The efficacy of topical metronidazole in the treatment of ocular rosacea. A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial. A randomized, double-blind, placebo-controlled trial of the combined effect of doxycycline hyclate 20-mg tablets and metronidazole 0.75% topical lotion in the treatment of rosacea. Combined effect of anti-inflammatory dose doxycycline (40-mg doxycycline, usp monohydrate controlled-release capsules) and metronidazole topical gel 1% in the treatment of rosacea. A comparison of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea. Efficacy of topical cyclosporine for the treatment of ocular rosacea. A multicenter study of topical azelaic acid 15% gel in combination with oral doxycycline as initial therapy and azelaic acid 15% gel as maintenance monotherapy. Efficacy and safety of once-daily metronidazole 1% gel compared with twice-daily azelaic acid 15% gel in the treatment of rosacea. A double-blind trial of metronidazole versus oxytetracycline therapy for rosacea. Topical metronidazole therapy for rosacea. Topical metronidazole in the treatment of rosacea. A double-blind study of I% metronidazole cream versus systemic oxytetracycline therapy for rosacea. Comparison of efficacy of azithromycin vs. doxycycline in the treatment of rosacea: a randomized open clinical trial. Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline, USP capsules) administered once daily for treatment of rosacea. A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1 percent cream to vehicle in patients with rosacea. Comparative study of some treatment modalities of rosacea. Once-daily topical metronidazole cream formulations in the treatment of the papules and pustules of rosacea. Topical metronidazole maintains remissions of rosacea. Efficacy and safety of azelaic acid (15%) gel as a new treatment for papulopustular rosacea: results from two vehicle-controlled, randomized phase III studies. Randomized placebo-controlled trial of metronidazole 1% cream with sunscreen SPF 15 in treatment of rosacea. Placebo controlled trial of fusidic acid gel and oxytetracycline for recurrent blepharitis and rosacea. Azelaic acid 15% gel once daily versus twice daily in papulopustular rosacea. Treatment of rosacea by metronidazole. Treatment of rosacea with i% metronidazole cream. A double-blind study. A randomized trial of topical cyclosporin 0.05% in topical steroid-resistant atopic keratoconjunctivitis. Failure of topically applied antibiotics, added to systemic prophylaxis, to reduce perineal wound infection in abdominoperineal excision of the rectum. Fosfomycin/metronidazole compared with doxycycline/metronidazole for the prophylaxis of infection after elective colorectal surgery. A randomised double-blind multicentre trial in 517 patients. Single-dose chemoprophylaxis in elective colorectal surgery. A comparison between doxycycline plus metronidazole and doxycycline. A prospective, randomized, double-blind studyof single high dose versus multiple standard dose gentamicin both in combination withmetronidazole for colorectal surgicalprophylaxis. A double-blind study of the efficacy of metronidazole gel in the treatment of malodorous fungating tumours. A double-blind trial of a single intravenous dose of metronidazole as prophylaxis against wound infection following appendicectomy. Single-dose intravenous metronidazole v. doxycycline prophylaxis in colorectal surgery. An open prospective, randomized trial. Combination sodium sulfacetamide 10% and sulfur 5% cream with sunscreens versus metronidazole 0.75% cream for rosacea. Double-blind comparison of azelaic acid 20% cream and its vehicle in treatment of papulo-pustular rosacea. The treatment of acute infectious conjunctivitis with fusidic acid: a randomised controlled trial. Systemic prophylaxis with gentamicin-metronidazole in appendicectomy and colorectal surgery: a prospective controlled clinical study. A comparison of oral azithromycin with topical oxytetracycline/polymyxin for the treatment of trachoma in children. Multicenter prospective randomized trial comparing ceftazidime plus co-trimoxazole with chloramphenicol plus doxycycline and co-trimoxazole for treatment of severe melioidosis. Multicenter comparison of clotrimazole vaginal tablets, oral metronidazole, and vaginal suppositories containing sulfanilamide, aminacrine hydrochloride, and allantoin in the treatment of symptomatic trichomoniasis. Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis. A comparison of chloramphenicol, trimethoprim-sulfamethoxazole, and doxycycline with doxycycline alone as maintenance therapy for melioidosis. Failure of single-dose metronidazole prophylaxis in colorectal surgery. No benefit from high dosage or combination with nalidixic acid. Clinical cure of bacterial conjunctivitis with azithromycin 1%: vehicle-controlled, double-masked clinical trial.
The purpose of the study is to investigate the efficacy of metronidazole topical gel in the treatment of ocular rosacea.
                Ten patients with ocular rosacea were treated prospectively with lid hygiene and topical metronidazole applied to the lid margin in one eye and lid hygiene alone in the fellow eye. The treatment period was 12 weeks. A masked observer graded the ocular findings at the initial visit and at the conclusion of the treatment period. Pretreatment scores were compared with post-treatment scores with respect to ocular surface, eyelid margin, and combined eyelid plus ocular surface.
                Eight of ten treated eyes improved, whereas only five of ten control eyes improved. There was a statistically significant improvement in the eyelid score in both the treated and control groups (P = 0.003, P = 0.025, respectively), but no significant improvement in the ocular surface score in either group. When the pretreatment and post-treatment eyelid and ocular surface scores were combined, there was a significant improvement in the treated eyes but not in the control eyes (P = 0.022, P = 0.10, respectively). No adverse effects of the metronidazole treatment were encountered in this study.
                Metronidazole topical gel may be a safe and effective means of treating rosacea blepharitis. To compare the efficacy and safety of a novel formulation of 15% azelaic acid gel (Finacea; Berlex Laboratories, Inc, Montville, NJ) with 0.75% metronidazole gel (MetroGel; Galderma Laboratories LP, Fort Worth, Tex) as topical therapy for moderate, papulopustular facial rosacea.
                Multicenter, double-blind, randomized, parallel-group study.
                Thirteen US centers.
                A total of 251 patients with papulopustular rosacea with persistent erythema and telangiectasia.
                Patients were randomized to receive azelaic acid gel or metronidazole gel twice daily for 15 weeks.
                Nominal and percent change in inflammatory lesion count, change in erythema and telangiectasia severity ratings, investigator's global assessment of rosacea, and investigator's and patient's overall improvement ratings.
                Azelaic acid gel was superior to metronidazole gel in reduction of mean nominal lesion count (-12.9 vs -10.7, respectively) (P =.003) and mean percent decrease in inflammatory lesions (-72.7% vs -55.8%, respectively) (P<.001). With respect to erythema severity, 56% of azelaic acid gel-treated patients were rated improved vs 42% of metronidazole gel-treated patients (P =.02). The effectiveness of metronidazole gel on these variables seemed to plateau after week 8, whereas azelaic acid gel demonstrated progressive improvement through week 15. Neither treatment had a clinically appreciable effect on telangiectasia. Both the investigator's global assessment (P =.02) and overall assessment of improvement (P =.005) showed a significant therapeutic advantage for azelaic acid gel. Azelaic acid gel also scored higher on the patient's overall assessment of efficacy. Both treatments were rated as having high cosmetic acceptability. No serious or systemic treatment-related adverse events were reported in either group.
                Use of 15% azelaic acid gel twice daily for 15 weeks demonstrated significant superiority over using 0.75% metronidazole gel in improving principal signs of rosacea (inflammatory lesions and erythema). Subantimicrobial doses of doxycycline may improve outcomes in rosacea when combined with topical metronidazole and used as maintenance monotherapy.
                The purpose of this study was to evaluate the safety and efficacy of doxycycline hyclate 20 mg (subantimicrobial dose doxycycline) administered twice daily as an adjunct to metronidazole 0.75% topical lotion in the treatment of rosacea.
                Patients received subantimicrobial doses of doxycycline twice daily plus metronidazole (n = 20) or placebo plus metronidazole (n = 20) for 12 weeks. Subantimicrobial-dose doxycycline or placebo monotherapy continued for 4 weeks. The primary efficacy measure was change from baseline in total inflammatory lesions at weeks 2 and 16.
                Total inflammatory lesions were reduced significantly (P =.048) by week 4 and by all subsequent visits in the subantimicrobial-dose doxycycline/metronidazole group compared with placebo/metronidazole. Changes from baseline increased over time and were maintained during subantimicrobial-dose doxycycline monotherapy.
                Adjunctive use of subantimicrobial dose doxycycline significantly reduced the clinical signs of rosacea compared with metronidazole alone and may be useful maintenance monotherapy. Research into the pathophysiology of rosacea suggests a central role for inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS), and matrix metalloproteinases (MMPs). Effective treatments for rosacea, including topical metronidazole and systemic antibiotics, have anti-inflammatory activity, which may be more important than their antimicrobial activity in this setting. Phase III studies have substantiated the efficacy of anti-inflammatory dose doxycycline (40-mg doxycycline monohydrate controlled-release capsules) administered once daily for the treatment of inflammatory lesions of rosacea. Results of a 16-week, randomized, double-blind, placebo-controlled study of anti-inflammatory dose doxycycline plus topical metronidazole gel 1% for mild to moderate rosacea are presented here. At week 12, metronidazole was discontinued and patients continued on either placebo or doxycycline. Combination therapy significantly reduced inflammatory lesion counts as early as week 4 and through week 12 compared to topical metronidazole 1% gel monotherapy. The combined therapy appeared effective and well-tolerated. Although it is important for physicians to have sufficient clinical data on which to base treatment decisions, little comparative data exist regarding newer treatment modalities for rosacea.
                The goal of the study was to compare the efficacy and safety of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea. Parameters of patient satisfaction to treatment were also assessed.
                Forty patients with the clinical manifestation of symmetric facial rosacea were investigated in this single-center, double-blind, randomized, contralateral split-face comparison clinical trial.
                After 15 weeks of treatment, both azelaic acid and metronidazole induced significant, albeit equal reductions in the number of inflammatory lesions (pustules and papules). A significantly higher physician rating of global improvement was achieved with azelaic acid. Changes in the rosacea signs and symptoms of dryness, burning, telangiectasia, and itching were equal between treatments. A reduction in erythema tended toward significance with azelaic acid at week 15. A trace amount of stinging on application was noted with azelaic acid; however, such discomfort did not appear to concern patients because their overall impression of azelaic acid was superior to that of metronidazole.
                Azelaic acid 20% cream provides an effective and safe alternative to metronidazole 0.75% cream with the added benefit of increased patient satisfaction. This study was designed to compare the efficacy of cyclosporine ophthalmic emulsion 0.05% with an artificial tear solution for the treatment of rosacea-associated eyelid and corneal pathology.
                Double-masked, randomized, 3-month clinical trial of 37 patients with rosacea-associated eyelid and corneal changes (defined as lid margin telangiectasia, meibomian gland inspissation, and/or fullness of the lid margin). All findings were standardized and compared to photographs for grading.
                There was a statistically significant increase in Schirmer (with anesthesia) scores of 2.7+/-2.2 mm after 3 months of treatment in the topical cyclosporine group (P<0.001), compared with a mean decrease of -1.4+/-4.6 mm (P=0.271) in the artificial tears group. The mean tear break-up time score significantly improved in the topical cyclosporine group (mean increase of 3.56+/-1.5 seconds, P<0.001), but worsened in the control group, although this change was not significantly significant (mean decrease of -0.04+/-1.6 seconds, P=0.929). The topical cyclosporine group exhibited a significantly greater mean reduction in corneal staining scores (-1.3+/-0.53) compared with the control group (-0.2+/-0.83; between groups P<0.001). The topical cyclosporine group had a greater improvement in Ocular Surface Disease Index scores than those using artificial tears (P=0.022). Limitations of the study included an older, predominantly Caucasian patient population and short trial length.
                Topical cyclosporine 0.05% is more effective than artificial tears for the treatment of rosacea-associated lid and corneal changes. This two-phase, multicenter study was undertaken to examine the safety and efficacy of combination therapy with oral doxycycline and topical azelaic acid (AzA) 15% gel in moderate-to-severe papulopustular rosacea and to determine the effect of subsequent maintenance monotherapy with AzA 15% gel alone. In the initial open-label, non-randomized phase of the study, subjects (n=172) received topical AzA 15% gel and oral doxycycline (100 mg), both twice daily, for < or = 12 weeks. In the second, double-blind study phase, subjects who had initially undergone at least four weeks of combination treatment in phase 1 and who achieved > or = 75% inflammatory lesion count reduction (n=136) were randomized to receive either AzA 15% gel or its vehicle twice daily for an additional 24 weeks. Assessments of efficacy were obtained at four-week intervals throughout both phases of the study and included change in inflammatory lesion count, investigator global assessment (IGA) of rosacea severity, and separate assessments of erythema and telangiectasia severity. At the last visit for each phase of the study, the investigator and participant each rated overall improvement, with the participant rating cosmetic acceptability and the investigator rating treatment as "success" or "failure" based on IGA score. During the second phase of the trial, the rate of relapse -- defined as either a 50% deterioration in the lesion count improvement from phase 1, an increase in erythema intolerable to the subject or maintenance therapy failure as judged by the investigator and/or the subject -- was obtained. Safety assessments were conducted for both phases of the study and included analysis of adverse events (AEs) and a rating of cutaneous tolerability by the subject. By week 12 of the open-label phase of the study, 81.4% of subjects had reached a 75% or greater reduction in inflammatory lesion count, and 64% of patients achieved treatment success. During the second study phase (maintenance phase), AzA 15% gel consistently provided a better maintenance response than vehicle, with maintenance of remission in 75% of patients over the six-month duration of the maintenance phase. Additionally AzA 15% gel showed a statistically significantly lower deterioration in absolute inflammatory lesion counts than did vehicle after 8, 16, 20 and 24 weeks of maintenance therapy. No serious treatment-related AEs were encountered in the study, and 98.5% of subjects were satisfied with the local tolerability of both AzA gel and vehicle. Rosacea is an inflammatory dermatologic disorder characterized by the presence of facial erythema, visible blood vessels, papules, and pustules. The National Rosacea Society has established a classification system that identifies 4 distinct rosacea subtypes based on clinical presentation: erythematotelangiectatic, papulopustular, phymatous, and ocular. The goal of topical therapy for rosacea is to reduce inflammatory lesion counts; decrease intensity of erythema; and reduce symptoms such as stinging, burning, and pruritus. Metronidazole and azelaic acid are thought to reduce the inflammation associated with rosacea by inhibiting the production of reactive oxygen species produced by neutrophils. Both metronidazole 1% gel and azelaic acid 15% gel recently have been approved for the treatment of rosacea. The current study was conducted to compare the once-daily application of metronidazole 1% gel with twice-daily applications of azelaic acid 15% gel for the treatment of patients with moderate rosacea (N=160). Both treatments showed similar reductions in inflammatory lesion counts (77% for metronidazole 1% gel and 80% for azelaic acid 15% gel) and high success rates in both global severity (53.7% vs 56.4% for metronidazole 1% gel and azelaic acid 15% gel, respectively) and erythema (42.7% vs 42.3% for metronidazole 1% gel and azelaic acid 15% gel, respectively). On average, the efficacy (including reduction in erythema) of the once-daily application of metronidazole 1% gel and twice-daily applications of azelaic acid 15% gel were similar. Forty patients with papulo-pustular rosacea were treated for 12 weeks on a random double-blind basis either with oxytetracycline 250 mg twice daily or with metronidazole 200 mg twice daily. Both drugs produced an improvement which was greater after 12 weeks than after 6 weeks, but there was no significant difference between them. Metronidazole appears to be a safe and effective drug for the treatment of rosacea. Forty patients with rosacea were treated topically with 0.75% metronidazole gel in a randomized split-face double-blind paired-comparison trial. With twice-daily applications, 36.7, 48.5, and 65.1 mean percent reductions in total papules and pustules were noted over baseline at 3, 6, and 9 weeks, respectively, on the side of the face receiving metronidazole therapy. Therapy with vehicle alone produced a maximum mean percent reduction of 14.9 at nine weeks. Erythema also responded but was less improved by the end of nine weeks of therapy. A mild increase in telangiectasia was noted on both actively treated and placebo-treated sides. The gel was locally well tolerated. Only two of 40 patients failed to complete the trial, both because of flares of rosacea (one at two days, and one at five weeks). No systemic symptoms were noted, and no consistent abnormalities were found in the results of laboratory studies (hematology, chemistry, and urinalysis). Topical metronidazole gel therapy appears to be a safe and efficacious therapy in the treatment of moderate to severe rosacea. One percent metronidazole in an emollient cream base was compared with 250 mg oral tetracycline taken twice daily for the treatment of seventy-five patients with rosacea. After eight weeks of treatment there was no statistically significant difference between the results of the two treatments. Tetracycline did have a more rapid onset of effect on papules and pustules. Both treatments were well tolerated. In a randomized double-blind trial fifty-one patients with rosacea were treated for 2 months with either I% metronidazole cream and placebo tablets or with 250 mg oxytetracycline tablets taken twice daily, and placebo cream (the cream base). The patients were assessed before and at the end of the trial, using the following criteria: (1) overall clinical assessment, (2) lesion counts, (3) degree of erythema, (4) independent photographic evaluation, (5) patients' opinion. An improvement was shown in 90% of the patients of both groups, and there was no significant difference between the two treatments. Rosacea is a common inflammatory disorder of the skin. Systemic antibiotics currently used in the treatment of rosacea are sometimes associated with uncomfortable side effects. Therefore, a need for an effective agent with few side effects and good patient compliance exists. Azithromycin, a macrolide antibiotic with prolonged mode of action, has recently been found to be an effective alternative in the treatment of inflammatory acne.
                For evaluation of the efficacy of azithromycin in the treatment of rosacea, we planned a randomized, open, clinical trial study to compare the efficacy of azithromycin with doxycycline in the treatment of this disease. Sixty-seven patients were randomized to receive either azithromycin 500 mg thrice weekly (on Monday, Wednesday, and Saturday) in the first, 250 mg thrice weekly (on Monday, Wednesday, and Saturday) in the second, and 250 mg twice weekly (on Tuesday, and Saturday) in the third month. The other group was given doxycycline 100 mg/day for the three months. Clinical assessment was made at baseline, at the end of first, second, third, and 2 months after treatment. Side affects were recorded. The limitation of this study is that there was no blindness.
                Statistically significant improvement was obtained with both drugs. Neither drug was shown to be more effective than the other. In the azithromycin group four patients had diarrhea, while epigastric burning was seen in two patients using doxycycline.
                This study indicates that azithromycin is at least as effective as doxycycline in the treatment of rosacea. Doxycycline monotherapy at antimicrobial doses has been shown to be effective for the treatment of rosacea.
                To evaluate the efficacy and safety of once-daily anti-inflammatory dose doxycycline for the treatment of rosacea.
                In two phase III, parallel-group, multicenter, randomized, double-blind, placebo-controlled studies (studies 301 and 302), patients received 40-mg of controlled-release doxycycline (n = 269) or placebo (n = 268) for 16 weeks. The primary efficacy end point was the mean change from baseline in facial inflammatory lesion count.
                The mean lesion count at baseline was approximately 20 in each study arm. At week 16, the mean change from baseline in lesion count in the active-treatment groups was -11.8 in study 301 and -9.5 in study 302 compared with -5.9 and -4.3, respectively, in the placebo groups (P < .001 for both comparisons). Anti-inflammatory dose doxycycline was well tolerated; the most common adverse events were nasopharyngitis (4.8%), diarrhea (4.4%), and headache (4.4%).
                In both studies, the reduction of inflammatory lesion counts did not plateau within the 16-week time frame in either treatment group. Rosacea is often treated for a period of months or years. The duration of the studies did not allow for assessment of safety beyond 16 weeks or whether the progressive improvement seen with active treatment would continue beyond 16 weeks. Neither study assessed the effect of treatment in patients with only erythematotelangiectatic (subtype 1) rosacea.
                Once-daily anti-inflammatory dose doxycycline appears to be effective and safe for the treatment of rosacea. The efficacy and safety of a new formulation of metronidazole 1 percent cream applied once daily was compared to vehicle cream in a double-blind, randomized, parallel group, ten-week clinical study. The results showed that metronidazole 1 percent cream was significantly better than vehicle in reducing the lesions of rosacea, improving erythema, and physician's global rosacea scores. The incidence of adverse events related to the skin was low. Rosacea is a disease of complex pathogenesis and variable response to various therapeutic methods. Aim of the work To evaluate and compare the efficacy, safety and side effects of some topical lines of treatment of rosacea.
                The study included 24 patients (23 females and 1 male) with rosacea on the face. They were classified into three groups--each including eight patients (16 face sides)--and treated with one of three topical agents (azelaic acid 20% cream, metronidazole 0.75% cream or permethrin 5% cream) on one side of the face and another one on the other side twice daily for 15 weeks.
                There was a significant improvement of lesions after 15 weeks of topical treatment with the three agents. Azelaic acid cream was significantly more effective on inflammatory lesions but not erythema than the other two creams. Side effects--mostly transient--were observed with topical creams with no significant difference. They included itching, burning sensation, oedema and scales. Patients who used azelaic acid 20% cream were more satisfied than with other modalities.
                Azelaic acid 20% cream provides an effective and safe alternative to metronidazole 0.75% cream or permethrin 5% cream with the added benefit of increased patient satisfaction. The papules and pustules of rosacea can be effectively treated with topical metronidazole. The optimal concentrations of metronidazole and optimum frequencies of application are uncertain. Traditionally, twice-daily applications have been advised, based on the pharmacokinetic profile of metronidazole. Once-daily applications may be safer and less expensive, and they may enhance patient compliance.
                We compared the efficacy and safety of 2 commercially available topical metronidazole formulations (0.75% metronidazole cream formulation and 1.0% metronidazole cream formulation) when both were used in a once-daily regimen.
                A multicenter, randomized, investigator-blind, parallel group trial was conducted at 3 separate clinical sites located in 3 US cities. The study enrolled 72 rosacea patients with at least 8 to 50 inflammatory facial lesions (pustules and papules) and moderately severe facial erythema. Patients were randomly assigned to receive either 0.75% metronidazole cream or 1.0% metronidazole cream and instructed to apply the medication once daily for 12 weeks. Patients' lesions were evaluated at baseline and at weeks 3, 6, 9, and 12.
                There were no significant differences between treatment groups for any of the efficacy parameters evaluated. The overall median percentage change in lesion count at end point for patients in the 0.75% metronidazole cream treatment group was -62% compared with -60% for the 1.0% metronidazole cream treatment group. The overall percentage change in erythema scores at endpoint for patients in the 0.75% metronidazole cream treatment group was -26% compared with -30% for patients in the 1.0% metronidazole cream treatment group. Regarding physician assessment of global severity, 57% of subjects (20/35) in the 0.75% metronidazole cream group compared with 37% of subjects (13/35) in the 1.0% metronidazole cream group were rated as having a clear to mild condition at end point. Both drugs were well tolerated; there was no significant difference in the number of drug-related adverse events between the two agents.
                This controlled trial demonstrates that both 0.75% metronidazole cream and 1.0% metronidazole cream, when used once daily, provide well-tolerated efficacy for moderate to severe rosacea. Rosacea is a chronic skin disease that requires long-term therapy. Oral antibiotics and topical metronidazole successfully treat rosacea. Because long-term use of systemic antibiotics carries risks for systemic complications and adverse reactions, topical treatments are preferred.
                To determine if the use of topical metronidazole gel (Metrogel) could prevent relapse of moderate to severe rosacea.
                A combination of oral tetracycline and topical metronidazole gel was used to treat 113 subjects with rosacea (open portion of the study). Successfully treated subjects (n = 88) entered a randomized, double-blind, placebo-controlled study applying either 0.75% topical metronidazole gel (active agent) or topical metronidazole vehicle gel (placebo) twice daily (blinded portion of the study).
                Subjects were enrolled at 6 separate sites in large cities at sites associated with major medical centers.
                One hundred thirteen subjects with at least 6 inflammatory papules and pustules, moderate to severe facial erythema and telangiectasia entered the open phase of the study. Eighty-eight subjects responded to treatment with systemic tetracycline and topical metronidazole gel as measured by at least a 70% reduction in the number of inflammatory lesions. These subjects were randomized to receive 1 of 2 treatments: either 0.75% metronidazole gel or placebo gel.
                Subjects were evaluated monthly for up to 6 months to determine relapse rates.
                Inflammatory papules and pustules were counted at each visit. Relapse was determined by the appearance of a clinically significant increase in the number of papules and pustules. Prominence of telangiectases and dryness (roughness and scaling) were also observed.
                In the open phase, treatment with tetracycline and metronidazole gel eliminated all papules and pustules in 67 subjects (59%). The faces of 104 subjects (92%) displayed fewer papules and pustules after treatment, and 82 subjects (73%) exhibited less erythema. In the randomized double-blind phase, the use of topical metronidazole significantly prolonged the disease-free interval and minimized recurrence compared with subjects treated with the vehicle. Eighteen (42%) of 43 subjects applying the vehicle experienced relapse, compared with 9 (23%) of 39 subjects applying metronidazole gel (P<.05). The metronidazole group had fewer papules and/or pustules after 6 months of treatment (P<.01). Relapse of erythema also occurred less often in subjects treated with metronidazole (74% vs 55%).
                In a majority of subjects studied, continued treatment with metronidazole gel alone maintains remission of moderate to severe rosacea induced by treatment with oral tetracycline and topical metronidazole gel. Rosacea is a common, chronic dermatosis for which safe and effective new treatment options are needed.
                The objective of these studies was to evaluate the efficacy, tolerability, and safety of a new formulation of 15% azelaic acid (15%) gel (AzA gel), for the topical treatment of moderate, papulopustular rosacea.
                Two multicenter, double-blind, randomized, parallel-group, vehicle-controlled studies were conducted using identical study designs, patient-selection criteria, and efficacy end points. Overall, 329 patients were enrolled in study 1 and 335 patients in study 2.
                Both studies consistently demonstrated the superiority of AzA gel over vehicle in the topical treatment of moderate, papulopustular rosacea. AzA gel yielded statistically significantly higher reductions in mean inflammatory lesion count than vehicle: 58% versus 40%, study 1 (P =.0001); 51% versus 39%, study 2 (P =.0208). Significantly higher proportions of patients treated with AzA gel experienced improvement in erythema compared with vehicle gel: 44% versus 29%, study 1 (P =.0017); 46% versus 28%, study 2 (P =.0005). Using the investigator's global assessment, therapeutic success in terms of a clear, minimal, or mild final result was achieved in 61% and 62% of patients treated with AzA gel in studies 1 and 2, respectively, which was significantly superior to the result achieved with vehicle (40% and 48%, respectively) (P <.0001, study 1; P =.0127, study 2). No serious, treatment-related adverse events were reported.
                The results of these 2 controlled studies demonstrate that AzA gel, used twice daily, is an efficacious, safe, and well-tolerated topical treatment for moderate, papulopustular rosacea. Rosacea is a photoaggravated dermatosis responsive to treatment with topical and oral antibiotics. A formulation combining metronidazole 1% cream with sunscreen SPF 15 was developed for the treatment of rosacea.
                The objective of this study was to determine the safety and efficacy of a formulation combining metronidazole 1% cream with sunscreen SPF 15 in the treatment of moderate to severe rosacea.
                One hundred and twenty patients with moderate to severe rosacea were enrolled for a randomized, placebo-controlled (vehicle containing sunscreen with SPF 15), double-blind study. Study cream was applied twice daily to the entire face over a 12-week period.
                Treatment with metronidazole 1% cream with sunscreen SPF 15 resulted in significant improvement (p <0.05) in inflammatory lesion count, erythema and telangiectasiae scores, and investigator and patient global assessment scores compared with baseline and placebo. Adverse reactions related to study medication were typically mild, occurred at the site of application, and were reversible. There was no difference between the safety profiles of metronidazole 1% cream with sunscreen SPF 15 and placebo.
                The combined topical formulation of metronidazole 1% cream with sunscreen SPF 15 was an effective, well-tolerated topical agent for the treatment of moderate to severe rosacea. A prospective, randomised, double blind, partial crossover, placebo controlled trial has been conducted to compare the performance of topical fusidic acid gel (Fucithalmic) and oral oxytetracycline as treatment for symptomatic chronic blepharitis. Treatment success was judged both by a reduction in symptoms and clinical examination before and after therapy. Seventy five per cent of patients with blepharitis and associated rosacea were symptomatically improved by fusidic acid gel and 50% by oxytetracycline, but fewer (35%) appeared to benefit from the combination. Patients with chronic blepharitis of other aetiologies did not respond to fusidic acid gel but 25% did benefit from oxytetracycline and 30% from the combination. Our results demonstrate the need to investigate patients with blepharitis for concomitant rosacea as they respond well to targeted therapy. Twice-daily azelaic acid (AzA) is the conventional regimen for papulopustular rosacea, but once-daily AzA may be equally effective, with greater convenience and dosing flexibility. In order to test this hypothesis, an exploratory study was conducted.
                The evaluable efficacy population of this 12-week double-blind, parallel-group study included 72 patients and the population that was used to report safety results included 92 patients. Baseline characteristics were comparable between the once-daily and twice-daily study groups. Evaluations were performed at baseline and at weeks 4, 8, and 12.
                No significant difference was found between the once-daily and twice-daily groups at the end of study therapy in mean investigator global assessment (IGA) scores, treatment success, or treatment response. The mean number of inflammatory lesions, the intensity of erythema intensity, and the intensity of telangiectasia at treatment end were likewise not significantly different (P>.205 for all). More than 90% of subjects in each group rated cosmetic acceptability of this AzA gel as satisfactory or better.
                Based on these findings and those of prior studies, once-daily AzA 15% gel can therefore be utilized as a safe, effective, and economical dosing option for the treatment of mild-to-moderate papulopustular rosacea. Once-daily dosing of AzA 15% gel was well accepted by patients and can offer considerable dosing flexibility and convenience for the patient as well as for the dermatologist. A double-blind trial in twenty-nine patients with rosacea showed that, after 6 weeks' treatment, metronidazole was therapeutically superior to a placebo (P less than 0-02). It was particularly effective against papules and pustules. The mode of action of metronidazole and other antibiotics in rosacea is not known. Eighty-one patients with rosacea were treated with either I% metronidazole cream or the cream base as a placebo for two months. The trial was performed double-blind, and the patients were assessed once each month. The variates studied were: (I) overall clinical assessment, (2) lesion counts, (3) degree of erythema, (4) independent photographic evaluation, and (5) patient's opinion. Four patients dropped out of the trial (one treated with metronidazole, three with placebo). In all the variates, I% metronidazole cream proved to be significantly more effective than placebo. To evaluate the short-term efficacy and safety of topical cyclosporin A 0.05% in the treatment of patients with severe, steroid-resistant atopic keratoconjunctivitis (AKC).
                Multicenter, placebo-controlled, double-masked, randomized trial.
                Twenty-two patients with AKC refractory to topical steroid treatment.
                Patients were randomly assigned (1:1) to treatment with topical 0.05% cyclosporin A eyedrops or a placebo (artificial tears) for a period of 28 days, 6 times daily during the first 2 weeks and 4 times daily during the last 2 weeks.
                Symptoms (itching, tearing, discomfort, mucous discharge, and photophobia) and signs (bulbar conjunctival hyperemia, upper tarsal conjunctival papillae, punctate keratitis, corneal neovascularization, cicatrizing conjunctivitis, and blepharitis) of AKC recorded on the day of enrollment and at the end of the treatment period.
                A composite score computed by summing the severity grade over all 5 symptoms and 6 signs of AKC for each patient indicated a greater improvement in the cyclosporin A group relative to the placebo at the end of the 4-week treatment period (P = 0.048 and P = 0.002, for symptoms and signs, respectively). No adverse effects of the treatment with cyclosporin A 0.05% eyedrops were observed.
                Topical cyclosporin A 0.05% seems to be safe and have some effect in alleviating signs and symptoms of severe AKC refractory to topical steroid treatment. In a prospective, randomized trial, prophylactic use of topical antibiotics in addition to systemic prophylaxis was studied in patients undergoing abdominoperineal amputation of the rectum. All patients received gentamicin 80 mg and metronidazole 500 mg intravenously at induction of anesthesia, followed by the same dose 8 hourly for 48 hours. In accordance with the randomization, half of the patients were additionally given gentamicin 160 mg + metronidazole 400 mg topically into the perineal wound at closure. Perineal wound infection appeared in 19 of the 41 patients who received both systemic and topical prophylaxis, and in 18 of the 38 with only systemic antibiotics. Cell-mediated immunity was preoperatively assessed with a skin test (Multitest) in all but three patients. Impairment of cell-mediated immunity was associated with significantly heightened rate of wound infection, and these patients did not benefit from topical antibiotics. To find out if fosfomycin together with metronidazole was any better than doxycycline with metronidazole for the prophylaxis of infection before elective colorectal operations.
                Multicentre, double blind, random control trial.
                Nine Swedish hospitals. SUBJECTS-559 patients admitted for elective colorectal operations.
                Fosfomycin 8 g and metronidazole 1 g before operation and fosfomycin 8 g eight hours afterwards, or doxycycline 400 mg and metronidazole 1 g before operation, and placebo eight hours afterwards.
                Incidence of all types of infection, mortality, and side effects.
                There were no significant differences between the groups for any of the outcome measures studied, the overall abdominal infection rates (wound, deep, and septicaemia) being 4.6% and 7.4%, and the remote infection rates (pneumonia, urinary tract, and central venous line) 15.1% and 12.8%, respectively. Of the predictors studied, only duration of operation was significantly related to risk of infection.
                The combination of fosfomycin and metronidazole was as safe and effective as that of doxycycline and metronidazole in preventing infections after elective colorectal operations. In a prospective, randomized double-blind study either 400 mg of doxycycline + 1500 mg of metronidazole (D + M) or 400 mg of doxycycline (D) alone were given intravenously as a single preoperative dose to patients admitted for elective colorectal surgery. A comparison of the rate of postoperative septic complications was made. After excluding drop-out patients, 261 patients remained for evaluation. In 135 patients with D + M treatment there were four postoperative septic complications (3.0%). In 126 patients with D treatment 20 septic complications related to the surgical procedure occurred (15.9%). The difference is highly significant (p less than 0.005). Most postoperative infections were superficial wound infections (14 of 24 patients), and the mean hospital stay in the two treatment groups was equal. Bacteriologic studies showed a highly significant reduction in anaerobes in cultures from perioperative intra-abdominal fluid in the D + M treatment group. The study has thus showed that the addition of metronidazole, an efficient agent against anaerobic bacteria, to an antimicrobial agent against aerobic bacteria significantly reduces postoperative septic complications in elective colorectal surgery. Single, high dose regimens of gentamicin plus metronidazole for colorectal surgical prophylaxis have not been adequately studied. Patients received single high dose gentamicin (4.5 mg/kg) plus metroni-dazole (500 mg) preoperatively or multiple standard dose gentamicin (1.5 mg/kg) plus metronidazole (500 mg) preoperatively and every 8h for 24h postoperatively. The deep surgical site infection (SSI) rates were 8.1% (6/74) and 6.9% (5/72) in the single high dose and multiple standard dose groups, respectively (P= 0.94). There was a trend towards fewer superficial SSIs in the single high dose group with infection rates of 18.9% (14/74) vs. 30.6% (22/72) (P= 0.05). Diabetes mellitus (odds ratio = 7.04) and surgery duration of longer than 3h (odds ratio = 5.46) were independent risk factors for the development of SSIs. A subset analysis of prolonged operations found significantly fewer superficial SSIs in the single high dose group than in the multiple standard dose group with rates of 22.2% (6/27) vs. 55% (11/20), respectively (P= 0.021). Single high dose gentamicin plus metronidazole preoperatively was at least as effective as the multiple standard dose regimen and may be more effective for prolonged operations.
                Copyright 2000 The Hospital Infection Society. A double-blind placebo-controlled trial was undertaken to assess the value of topical metronidazole gel preparation in the palliation of the offensive odour of fungating tumours. This 5 day trial was followed by a 6 day period during which all patients received the active gel. Subjective odour assessments were performed by both patients and medical staff. 11 patients were entered and the randomisation was then halted because of an obvious overall benefit over the whole 11 days. There was a non-significant trend in favour of the active treatment during the initial double-blind placebo-controlled phase of the trial, and no side-effects were observed. One hundred patients undergoing appendicectomy through a right iliac fossa incision were randomized to receive normal saline or 500 mg metronidazole as an intravenous infusion during the operation. One patient in the saline group developed an erythematous rash. There were 13 wound infections (as defined by the discharge of pus), 12 (out of 51) in the saline group and 1 (out of 49) in the metronidazole group. Bacteroides spp. were frequently cultured from the lumen of removed appendices and from pus obtained from infected wounds. This work supports the value of metronidazole but suggests that a single-dose regimen is adequate for prophylaxis. In an open prospective, randomized study of antimicrobial prophylaxis in colorectal surgery, using a single intravenous dose, metronidazole (1 g) was more effective than doxycycline (0.2 g). The difference in infection rates (2/41 = 5% v. 7/33 = 21%) was statistically significant. Prolonged administration of either agent (2-7 days) yielded results comparable to those with single doses. Five emergency cases were admitted to the study. In two of them, a metronidazole-based therapeutic regimen prevented postoperative infection, whereas infection occurred in all 3 patients given doxycycline therapy. The total infection rate after elective surgery was 4% with metronidazole and 25% with doxycycline prophylaxis. The infections in the metronidazole group were superficial and caused by Escherichia coli, whereas half of the infections in the doxycycline group were intra-abdominal and due to intestinal aerobic and/or anaerobic bacteria. In contrast to doxycycline, therefore, metronidazole prevented postoperative anaerobic infection and was associated with low incidence of aerobic infection. Topical metronidazole and combination sodium sulfacetamide and sulfur commonly are used to treat rosacea. Recently, the relative efficacy and safety of sodium sulfacetamide 10% and sulfur 5% cream with sunscreens (Rosac Cream) (n = 75) and metronidazole 0.75% cream (Metrocream) (n = 77) were compared in an investigator-blinded, randomized, parallel-group study at 6 sites. After 12 weeks of treatment with sodium sulfacetamide 10% and sulfur 5% cream with sunscreens, there was a significantly greater percentage reduction (80%) in inflammatory lesions compared with metronidazole 0.75% cream (72%)(P = .04), as well as a significantly greater percentage of subjects with improved erythema (69% vs 45%, respectively; P = .0007). In addition, the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens group had a significantly greater proportion of subjects with success in global improvement at week 12 compared with the metronidazole 0.75% cream group (79% vs 59%, respectively; P = .01). There was no significant difference between treatment groups in the percentage of subjects with improvement in investigator global severity. Overall tolerance was good or excellent in 85% of subjects in the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens group and in 97% of subjects in the metronidazole 0.75% cream group. Seven subjects had poor tolerance to the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens, possibly caused by a sulfa drug allergy. Previous investigations have indicated that topical azelaic acid has beneficial effects in rosacea. This 3-month randomized, double-blind, multicentre study compared the efficacy and safety of azelaic acid 20% cream with its vehicle, in the treatment of papulo-pustular rosacea. A total of 116 patients were enrolled in the study and medication was applied twice daily. Azelaic acid cream produced significantly greater mean reductions in total inflammatory lesions than did vehicle (azelaic acid: 73.4%; vehicle: 50.6%; (p = 0.011), and erythema severity score (azelaic acid: 47.9%; vehicle: 37.9%; (p = 0.031). Azelaic acid cream treatment also resulted in significantly more favourable overall improvements than vehicle in both physician (p = 0.020) and patient ratings (p = 0.042). Neither azelaic acid cream nor vehicle produced any clinically relevant improvement in telangiectasia. Local adverse events were transient and mainly mild or moderate, and rates were similar for azelaic acid cream (39.5%) and vehicle (38.5%). Burning was the symptom most frequently reported. More than 90% of patients rated the overall local tolerability of their treatment as good or acceptable. In conclusion, azelaic acid 20% cream is effective and well tolerated in the treatment of papulo-pustular rosacea. Acute infectious conjunctivitis is a common disorder in primary care. Despite a lack of evidence regarding the effectiveness of topical antibiotics for the treatment of acute infectious conjunctivitis, most patients presenting in primary care with the condition receive topical antibiotics. In The Netherlands, fusidic acid is most frequently prescribed.
                To assess the effectiveness of fusidic acid gel compared to placebo for acute infectious conjunctivitis.
                Double-blind randomised placebo-controlled trial.
                Twenty-five Dutch primary care centres.
                Adults presenting with a red eye and either (muco)purulent discharge or glued eyelid(s) were allocated to either one drop of fusidic acid gel 1% or placebo, four times daily during one week. The main outcome measure was the difference in recovery rates at 7 days. Secondary outcome measures were difference in bacterial eradication rates, a survival time analysis of the duration of symptoms, and the difference in recovery rates in culture-positive and culture-negative patients.
                One hundred and eighty-one patients were randomised and 163 patients were analysed. Forty-five of the 73 patients in the treatment and 53 of the 90 patients in the placebo group recovered (adjusted risk difference = 5.3% [95% confidence interval {CI} = -11 to 18]). There was no difference between the median duration of symptoms in the two groups. At baseline, the prevalence of a positive bacterial culture was 32% (58/181). The bacterial eradication rate was 76% in the treatment and 41% in the placebo group (risk difference = 35% [95% CI = 9.3 to 60.4]). In culture positive patients, the treatment effect tended to be strong (adjusted risk difference = 23% [95% CI = -6 to 42]).
                At 7 days, cure rates in the fusidic acid gel and placebo group were similar, but the confidence interval was too wide to clearly demonstrate their equivalence. These findings do not support the current prescription practices of fusidic acid by GPs. A prospective, randomized, clinical study was carried out in 188 patients undergoing appendicectomy or colorectal surgery to test the efficacy of prophylactic, parenterally-administered antibiotics in the prevention of infection. The results show the effectiveness of the association gentamicin-metronidazole (9.4% of infections), compared to the control group with no antibiotics (39.1% of infections), X2 = 14.1; P less than 0.001). Trachoma, an infectious keratoconjunctivitis caused by Chlamydia trachomatis, is a leading cause of preventable blindness in developing countries. In this study we compared oral azithromycin with oxytetracycline/polymyxin eye ointment (once daily for 5 days every 4 weeks; total of six treatment cycles) for the treatment of active endemic trachoma in 168 rural Egyptian children. A suspension of azithromycin was administered to children as a dose of 20 mg/kg by one of three schedules: a single dose, one dose a week for 3 weeks, and one dose every 4 weeks for a total of six doses. The children's clinical status and chlamydial infection rates were evaluated for 1 year. The clinical cure rates were 35% 2 months after initial treatment, 16% at 8 months (during the annual autumn epidemic of purulent conjunctivitis), and 47% at 1 year. The pretreatment chlamydial infection rate of 33% (determined by direct immunofluorescence) decreased to 5% at 2 months and was 9% at 12 months. There were no significant clinical or laboratory differences among the four treatment groups. Thus, 1-6 doses of azithromycin were equivalent to 30 days of topical oxytetracycline/polymyxin ointment and may offer an effective alternative means of controlling endemic trachoma. A prospective randomized trial was conducted at Srinagarind and Khon Kaen hospitals. Ceftazidime (100 mg/kg of body weight per day) and co-trimoxazole (trimethoprim, 8 mg/kg/day; sulfamethoxazole, 40 mg/kg/day) therapy was compared with conventional therapy (chloramphenicol, 100 mg/kg/day; doxycycline, 4 mg/kg/day; trimethoprim, 8 mg/kg/day; sulfamethoxazole, 40 mg/kg/day) in the treatment of 64 patients with bacteriologically confirmed cases of severe melioidosis who were admitted during September 1986 to January 1989. Of 61 evaluable patients (3 were excluded because of severe drug allergies), 42 were septicemic, and 31 of these patients had the most severe form, disseminated septicemic melioidosis. Their cumulative mortalities on day 7 were compared. There were significantly lower overall mortalities from melioidosis, septicemic melioidosis, and disseminated septicemic melioidosis in the group receiving the new treatment compared with those in the group receiving the conventional treatment (47 versus 18.5% [P = 0.039], 57.7 versus 25% [P = 0.039], and 82.3 versus 30.7% [P = 0.006], respectively); but the differences could have been influenced by the greater severity of illness, e.g., shock at initial presentation, in the patients who received the conventional treatment. Among patients with disseminated septicemia and initial shock, there was no significant difference in mortality between the regimens. Both regimens effectively eradicated bacteria from the circulation within 24 h (97 versus 96%, respectively). We recommend ceftazidime and co-trimoxazole as the drugs of choice for treatment of severe melioidosis, especially in those patients with disseminated septicemia. Trichomonas vaginalis is a common vaginal pathogen. Oral metronidazole is the drug of choice for the treatment of trichomoniasis. Oral metronidazole, however, may cause unpleasant side effects and is contraindicated during the first trimester of pregnancy. In vitro studies and preliminary clinical data have suggested that intravaginal clotrimazole may be effective against this pathogen.
                To compare the efficacy of clotrimazole vaginal tablets, oral metronidazole, and vaginal suppositories containing sulfanilamide, aminacrine, and allantoin (AVC suppositories) in the treatment of women with symptomatic trichomoniasis.
                In a multicenter, open-label trial conducted in 1982 and 1983, 168 symptomatic women with microscopically evident vaginal trichomoniasis were randomized to receive any of 2 g of metronidazole as a single oral dose, two 100-mg clotrimazole vaginal tablets once a day for 7 days, or vaginal suppositories containing 1.05 g of sulfanilamide, 14 mg of aminacrine hydrochloride, and 140 mg of allantoin (AVC suppositories) twice a day for 7 days. Wet mounts and cultures were repated at 1 to 2 and 4 to 6 weeks after completion of treatment.
                The number of patients who had positive cultures after treatment were 40/45 (88.9%) in the clotrimazole group, 35/43 (81.4%) in the AVC suppository group, and 9/45 (20%) in the metronidazole group (P < 0.001). All treatments were associated with a reduction in reported symptoms. Oral metrohidazole was more effective in reducing symptoms than either of the topical preparations. Adverse events, mostly mild or moderate in severity, were reported by 7 (14.6%) of 48 patients who had received oral metronidazole and 4 (7.8%) of 51 women who used AVC suppositories. There were no adverse events reported by the 50 women who used clotrimazole vaginal tablets.
                Oral metronidazole was more effective in eradicating T. vaginalis than clotrimazole vaginal tablets or AVC vaginal suppositories. All three regimens reduced symptoms; oral metronidazole was more effective in reducing symptoms than either topical preparation. A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids, azathioprine, and photochemotherapy. 33 patients took part in a double-blind, placebo-controlled, crossover study to assess the efficacy and safety of cyclosporin (5 mg/kg per day) in adults with severe refractory atopic dermatitis. Treatments were given for eight weeks each with one group (n = 16) receiving placebo followed by cyclosporin and another (n = 17) receiving cyclosporin and then placebo. Disease activity, extent of disease, sleep and itch, topical steroid use, and adverse events were assessed every two weeks. Both extent and activity of dermatitis were significantly improved (p less than 0.001) as were subjective measures of disease. 20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo, although no patient required withdrawal from the study. Cyclosporin therapy led to an increase in the mean serum urea, creatinine, and bilirubin concentrations, although only the rise in bilirubin was significant (p = 0.001). Our results confirm that cyclosporin is a safe and effective short-term treatment for severe, refractory atopic dermatitis. A prospective, open, randomized, comparative treatment trial was conducted to compare the therapeutic efficacy of the conventional four-drug combination (chloramphenicol, trimethoprim-sulfamethoxazole, and doxycycline) with that of doxycycline alone in oral maintenance treatment of melioidosis. Adult Thai patients with culture-confirmed melioidosis were randomized to receive treatment with either regimen for a minimum of 12 weeks, usually following intravenous treatment of severe disease. The main outcome measure was culture-confirmed relapse. One hundred sixteen patients were enrolled; 109 had culture-confirmed melioidosis, and 87 were considered evaluable (43 had received doxycycline). Culture-confirmed relapse occurred in one patient randomized to the conventional regimen and in 11 (25.6%) randomized to the doxycycline regimen (P = .009), and treatment failed for 8 (18.2%) versus 20 (46.5%), respectively (P = .009). Adverse effects occurred in 26% of patients overall. Doxycycline alone cannot be recommended for a first-line regimen of oral maintenance treatment of melioidosis. In an open prospective study of postoperative infectious complications, patients undergoing elective colorectal surgery were randomly allocated to one of three groups receiving parenteral single-dose antimicrobial prophylaxis (1 g or 3 g metronidazole or 1 g metronidazole + 3 g nalidixic acid). Because of an unacceptably high rate of surgical infection in all three groups (36%, 29% and 39%, p greater than 0.1) among the first 103 evaluable patients, the study was discontinued. Nalidixic acid--though effective in in vitro tests of bacterial susceptibility--thus was found to be of little or no value as prophylaxis against Gram-negative infection. As the observed infection rate when metronidazole was given at the start of operation was seven-fold that previously found in the same department when 1 g metronidazole was administered 3-4 hours preoperatively (28/103 vs. 2/50, p less than 0.01), the timing of metronidazole prophylaxis was assumed to be potentially important for its ability to protect also against aerobic postoperative infection. To analyze the effect of azithromycin 1% ophthalmic solution in DuraSite (InSite Vision, Inc, Alameda, California, USA) on bacterial conjunctivitis.
                Prospective, randomized, vehicle-controlled, parallel-group, double-masked multicenter clinical study.
                Eligible male or female participants with a clinical diagnosis of acute bacterial conjunctivitis were randomized to either 1% azithromycin in DuraSite or vehicle for five days. Infected eyes were dosed twice daily on days 1 and 2 and once daily on days 3 through 5. Conjunctival cultures were obtained at baseline, visit 2 (day 3 or 4), and visit 3 (day 6 or 7). The primary end point was clinical resolution of signs and symptoms (rating of zero on ocular discharge, bulbar and palpebral injection) at visit 3. Efficacy measures were clinical resolution and bacterial eradication as evaluated in the per-protocol population. Safety was assessed by adverse events, slit-lamp findings, and ophthalmoscopy.
                Two hundred and seventy-nine participants (n = 130, 1% azithromycin in DuraSite; n = 149, vehicle), age one to 96 years, were evaluated for efficacy. Clinical resolution with azithromycin ophthalmic solution was statistically significant compared with that of vehicle (P = .030) at visit 3. Bacterial eradication rates with azithromycin ophthalmic solution reached 88.5% at visit 3 (P < .001) and included some pathogens resistant to azithromycin in vitro. Overall, adverse event rates were similar in both treatment groups.
                Azithromycin 1% ophthalmic solution in DuraSite showed statistically significant differences in clinical resolution and bacterial eradication rates when compared with vehicle. Because it was well tolerated in this population, it may be a viable treatment option for children and adults with bacterial conjunctivitis.
Although the majority of included studies were assessed as being at high or unclear risk of bias there was some evidence to support the effectiveness of topical metronidazole, azelaic acid, and doxycycline (40 mg) in the treatment of moderate to severe rosacea, and cyclosporine 0.05% ophthalmic emulsion for ocular rosacea. Further well-designed, adequately-powered randomised controlled trials are required.