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Expert Opinion on Drug Safety 2016Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its... (Comparative Study)
Comparative Study Review
INTRODUCTION
Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its classification alongside the tetracyclines - class D drugs, contraindicated in pregnancy and in children under 8 years of age. Doxycycline-treatable diseases are emerging as leading causes of undifferentiated febrile illness in Southeast Asia. For example scrub typhus and murine typhus have an unusually severe impact on pregnancy outcomes, and current mortality rates for scrub typhus reach 12-13% in India and Thailand. The emerging evidence for these important doxycycline-treatable diseases prompted us to revisit doxycycline usage in pregnancy and childhood.
AREAS COVERED
A systematic review of the available literature on doxycycline use in pregnant women and children revealed a safety profile of doxycycline that differed significantly from that of tetracycline; no correlation between the use of doxycycline and teratogenic effects during pregnancy or dental staining in children was found.
EXPERT OPINION
The change of the US FDA pregnancy classification scheme to an evidence-based approach will enable adequate evaluation of doxycycline in common tropical illnesses and in vulnerable populations in clinical treatment trials, dosage-optimization pharmacokinetic studies and for the empirical treatment of undifferentiated febrile illnesses, especially in pregnant women and children.
Topics: Age Factors; Animals; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Contraindications; Doxycycline; Female; Humans; Infant; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome
PubMed: 26680308
DOI: 10.1517/14740338.2016.1133584 -
Journal of the American Academy of... May 2024Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older.
BACKGROUND
Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older.
OBJECTIVE
The objective of this study was to provide evidence-based recommendations for the management of acne.
METHODS
A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations.
RESULTS
This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements.
LIMITATIONS
Analysis is based on the best available evidence at the time of the systematic review.
CONCLUSIONS
These guidelines provide evidence-based recommendations for the management of acne vulgaris.
Topics: Adult; Adolescent; Humans; Acne Vulgaris; Benzoyl Peroxide; Anti-Bacterial Agents; Isotretinoin; Retinoids; Dermatologic Agents
PubMed: 38300170
DOI: 10.1016/j.jaad.2023.12.017 -
Journal of the American Dental... Jul 2015Conduct a systematic review and meta-analysis on nonsurgical treatment of patients with chronic periodontitis by means of scaling and root planing (SRP) with or without... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Conduct a systematic review and meta-analysis on nonsurgical treatment of patients with chronic periodontitis by means of scaling and root planing (SRP) with or without adjuncts.
METHODS
A panel of experts convened by the American Dental Association Council on Scientific Affairs conducted a search of PubMed (MEDLINE) and Embase for randomized controlled trials of SRP with or without the use of adjuncts with clinical attachment level (CAL) outcomes in trials at least 6 months in duration and published in English through July 2014. The authors assessed individual study bias by using the Cochrane Risk of Bias Tool and conducted meta-analyses to obtain the summary effect estimates and their precision and to assess heterogeneity. The authors used funnel plots and Egger tests to assess publication bias when there were more than 10 studies. The authors used a modified version of the US Preventive Services Task Force methods to assess the overall level of certainty in the evidence.
RESULTS
The panel included 72 articles on the effectiveness of SRP with or without the following: systemic antimicrobials, a systemic host modulator (subantimicrobial-dose doxycycline), locally delivered antimicrobials (chlorhexidine chips, doxycycline hyclate gel, and minocycline microspheres), and a variety of nonsurgical lasers (photodynamic therapy with a diode laser, a diode laser, neodymium:yttrium-aluminum-garnet lasers, and erbium lasers).
CONCLUSIONS AND PRACTICAL IMPLICATIONS
With a moderate level of certainty, the panel found approximately a 0.5-millimeter average improvement in CAL with SRP. Combinations of SRP with assorted adjuncts resulted in a range of average CAL improvements between 0.2 and 0.6 mm over SRP alone. The panel judged the following 4 adjunctive therapies as beneficial with a moderate level of certainty: systemic subantimicrobial-dose doxycycline, systemic antimicrobials, chlorhexidine chips, and photodynamic therapy with a diode laser. There was a low level of certainty in the benefits of the other included adjunctive therapies. The panel provides clinical recommendations in the associated clinical practice guideline.
Topics: Chronic Periodontitis; Dental Scaling; Humans; Root Planing; Treatment Outcome
PubMed: 26113099
DOI: 10.1016/j.adaj.2015.01.028 -
Clinical Infectious Diseases : An... Feb 2023Doxycycline has been recommended as a treatment option for non-severe community-acquired pneumonia (CAP) in adults. We sought to review the evidence for the efficacy of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Doxycycline has been recommended as a treatment option for non-severe community-acquired pneumonia (CAP) in adults. We sought to review the evidence for the efficacy of doxycycline in adult patients with mild-to-moderate CAP.
METHODS
We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) of doxycycline versus comparator to assess the clinical efficacy. The primary outcome was the clinical cure rate. Random effects model meta-analyses were used to generate pooled odds ratio (OR) and evaluate heterogeneity (I2). Risk of bias (RoB) and quality of evidence (QoE) were evaluated using the Cochrane Risk of Bias 2.0 tool and GRADE methods, respectively.
RESULTS
We included 6 RCTs with 834 clinically evaluable patients. The trials were performed between 1984 and 2004. Comparators were 3 macrolides (roxithromycin, spiramycin, and erythromycin) and 3 fluoroquinolones (ofloxacin, fleroxacin, and levofloxacin). Four trials had an overall high RoB. The clinical cure rate was similar between the doxycycline and comparator groups (87.2% [381/437] vs 82.6% [328/397]; OR 1.29 [95% confidence interval {CI}: .73-2.28]; I2 = 30%; low QoE). Subgroup analysis of two studies with a low RoB showed significantly higher clinical cure rates in the doxycyline group (87.1% [196/225] vs 77.8% [165/212]; OR 1.92 [95% CI: 1.15-3.21]; P = .01; I2 = 0%). Adverse event rates were comparable between the doxycycline and comparator groups.
CONCLUSIONS
The efficacy of doxycycline was comparable to macrolides or fluoroquinolones in mild-to-moderate CAP and thus represents a viable treatment option. Considering the lack of recent trials, it warrants large-scale clinical trials.
Topics: Adult; Humans; Doxycycline; Randomized Controlled Trials as Topic; Anti-Bacterial Agents; Macrolides; Fluoroquinolones; Pneumonia
PubMed: 35903011
DOI: 10.1093/cid/ciac615 -
Pediatrics Jul 2023The use of antibiotics in young children is widespread and may lead to adverse effects on dental health, including staining, developmental defects, and dental caries.
CONTEXT
The use of antibiotics in young children is widespread and may lead to adverse effects on dental health, including staining, developmental defects, and dental caries.
OBJECTIVE
To systematically review the effects of early childhood antibiotic exposure on dental health.
DATA SOURCES
Medline (Ovid/PubMed), Embase (Ovid) and Cochrane databases. Study bias was assessed using the Newcastle-Ottawa Scale.
STUDY SELECTION
English language articles that reported antibiotic exposure before 8 years of age and 1 or more of the relevant outcomes (dental caries, intrinsic tooth staining, or developmental defects of enamel) were included.
DATA EXTRACTION
Data on study population, design, type of antibiotic, outcome measurement, and results were extracted from the identified studies.
RESULTS
The initial search yielded 1003 articles of which 34 studies were included. Five of the 18 studies on tetracycline described a dose response relationship between exposure to tetracycline doses of > 20 mg/kg per day and dental staining. Early childhood exposure to doxycycline (at any dose) was not associated with dental staining. There was no clear association between any early childhood antibiotic exposure and dental caries or enamel defects.
LIMITATIONS
In all included studies, the main limitations and sources of bias were the lack of comparison groups, inconsistent outcome measures, and lack of adjustment for relevant confounders.
CONCLUSIONS
There was no evidence that newer tetracycline formulations (doxycycline and minocycline) at currently recommended dosages led to adverse effects on dental health. Findings regarding antibiotic exposure and developmental defects of enamel or dental caries were inconsistent. Further prospective studies are warranted.
Topics: Child; Child, Preschool; Humans; Infant; Anti-Bacterial Agents; Doxycycline; Dental Caries; Bias; Databases, Factual
PubMed: 37264510
DOI: 10.1542/peds.2023-061350 -
The Cochrane Database of Systematic... Apr 2015Rosacea is a common chronic skin condition affecting the face, characterised by flushing, redness, pimples, pustules and dilated blood vessels. The eyes are often... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rosacea is a common chronic skin condition affecting the face, characterised by flushing, redness, pimples, pustules and dilated blood vessels. The eyes are often involved and thickening of the skin with enlargement (phymas), especially of the nose, can occur in some people. A range of treatment options are available but it is unclear which are most effective.
OBJECTIVES
To assess the efficacy and safety of treatments for rosacea.
SEARCH METHODS
We updated our searches, to July 2014, of: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2014, Issue 6), MEDLINE (from 1946), EMBASE (from 1974) and Science Citation Index (from 1988). We searched five trials registers and checked reference lists for further relevant studies.
SELECTION CRITERIA
Randomised controlled trials in people with moderate to severe rosacea.
DATA COLLECTION AND ANALYSIS
Study selection, data extraction, risk of bias assessment and analyses were carried out independently by two authors.
MAIN RESULTS
We included 106 studies, comprising 13,631 participants. Sample sizes of 30-100 and study duration of two to three months were most common. More women than men were included, mean age of 48.6 years, and the majority had papulopustular rosacea, followed by erythematotelangiectatic rosacea.A wide range of comparisons (67) were evaluated. Topical interventions: metronidazole, azelaic acid, ivermectin, brimonidine or other topical treatments. Systemic interventions: oral antibiotics, combinations with topical treatments or other systemic treatments, i.e. isotretinoin. Several studies evaluated laser or light-based treatment.The majority of studies (57/106) were assessed as 'unclear risk of bias', 37 'high risk ' and 12 'low risk'. Twenty-two studies provided no usable or retrievable data i.e. none of our outcomes were addressed, no separate data reported for rosacea or limited data in abstracts.Eleven studies assessed our primary outcome 'change in quality of life', 52 studies participant-assessed changes in rosacea severity and almost all studies addressed adverse events, although often only limited data were provided. In most comparisons there were no statistically significant differences in number of adverse events, most were mild and transient. Physician assessments including investigators' global assessments, lesion counts and erythema were evaluated in three-quarters of the studies, but time needed for improvement and duration of remission were incompletely or not reported.The quality of the body of evidence was rated moderate to high for most outcomes, but for some outcomes low to very low.Data for several outcomes could only be pooled for topical metronidazole and azelaic acid. Both were shown to be more effective than placebo in papulopustular rosacea (moderate quality evidence for metronidazole and high for azelaic acid). Pooled data from physician assessments in three trials demonstrated that metronidazole was more effective compared to placebo (risk ratio (RR) 1.98, 95% confidence interval (CI) 1.29 to 3.02). Four trials provided data on participants' assessments, illustrating that azelaic acid was more effective than placebo (RR 1.46, 95% CI 1.30 to 1.63). The results from three studies were contradictory on which of these two treatments was most effective.Two studies showed a statistically significant and clinically important improvement in favour of topical ivermectin when compared to placebo (high quality evidence). Participants' assessments in these studies showed a RR of 1.78 (95% CI 1.50 to 2.11) and RR of 1.92 (95% CI 1.59 to 2.32),which were supported by physicians' assessments. Topical ivermectin appeared to be slightly more effective than topical metronidazole for papulopustular rosacea, based on one study, for improving quality of life and participant and physician assessed outcomes (high quality evidence for these outcomes).Topical brimonidine in two studies was more effective than vehicle in reducing erythema in rosacea at all time points over 12 hours (high quality evidence). At three hours the participants' assessments had a RR of 2.21 (95% CI 1.52 to 3.22) and RR of 2.00 (95% CI 1.33 to 3.01) in favour of brimonidine. Physicians' assessments confirmed these data. There was no rebound or worsening of erythema after treatment cessation.Topical clindamycin phosphate combined with tretinoin was not considered to be effective compared to placebo (moderate quality evidence).Topical ciclosporin ophthalmic emulsion demonstrated effectiveness and improved quality of life for people with ocular rosacea (low quality evidence).Of the comparisons assessing oral treatments for papulopustular rosacea there was moderate quality evidence that tetracycline was effective but this was based on two old studies of short duration. Physician-based assessments in two trials indicated that doxycycline appeared to be significantly more effective than placebo (RR 1.59, 95% CI 1.02 to 2.47 and RR 2.37, 95% CI 1.12 to 4.99) (high quality evidence). There was no statistically significant difference in effectiveness between 100 mg and 40 mg doxycycline, but there was evidence of fewer adverse effects with the lower dose (RR 0.25, 95% CI 0.11 to 0.54) (low quality evidence). There was very low quality evidence from one study (assessed at high risk of bias) that doxycycline 100 mg was as effective as azithromycin. Low dose minocycline (45 mg) was effective for papulopustular rosacea (low quality evidence).Oral tetracycline was compared with topical metronidazole in four studies and showed no statistically significant difference between the two treatments for any outcome (low to moderate quality evidence).Low dose isotretinoin was considered by both the participants (RR 1.23, 95% CI 1.05 to 1.43) and physicians (RR 1.18, 95% CI 1.03 to 1.36) to be slightly more effective than doxycycline 50-100 mg (high quality evidence).Pulsed dye laser was more effective than yttrium-aluminium-garnet (Nd:YAG) laser based on one study, and it appeared to be as effective as intense pulsed light therapy (both low quality evidence).
AUTHORS' CONCLUSIONS
There was high quality evidence to support the effectiveness of topical azelaic acid, topical ivermectin, brimonidine, doxycycline and isotretinoin for rosacea. Moderate quality evidence was available for topical metronidazole and oral tetracycline. There was low quality evidence for low dose minocycline, laser and intense pulsed light therapy and ciclosporin ophthalmic emulsion for ocular rosacea. Time needed to response and response duration should be addressed more completely, with more rigorous reporting of adverse events. Further studies on treatment of ocular rosacea are warranted.
Topics: Anti-Infective Agents; Brimonidine Tartrate; Cyclosporine; Dermatologic Agents; Dicarboxylic Acids; Doxycycline; Female; Humans; Ivermectin; Male; Metronidazole; Middle Aged; Ophthalmic Solutions; Quinoxalines; Randomized Controlled Trials as Topic; Rosacea; Tetracycline
PubMed: 25919144
DOI: 10.1002/14651858.CD003262.pub5 -
The Journal of Laryngology and Otology May 2023The objective of this systematic review and meta-analysis was to evaluate the role of doxycycline in the management of chronic rhinosinusitis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective of this systematic review and meta-analysis was to evaluate the role of doxycycline in the management of chronic rhinosinusitis.
METHOD
This was a systematic review using Ovid Medline, Cinahl, Scopus and Cochrane and was limited to meta-analyses, systematic reviews and randomised, clinical trials. A combination of the following search terms was used: 'sinusitis', 'nasal polyps', 'doxycycline' and 'tetracycline'. Raw means and standard deviations were extracted from the included studies. The meta-analysis was performed using mean differences of pre- versus post-doxycycline treatment.
RESULTS
A total of 279 studies were screened, of which 5 studies met the criteria (all randomised, controlled trials published between 2010 and 2021). The interventions, endpoints and measured outcomes varied across all studies. Meta-analysis performed on pre- versus post-doxycycline treatment for Sino-Nasal Outcome Test-22, nasal polyp scores and symptom scores did not yield statistically significant results.
CONCLUSION
This review identified a small number of high-quality studies on the use of doxycycline in chronic rhinosinusitis. There does not seem to be convincing evidence for the routine use of doxycycline in patients with chronic rhinosinusitis. Further research may try to identify certain phenotypes of chronic rhinosinusitis that may better respond to doxycycline.
Topics: Humans; Rhinitis; Quality of Life; Doxycycline; Nasal Polyps; Anti-Bacterial Agents; Sinusitis; Chronic Disease
PubMed: 35919933
DOI: 10.1017/S0022215122001803 -
BMC Infectious Diseases Nov 2021In areas where Lyme disease is endemic, bites from ticks are common, but no vaccine is currently available against Lyme disease for humans. Therefore, the feasibility of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In areas where Lyme disease is endemic, bites from ticks are common, but no vaccine is currently available against Lyme disease for humans. Therefore, the feasibility of using antibiotic prophylaxis to prevent Lyme disease after a tick bite is worth further exploration. Previous meta-analyses lack sufficient power to demonstrate the efficacy of about antibiotic prophylaxis for the prevention of Lyme disease following a tick bite. In this study, we explored more precise evidence and attempted to identify and update optimum treatment strategies.
METHODS
We searched PubMed, Embase, and the Cochrane Library for studies until March 23, 2021. We included studies if the enrolled patients were randomly allocated to a treatment or control group within 72 h following a tick bite and had no clinical evidence of Lyme disease at enrolment. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for data abstraction. Two authors (GZZ and XX) independently reviewed the abstracts and identified articles for detailed assessment. We used a random-effects model to calculate the pooled results and reported the 95% confidence interval (CI). Study quality was assessed using a modified Jadad scale, and publication bias was assessed using Egger's test. We calculated the risk ratio (RR) for the rates of unfavorable events in patients who received intervention versus the control group. This study is registered with PROSPERO, number CRD42021245002.
RESULTS
Six studies (3,766 individuals) were included. The pooled rate of unfavorable events in persons receiving treatment and the control group were 0.4% (95%CI: 0.1-1.1%) and 2.2% (95%CI: 1.6-3.0%), respectively. The pooled RR was 0.38 (95%CI: 0.22-0.66). Subgroup analysis revealed that the pooled RR was 0.29 (95%CI: 0.14-0.60) in the single-use 200-mg doxycycline group; 0.28 (95%CI: 0.05-1.67) in a 10-day course group (Amoxicillin, Penicillin or tetracycline); and 0.73 (95%CI: 0.25-2.08) in a topical antibiotic treatment group (Azithromycin).
CONCLUSIONS
The available evidence supports the use of antibiotics for the prevention of Lyme disease, and reveals advantages of using single-dose; however, further confirmation is needed.
Topics: Amoxicillin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Doxycycline; Humans; Lyme Disease; Randomized Controlled Trials as Topic; Tick Bites
PubMed: 34749665
DOI: 10.1186/s12879-021-06837-7 -
Doxycycline and minocycline in Helicobacter pylori treatment: A systematic review and meta-analysis.Helicobacter Oct 2021The decreasing Helicobacter pylori eradication rate and the increasing antibiotic resistance trend are of great concern. Therefore, new and effective therapies are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
The decreasing Helicobacter pylori eradication rate and the increasing antibiotic resistance trend are of great concern. Therefore, new and effective therapies are needed for H. pylori infection. We conducted a systematic review and meta-analysis to assess the efficacy and safety of semisynthetic tetracycline regimens in H. pylori treatment.
METHODS
PubMed, EMBASE, and the Cochrane library were searched. The outcome indicators were the eradication rate, risk ratio (RR, ie, the risk of the semisynthetic tetracycline regimen relative to the control), and 95% confidence interval (95% CI). Controls were patients undergoing any other treatment without semisynthetic tetracycline.
RESULTS
Twenty-three studies with 5240 participants were included. The eradication rates of triple regimens with semisynthetic tetracyclines in most studies were less than 70% in both the intention-to-treat (ITT) and the per-protocol (PP) analyses. The pooled eradication rates of quadruple therapies with doxycycline and controls were 95% and 84% in the PP analyses, respectively. The pooled RR associated with efficacy in the quadruple therapy with doxycycline group compared with the control group was 1.12 (95% CI: 1.04-1.20) in the PP analysis. The pooled RR of side effects in the quadruple therapy with doxycycline group compared with the control group was 1.01 (95% CI: 0.65-1.55).
CONCLUSION
Seven-day and ten-day quadruple therapy with doxycycline might be an optional first-line therapy. The safety of regimens containing semisynthetic tetracyclines was relatively satisfactory. However, the triple regimen is not recommended.
Topics: Amoxicillin; Anti-Bacterial Agents; Doxycycline; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Minocycline; Treatment Outcome
PubMed: 34318971
DOI: 10.1111/hel.12839 -
Digestion 2016Since resistance of Helicobacter pylori is developing very fast all over the world, new treatment regimens for eradication are urgently needed. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Since resistance of Helicobacter pylori is developing very fast all over the world, new treatment regimens for eradication are urgently needed.
AIM
To compare eradication success rate of H. pylori treatment regimens with and without doxycycline.
METHODS
English medical literature searches were conducted for regimens including doxycycline for eradication of H. pylori. Searches were performed up to August 31, 2015, using MEDLINE, PubMed, EMBASE, Scopus and CENTRAL. Meta-analysis was performed by using comprehensive meta-analysis software. Pooled ORs and 95% CIs were calculated comparing treatment regimens for eradication of H. pylori infection with and without doxycycline.
RESULTS
The OR for eradication success rate in a fixed model was in favor for treatment regimens with doxycycline: 1.292, 95% CI 1.048-1.594, p = 0.016. There was no significant heterogeneity in the included studies: Q = 15.130, d.f. (Q) = 8, I2 = 47.126, p > 0.10. When treatment regimens with doxycycline were compared only with treatment regimens with tetracycline, no significant difference was found in eradication success rate: OR 0.95, 95% CI 0.68-1.32, p = 0.77. But when treatment regimens with doxycycline were compared with treatment regimens without tetracycline, the OR in favor of doxycycline was even higher: OR 1.59, 95% CI 1.21-2.09, p < 0.001.
CONCLUSION
In this meta-analysis, we confirmed doxycycline efficiency in the eradication of H. pylori. Thus, triple, quadruple or even high dose dual therapy with regimens containing doxycycline should be considered.
Topics: Amoxicillin; Antacids; Anti-Bacterial Agents; Clarithromycin; Doxycycline; Drug Therapy, Combination; Esomeprazole; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Lansoprazole; Metronidazole; Proton Pump Inhibitors; Ranitidine; Tetracycline
PubMed: 26849820
DOI: 10.1159/000443683