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The Cochrane Database of Systematic... Feb 2017Pressure ulcers are common in clinical practice and pose a significant health problem worldwide. Apart from causing suffering to patients, they also result in longer... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pressure ulcers are common in clinical practice and pose a significant health problem worldwide. Apart from causing suffering to patients, they also result in longer hospital stays and increase the cost of health care. A variety of methods are used for treating pressure ulcers, including pressure relief, patient repositioning, biophysical strategies, nutritional supplementation, debridement, topical negative pressure, and local treatments including dressings, ointments and creams such as bacitracin, silver sulphadiazine, neomycin, and phenytoin. Phenytoin is a drug more commonly used in the treatment of epilepsy, but may play an important role in accelerating ulcer healing.
OBJECTIVES
To assess the effects of topical phenytoin on the rate of healing of pressure ulcers of any grade, in any care setting.
SEARCH METHODS
In September 2016, we searched the following electronic databases to identify relevant randomized clinical trials: the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library); Ovid MEDLINE; Ovid Embase; and EBSCO CINAHL Plus. We handsearched conference proceedings from the European Pressure Ulcer Advisory Panel, European Wound Management Association and the Tissue Viability Society for all available years. We searched the references of the retrieved trials to identify further relevant trials. We also searched clinical trials registries to identify ongoing and unpublished studies. There were no restrictions with respect to language, date of publication or study setting.
SELECTION CRITERIA
We included all randomized controlled trials (RCTs) addressing the effects (both benefits and harms) of topical phenytoin on the healing of pressure ulcers of any grade compared with placebo or alternative treatments or no therapy, irrespective of blinding, language, and publication status.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, extracted information on participants, interventions, methods and results and assessed risk of bias using Cochrane methodological procedures. For dichotomous variables, we calculated the risk ratio (RR) with 95% confidence interval (CI). For continuous variables, we calculated the mean difference with 95% CI. We rated the quality of the evidence by using Grading of Recommendations, Assessment, Development and Evaluation approach (GRADE).
MAIN RESULTS
Three small RCTs met our inclusion criteria and included a total of 148 participants. These compared three treatments with topical phenytoin: hydrocolloid dressings, triple antibiotic ointment and simple dressings. In the three RCTs, 79% of participants had grade II ulcers, and 21% of participants had grade I ulcers; no participants had grade III or IV ulcers. Two RCTs had a high risk of bias overall and the other RCT was at unclear risk of bias due to poor reporting. Two RCTs had three intervention arms and the other had two intervention arms.Two studies compared topical phenytoin with hydrocolloid dressing (84 participants analysed). The available data suggest that hydrocolloid dressings may improve ulcer healing compared to topical phenytoin (39.3% ulcers healed for phenytoin versus 71.4% ulcers healed for hydrocolloid dressings (RR 0.55, 95% CI 0.33 to 0.92; 56 participants, 1 study; low quality evidence). We downgraded the evidence twice: once due to serious limitations (high risk of bias) and once due to the small sample size and small number of events. Two studies compared topical phenytoin with simple dressings (81 participants analysed). From the available data, we are uncertain whether topical phenytoin improves ulcer healing compared to simple dressings (39.3% ulcers healed for phenytoin versus 29.6% ulcers healed for the simple dressing (RR 1.33, 95% CI 0.63 to 2.78; 55 participants, 1 study; very low quality evidence). This evidence was downgraded once due to serious limitations (high risk of bias) and twice due to the low number of outcome events and resulting wide CI which included the possibility of both increased healing and reduced healing. We therefore considered it to be insufficient to determine the effect of topical phenytoin on ulcer healing. One study compared topical phenytoin with triple antibiotic ointment, however, none of the outcomes of interest to this review were reported. No adverse drug reactions or interactions were detected in any of the three RCTs. Minimal pain was reported in all groups in one trial that compared topical phenytoin with hydrocolloid dressings and triple antibiotic ointment.
AUTHORS' CONCLUSIONS
This review has considered the available evidence and the result shows that it is uncertain whether topical phenytoin improves ulcer healing for patients with grade I and II pressure ulcers. No adverse events were reported from three small trials and minimal pain was reported in one trial. Therefore, further rigorous, adequately powered RCTs examining the effects of topical phenytoin for treating pressure ulcers, and to report on adverse events, quality of life and costs are necessary.
Topics: Administration, Topical; Anti-Bacterial Agents; Bandages; Bandages, Hydrocolloid; Dermatologic Agents; Humans; Ointments; Phenytoin; Pressure Ulcer; Randomized Controlled Trials as Topic
PubMed: 28225152
DOI: 10.1002/14651858.CD008251.pub2 -
The Cochrane Database of Systematic... Mar 2017Clostridium difficile (C. difficile) is recognized as a frequent cause of antibiotic-associated diarrhoea and colitis. This review is an update of a previously published... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Clostridium difficile (C. difficile) is recognized as a frequent cause of antibiotic-associated diarrhoea and colitis. This review is an update of a previously published Cochrane review.
OBJECTIVES
The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile-associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms.
SEARCH METHODS
We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials.
SELECTION CRITERIA
Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review.
DATA COLLECTION AND ANALYSIS
Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed-effect model, except where significant heterogeneity was detected, at which time a random-effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost.
MAIN RESULTS
Twenty-two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy-two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy-one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly-seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo-controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co-morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co-morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary).
AUTHORS' CONCLUSIONS
No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest.
Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Bacitracin; Clostridioides difficile; Diarrhea; Enterocolitis, Pseudomembranous; Fidaxomicin; Humans; Metronidazole; Randomized Controlled Trials as Topic; Teicoplanin; Treatment Outcome; Vancomycin
PubMed: 28257555
DOI: 10.1002/14651858.CD004610.pub5 -
The Cochrane Database of Systematic... Sep 2020Ophthalmia neonatorum is an infection of the eyes in newborns that can lead to blindness, particularly if the infection is caused by Neisseria gonorrhoeae. Antiseptic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ophthalmia neonatorum is an infection of the eyes in newborns that can lead to blindness, particularly if the infection is caused by Neisseria gonorrhoeae. Antiseptic or antibiotic medication is dispensed into the eyes of newborns, or dispensed systemically, soon after delivery to prevent neonatal conjunctivitis and potential vision impairment.
OBJECTIVES
1. To determine if any type of systemic or topical eye medication is better than placebo or no prophylaxis in preventing ophthalmia neonatorum. 2. To determine if any one systemic or topical eye medication is better than any other medication in preventing ophthalmia neonatorum.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, LILACS, and three trials registers, date of last search 4 October 2019. We also searched references of included studies and contacted pharmaceutical companies. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials of any topical, systemic, or combination medical interventions used to prevent ophthalmia neonatorum in newborns compared with placebo, no prophylaxis, or with each other.
DATA COLLECTION AND ANALYSIS
We used standard methods expected by Cochrane. Outcomes were: blindness or any adverse visual outcome at 12 months, conjunctivitis at 1 month (gonococcal (GC), chlamydial (CC), bacterial (BC), any aetiology (ACAE), or unknown aetiology (CUE)), and adverse effects. MAIN RESULTS: We included 30 trials with a total of 79,198 neonates. Eighteen studies were conducted in high-income settings (the USA, Europe, Israel, Canada), and 12 were conducted in low- and middle-income settings (Africa, Iran, China, Indonesia, Mexico). Fifteen of the 30 studies were quasi-randomised. We judged every study to be at high risk of bias in at least one domain. Ten studies included a comparison arm with no prophylaxis. There were 14 different prophylactic regimens and 12 different medications in the 30 included studies. Any prophylaxis compared to no prophylaxis Unless otherwise indicated, the following evidence comes from studies assessing one or more of the following interventions: tetracycline 1%, erythromycin 0.5%, povidone-iodine 2.5%, silver nitrate 1%. None of the studies reported data on the primary outcomes: blindness or any adverse visual outcome at any time point. There was only very low-certainty evidence on the risk of GC with prophylaxis (4/5340 newborns) compared to no prophylaxis (5/2889) at one month (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.24 to 2.65, 3 studies). Low-certainty evidence suggested there may be little or no difference in effect on CC (RR 0.96, 95% CI 0.57 to 1.61, 4874 newborns, 2 studies) and BC (RR 0.84, 95% CI 0.37 to 1.93, 3685 newborns, 2 studies). Moderate-certainty evidence suggested a probable reduction in risk of ACAE at one month (RR 0.65, 95% 0.54 to 0.78, 9666 newborns, 8 studies assessing tetracycline 1%, erythromycin 0.5%, povidone-iodine 2.5%, silver nitrate 1%, colostrum, bacitracin-phenacaine ointment). There was only very low-certainty evidence on CUE (RR 1.75, 95% CI 0.37 to 8.28, 330 newborns, 1 study). Very low-certainty evidence on adverse effects suggested no increased nasolacrimal duct obstruction (RR 0.93, 95% CI 0.68 to 1.28, 404 newborns, 1 study of erythromycin 0.5% and silver nitrate 1%) and no increased keratitis (single study of 40 newborns assessing silver nitrate 1% with no events). Any prophylaxis compared to another prophylaxis Overall, evidence comparing different interventions did not suggest any consistently superior intervention. However, most of this evidence was of low-certainty and was extremely limited.
AUTHORS' CONCLUSIONS
There are no data on whether prophylaxis for ophthalmia neonatorum prevents serious outcomes such as blindness or any adverse visual outcome. Moderate-certainty evidence suggests that the use of prophylaxis may lead to a reduction in the incidence of ACAE in newborns but the evidence for effect on GC, CC or BC was less certain. Comparison of individual interventions did not suggest any consistently superior intervention, but data were limited. A trial comparing tetracycline, povidone-iodine (single administration), and chloramphenicol for GC and CC could potentially provide the community with an effective, universally applicable prophylaxis against ophthalmia neonatorum.
Topics: Anti-Infective Agents; Bias; Blindness; Erythromycin; Humans; Infant, Newborn; Ophthalmia Neonatorum; Povidone-Iodine; Randomized Controlled Trials as Topic; Silver Nitrate; Tetracycline; Trachoma; Vision Disorders
PubMed: 32959365
DOI: 10.1002/14651858.CD001862.pub4 -
The Cochrane Database of Systematic... Jul 2020Burn injuries are an important health problem. They occur frequently in the head and neck region. The face is the area central to a person's identity that provides our...
BACKGROUND
Burn injuries are an important health problem. They occur frequently in the head and neck region. The face is the area central to a person's identity that provides our most expressive means of communication. Topical interventions are currently the cornerstone of treatment of burns to the face.
OBJECTIVES
To assess the effects of topical interventions on wound healing in people with facial burns of any depth.
SEARCH METHODS
In December 2019 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that evaluated the effects of topical treatment for facial burns were eligible for inclusion in this review.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, data extraction, risk of bias assessment and GRADE assessment of the certainty of the evidence.
MAIN RESULTS
In this first update, we included 12 RCTs, comprising 507 participants. Most trials included adults admitted to specialised burn centres after recent burn injuries. Topical agents included antimicrobial agents (silver sulphadiazine (SSD), Aquacel-Ag, cerium-sulphadiazine, gentamicin cream, mafenide acetate cream, bacitracin), non-antimicrobial agents (Moist Exposed Burn Ointment (MEBO), saline-soaked dressings, skin substitutes (including bioengineered skin substitute (TransCyte), allograft, and xenograft (porcine Xenoderm), and miscellaneous treatments (growth hormone therapy, recombinant human granulocyte-macrophage colony-stimulating factor hydrogel (rhGMCS)), enzymatic debridement, and cream with Helix Aspersa extract). Almost all the evidence included in this review was assessed as low or very low-certainty, often because of high risk of bias due to unclear randomisation procedures (i.e. sequence generation and allocation concealment); lack of blinding of participants, providers and sometimes outcome assessors; and imprecision resulting from few participants, low event rates or both, often in single studies. Topical antimicrobial agents versus topical non-antimicrobial agents There is moderate-certainty evidence that there is probably little or no difference between antimicrobial agents and non-antimicrobial agents (SSD and MEBO) in time to complete wound healing (hazard ratio (HR) 0.84 (95% confidence interval (CI) 0.78 to 1.85, 1 study, 39 participants). Topical antimicrobial agents may make little or no difference to the proportion of wounds completely healed compared with topical non-antimicrobial agents (comparison SSD and MEBO, risk ratio (RR) 0.94, 95% CI 0.68 to 1.29; 1 study, 39 participants; low-certainty evidence). We are uncertain whether there is a difference in wound infection (comparison topical antimicrobial agent (Aquacel-Ag) and MEBO; RR 0.38, 95% CI 0.12 to 1.21; 1 study, 40 participants; very low-certainty evidence). No trials reported change in wound surface area over time or partial wound healing. There is low-certainty evidence for the secondary outcomes scar quality and patient satisfaction. Two studies assessed pain but it was incompletely reported. Topical antimicrobial agents versus other topical antimicrobial agents It is uncertain whether topical antimicrobial agents make any difference in effects as the evidence is low to very low-certainty. For primary outcomes, there is low-certainty evidence for time to partial (i.e. greater than 90%) wound healing (comparison SSD versus cerium SSD: mean difference (MD) -7.10 days, 95% CI -16.43 to 2.23; 1 study, 142 participants). There is very low-certainty evidence regarding whether topical antimicrobial agents make a difference to wound infection (RR 0.73, 95% CI 0.46 to 1.17; 1 study, 15 participants). There is low to very low-certainty evidence for the proportion of facial burns requiring surgery, pain, scar quality, adverse effects and length of hospital stay. Skin substitutes versus topical antimicrobial agents There is low-certainty evidence that a skin substitute may slightly reduce time to partial (i.e. greater than 90%) wound healing, compared with a non-specified antibacterial agent (MD -6.00 days, 95% CI -8.69 to -3.31; 1 study, 34 participants). We are uncertain whether skin substitutes in general make any other difference in effects as the evidence is very low certainty. Outcomes included wound infection, pain, scar quality, adverse effects of treatment and length of hospital stay. Single studies showed contrasting low-certainty evidence. A bioengineered skin substitute may slightly reduce procedural pain (MD -4.00, 95% CI -5.05 to -2.95; 34 participants) and background pain (MD -2.00, 95% CI -3.05 to -0.95; 34 participants) compared with an unspecified antimicrobial agent. In contrast, a biological dressing (porcine Xenoderm) might slightly increase pain in superficial burns (MD 1.20, 95% CI 0.65 to 1.75; 15 participants (30 wounds)) as well as deep partial thickness burns (MD 3.00, 95% CI 2.34 to 3.66; 10 participants (20 wounds)), compared with antimicrobial agents (Physiotulle Ag (Coloplast)). Miscellaneous treatments versus miscellaneous treatments Single studies show low to very low-certainty effects of interventions. Low-certainty evidence shows that MEBO may slightly reduce time to complete wound healing compared with saline soaked dressing (MD -1.7 days, 95% CI -3.32 to -0.08; 40 participants). In addition, a cream containing Helix Aspersa may slightly increase the proportion of wounds completely healed at 14 days compared with MEBO (RR 4.77, 95% CI 1.87 to 12.15; 43 participants). We are uncertain whether any miscellaneous treatment in the included studies makes a difference in effects for the outcomes wound infection, scar quality, pain and patient satisfaction as the evidence is low to very low-certainty.
AUTHORS' CONCLUSIONS
There is mainly low to very low-certainty evidence on the effects of any topical intervention on wound healing in people with facial burns. The number of RCTs in burn care is growing, but the body of evidence is still hampered due to an insufficient number of studies that follow appropriate evidence-based standards of conducting and reporting RCTs.
Topics: Administration, Topical; Anti-Infective Agents; Bias; Burns; Carboxymethylcellulose Sodium; Facial Injuries; Humans; Randomized Controlled Trials as Topic; Skin, Artificial; Wound Healing
PubMed: 32725896
DOI: 10.1002/14651858.CD008058.pub3 -
Pathogens and Global Health Mar 2019Clostridium species are ubiquitous and associated with various diseases in animals and humans. However, there is little knowledge about the prevalence of their... (Meta-Analysis)
Meta-Analysis
Clostridium species are ubiquitous and associated with various diseases in animals and humans. However, there is little knowledge about the prevalence of their resistance to antibiotics in Iran. Therefore, the aim of this study was to determine the prevalence of antibiotic-resistant Clostridium species in Iran through a meta-analysis of eligible studies published up until December 2018. Fourteen articles on the drug resistance of Clostridium species in Iran were included in the current study following a search in PubMed, Scopus and Google Scholar databases using relevant keywords and screening based on inclusion and exclusion criteria. Antibiotic resistance rates of C. difficile to ampicillin (42.8%), ciprofloxacin (69.5%), clindamycin (84.3%), erythromycin (61.5%), gentamicin (93.5%), nalidixic acid (92.9%), tetracycline (32.5%), imipenem (39.6%), levofloxacin (93.4%), ertapenem (58.7%), piperacillin/tazobactam (56.5%), kanamycin (100%), colistin (100%), ceftazidime (76%), amikacin (76.5%), moxifloxacin (67.9%) and cefotaxime (95%) were high. In addition, resistance of C. perfringens to ampicillin (25.8%), erythromycin (32.9%), gentamicin (45.4%), nalidixic acid (52.5%), tetracycline (19.5%), penicillin (21.8%), trimethoprim-sulfamethoxazole (32.1%), amoxicillin (19.3%), imipenem (38%), cloxacillin (100%), oxacillin (45.6%), bacitracin (89.1%) and colistin (40%) was high. Metronidazole and vancomycin, as the first-line therapies, fidaxomicin, tetracyclines (except tetracycline), rifampicin and chloramphenicol can still be used for the treatment of C. difficile infections. However, the present results do not recommend the use of penicillin, bacitracin and tetracycline for the treatment of C. perfringens infections in humans and domestic animals in Iran.
Topics: Animal Diseases; Animals; Anti-Bacterial Agents; Clostridium; Clostridium Infections; Drug Resistance, Bacterial; Humans; Iran; Prevalence
PubMed: 30961444
DOI: 10.1080/20477724.2019.1603003 -
The Cochrane Database of Systematic... Nov 2016Ear discharge (otorrhoea) is common in children with grommets (ventilation/tympanostomy tubes); the proportion of children developing discharge ranges from 25% to 75%.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ear discharge (otorrhoea) is common in children with grommets (ventilation/tympanostomy tubes); the proportion of children developing discharge ranges from 25% to 75%. The most common treatment strategies include oral broad-spectrum antibiotics, antibiotic eardrops or those containing a combination of antibiotic(s) and a corticosteroid, and initial observation. Important drivers for one strategy over the other are concerns over the side effects of oral antibiotics and the potential ototoxicity of antibiotic eardrops.
OBJECTIVES
To assess the benefits and harms of current treatment strategies for children with ear discharge occurring at least two weeks following grommet (ventilation tube) insertion.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the ENT Trials Register, CENTRAL (2016, Issue 5), multiple databases and additional sources for published and unpublished trials (search date 23 June 2016).
SELECTION CRITERIA
Randomised controlled trials comparing at least two of the following: oral antibiotics, oral corticosteroids, antibiotic eardrops (with or without corticosteroid), corticosteroid eardrops, microsuction cleaning of the ear canal, saline rinsing of the ear canal, placebo or no treatment. The main comparison of interest was antibiotic eardrops (with or without corticosteroid) versus oral antibiotics.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. Primary outcomes were: proportion of children with resolution of ear discharge at short-term follow-up (less than two weeks), adverse events and serious complications. Secondary outcomes were: proportion of children with resolution of ear discharge at intermediate- (two to four weeks) and long-term (four to 12 weeks) follow-up, proportion of children with resolution of ear pain and fever at short-term follow-up, duration of ear discharge, proportion of children with chronic ear discharge, ear discharge recurrences, tube blockage, tube extrusion, health-related quality of life and hearing. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.
MAIN RESULTS
We included nine studies, evaluating a range of treatments, with 2132 children who developed acute ear discharge beyond the immediate postoperative period. We judged the risk of bias to be low to moderate in most studies. Antibiotic eardrops (with or without corticosteroid) versus oral antibioticsAntibiotic eardrops with or without corticosteroid were more effective than oral antibiotics in terms of:- resolution of discharge at one week (one study, 42 children, ciprofloxacin eardrops versus amoxicillin: 77% versus 30%; risk ratio (RR) 2.58, 95% confidence interval (CI) 1.27 to 5.22; moderate-quality evidence);- resolution of discharge at two weeks (one study, 153 children, bacitracin-colistin-hydrocortisone eardrops versus amoxicillin-clavulanate: 95% versus 56%; RR 1.70, 95% CI 1.38 to 2.08; moderate-quality evidence);- duration of discharge (two studies, 233 children, ciprofloxacin eardrops versus amoxicillin: median 4 days versus 7 days and bacitracin-colistin-hydrocortisone eardrops versus amoxicillin-clavulanate: 4 days versus 5 days; moderate-quality evidence);- ear discharge recurrences (one study, 148 children, bacitracin-colistin-hydrocortisone eardrops versus amoxicillin-clavulanate: 0 versus 1 episode at six months; low-quality evidence); and- disease-specific quality of life (one study, 153 children, bacitracin-colistin-hydrocortisone eardrops versus amoxicillin-clavulanate: difference in change in median Otitis Media-6 total score (range 6 to 42) at two weeks: -2; low-quality evidence).We found no evidence that antibiotic eardrops were more effective in terms of the proportion of children developing chronic ear discharge or tube blockage, generic quality of life or hearing.Adverse events occurred at similar rates in children treated with antibiotic eardrops and those treated with oral antibiotics, while no serious complications occurred in either of the groups. Other comparisons(a) Antibiotic eardrops with or without corticosteroid were more effective thancorticosteroid eardrops in terms of:- duration of ear discharge (one study, 331 children, ciprofloxacin versus ciprofloxacin-fluocinolone acetonide versus fluocinolone acetonide eardrops: median 5 days versus 7 days versus 22 days; moderate-quality evidence).(b) Antibiotic eardrops were more effective than saline rinsing of the ear canal in terms of:- resolution of ear discharge at one week (one study, 48 children, ciprofloxacin eardrops versus saline rinsing: 77% versus 46%; RR 1.67, 95% CI 1.04 to 2.69; moderate-quality evidence);but not in terms of tube blockage. Since the lower limit of the 95% CI for the effect size for resolution of ear discharge at one week approaches unity, a trivial or clinically irrelevant difference cannot be excluded.(c) Eardrops containing two antibiotics and a corticosteroid (bacitracin-colistin-hydrocortisone) were more effective than no treatment in terms of:- resolution of discharge at two weeks (one study; 151 children: 95% versus 45%; RR 2.09, 95% CI 1.62 to 2.69; moderate-quality evidence);- duration of discharge (one study; 147 children, median 4 days versus 12 days; moderate-quality evidence);- chronic discharge (one study; 147 children; RR 0.08, 95% CI 0.01 to 0.62; low-quality evidence); and- disease-specific quality of life (one study, 153 children, difference in change in median Otitis Media-6 total score (range 6 to 42) between groups at two weeks: -1.5; low-quality evidence).We found no evidence that antibiotic eardrops were more effective in terms of ear discharge recurrences or generic quality of life.(d) Eardrops containing a combination of an antibiotic and a corticosteroid were more effective than eardrops containing antibiotics (low-quality evidence) in terms of:- resolution of ear discharge at short-term follow-up (two studies, 590 children: 35% versus 20%; RR 1.76, 95% CI 1.33 to 2.31); and- duration of discharge (three studies, 813 children);but not in terms of resolution of discharge at intermediate-term follow-up or proportion of children with tube blockage. However, there is a substantial risk of publication bias, therefore these findings should be interpreted with caution.
AUTHORS' CONCLUSIONS
We found moderate to low-quality evidence that antibiotic eardrops (with or without corticosteroid) are more effective than oral antibiotics, corticosteroid eardrops and no treatment in children with ear discharge occurring at least two weeks following grommet insertion. There is some limited, inconclusive evidence that antibiotic eardrops are more effective than saline rinsing. There is uncertainty whether antibiotic-corticosteroid eardrops are more effective than eardrops containing antibiotics only.
Topics: Administration, Oral; Adrenal Cortex Hormones; Anti-Bacterial Agents; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Infant, Newborn; Male; Middle Ear Ventilation; Otitis Media with Effusion; Sodium Chloride; Therapeutic Irrigation; Time Factors
PubMed: 27854381
DOI: 10.1002/14651858.CD011684.pub2 -
The Cochrane Database of Systematic... Nov 2016Surgical site infections (SSI) can delay wound healing, impair cosmetic outcome and increase healthcare costs. Topical antibiotics are sometimes used to reduce microbial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Surgical site infections (SSI) can delay wound healing, impair cosmetic outcome and increase healthcare costs. Topical antibiotics are sometimes used to reduce microbial contaminant exposure following surgical procedures, with the aim of reducing SSIs.
OBJECTIVES
The primary objective of this review was to determine whether the application of topical antibiotics to surgical wounds that are healing by primary intention reduces the incidence of SSI and whether it increases the incidence of adverse outcomes (allergic contact dermatitis, infections with patterns of antibiotic resistance and anaphylaxis).
SEARCH METHODS
In May 2015 we searched: the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL. We also searched clinical trial registries for ongoing studies, and bibliographies of relevant publications to identify further eligible trials. There was no restriction of language, date of study or setting. The search was repeated in May 2016 to ensure currency of included studies.
SELECTION CRITERIA
All randomized controlled trials (RCTs) and quasi-randomised trials that assessed the effects of topical antibiotics (any formulation, including impregnated dressings) in people with surgical wounds healing by primary intention were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies and independently extracted data. Two authors then assessed the studies for risk of bias. Risk ratios were calculated for dichotomous variables, and when a sufficient number of comparable trials were available, trials were pooled in a meta-analysis.
MAIN RESULTS
A total of 10 RCTs and four quasi-randomised trials with 6466 participants met the inclusion criteria. Six studies involved minor procedures conducted in an outpatient or emergency department setting; eight studies involved major surgery conducted in theatre. Nine different topical antibiotics were included. We included two three-arm trials, two four-arm trials and 10 two-arm trials. The control groups comprised; an alternative topical antibiotic (two studies), topical antiseptic (six studies) and no topical antibiotic (10 studies), which comprised inert ointment (five studies) no treatment (four studies) and one study with one arm of each.The risk of bias of the 14 studies varied. Seven studies were at high risk of bias, five at unclear risk of bias and two at low risk of bias. Most risk of bias concerned risk of selection bias.Twelve of the studies (6259 participants) reported infection rates, although we could not extract the data for this outcome from one study. Four studies (3334 participants) measured allergic contact dermatitis as an outcome. Four studies measured positive wound swabs for patterns of antimicrobial resistance, for which there were no outcomes reported. No episodes of anaphylaxis were reported. Topical antibiotic versus no topical antibioticWe pooled the results of eight trials (5427 participants) for the outcome of SSI. Topical antibiotics probably reduce the risk of SSI in people with surgical wounds healing by primary intention compared with no topical antibiotic (RR 0.61, 95% CI 0.42 to 0.87; moderate-quality evidence downgraded once for risk of bias). This equates to 20 fewer SSIs per 1000 patients treated with topical antibiotics (95% CI 7 to 29) and a number needed to treat for one additional beneficial outcome (NNTB) (i.e. prevention of one SSI) of 50.We pooled the results of three trials (3012 participants) for the outcome of allergic contact dermatitis, however this comparison was underpowered, and it is unclear whether topical antibiotics affect the risk of allergic contact dermatitis (RR 3.94, 95% CI 0.46 to 34.00; very low-quality evidence, downgraded twice for risk of bias, once for imprecision). Topical antibiotic versus antiseptic We pooled the results of five trials (1299 participants) for the outcome of SSI. Topical antibiotics probably reduce the risk of SSI in people with surgical wounds healing by primary intention compared with using topical antiseptics (RR 0.49, 95% CI 0.30 to 0.80; moderate-quality evidence downgraded once for risk of bias). This equates to 43 fewer SSIs per 1000 patients treated with topical antibiotics instead of antiseptics (95% CI 17 to 59) and an NNTB of 24.We pooled the results of two trials (541 participants) for the outcome of allergic contact dermatitis; there was no clear difference in the risk of dermatitis between topical antibiotics and antiseptics, however this comparison was underpowered and a difference cannot be ruled out (RR 0.97, 95% CI 0.52 to 1.82; very low-quality evidence, downgraded twice for risk of bias and once for imprecision). Topical antibiotic versus topical antibioticOne study (99 participants) compared mupirocin ointment with a combination ointment of neomycin/polymyxin B/bacitracin zinc for the outcome of SSI. There was no clear difference in the risk of SSI, however this comparison was underpowered (very low-quality evidence downgraded twice for risk of bias, once for imprecision).A four-arm trial involved two antibiotic arms (neomycin sulfate/bacitracin zinc/polymyxin B sulphate combination ointment versus bacitracin zinc, 219 participants). There was no clear difference in risk of SSI between the combination ointment and the bacitracin zinc ointment. The quality of evidence for this outcome was low, downgraded once for risk of bias, and once for imprecision.
AUTHORS' CONCLUSIONS
Topical antibiotics applied to surgical wounds healing by primary intention probably reduce the risk of SSI relative to no antibiotic, and relative to topical antiseptics (moderate quality evidence). We are unable to draw conclusions regarding the effects of topical antibiotics on adverse outcomes such as allergic contact dermatitis due to lack of statistical power (small sample sizes). We are also unable to draw conclusions regarding the impact of increasing topical antibiotic use on antibiotic resistance. The relative effects of different topical antibiotics are unclear.
Topics: Administration, Topical; Anti-Bacterial Agents; Anti-Infective Agents, Local; Dermatitis, Allergic Contact; Drug Resistance, Bacterial; Humans; Randomized Controlled Trials as Topic; Surgical Wound Infection; Wound Healing
PubMed: 27819748
DOI: 10.1002/14651858.CD011426.pub2 -
The Lancet. Infectious Diseases Sep 2018Several new treatments for Clostridium difficile infections have been investigated. We aimed to compare and rank treatments for non-multiply recurrent infections with C... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Several new treatments for Clostridium difficile infections have been investigated. We aimed to compare and rank treatments for non-multiply recurrent infections with C difficile in adults.
METHODS
We did a random effects network meta-analysis within a frequentist setting to obtain direct and indirect comparisons of trials. We searched MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for published and unpublished trials from the creation of these databases until June 30, 2017. We included randomised controlled trials of treatments for non-multiply recurrent infections with confirmed C difficile in adults (at least 18 years) that reported both primary cure and recurrence rates, and we used the Cochrane Risk of Bias tool to appraise trial methods. For our analysis, we extracted the total numbers of patients with primary cure and recurrence from published and unpublished reports. The primary outcome was sustained symptomatic cure, defined as the number of patients with resolution of diarrhoea minus the number with recurrence or death.
FINDINGS
Of 23 004 studies screened, 24 trials, which comprised 5361 patients and 13 different treatments, were included in the analysis. The overall quality of evidence was rated as moderate to low. For sustained symptomatic cure, fidaxomicin (odds ratio 0·67, 95% CI 0·55-0·82) and teicoplanin (0·37, 0·14-0·94) were significantly better than vancomycin. Teicoplanin (0·27, 0·10-0·70), ridinilazole (0·41, 0·19-0·88), fidaxomicin (0·49, 0·35-0·68), surotomycin (0·66, 0·45-0·97), and vancomycin (0·73, 0·56-0·95) were better than metronidazole. Bacitracin was inferior to teicoplanin (0·22, 0·06-0·77) and fidaxomicin (0·40, 0·17-0·94), and tolevamer was inferior to all drugs except for LFF571 (0·50, 0·18-1·39) and bacitracin (0·67, 0·28-1·58). Global heterogeneity of the entire network was low (Cochran's Q=15·70; p=0·47).
INTERPRETATION
Among the treatments for non-multiply recurrent infections by C difficile, the highest quality evidence indicates that fidaxomicin provides a sustained symptomatic cure most frequently. Fidaxomicin is a better treatment option than vancomycin for all patients except those with severe infections with C difficile and could be considered as a first-line therapy. Metronidazole should not be recommended for treatment of C difficile.
FUNDING
None.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Female; Humans; Male; Middle Aged; Network Meta-Analysis
PubMed: 30025913
DOI: 10.1016/S1473-3099(18)30285-8 -
The Japanese Dental Science Review Nov 2020This review aimed to evaluate the effects of the local delivery of antibiotics incorporated in implant surfaces on some quantitative parameters of bone formation. (Review)
Review
PURPOSE
This review aimed to evaluate the effects of the local delivery of antibiotics incorporated in implant surfaces on some quantitative parameters of bone formation.
MATERIALS AND METHODS
An electronic search was undertaken in three databases (PubMed, Scopus, Embase) in addition to hand searching. The search was limited to animal experiments using endosseous implants combined with localized antibiotics release. Meta-analyses were performed for the percentages of bone volume (BV) and bone-to-implant contact (BIC).
RESULTS
Nine studies met the inclusion criteria. Several methods were identified for local delivery of antibiotics at the bone-implant interface, but the most commonly used method was by coating (incorporating the implant surface with the antibiotic agents). Different antibiotic agents were used, namely bacitracin, doxycycline, enoxacin, gentamicin, minocycline, tobramycin, and vancomycin. There was no statistically significant difference in the percentage of BIC between implants with or without localized antibiotic release ( = 0.59). The meta-analysis revealed higher BV around implants coated with antibiotics compared to control groups (without antibiotics) ( < 0.01).
CONCLUSION
It is suggested that the local administration of antibiotics around implants did not adversely affect the percentage of direct bone contact around implants, with a tendency for a slightly better bone formation around implants when combined with local administration of antibiotics. It is a matter of debate whether these in vivo results will have the same effect in the clinical setting. However, the risk of bias of these studies may, to some extent, question the validity of these results.
PubMed: 33294060
DOI: 10.1016/j.jdsr.2020.09.003 -
Alimentary Pharmacology & Therapeutics Dec 1997A systematic review of controlled trials of therapy of Clostridium difficile intestinal infection using methodology described by the Cochrane Collaboration. (Meta-Analysis)
Meta-Analysis
AIM
A systematic review of controlled trials of therapy of Clostridium difficile intestinal infection using methodology described by the Cochrane Collaboration.
METHODS
Trials were identified by searching computer databases over the years 1978-1996. Trials were included if they were (a) prospective randomized, controlled trials and (b) included patients with symptomatic disease. The primary end-point was clinical resolution of diarrhoea. Secondary end-points were clinical relapse and stool clearance of C. difficile and C. difficile toxin.
RESULTS
Nine trials (469 patients) satisfying the inclusion criteria were identified. Two trials were placebo controlled. Six trials compared vancomycin to other antibiotics (fusidic acid, bacitracin, teicoplanin and metronidazole). For clinical resolution response rates ranged from 21 (placebo) to 100% (vancomycin). On pooling the trials, no antibiotic showed clear therapeutic superiority. Rates of clinical relapse ranged from 5 to 42%. Only one trial showed significant advantage of one antibiotic over another for prevention of relapse (teicoplanin vs. fusidic acid).
CONCLUSION
The published data are limited, and further studies are required.
Topics: Anti-Bacterial Agents; Clostridioides difficile; Enterocolitis, Pseudomembranous; Humans; Quality Control; Randomized Controlled Trials as Topic; Recurrence
PubMed: 9663822
DOI: 10.1046/j.1365-2036.1997.00269.x