19%, respectively. Responders and non-responders could not be distinguished by mean baseline HIV RNA or CD4 cell count, duration of prior protease inhibitor (PI) use, introduction of an initial non-nucleoside reverse transcriptase inhibitor or the number of antiretroviral agents changed when nelfinavir was added, likely reflecting the homogeneity of the population studied. The only parameter predictive of response was virus genotype. Response rates were lower in patients with increasing numbers of primary (P=0.045) or secondary (P=0.001) PI mutations. The addition of increasing numbers of reverse transcriptase mutations further impaired response rates (P=0.004).

Improvement of HIV-specific immunity in HIV-infected twins treated with highly active antiretroviral therapy, interleukin 2, and syngeneic adoptively transferred cells.

Five HIV-seropositive twins were treated with HAART and given cycles of treatment consisting of adoptive cellular therapy from their HIV-seronegative identical twins followed by a 5-day course of intravenous IL-2. Changes in absolute and percent CD4(+) and CD8(+) cell count were monitored and compared with changes in these parameters occurring in seven age-, sex-, and disease stage-matched HIV-infected patients treated with HAART alone. Increase in the magnitude and breadth of HIV-specific immune responses was monitored in three twin subjects who received multiple treatment cycles. Absolute and percent CD4(+) cell counts rose dramatically and to significantly higher levels in the recipient twins than in control subjects treated with HAART only. The subjects who received multiple cycles of treatment developed new and increased levels of HIV-specific activated and memory cytotoxic T lymphocyte responses, and interferon gamma-secreting effector cells. Treatment consisting of HAART, adoptive cellular therapy, and IL-2 was superior to treatment with HAART alone for improving absolute and percent CD4(+) cell counts and inducing new, or increasing the magnitude of, HIV-specific immune responses in HIV infected patients.

Trimethoprim-sulfamethoxazole induced aseptic meningitis in a renal transplant patient.

A 45-year-old man underwent renal transplant for end-stage renal disease complicating systemic lupus erythematosis. Within 24 hours of initiating Pneumocystis carinii pneumonia (PCP) prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) he developed fever and confusion. Cerebrospinal fluid examination revealed a pleocytosis but cultures were negative. The patient improved within three days after cessation of the TMP-SMX but symptoms recurred rapidly upon drug rechallenge. Drug-induced aseptic meningitis is an uncommon but well described clinical entity. This is the first case described in a patient following renal transplantation. The literature is reviewed and the clinical features, diagnostic challenges and possible mechanisms of TMP-SMX-induced aseptic meningitis are discussed. This problem may be more common in the transplant population than is recognized given the difficulty of diagnosis combined with the widespread use of TMP-SMX as PCP prophylaxis.

The effect of infection and lag screw fixation on the union of membranous bone grafts in a rabbit model.

Infection complicating craniofacial procedures contributes significantly to patient morbidity and health care costs. The role of fixation materials in this setting remains unclear. As foreign material, does fixation hardware increase patients' susceptibility to developing postoperative infection? Furthermore, once infection is established, should fixation hardware be removed? To answer these questions, we performed an onlay membranous bone grafting procedure to the mandible in 94 New Zealand White rabbits, applied lag-screw fixation in half the animals, and inoculated the wounds with different bacterial doses. We quantified the differential rates of infection and rates of graft union in the presence of infection. The infection rates for the rigidly fixated group were not significantly different from the rates for the nonfixated group for a range of bacterial inoculum doses. There was no significant difference in the rates of resolution of infection and sepsis between the two groups. Gross and histologic assessments revealed a significantly lower union rate for infected grafts when compared with uninfected grafts. Furthermore, grafts rigidly fixated with a lag screw showed a higher rate of union when compared with nonfixated grafts in the presence of infection. In the absence of infection, the union rates for fixated and nonfixated groups did not differ significantly. While fixation hardware has been cited as a risk factor for postoperative infection, we were unable to show that lag-screw fixation contributes to this risk. Although infection impaired the union of membranous bone grafts to the recipient mandible, fixation of the grafts with a lag screw significantly decreased this deleterious effect of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of infection and lag screw fixation on revascularization and new bone deposition in membranous bone grafts in a rabbit model.

We have suggested that rigid fixation of membranous bone grafts in the presence of infection may improve graft-recipient bone union by facilitating graft revascularzation. To test this hypothesis, we grafted autogenous membranous bone grafts to the mandibles of 94 New Zealand White rabbits. Lag screw fixation was applied in half the animals. The wounds were inoculated with a range of Staphylococcus aureus doses. Infected and noninfected rabbits were injected weekly over a 5-week course with fluorescein bone markers and with a marker of vascular endothelium (procion red) just prior to sacrifice. Revascularization and new bone deposition in the grafts were then quantified histologically for the 75 rabbits available for data collection. Infection decreased the amount of graft revascularized and the amount of new bone deposited for both rigidly fixated and nonfixated grafts. Grafts fixated with a lag screw showed a greater amount of revascularization and new bone deposition in the presence and absence of infection when compared with nonfixated grafts, supporting the hypothesis that rigid fixation of membranous bone grafts in the presence of infection may promote graft survival and union by improving revascularization and osteogenesis within the graft.

A large prospective study assessing injection site reactions, quality of life and preference in patients using the Biojector vs standard needles for enfuvirtide administration.

OBJECTIVES: To determine the severity of injection site reactions (ISRs), patient quality of life (QoL) and preference when enfuvirtide is administered by the Biojector (Bioject, Medical Technologies, Inc., Tualatin, OR, USA) relative to standard needles. METHODS: A total of 201 HIV-positive patients on stable enfuvirtide-based therapy (n=184) or initiating such therapy (n=17) were evaluated prospectively after switching from standard needles to the Biojector system. Patients used needles for a minimum of 2 weeks prior to switching to the Biojector. Questionnaires to assess the incidence and severity of ISRs (31-item score) and QoL [Medical Outcomes Study HIV Health Survey (MOS-HIV)] were administered at baseline and following a minimum of 14 days of Biojector use. RESULTS: The median changes in ISR score and number of ISRs following a median of 1.0 month [interquartile range (IQR) 0.9, 1.3] of Biojector use were -3 (IQR -7, 1) and -1 (IQR -3, 1), respectively. The severity of pain (P<0.0001), induration (P<0.0001), pruritus (P<0.0001), nodules (P<0.0001) and erythema (P<0.0001) all decreased with the Biojector. Administration of enfuvirtide with the Biojector was associated with an improved patient QoL (P<0.0001), and was preferred by 72% of patients. CONCLUSIONS: Compared with needles, the Biojector was associated with a decreased severity of ISRs and improved QoL in patients taking enfuvirtide.

Direct isolation of atypical thermophilic Campylobacter species from human feces on selective agar medium.

Campylobacter upsaliensis is the name which has been proposed for a new group of thermophilic campylobacter strains which differ from C. jejuni and C. coli in having a negative or weak catalase reaction. Primary isolation of these strains from human feces has been achieved only by use of filtration techniques. We report here direct isolation of strains corresponding to C. upsaliensis from stools of six children. The strains were isolated on a newly described campylobacter-selective medium. The strains were oxidase positive, hippurate negative, nitrate positive, negative for H2S in triple sugar iron, and susceptible to cephalothin (30-micrograms disk) and nalidixic acid (30-micrograms disk), and they grew at 37 and 43 degrees C, but not at 25 degrees C. The selective medium used was a blood-free, charcoal-based medium consisting of Columbia agar base, activated charcoal, cefoperazone (32 micrograms/ml), vancomycin (20 micrograms/ml), and cycloheximide (100 micrograms/ml). The medium supported the growth of the weakly reacting or catalase-negative strains, with colony counts equivalent to those obtained on antibiotic-free horse blood agar. These strains could not be isolated directly from stool on Skirrow medium, and colony counts confirmed that this medium could not support a low inoculum of these organisms. The clinical significance of these strains is unknown. We conclude that C. upsaliensis can be isolated directly from stool by using a selective medium, without the need for filtration.

Rifabutin-associated uveitis.

OBJECTIVE: To review rifabutin-associated uveitis and discuss the mechanism and potential role of drug interactions with clarithromycin and fluconazole in contributing to this adverse event. DATA SOURCES: A MEDLINE search (1991 through September 1994) of English-language literature using the main MeSH headings "rifabutin" and "uveitis" and the subheadings "adverse effects" and "chemically induced." Relevant articles also were selected from references of identified articles. Abstracts from recent medical conferences of infectious diseases, pharmacology, and HIV were screened for additional data. STUDY SELECTION AND DATA EXTRACTION: All articles and abstracts reporting uveitis potentially related to rifabutin were considered for inclusion. Fifty-four cases were identified. Pertinent information from the case reports, as judged by the authors, was selected and synthesized for discussion. DATA SYNTHESIS: Rifabutin is being prescribed increasingly for the treatment and prophylaxis of Mycobacterium avium complex (MAC) infection in the HIV-infected population. Uveitis was initially thought to be a rare, dose-limited complication of rifabutin therapy. In an early dose-ranging tolerance study, uveitis was associated with daily doses of 1200 mg or more. Because this toxicity appeared to be dose-related, lower dosages (300-600 mg/d) of rifabutin were selected for study in subsequent clinical trials. More recent reports noting the association of uveitis with these lower dosages of rifabutin have raised concerns about the prevalence of this adverse event. In the 54 identified cases, patients presented with symptoms of unilateral or bilateral uveitis from 2 weeks to more than 7 months following initiation of rifabutin therapy. In all reported cases, patients were receiving concurrent therapy with clarithromycin and/or fluconazole, both of which have inhibitory effects on rifabutin metabolism. In most cases, uveitis resolved within 1-2 months following discontinuation of rifabutin with or without administration of topical corticosteroids. CONCLUSIONS: Rifabutin is prescribed frequently for the prophylaxis and treatment of MAC infection, especially in patients with HIV. Uveitis is a rare, dose-related toxicity of this therapy. The risk of rifabutin-associated uveitis may be increased in patients receiving concurrent therapy with clarithromycin or fluconazole because of drug interactions. Patients receiving therapy with combinations of any of these agents should be warned about signs and symptoms of uveitis and be monitored closely for the development of rifabutin toxicity. If uveitis develops, rifabutin therapy should be discontinued promptly.

Reactivation and dissemination of blastomycosis complicating Hodgkin's disease: a case report and review of the literature.

Patients presenting with Hodgkin's disease (HD) may show lung involvement characterized by contiguous spread from ipsilateral hilar lymph nodes. Lung consolidation or noncontiguous pulmonary involvement makes an alternative diagnosis more likely. This report describes a patient with HD in whom concurrent pulmonary blastomycosis was recognized only after chemotherapy had started and dissemination had occurred. Although Blastomyces dermatitidis may behave as an opportunist pathogen, there are no previous reports of blastomycosis in patients with HD. Undiagnosed active opportunistic infection at the time of diagnosis of HD may complicate staging as well as treatment. Biopsy of lung lesions with stain and culture for opportunistic pathogens should be considered in patients with newly diagnosed HD disease and atypical patterns of lung involvement.

The effects of heterologous and homologous coat protein on alkaline disassembly of tobacco and tomato isolates of tobacco mosaic virus.

Tobacco (Tb) and tomato (Tm) isolates of tobacco mosaic virus (TMV) disassemble in dilute alkaline solutions (pH > 8.0). Tm-TMV is more sensitive to alkali than is Tb-TMV. Tb protein is, however, able to partially stabilize both Tm-TMV and Tb-TMV, thus retarding the rate of alkaline disassembly. Tm protein is unable to stabilize Tm-TMV and also increases the rate of alkaline disassembly of Tb-TMV.

A randomized trial of N-acetylcysteine for prevention of trimethoprim-sulfamethoxazole hypersensitivity reactions in Pneumocystis carinii pneumonia prophylaxis (CTN 057). Canadian HIV Trials Network 057 Study Group.

Hydroxylamine derivatives of sulfamethoxazole may be the reactive metabolites that cause adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMX). The increased frequency of reactions observed in HIV-positive individuals is hypothesized to be due to systemic glutathione deficiency and a decreased ability to scavenge these metabolites. Two hundred and thirty-eight patients were randomized to receive or not receive N-acetylcysteine (3 g of the 20% liquid solution) 1 hour before each dose of TMP-SMX (trimethoprim 80 mg, sulfamethoxazole 400 mg) twice daily, which was initiated as primary Pneumocystis carinii pneumonia prophylaxis. Forty-five patients had to discontinue TMP-SMX within 2 months because of fever, rash, or pruritus including 25 of 102 patients (25%) who were receiving TMP-SMX alone and 20 of 96 patients (21%) who were randomized to TMP-SMX and N-acetylcysteine. The difference between treatment groups is 4% (95% confidence interval [CI]: -16%, +9%). No independent association was found with the hypersensitivity reaction and age, gender, race, HIV risk factor, prior AIDS, concurrent use of fluconazole, or baseline CD4. N-acetylcysteine at a dose of 3 g twice daily could not be shown to prevent TMP-SMX hypersensitivity reactions in patients with HIV infection.

Use of fluconazole in the treatment of candidal endophthalmitis.

Candidal endophthalmitis is a sight-threatening ocular infection that most frequently occurs as a complication of candidemia. While amphotericin B is considered the gold standard for the treatment of most invasive fungal infections, the optimal management of candidal endophthalmitis has not been determined. Fluconazole, a triazole antifungal agent, has been shown to be effective in the management of a number of invasive fungal infections in both immunocompromised and immunocompetent hosts. We describe the clinical features and outcomes for six patients with candidal endophthalmitis who were treated with fluconazole at our institutions, and we review 21 additional cases reported in the English-language literature. In total, fluconazole has been used as the sole therapy for candidal endophthalmitis in 14 patients; 16 eyes were infected. Endophthalmitis was cured in 15 of 16 eyes (94%), including five infections that were complicated by vitreitis. Successful treatment required the administration of fluconazole (100-200 mg po) daily for approximately 2 months. In addition, fluconazole has been used in combination with pars plana vitrectomy for the successful treatment of four cases of candidal endophthalmitis that were complicated by moderate to severe vitreitis. Fluconazole appears to be a safe and effective alternative or addition to conventional treatments for the management of candidal endophthalmitis. Prospective evaluation is required to more clearly define the role of this antifungal agent in the management of ocular infections due to Candida species.