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The Cochrane Database of Systematic... Sep 2020Despite the health benefits of breastfeeding, initiation and duration rates continue to fall short of international guidelines. Many factors influence a woman's decision... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite the health benefits of breastfeeding, initiation and duration rates continue to fall short of international guidelines. Many factors influence a woman's decision to wean; the main reason cited for weaning is associated with lactation complications, such as mastitis. Mastitis is an inflammation of the breast, with or without infection. It can be viewed as a continuum of disease, from non-infective inflammation of the breast to infection that may lead to abscess formation.
OBJECTIVES
To assess the effectiveness of preventive strategies (for example, breastfeeding education, pharmacological treatments and alternative therapies) on the occurrence or recurrence of non-infective or infective mastitis in breastfeeding women post-childbirth.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (3 October 2019), and reference lists of retrieved studies.
SELECTION CRITERIA
We included randomised controlled trials of interventions for preventing mastitis in postpartum breastfeeding women. Quasi-randomised controlled trials and trials reported only in abstract form were eligible. We attempted to contact the authors to obtain any unpublished results, wherever possible. Interventions for preventing mastitis may include: probiotics, specialist breastfeeding advice and holistic approaches. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 10 trials (3034 women). Nine trials (2395 women) contributed data. Generally, the trials were at low risk of bias in most domains but some were high risk for blinding, attrition bias, and selective reporting. Selection bias (allocation concealment) was generally unclear. The certainty of evidence was downgraded due to risk of bias and to imprecision (low numbers of women participating in the trials). Conflicts of interest on the part of trial authors, and the involvement of industry funders may also have had an impact on the certainty of the evidence. Most trials reported our primary outcome of incidence of mastitis but there were almost no data relating to adverse effects, breast pain, duration of breastfeeding, nipple damage, breast abscess or recurrence of mastitis. Probiotics versus placebo Probiotics may reduce the risk of mastitis more than placebo (risk ratio (RR) 0.51, 95% confidence interval (CI) 0.35 to 0.75; 2 trials; 399 women; low-certainty evidence). It is uncertain if probiotics reduce the risk of breast pain or nipple damage because the certainty of evidence is very low. Results for the biggest of these trials (639 women) are currently unavailable due to a contractual agreement between the probiotics supplier and the trialists. Adverse effects were reported in one trial, where no woman in either group experienced any adverse effects. Antibiotics versus placebo or usual care The risk of mastitis may be similar between antibiotics and usual care or placebo (RR 0.37, 95% CI 0.10 to 1.34; 3 trials; 429 women; low-certainty evidence). The risk of mastitis may be similar between antibiotics and fusidic acid ointment (RR 0.22, 95% CI 0.03 to 1.81; 1 trial; 36 women; low-certainty evidence) or mupirocin ointment (RR 0.44, 95% CI 0.05 to 3.89; 1 trial; 44 women; low-certainty evidence) but we are uncertain due to the wide CIs. None of the trials reported adverse effects. Topical treatments versus breastfeeding advice The risk of mastitis may be similar between fusidic acid ointment and breastfeeding advice (RR 0.77, 95% CI 0.27 to 2.22; 1 trial; 40 women; low-certainty evidence) and mupirocin ointment and breastfeeding advice (RR 0.39, 95% CI 0.12 to 1.35; 1 trial; 48 women; low-certainty evidence) but we are uncertain due to the wide CIs. One trial (42 women) compared topical treatments to each other. The risk of mastitis may be similar between fusidic acid and mupirocin (RR 0.51, 95% CI 0.13 to 2.00; low-certainty evidence) but we are uncertain due to the wide CIs. Adverse events were not reported. Specialist breastfeeding education versus usual care The risk of mastitis (RR 0.93, 95% CI 0.17 to 4.95; 1 trial; 203 women; low-certainty evidence) and breast pain (RR 0.93, 95% CI 0.36 to 2.37; 1 trial; 203 women; low-certainty evidence) may be similar but we are uncertain due to the wide CIs. Adverse events were not reported. Anti-secretory factor-inducing cereal versus standard cereal The risk of mastitis (RR 0.24, 95% CI 0.03 to 1.72; 1 trial; 29 women; low-certainty evidence) and recurrence of mastitis (RR 0.39, 95% CI 0.03 to 4.57; 1 trial; 7 women; low-certainty evidence) may be similar but we are uncertain due to the wide CIs. Adverse events were not reported. Acupoint massage versus routine care Acupoint massage probably reduces the risk of mastitis compared to routine care (RR 0.38, 95% CI 0.19 to 0.78;1 trial; 400 women; moderate-certainty evidence) and breast pain (RR 0.13, 95% CI 0.07 to 0.23; 1 trial; 400 women; moderate-certainty evidence). Adverse events were not reported. Breast massage and low frequency pulse treatment versus routine care Breast massage and low frequency pulse treatment may reduce risk of mastitis (RR 0.03, 95% CI 0.00 to 0.21; 1 trial; 300 women; low-certainty evidence). Adverse events were not reported.
AUTHORS' CONCLUSIONS
There is some evidence that acupoint massage is probably better than routine care, probiotics may be better than placebo, and breast massage and low frequency pulse treatment may be better than routine care for preventing mastitis. However, it is important to note that we are aware of at least one large trial investigating probiotics whose results have not been made public, therefore, the evidence presented here is incomplete. The available evidence regarding other interventions, including breastfeeding education, pharmacological treatments and alternative therapies, suggests these may be little better than routine care for preventing mastitis but our conclusions are uncertain due to the low certainty of the evidence. Future trials should recruit sufficiently large numbers of women in order to detect clinically important differences between interventions and results of future trials should be made publicly available.
Topics: Anti-Bacterial Agents; Bias; Breast Feeding; Edible Grain; Female; Fusidic Acid; Humans; Massage; Mastitis; Mupirocin; Neuropeptides; Ointments; Patient Education as Topic; Placebos; Probiotics; Randomized Controlled Trials as Topic
PubMed: 32987448
DOI: 10.1002/14651858.CD007239.pub4 -
Pharmaceutics Aug 2022Drug design and development to overcome antimicrobial resistance continues to be an area of research due to the evolution of microbial resistance mechanisms and the...
BACKGROUND
Drug design and development to overcome antimicrobial resistance continues to be an area of research due to the evolution of microbial resistance mechanisms and the necessity for new treatments. Natural products have been used since the dawn of medicine to heal skin infections. The antimicrobial properties of fusidic acid, zinc sulfate, and copper sulfate have been studied and are well known. Furthermore, these compounds have different mechanisms of action in targeting microorganisms, either by inhibiting protein synthesis or bacterial cell walls. Therefore, their combination is expected to have synergistic activity in killing bacteria. However, the synergistic antimicrobial activity has not been evaluated in a cream formulation. Therefore, the objectives of this in vitro study were to develop and evaluate the synergistic efficacy of fusidic acid in combinations with natural products, including oleuropein, thyme oil, zinc sulfate, and copper sulfate, as a cream to eradicate fusidic-acid-resistant microorganisms in skin infections.
METHODS
Three different cream formulations were developed, compared, and labeled F1, F2, and F3. The compounds were studied for their antibacterial activity. In addition, the stability of the cream was investigated at 25 °C and 40 °C in plastic jars over three months.
RESULTS
The F2 formula has adequate physicochemical properties. Furthermore, it displays stable and better results than the marketed trade product and has potential inhibition zones (ZOI). Interestingly, considerable numbers (9.5%) of fusidic-acid-resistant Staphylococcus aureus (FRSA) isolates possessed a high resistance pattern with MIC ≥ 128 μg/mL. In contrast, most tested FRSA isolates (90.5%) had a low resistance pattern with MIC ≤ 8 μg/mL.
CONCLUSION
In conclusion, the F2 cream made with fusidic acid, oleuropein, thyme oil, zinc sulfate, and copper sulfate in the right amounts has stable physical and chemical properties and has potential against FRSA as an antimicrobial agent.
PubMed: 36015264
DOI: 10.3390/pharmaceutics14081638 -
The Cochrane Database of Systematic... Jan 2012Impetigo is a common, superficial bacterial skin infection, which is most frequently encountered in children. There is no generally agreed standard therapy, and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Impetigo is a common, superficial bacterial skin infection, which is most frequently encountered in children. There is no generally agreed standard therapy, and guidelines for treatment differ widely. Treatment options include many different oral and topical antibiotics as well as disinfectants. This is an updated version of the original review published in 2003.
OBJECTIVES
To assess the effects of treatments for impetigo, including non-pharmacological interventions and 'waiting for natural resolution'.
SEARCH METHODS
We updated our searches of the following databases to July 2010: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 2005), EMBASE (from 2007), and LILACS (from 1982). We also searched online trials registries for ongoing trials, and we handsearched the reference lists of new studies found in the updated search.
SELECTION CRITERIA
Randomised controlled trials of treatments for non-bullous, bullous, primary, and secondary impetigo.
DATA COLLECTION AND ANALYSIS
Two independent authors undertook all steps in data collection. We performed quality assessments and data collection in two separate stages.
MAIN RESULTS
We included 57 trials in the first version of this review. For this update 1 of those trials was excluded and 12 new trials were added. The total number of included trials was, thus, 68, with 5578 participants, reporting on 50 different treatments, including placebo. Most trials were in primary impetigo or did not specify this.For many of the items that were assessed for risk of bias, most studies did not provide enough information. Fifteen studies reported blinding of participants and outcome assessors.Topical antibiotic treatment showed better cure rates than placebo (pooled risk ratio (RR) 2. 24, 95% confidence interval (CI) 1.61 to 3.13) in 6 studies with 575 participants. In 4 studies with 440 participants, there was no clear evidence that either of the most commonly studied topical antibiotics (mupirocin and fusidic acid) was more effective than the other (RR 1.03, 95% CI 0.95 to 1.11).In 10 studies with 581 participants, topical mupirocin was shown to be slightly superior to oral erythromycin (pooled RR 1.07, 95% CI 1.01 to 1.13). There were no significant differences in cure rates from treatment with topical versus other oral antibiotics. There were, however, differences in the outcome from treatment with different oral antibiotics: penicillin was inferior to erythromycin, in 2 studies with 79 participants (pooled RR 1.29, 95% CI 1.07 to 1.56), and cloxacillin, in 2 studies with 166 participants (pooled RR 1.59, 95% CI 1.21 to 2.08).There was a lack of evidence for the benefit of using disinfectant solutions. When 2 studies with 292 participants were pooled, topical antibiotics were significantly better than disinfecting treatments (RR 1.15, 95% CI 1.01 to 1.32).The reported number of side-effects was low, and most of these were mild. Side-effects were more common for oral antibiotic treatment compared to topical treatment. Gastrointestinal effects accounted for most of the difference.Worldwide, bacteria causing impetigo show growing resistance rates for commonly used antibiotics. For a newly developed topical treatment, retapamulin, no resistance has yet been reported.
AUTHORS' CONCLUSIONS
There is good evidence that topical mupirocin and topical fusidic acid are equally, or more, effective than oral treatment. Due to the lack of studies in people with extensive impetigo, it is unclear if oral antibiotics are superior to topical antibiotics in this group. Fusidic acid and mupirocin are of similar efficacy. Penicillin was not as effective as most other antibiotics. There is a lack of evidence to support disinfection measures to manage impetigo.
Topics: Administration, Oral; Administration, Topical; Anti-Bacterial Agents; Erythromycin; Fusidic Acid; Humans; Impetigo; Mupirocin; Penicillins; Randomized Controlled Trials as Topic
PubMed: 22258953
DOI: 10.1002/14651858.CD003261.pub3 -
The Cochrane Database of Systematic... May 2022Corneal abrasion is a common disorder frequently faced by ophthalmologists, emergency physicians, and primary care physicians. Ocular antibiotics are one of the... (Review)
Review
BACKGROUND
Corneal abrasion is a common disorder frequently faced by ophthalmologists, emergency physicians, and primary care physicians. Ocular antibiotics are one of the management options for corneal abrasion. A comprehensive summary and synthesis of the evidence on antibiotic prophylaxis in traumatic corneal abrasion is thus far unavailable, therefore we conducted this review to evaluate the current evidence regarding this important issue.
OBJECTIVES
To assess the safety and efficacy of topical antibiotic prophylaxis following corneal abrasion. Our objectives were 1) to investigate the incidence of infection with antibiotics versus placebo or alternative antibiotics in people with corneal abrasion; and 2) to investigate time to clinical cure, defined as complete healing (re-epithelialization) of the epithelium, with antibiotics versus placebo or alternative antibiotics in people with corneal abrasion.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 4), Ovid MEDLINE, Embase.com, PubMed, the Latin American and Caribbean Health Sciences Literature database (LILACS), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 25 April 2021.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing antibiotic with another antibiotic or placebo in children and adults with corneal abrasion due to any cause.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology and assessed the certainty of the body of evidence for the prespecified outcomes using the GRADE classification.
MAIN RESULTS
Our search of the electronic databases yielded 8661 records. We screened 7690 titles and abstracts after removal of duplicates. We retrieved 32 full-text reports for further review. We included two studies that randomized a total of 527 eyes of 527 participants in the review. One study was conducted in Denmark, and one was conducted in India. The two studies did not examine most of our prespecified primary and secondary outcomes. The first study was a parallel-group RCT comparing chloramphenicol ocular ointment with fusidic acid ocular gels (frequency was not clearly reported). This study enrolled 153 participants older than 5 years of age with corneal abrasion in Denmark with a one-day follow-up duration. No participants had secondary infection in the fusidic acid group, whereas three (4.1%) participants in the chloramphenicol group had a slight reaction (risk ratio [RR] 0.15, 95% confidence interval [CI] 0.01 to 2.79; 144 participants; very low certainty evidence). Thirty-one (44.3%) participants in the fusidic acid arm and 34 (46.6%) participants in the chloramphenicol arm were cured (defined as the area of abrasion zero and no infection) at day 1 (RR 0.94, 95% CI 0.65 to 1.34; 144 participants; very low certainty evidence). Without providing specific data, the study reported that the degree of pain was not affected by the interventions received. The most common adverse events reported were itching and discomfort of the eye, which occurred in approximately one-third of participants in each group (low certainty evidence). A second multicenter, two-arm RCT conducted in India enrolled 374 participants older than 5 years of age with corneal abrasion who presented within 48 hours after injury. This study investigated the effect of a three-day course of either ocular ointment combinations of chloramphenicol-clotrimazole or chloramphenicol-placebo (all three times daily). At day 3, 169 (100%) participants in the chloramphenicol-clotrimazole arm and 203 (99%) out of 205 participants in the chloramphenicol-placebo arm were cured without any complication, defined as complete epithelialization of the cornea without evidence of infection (RR 1.01, 95% CI 0.99 to 1.03; 374 participants; very low certainty evidence). Four participants assigned to the chloramphenicol-placebo arm experienced mild adverse events: two participants (1%) had mild chemosis and irritation, and two (1%) had small single sterile corneal infiltrates (low certainty evidence).
AUTHORS' CONCLUSIONS
Given the low to very low certainty of the available evidence, any beneficial effects of antibiotic prophylaxis in preventing ocular infection or accelerating epithelial healing following a corneal abrasion remain unclear. Moreover, the current evidence is insufficient to support any antibiotic regimen being superior to another. There is a need for a well-designed RCT assessing the efficacy and safety of ocular antibiotics in the treatment of corneal abrasion with a particular focus on high-risk populations and formulation of interventions.
Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Child; Chloramphenicol; Clotrimazole; Corneal Injuries; Fusidic Acid; Humans; Multicenter Studies as Topic; Ointments
PubMed: 35622535
DOI: 10.1002/14651858.CD014617.pub2 -
Antibiotics (Basel, Switzerland) Aug 2022Physiological experimentation, transcriptomics, and metabolomics were engaged to compare a fusidic acid-resistant mutant SH10001st-2 to its parent strain SH1000....
Physiological experimentation, transcriptomics, and metabolomics were engaged to compare a fusidic acid-resistant mutant SH10001st-2 to its parent strain SH1000. SH10001st-2 harbored a mutation (H457Y) in the gene which encodes the fusidic acid target, elongation factor G, as well as mutations in a putative phage gene of unknown function. SH10001st-2 grew slower than SH1000 at three temperatures and had reduced coagulase activity, two indicators of the fitness penalty reported for -mediated fusidic acid- resistance in the absence of compensatory mutations. Despite the difference in growth rates, the levels of O consumption and CO production were comparable. Transcriptomic profiling revealed 326 genes were upregulated and 287 were downregulated in SH10001st-2 compared to SH1000. Cell envelope and transport and binding protein genes were the predominant functional categories of both upregulated and downregulated genes in SH10001st-2. Genes of virulence regulators, notably the and systems, were highly upregulated as were genes encoding capsule production. Contrary to what is expected of mid-exponential phase cells, genes encoding secreted virulence factors were generally upregulated while those for adhesion-associated virulence factors were downregulated in SH10001st-2. Metabolomic analysis showed an overall increase in metabolite pools in SH10001st-2 compared to SH1000, mostly for amino acids and sugars. Slowed growth and metabolite accumulation may be byproducts of mutation-mediated protein synthesis impairment, but the overall results indicate that SH10001st-2 is compensating for the H457Y fitness penalty by repurposing its virulence machinery, in conjunction with increasing metabolite uptake capacity, in order to increase nutrient acquisition.
PubMed: 36009920
DOI: 10.3390/antibiotics11081051 -
Cold Spring Harbor Perspectives in... Jan 2016Fusidic acid is an oral antistaphylococcal antibiotic that has been used in Europe for more than 40 years to treat skin infections as well as chronic bone and joint... (Review)
Review
Fusidic acid is an oral antistaphylococcal antibiotic that has been used in Europe for more than 40 years to treat skin infections as well as chronic bone and joint infections. It is a steroidal antibiotic and the only marketed member of the fusidane class. Fusidic acid inhibits protein synthesis by binding EF-G-GDP, which results in the inhibition of both peptide translocation and ribosome disassembly. It has a novel structure and novel mode of action and, therefore, there is little cross-resistance with other known antibiotics. Many mutations can occur in the FusA gene that codes for EF-G, and some of these mutations can result in high-level resistance (minimum inhibitory concentration [MIC] > 64 mg/L), whereas others result in biologically unfit staphylococci that require compensatory mutations to survive. Low-level resistance (<8 mg/L) is more common and is mediated by fusB, fusC, and fusD genes that code for small proteins that protect EF-G-GDP from binding fusidic acid. The genes for these proteins are spread by plasmids and can be selected mostly by topical antibiotic use. Reports of resistance have led to combination use of fusidic acid with rifampin, which is superseded by the development of a new dosing regimen for fusidic acid that can be used in monotherapy. It consists of a front-loading dose to decrease the potential for resistance development followed by a maintenance dose. This dosing regimen is now being used in clinical trials in the United States for skin and refractory bone and joint infections.
Topics: Acute Disease; Administration, Oral; Anti-Bacterial Agents; Chronic Disease; Drug Resistance, Bacterial; Drug Therapy, Combination; Fusidic Acid; Humans; Microbial Sensitivity Tests; Peptide Elongation Factor G; Protein Synthesis Inhibitors; Rifampin; Staphylococcal Infections
PubMed: 26729758
DOI: 10.1101/cshperspect.a025437 -
Mayo Clinic Proceedings Sep 2019
Topics: Administration, Topical; Diagnosis, Differential; Erythrasma; Fluorescence; Foot Dermatoses; Fusidic Acid; Humans; Male; Middle Aged; Tinea Pedis
PubMed: 31486384
DOI: 10.1016/j.mayocp.2019.04.022 -
Scientific Reports Jul 2023In this work, we present DrugSolver CavitomiX, a novel computational pipeline for drug repurposing and identifying ligands and inhibitors of target enzymes. The pipeline...
In this work, we present DrugSolver CavitomiX, a novel computational pipeline for drug repurposing and identifying ligands and inhibitors of target enzymes. The pipeline is based on cavity point clouds representing physico-chemical properties of the cavity induced solely by the protein. To test the pipeline's ability to identify inhibitors, we chose enzymes essential for SARS-CoV-2 replication as a test system. The active-site cavities of the viral enzymes main protease (M) and papain-like protease (Pl), as well as of the human transmembrane serine protease 2 (TMPRSS2), were selected as target cavities. Using active-site point-cloud comparisons, it was possible to identify two compounds-flufenamic acid and fusidic acid-which show strong inhibition of viral replication. The complexes from which fusidic acid and flufenamic acid were derived would not have been identified using classical sequence- and structure-based methods as they show very little structural (TM-score: 0.1 and 0.09, respectively) and very low sequence (~ 5%) identity to M and TMPRSS2, respectively. Furthermore, a cavity-based off-target screening was performed using acetylcholinesterase (AChE) as an example. Using cavity comparisons, the human carboxylesterase was successfully identified, which is a described off-target for AChE inhibitors.
Topics: Humans; Fusidic Acid; Acetylcholinesterase; COVID-19; Flufenamic Acid; SARS-CoV-2; Peptide Hydrolases; Papain
PubMed: 37479788
DOI: 10.1038/s41598-023-39071-z -
International Journal of Infectious... Dec 2020To synthesize and characterize the inclusion complexes of fusidic acid with β - cyclodextrin, followed by the evaluation of their antimicrobial activity against pure...
OBJECTIVES
To synthesize and characterize the inclusion complexes of fusidic acid with β - cyclodextrin, followed by the evaluation of their antimicrobial activity against pure strain (Staphylococcus aureus ATCC 25,923) and isolated Staphylococcus from clinical cases.
METHODS
The desired compounds were synthesized using molar ratio of fusidic acid: β-cyclodextrin of 1:1. Synthesized compounds were analyzed by Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Thermal Analysis, and the results confirmed the formation of inclusion compounds by fusidic acid with β-cyclodextrin.
RESULTS
Physical-chemical characterization confirmed the preparation of desired inclusion compounds, and the antimicrobial test confirmed that all compounds obtained have antimicrobial activity. Antimicrobial activity of freeze-drying complex againstS. aureus is similar with pure fusidic acid activity, being better than the cefoxitin one. Similar behavior was observed against methicillin-resistant S. aureus and S. epidermidis.
CONCLUSIONS
In the present work, three different inclusion complexes of fusidic acid were prepared using three different preparation methods. All inclusion complexes obtained presented good antimicrobial activity against differentS. aureus strains. Antimicrobial activity of these new prepared compounds was observed to be better than that of cefoxitin.
Topics: Anti-Bacterial Agents; Freeze Drying; Fusidic Acid; Humans; Methicillin-Resistant Staphylococcus aureus; Microscopy, Electron, Scanning; Spectroscopy, Fourier Transform Infrared; Staphylococcus aureus; X-Ray Diffraction; beta-Cyclodextrins
PubMed: 33011279
DOI: 10.1016/j.ijid.2020.09.1465