Dose-ranging efficacy of new once-daily extended-release minocycline for acne vulgaris. A double-blind comparison of topical clindamycin and oral minocycline in the treatment of acne vulgaris. Minocycline therapy in acne vulgaris. A comparison of the efficacy and safety of lymecycline and minocycline in patients with moderately severe acne vulgaris. Efficacy of minocycline compared with tetracycline in treatment of acne vulgaris. Multicenter randomized comparative double-blind controlled clinical trial of the safety and efficacy of zinc gluconate versus minocycline hydrochloride in the treatment of inflammatory acne vulgaris. Safety and efficacy of a new extended-release formulation of minocycline. Efficacy of oral antibiotics on acne vulgaris and their effects on quality of life: a multicenter randomized controlled trial using minocycline, roxithromycin and faropenem. Lymecycline in the treatment of acne: an efficacious, safe and cost-effective alternative to minocycline. [Treatment of acne vulgaris. A comparison of doxycycline versus minocycline]. Comparison of tazarotene and minocycline maintenance therapies in acne vulgaris: a multicenter, double-blind, randomized, parallel-group study. Minocycline versus doxycycline in the treatment of acne vulgaris. A double-blind study. Lymecycline and minocycline in inflammatory acne: a randomized, double-blind intent-to-treat study on clinical and in vivo antibacterial efficacy. Comparison of combined azelaic acid cream plus oral minocycline with oral isotretinoin in severe acne. Minocycline in acne vulgaris: a double-blind study. An accurate photographic method for grading acne: initial use in a double-blind clinical comparison of minocycline and tetracycline. Efficacy of low-dose cyproterone acetate compared with minocycline in the treatment of acne vulgaris. Randomised controlled multiple treatment comparison to provide a cost-effectiveness rationale for the selection of antimicrobial therapy in acne. A systemic type I 5 alpha-reductase inhibitor is ineffective in the treatment of acne vulgaris. Isotretinoin versus minocycline in cystic acne: a study of lipid metabolism. Oral spironolactone: an effective treatment for acne vulgaris in women.
A multicenter, 12-week, randomized, double-blinded, placebo-controlled, dose-ranging study was conducted in 233 subjects with moderate to severe facial acne vulgaris to determine the lowest effective once-daily oral dose of a new extended-release (ER) minocycline hydrochloride formulation with the safest adverse effect profile. Subjects randomly were assigned to treatment with daily dosages of ER-minocycline 1-, 2-, or 3-mg/kg tablets, or daily placebo tablets, for 84 days. At the end of the 12 weeks, the number of inflammatory lesions decreased approximately 50% from baseline levels in the dose groups. No dose-dependent effect was observed, with the percentage decrease in the number of inflammatory lesions in the 1-mg/kg treatment group being equal to or greater than higher doses. The pairwise difference between the ER-minocycline 1 mg/kg and placebo groups in the percentage decrease in inflammatory lesions was statistically significant (P = .015). Acute vestibular adverse events (AVAEs) appeared to be dose proportional, with the incidence being similar in the lowest (1 mg/kg) dosing group (24%) and in the placebo group (26%). Higher-dose regimens were associated with a higher incidence of central nervous system side effects and AVAEs. A 1-mg/kg daily dosage of the new ER-minocycline formulation is the lowest effective dose with the safest side effect profile, with higher-dose regimens offering no substantial therapeutic advantages. Sixty-six patients with moderate to severe facial acne vulgaris were entered in a 12-week double-blind study to compare the efficacy of topical clindamycin phosphate 1% twice daily and oral minocycline 50 mg twice daily. Both treatments gave significant overall improvements from baseline observations in acne grade and inflamed lesion counts, but not in noninflamed lesion counts. There were no significant differences between the two treatment groups in respect of acne grade, inflamed or non-inflamed lesion counts. Both treatment regimes were well tolerated. This study has shown that topical clindamycin twice daily is an effective alternative to oral minocycline 50 mg twice daily in the treatment of moderate to severe facial acne vulgaris. A double-blind, random distribution study showed that a lower than recommended dose of minocycline--50 mg twice daily--was as effective as a dose of 250 mg twice daily of tetracycline for treatment of acne vulgaris in comparable patient groups, and that minocycline produced no vestibular side effects at the lower dosage. Like tetracycline, minocycline did not produce the phototoxicity associated with demeclocycline or the life-threatening colitis associated with clindamycin. Patients in this study did not develop a resistance either to minocycline or to tetracycline. Studies of the use of minocycline in patients who have developed tetracycline resistance and long-range studies of patients on the new lower dose of minocycline are now underway. A multicentre, randomised, double-blind and double-dummy study was conducted to compare the efficacy and safety of lymecycline (n = 71) with that of minocycline (n = 73) in 144 patients with moderately severe acne vulgaris. Patients with an acne score of 1-5 on the Leeds scale received oral lymecycline, 300 mg/day for 2 weeks, then 150 mg/day for 10 weeks or oral minocycline, 100 mg/day for 2 weeks then 100 mg every other day for 10 weeks. Inflammatory, non-inflammatory and total lesion counts were determined at baseline (week 0) and after 4, 8 and 12 weeks' treatment, and global efficacy and safety assessments were made by the patient and investigator at the end of the study. Both treatments were equally effective at reducing differential lesion counts and improving acne condition and severity, with no significant differences between treatments. Inflammatory lesions were reduced by 50.6% and 52.2% with lymecycline and minocycline, respectively, and non-inflammatory lesions by 40.6% and 32.2%. Acne severity was reduced by 42.4% with lymecycline and by 47.9% with minocycline. A total of 4.3% of lymecycline recipients and 4.1% of minocycline recipients experienced treatment-related adverse events, the majority of which were mild in nature. Lymecycline was as effective as minocycline for the treatment of moderately severe acne vulgaris. Both treatments were well tolerated, although there were slightly fewer adverse gastrointestinal and dermatological effects with lymecycline. A double-blind evaluation of the efficacy and safety of minocycline hydrochloride and tetracycline hydrochloride was conducted and completed using 49 patients with Pillsbury grade 2 or grade 3 acne. For six months, half of the patients received minocycline and half received tetracycline. Although the differences between treatment groups were not statistically significant at any evaluation, more patients treated with minocycline reached and maintained a noninflammatory acne status in less time than did patients treated with tetracycline. After six weeks, twice as many patients in the group treated with minocycline had reached noninflammatory status. Side effects reported by 7 patients were equally distributed between treatment groups. No notable abnormalities were observed in the results of blood chemistry studies, hematologic tests, quantitative serum immunoglobulin determinations, or thyroid function tests in 20 of the patients examined. In addition to tetracyclines, zinc may constitute an alternative treatment in inflammatory lesions of acne.
                To evaluate the place of zinc gluconate in relation to antibiotics in the treatment of acne vulgaris.
                Zinc was compared to minocycline in a multicenter randomized double-blind trial. 332 patients received either 30 mg elemental zinc or 100 mg minocycline over 3 months. The primary endpoint was defined as the percentage of the clinical success rate on day 90 (i.e. more than 2/3 decrease in inflammatory lesions, i.e. papules and pustules).
                This clinical success rate was 31.2% for zinc and 63.4% for minocycline. Minocycline nevertheless showed a 9% superiority in action at 1 month and one of 17% at 3 months, with respect to the mean change in lesion count. Regarding safety, the majority of the adverse effects of zinc gluconate and of minocycline concerned the gastrointestinal system and were moderate (5 dropouts with zinc gluconate and 4 with minocycline).
                Minocycline and zinc gluconate are both effective in the treatment of inflammatory acne, but minocycline has a superior effect evaluated to be 17% in our study.
                Copyright 2001 S. Karger AG, Basel The complete safety and efficacy of a new extended-release (ER) minocycline hydrochloride formulation were assessed in an analysis of a phase 2 dose-finding study and 2 phase 3 safety and efficacy studies. The studies were similar in design, subject populations, and shared common dose groups of subjects given ER minocycline 1 mg/kg daily or placebo over 12 weeks. The similar designs were prospective, multicenter, randomized, double-blinded, and placebo-controlled. A total of 1038 subjects with moderate to severe acne were available for the pooled analysis. Independently, each study showed that treatment with ER-minocycline significantly reduced (P < .001) the number of inflammatory lesions and significantly improved (P < .001) their Evaluator's Global Severity Assessment (EGSA) scores (phase 3 studies). Analysis of the pooled population confirmed the results of the individual studies. The percentage of subjects reporting acute vestibular adverse events (AVAEs) was comparable between those receiving the ER-minocycline 1-mg/kg dose and placebo (approximately 10% of subjects in each group) for both the individual studies and the pooled population. It was concluded that a novel ER-minocycline formulation that delivers consistent levels of drug at a 1-mg/kg dose reduces dose-dependent AVAEs while reducing inflammatory lesions and improving the overall appearance of patients with acne vulgaris. There are few clinical studies which compare the efficacy and patient satisfaction for oral antibiotics to treat inflammatory acne. To clarify the difference between oral antibiotics, acne patients with moderate to severe inflammatory eruptions were randomized into three groups, and each patient was given minocycline (MINO), roxithromycin (RXM) or faropenem (FRPM) for 4 weeks, followed by 4 weeks of observation without any oral antibiotics. We estimated the reduction rate of inflammatory lesion counts, the scale of Skindex-16 which represents patient quality of life (QOL), and minimum inhibitory concentrations required to inhibit the growth of 90% of Propionibacterium acnes isolated from acne patients (MIC(90) ). In all three groups, inflammatory lesion counts, and emotional and total score of Skindex-16 were significantly improved (P<0.05) after 4 weeks treatment, and these effects were maintained for the following 4 weeks. Dizziness/nausea in two patients (4.1%) of the MINO group and diarrhea in three patients (5.9%) of the FRPM group were observed. There was no significant difference of percentage reduction in inflammatory lesion counts and incident rates of side-effects between these three oral antibiotics. MIC(90) of MINO was 0.25 μg/mL before and after treatment, but MIC(90) of RXM had increased from 0.25 μg/mL to more than 32 μg/mL after treatment. MIC(90) of FRPM was 0.06 μg/mL or less for all strains before and after treatment. Our randomized controlled clinical trial suggested that MINO, RXM and FRPM were efficient to improve inflammatory acne and patient QOL, and there was no significant difference between them.
                © 2010 Japanese Dermatological Association. A comparison of efficacy, safety and cost-effectiveness of lymecycline and minocycline in the treatment of acne vulgaris has been addressed. This was a multicenter, randomized, investigator-masked, parallel group trial involving patients with moderate to moderately severe acne vulgaris, receiving either lymecycline or minocycline for 12 weeks. Efficacy and safety evaluation was performed at baseline and at weeks 4, 8, and 12 and completed by a pharmacoeconomic analysis including week 12 data. One hundred and thirty-six patients were enrolled. At week 12, the mean percent reductions in inflammatory count were 63 % and 65 %, and for total lesions counts 58 % and 56 % for lymecycline and for minocycline respectively. Median percent reduction in non-inflammatory count were 54 % and 47 % for lymecycline and for minocycline respectively. Eighty-seven per cent of all patients tolerated the treatments well. Treatment with lymecycline was found to be 4 times more cost-effective than with minocycline. Results showed that lymecycline has a comparable efficacy and safety profile to minocycline while being 4 times more cost-effective. In the course of a randomized, comparative, clinical study, 50 patients with acne vulgaris received systemic treatment with a single daily dose of 50 mg doxycycline or two daily doses of 50 mg minocycline. At the completion of the 12-week treatment, cure or improvement of acne was found in 78% of the patients in the doxycycline group compared to 82% in the minocycline group. The rate of unsatisfactory therapeutic results was 22% in the doxycycline group and 18% in the group of patients treated with minocycline. The results showed no significant difference between the clinical efficacy of treating acne vulgaris with doxycycline at a daily dose of 50 mg and 100 mg of minocycline daily, a fact which has already been demonstrated by earlier studies. To evaluate the efficacy of 3 maintenance regimens (topical tazarotene, oral minocycline hydrochloride, or both) in sustaining improvement in acne.
                Multicenter, open-label treatment phase followed by double-blind, randomized, parallel-group maintenance phase.
                Ambulatory patients in research or referral centers.
                Volunteer sample of 189 patients with moderately severe to severe acne vulgaris (110 entered maintenance phase, 90 completed, and 2 discontinued because of adverse events).
                All patients were treated with 0.1% tazarotene gel (each evening) and a 100-mg capsule (twice daily) of minocycline hydrochloride for up to 12 weeks. Patients with 75% or greater global improvement at week 12 were randomly assigned to 12 weeks of maintenance therapy with tazarotene gel plus placebo capsules, vehicle gel plus minocycline capsules, or tazarotene gel plus minocycline capsules.
                Overall disease severity, global improvement, and lesion counts.
                All regimens were effective in sustaining improvements in acne. After 12 weeks of maintenance therapy, the mean reductions from baseline in noninflammatory and inflammatory lesion count, respectively, were 60% and 54% with tazarotene, 52% and 66% with minocycline, and 64% and 66% with tazarotene plus minocycline. At week 24, more than 80% of patients in each group had maintained a 50% or greater global improvement from baseline, and more than 50% had maintained a 75% or greater global improvement.
                A high percentage of patients with moderately severe to severe acne can maintain improvement in their condition with topical retinoid monotherapy. Maintenance with combination tazarotene and minocycline therapy showed a trend for greater efficacy but no statistical significance vs tazarotene alone. Topical retinoid monotherapy should be considered for maintenance to help minimize antibiotic exposure. nan Some antibiotics represent a mainstay in acne treatment. However, studies comparing their efficacies are rare.
                To evaluate the clinical and in vivo antibacterial effect of lymecycline and minocycline at different dosages.
                Eighty-six patients with moderate to severe acne were enrolled in a randomized, double-blind, intent-to-treat study comparing in three parallel groups the effect of (1) lymecycline 300 mg daily for 12 weeks, (2) minocycline 50 mg daily for 12 weeks and (3) minocycline 100 mg daily for 4 weeks followed by 50 mg daily for 8 weeks. Evaluations were made at the screening visit and at five on-treatment visits. They consisted of clinical counts of acne lesions and evaluations of bacterial viability using dual flow cytometry performed on microorganisms collected from sebaceous infundibula by cyanoacrylate strippings.
                Patients receiving minocycline 100/50 mg had the best clinical outcome, particularly in the reduction of the number of papules. By the end of the trial, the microbial response to minocycline 100/ 50 mg was also superior to either of the other two treatments. There were less live and more dead bacteria.
                In this trial, minocycline 100/50 mg was superior for the treatment of inflammatory acne when compared to lymecycline 300 mg and minocycline 50 mg.
                Copyright 2002 S. Karger AG, Basel The primary aim of the study was to establish the clinical efficacy and safety of a combined treatment consisting of topical 20% azelaic acid (AA) cream and the oral antibiotic minocycline in the therapy of severe inflammatory acne (nodular papulopustular acne and acne conglobata) in a comparison with oral isotretinoin therapy. The secondary aim was to establish the value of AA cream as maintenance therapy in the prevention of recurrent acne.
                This open-label but randomised study involved 85 patients with nodular papulopustular acne or acne conglobata (Leeds grading scale > 4) who were treated for 6 months. In an immediately subsequent 3-month second phase, eligible patients from the initial combination group used the AA cream as maintenance therapy, while the eligible patients from the isotretinoin group served as untreated control.
                A 6-month course of treatment with topical 20% AA cream plus oral minocycline in 50 patients proved to be effective in nodular forms of acne (median reduction of facial comedones: 70%; of papules and pustules: 88%; of deep inflammatory acne lesions: 100%). Overall, the combined treatment was not quite as effective as treatment with oral isotretinoin (35 patients; reduction of comedones: 83%; of papules and pustules: 97%; of deep inflammatory acne lesions: 100%). In the 3-month maintenance therapy phase, about half of the patients who received AA monotherapy maintained the very good facial result achieved by the end of phase I. A similar rate was found in the patients of the isotretinoin group, who received no further active acne treatment. In the other 50% of patients, differences existed between the groups as regards the degree of deterioration: Marked deterioration occurred more frequently under AA treatment, while only slight deterioration was more frequent in the isotretinoin group. The combination was tolerated much better than isotretinoin. The incidence of local side effects observed under the combination of AA and minocycline (36.5%, mainly transient burning and itching of mild or moderate intensity) was considerably lower than that seen with isotretinoin (65.7%). The rate of local side effects of marked intensity observed under the combination, i.e. 6%, was well within the range of 5-10% previously reported for AA. The incidence of systemic side effects was lower (8%, mainly gastrointestinal symptoms) under the combined therapy than under isotretinoin (14.3%).
                The combination of topical 20% AA cream and oral minocycline is an highly effective treatment in severe forms of acne. It is better tolerated and associated with fewer risks than oral isotretinoin - in particular, there is no risk of teratogenicity. The combination can be regarded as a valuable alternative in patients for whom isotretinoin is not indicated, who do not wish to use or can not tolerate isotretinoin therapy and particularly in female acne patients of child-bearing potential. Topical 20% AA cream can be used successfully as maintenance therapy to prolong the recurrence-free interval. nan This investigation utilized an accurate photographic method and grading scale for evaluating acne in sixty-two patients. During a randomized double-blind clinical study in which half of the patients received minocycline and half, tetracycline, photographs of facial or body acne were taken at baseline and every 2 weeks over a 12-week period of therapy. In addition to on-site blinded gradings by both the investigator and the patients, separate assessments were made by two independent dermatologists utilizing the scale and the transparencies taken during the study. A reasonable agreement was found between the investigator, the patients, and the independent dermatologists, indicating the usefulness of this method. The investigator's rating of acne severity disclosed a significantly (p less than or equal to 0.05) more rapid clinical response at weeks 2 and 8 in the patients who received minocycline than in those who received tetracycline. Also, the assessment of one of the independent dermatologists showed a significantly (p = 0.024) better response to minocycline than to tetracycline at week 8 of therapy. The incidence of adverse clinical experiences was lower in the minocycline-treated group (10%) than in the tetracycline-treated group (22%). nan To determine the relative efficacy and cost-effectiveness of five of the most commonly used antimicrobial preparations for treating mild to moderate facial acne in the community; the propensity of each regimen to give rise to local and systemic adverse events; whether pre-existing bacterial resistance to the prescribed antibiotic resulted in reduced efficacy; and whether some antimicrobial regimens were less likely to give rise to resistant propionibacterial strains.
                This was a parallel group randomised assessor-blind controlled clinical trial. It was a pragmatic design with intention-to-treat analysis. All treatments were given for 18 weeks, after a 4-week treatment free period. Outcomes were measured at 0, 6, 12 and 18 weeks.
                Primary care practices and colleges in and around Nottingham and Leeds, and one practice in Stockton-on-Tees, England.
                Participants were 649 people aged 12--39 years, all with mild to moderate inflammatory acne of the face.
                Study participants were randomised into one of five groups: 500 mg oral oxytetracycline (non-proprietary) twice daily (b.d.) + topical vehicle control b.d.; 100 mg oral Minocin MR (minocycline) once daily (o.d.) + topical vehicle control b.d.; topical Benzamycin (3% erythromycin + 5% benzoyl peroxide) b.d. + oral placebo o.d.; topical Stiemycin (2% erythromycin) o.d. + topical Panoxyl Aquagel (5% benzoyl peroxide) o.d. + oral placebo o.d., and topical Panoxyl Aquagel (5% benzoyl peroxide) b.d. + oral placebo o.d. (the active comparator group).
                The two primary outcome measures were: (1) the proportion of patients with at least moderate self-assessed improvement as recorded on a six-point Likert scale, and (2) change in inflamed lesion count (red spots).
                The best response rates were seen with two of the topical regimens (erythromycin plus benzoyl peroxide administered separately o.d. or in a combined proprietary formulation b.d.), compared with benzoyl peroxide alone, oxytetracycline (500 mg b.d.) and minocycline (100 mg o.d.), although differences were small. The percentage of participants with at least moderate improvement was 53.8% for minocycline (the least effective) and 66.1% for the combined erythromycin/benzoyl peroxide formulation (the most effective); the adjusted odds ratio for these two treatments was 1.74 [95% confidence interval (CI) 1.04 to 2.90]. Similar efficacy rankings were obtained using lesion counts, acne severity scores and global rating by assessor. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective regimen (ratio of means 12.3; difference in means -0.051 units/GBP, 95% CI -0.063 to -0.039). The efficacy of oxytetracycline was similar to that of minocycline, but at approximately one-seventh of the cost. For all regimens, the largest reductions in acne severity were recorded in the first 6 weeks. Reductions in disability scores using the Dermatology Quality of Life Scales were largest for both topical erythromycin-containing regimens and minocycline. The two topical erythromycin-containing regimens produced the largest reductions in the prevalence and population density of cutaneous propionibacteria, including antibiotic-resistant variants, and these were equally effective in participants with and without erythromycin-resistant propionibacteria. The clinical efficacy of both tetracyclines was compromised in participants colonised by tetracycline-resistant propionibacteria. None of the regimens promoted an overall increase in the prevalence of antibiotic-resistant strains. Systemic adverse events were more common with the two oral antibiotics. Local irritation was more common with the topical treatments, particularly benzoyl peroxide. Residual acne was present in most participants (95%) at the end of the study.
                The response of mild to moderate inflammatory acne to antimicrobial treatment in the community is not optimal. Only around half to two-thirds of trial participants reported at least a moderate improvement over an 18-week study period; extending treatment beyond 12 weeks increased overall benefit slightly. Around one-quarter dropped out when using such treatments, and 55% sought further treatment after 18 weeks. Topical antimicrobial therapies performed at least as well as oral antibiotics in terms of clinical efficacy. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective therapy for facial acne. The efficacy of all three topical regimens was not compromised by pre-existing propionibacterial resistance. Benzoyl peroxide was associated with a greater frequency and severity of local irritant reactions. It is suggested that the use of a combination of topical benzoyl peroxide and erythromycin gives less irritation and better quality of life. There was little difference between erythromycin plus benzoyl peroxide administered separately and the combined proprietary formulation in terms of efficacy or local irritation, except that the former was nearly three times more cost-effective. The data on cost-effectiveness, and outcomes in patients with resistant propionibacterial floras, did not support the first line use of minocycline for mild to moderate inflammatory acne of the face. Three priority areas for clinical research in acne are: defining end-points in acne trials (i.e. what is a satisfactory outcome?); developing and validating better patient-based measures for assessing treatment effects on facial and truncal acne; and exploring patient characteristics that may modify treatment effects (efficacy and tolerability). Excessive sebum production is a central aspect of the pathophysiology of acne vulgaris. Sebaceous gland function is under androgen control and it is hypothesized that dihydrotestosterone is formed by the action of 5 alpha-reductase. Type I is the controlling isoenzyme. This study describes a 3-month, multicenter, randomized, placebo-controlled clinical trial with a potent, selective inhibitor of type I 5 alpha-reductase used alone and in combination with systemic minocycline. Inhibition of type I 5 alpha-reductase was not associated with clinical improvement of acne when used alone and did not enhance the clinical benefit of systemic minocycline. These results indicate the need for further work at the molecular level to better understand the action of androgens on sebaceous gland function. We have recently reported that patients with severe nodular cystic acne have much lower levels of HDL-cholesterol, apolipoprotein A and hepatic lipoprotein lipase than healthy controls or subjects with acne vulgaris. Since isotretinoin is very effective in the treatment of the nodular cystic acne but has been shown to increase blood lipid levels, we decided to compare its clinical effectiveness and its effects on lipid metabolism with those of minocycline in patients with nodular cystic acne. After 20 weeks, the number and mean diameter of the cysts were definitely decreased in both groups, but the improvement was more striking in the isotretinoin-treated group. At the end of the treatment, the HDL-C and hepatic lipoprotein lipase levels in this group were increased toward normal, but not in the minocycline-treated group. Our study showed a significant remission in the acne of patients treated with isotretinoin but not in that of the minocycline-treated patients. Furthermore isotretinoin can also correct the altered lipid metabolism in these patients. The effect of oral spironolactone (200 mg daily) on acne vulgaris has been studied in 21 women in a randomized, placebo-controlled, double-blind crossover study using 3 month treatment periods. Compared with placebo, spironolactone produced significant improvement as assessed by subjective benefit (P less than 0. 001), number of inflamed lesions (P less than 0 . 001) and by an independently evaluated photographic method (P less than 0 .02). There was a fall in sex hormone binding globulin but no significant changes in plasma testosterone and derived free testosterone. Initial plasma androgen levels were no higher in responders than in non-responders, nor did oral contraceptive use appear to affect clinical response. Spironolactone is a useful alternative therapy for women with acne vulgaris.
Minocycline is an effective treatment for moderate to moderately-severe inflammatory acne vulgaris, but there is still no evidence that it is superior to other commonly-used therapies. This review found no reliable evidence to justify the reinstatement of its first-line use, even though the price-differential is less than it was 10 years ago. Concerns remain about its safety compared to other tetracyclines.