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Microbial Pathogenesis Nov 2022Vibrio cholera (V. cholera) is a facultative pathogen that colonizes the small intestine and produces cholerae toxin as the primary virulence factor that causes cholera... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vibrio cholera (V. cholera) is a facultative pathogen that colonizes the small intestine and produces cholerae toxin as the primary virulence factor that causes cholera and fatal diarrhea in humans. In recent decades, V. cholera has emerged as a notorious multidrug-resistant enteric pathogen. This meta-analysis estimated the pooled proportion of V. cholera antimicrobial resistance against RNA and DNA effective antibiotics.
METHOD
A systematic search was performed for relevant literature until 05 June 2021 in PubMed, Scopus, Embase, and Web of Science databases. Freeman-Tukey double arcsine transformation was performed to estimate weighted pooled resistance (WPR).
RESULTS
The meta-analysis were included 164 articles. The WPR of V. cholera were as follows 76% [67,84] to furazolidone, 65% [29,94] to nitrofurantoin, 55% [44,66] to nalidixic acid, 10% [2,23] to rifampicin, 4%(0, 12) to novobiocin, 4% [2,6] to norfloxacin, 3% [1,4] to ciprofloxacin, 1%(0, 3) to sparofloxacin, 0%(0, 3) to levofloxacin, 0%(0, 2) to ofloxacin, 0%(0, 0) to gatifloxacin.
CONCLUSION
V. cholera is a severe problem in Asia and Africa, especially in South Asian countries. The resistance patterns are various in geographical regions. novobiocin 0% (0, 0), and ofloxacin 0% (0, 1) in Africa, gatifloxacin 0% (0, 0), and levofloxacin 0% (0, 6) in Asia and ciprofloxacin 0% (0, 2) in North America are most effective antibiotis. The resistance rate to furazolidone, nalidixic acid, nitrofurantoin, and cephalothin has increased over the years. Monitoring antibiotic resistance and prescribing an appropriate antibiotic is vital to control resistance.
Topics: Humans; Anti-Bacterial Agents; Cephalothin; Cholera; Cholera Toxin; Ciprofloxacin; Furazolidone; Gatifloxacin; Levofloxacin; Microbial Sensitivity Tests; Nalidixic Acid; Nitrofurantoin; Norfloxacin; Novobiocin; Rifampin; Vibrio cholerae; Virulence Factors; Drug Resistance, Bacterial
PubMed: 35537594
DOI: 10.1016/j.micpath.2022.105514 -
The American Journal of Gastroenterology Aug 2022Antimicrobial resistance among Helicobacter pylori strains has been rising globally, leading to declining eradication rates. We performed a systematic review and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Antimicrobial resistance among Helicobacter pylori strains has been rising globally, leading to declining eradication rates. We performed a systematic review and meta-analysis of the resistance patterns of H. pylori strains in the United States between 2011 and 2021.
METHODS
Ovid MEDLINE, Embase, CINAHL, and Cochrane CENTRAL databases were searched for manuscripts and conference abstracts published between 2011 and 2021 reporting H. pylori antibiotic resistance. A mixed-effects model estimated pooled rates of resistance to clarithromycin, amoxicillin, metronidazole, tetracycline, rifabutin, levofloxacin, or a combination of these, with 95% confidence intervals (CIs).
RESULTS
A total of 19 studies including 2,660 samples, met inclusion criteria. The pooled rate of resistance to metronidazole was 42.1% (95% CI 27.3%-58.6%), levofloxacin 37.6% (95% CI 26.3%-50.4%), clarithromycin 31.5% (95% CI 23.6%-40.6%), amoxicillin 2.6% (95% CI 1.4%-5.0%), tetracycline 0.87% (95% CI 0.2%-3.8%), rifabutin 0.17% (95% CI 0.00%-10.9%), and dual clarithromycin and metronidazole 11.7% (95% CI 0.1%-94.0%). Considerable data heterogeneity was evident for pooled resistance prevalence rates (I 2 > 50%), with the exception of rifabutin resistance.
DISCUSSION
Metronidazole, levofloxacin, and clarithromycin resistance rates each exceed 30%; thus, choosing an empiric antibiotic regimen without knowledge of the likely pattern of antibiotic resistance is not appropriate. Resistance to tetracycline, rifabutin, and amoxicillin remains low. Given the scarcity of available data with considerable heterogeneity among studies, continued surveillance, ideally with a more systematic approach to data collection, is an increasingly important goal in H. pylori management.
Topics: Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Resistance, Bacterial; Drug Resistance, Microbial; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Metronidazole; Rifabutin; Tetracycline; United States
PubMed: 35509128
DOI: 10.14309/ajg.0000000000001828 -
American Journal of Ophthalmology Aug 2022To summarize key findings from a Cochrane systematic review of the effectiveness and safety of topical pharmacologic interventions compared with active control or... (Review)
Review
PURPOSE
To summarize key findings from a Cochrane systematic review of the effectiveness and safety of topical pharmacologic interventions compared with active control or placebo for epidemic keratoconjunctivitis (EKC).
DESIGN
Systematic review.
METHODS
We included randomized controlled trials that compared antiseptic agents, virustatic agents, or immune-modulating topical therapies with placebo or an active control. We adhered to Cochrane methods for trial selection, data extraction, risk of bias evaluation, and data synthesis.
RESULTS
Ten randomized controlled trials with 892 participants with acute or chronic EKC were included. Eight trials compared interventions with artificial tears or saline (n = 4) or with steroids (n = 4); two 3-arm trials contributed data to both comparisons. Estimates suggested that compared with tears, after povidone-iodine (PVP-I) alone (2 studies, 409 participants) more participants with acute EKC had resolution of symptoms (risk ratio [RR] 1.15 [95% confidence interval {CI} 1.07-1.24]) and signs (RR 3.19 [95% CI 2.29-4.45]) within 10 days. In 2 trials comparing treatments with steroid alone or steroid with levofloxacin, fewer eyes treated with PVP-I or polyvinyl alcohol iodine (PVA-I) plus steroid developed subepithelial infiltrates within 21 days (RR 0.08 [95% CI 0.01-0.55]; 69 eyes). No treatment was shown to improve resolution of infiltrates.
CONCLUSIONS
Low- to very low-level certainty of evidence suggested that PVP-I or PVA-I with steroid may confer some benefit in acute EKC, but imprecision from small sample sizes, the potential risk of bias from inadequate reporting or trial design, and variability in participant selection, outcome measurement, and reporting limit the amount and quality of evidence.
Topics: Anti-Infective Agents, Local; Humans; Keratoconjunctivitis; Lubricant Eye Drops; Povidone-Iodine
PubMed: 35331686
DOI: 10.1016/j.ajo.2022.03.018 -
The Cochrane Database of Systematic... Mar 2022Viruses cause about 80% of all cases of acute conjunctivitis. Human adenoviruses are believed to account for 65% to 90% of cases of viral conjunctivitis, or 20% to 75%... (Review)
Review
BACKGROUND
Viruses cause about 80% of all cases of acute conjunctivitis. Human adenoviruses are believed to account for 65% to 90% of cases of viral conjunctivitis, or 20% to 75% of all causes of infectious keratoconjunctivitis worldwide. Epidemic keratoconjunctivitis (EKC) is a highly contagious subset of adenoviral conjunctivitis that has been associated with large outbreaks at military installations and at medical facilities. It is accompanied by severe conjunctival inflammation, watery discharge, and light sensitivity, and can lead to chronic complications such as corneal and conjunctival scarring with discomfort and poor quality of vision. Due to a lack of consensus on the efficacy of any pharmacotherapy to alter the clinical course of EKC, no standard of care exists, therefore many clinicians offer only supportive care.
OBJECTIVES
To assess the efficacy and safety of topical pharmacological therapies versus placebo, an active control, or no treatment for adults with EKC.
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; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), with no restrictions on language or year of publication. The date of the last search was 27 April 2021.
SELECTION CRITERIA
We included randomized controlled trials in which antiseptic agents, virustatic agents, or topical immune-modulating therapy was compared with placebo, an active control, or no treatment.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology.
MAIN RESULTS
We identified 10 studies conducted in Asia, Europe, the Middle East, and North Africa with a total of 892 participants who were treated for 7 days to 6 months and followed for 7 days up to 1.5 years. Study characteristics and risk of bias In most studies participants were predominantly men (range: 44% to 90%), with an age range from 9 to 82 years. Three studies reported information on trial registration, but we found no published study protocol. The majority of trials had small sample sizes, ranging from 18 to 90 participants enrolled per study; the only exception was a trial that enrolled 350 participants. We judged most studies to be at high or unclear risk of bias across risk of bias domains. Findings We included 10 studies of 892 EKC participants and estimated combined intervention effects in analyses stratified by steroid-containing control treatment or artificial tears. Six trials contributed to the comparisons of topical interventions (povidone-iodine [PVP-I], trifluridine, ganciclovir, dexamethasone plus neomycin) with artificial tears (or saline). Very low certainty evidence from two trials comparing trifluridine or ganciclovir with artificial tears showed inconsistent effects on shortening the mean duration of cardinal symptoms or signs of EKC. Low certainty evidence based on two studies (409 participants) indicated that participants treated with PVP-I alone more often experienced resolution of symptoms (risk ratio (RR) 1.15, 95% confidence interval (CI) 1.07 to 1.24) and signs (RR 3.19, 95% CI 2.29 to 4.45) during the first week of treatment compared with those treated with artificial tears. Very low certainty evidence from two studies (77 participants) suggested that PVP-I or ganciclovir prevented the development of subepithelial infiltrates (SEI) when compared with artificial tears within 30 days of treatment (RR 0.24, 95% CI 0.10 to 0.56). Four studies compared topical interventions (tacrolimus, cyclosporin A [CsA], trifluridine, PVP-I + dexamethasone) with topical steroids, and one trial compared fluorometholone (FML) plus polyvinyl alcohol iodine (PVA-I) with FML plus levofloxacin. Evidence from one trial showed that more eyes receiving PVP-I 1.0% plus dexamethasone 0.1% had symptoms resolved by day seven compared with those receiving dexamethasone alone (RR 9.00, 95% CI 1.23 to 66.05; 52 eyes). In two trials, fewer eyes treated with PVP-I or PVA-I plus steroid developed SEI within 15 days of treatment compared with steroid alone or steroid plus levofloxacin (RR 0.08, 95% CI 0.01 to 0.55; 69 eyes). One study found that CsA was no more effective than steroid for resolving SEI within four weeks of treatment (RR 0.84, 95% CI 0.67 to 1.06; N = 88). The evidence from trials comparing topical interventions with steroids was overall of very low level certainty. Adverse effects Antiviral or antimicrobial agents plus steroid did not differ from artificial tears in terms of ocular discomfort upon instillation (RR 9.23, 95% CI 0.61 to 140.67; N = 19). CsA and tacrolimus eye drops were associated with more cases of severe ocular discomfort, and sometimes intolerance, when compared with steroids (RR 4.64, 95% CI 1.15 to 18.71; 2 studies; N = 141). Compared with steroids, tacrolimus did not increase the risk of elevated intraocular pressure (RR 0.07, 95% CI 0 to 1.13; 1 study; N = 80), while trifluridine conferred no additional risk compared to tear substitute (RR 5.50, 95% CI 0.31 to 96.49; 1 study; N = 97). Overall, bacterial superinfection was rare (one in 23 CsA users) and not associated with use of the intervention steroid (RR 3.63, 95% CI 0.15 to 84.98; N = 51). The evidence for all estimates was of low or very low certainty.
AUTHORS' CONCLUSIONS
The evidence for the seven specified outcomes was of low or very low certainty due to imprecision and high risk of bias. The evidence that antiviral agents shorten the duration of symptoms or signs when compared with artificial tears was inconclusive. Low certainty evidence suggests that PVP-I alone resolves signs and symptoms by seven days relative to artificial tears. PVP-I or PVA-I, alone or with steroid, is associated with lower risks of SEI development than artificial tears or steroid (very low certainty evidence). The currently available evidence is insufficient to determine whether any of the evaluated interventions confers an advantage over steroids or artificial tears with respect to virus eradication or its spread to initially uninvolved fellow eyes. Future updates of this review should provide evidence of high-level certainty from trials with larger sample sizes, enrollment of participants with similar durations of signs and symptoms, and validated methods to assess short- and long-term outcomes.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Conjunctivitis; Conjunctivitis, Viral; Cyclosporine; Dexamethasone; Female; Fluorometholone; Ganciclovir; Humans; Keratoconjunctivitis; Levofloxacin; Lubricant Eye Drops; Male; Middle Aged; Povidone-Iodine; Tacrolimus; Trifluridine; Young Adult
PubMed: 35238405
DOI: 10.1002/14651858.CD013520.pub2 -
Journal of Clinical Gastroenterology Feb 2022Eradication of Helicobacter pylori infection is challenging. We aimed to determine the optimal first-line H. pylori treatments at global and regional levels. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Eradication of Helicobacter pylori infection is challenging. We aimed to determine the optimal first-line H. pylori treatments at global and regional levels.
METHODS
We searched Embase, PubMed, Cochrane CENTRAL, Web of Science, Scopus, WHO ICTRP, ClinicalTrials.gov, and ISRCTN registry, for randomized controlled trials published during 2011-2020. Utilizing a network meta-analysis in a Bayesian framework, success rates of 23 regimens were compared. The effect size was standardized risk ratio (RR) with 95% credible interval (CrI). Pooled eradication rate (ER) with 95% CrI was also reported for top combinations. The reference regimen was 7-day clarithromycin-based triple therapy.
RESULTS
This review identified 121 trials comprising 34,759 participants. Globally, 14-day levofloxacin-based sequential therapy was the most efficient (RR: 1.43; 95% CrI, 1.26-1.59) with low certainty of evidence, followed by modified bismuth-containing quadruple therapy (proton pump inhibitor+bismuth compounds+clarithromycin+amoxicillin) for 10 days (RR: 1.35; 95% CrI, 1.22-1.48) and 14 days (RR: 1.27; 95% CrI, 1.12-1.42), and 14-day hybrid therapy (RR: 1.27; 95% CrI, 1.19-1.36). The corresponding ERs were 98.7% (95% CrI, 86.9-100.0), 93.2% (95% CrI, 84.2-100.0), 87.6% (95% CrI, 82.1-93.8), and 87.6% (95% CrI, 77.3-98.0), respectively. Continentally, the most effective combinations were: 10-day clarithromycin-based sequential therapy [(RR: 1.21; 95% CrI, 1.02-1.42), (ER: 89.5%, 95% CrI, 75.5-100.0)] for Africa, 14-day levofloxacin-based sequential therapy [(RR: 1.41; 95%CrI, 1.27-1.58), (ER: 98.7%, 95% CrI, 88.9-100.0)] for Asia, and 14-day clarithromycin-based triple therapy [(RR: 1.58; 95% CrI, 1.25-2.04), (ER: 94.8%; 95% CrI, 75.0-100.0)] for Europe. For Northern America, no sufficient data were found for network meta-analysis. In South America, none of the combinations were superior to the reference regimen.
CONCLUSION
Although results of this network meta-analysis revealed optimal combinations for empiric therapy, the treatment preference would be based on the local pattern of antibacterial resistance, when the necessary information exists.
Topics: Amoxicillin; Anti-Bacterial Agents; Bayes Theorem; Clarithromycin; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Network Meta-Analysis; Proton Pump Inhibitors
PubMed: 34855643
DOI: 10.1097/MCG.0000000000001641 -
Journal of Global Antimicrobial... Jun 2022Despite excessive resistance of Helicobacter pylori to clarithromycin among the Iranian population, clarithromycin-based therapy is still prescribed in Iran. Recent... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Despite excessive resistance of Helicobacter pylori to clarithromycin among the Iranian population, clarithromycin-based therapy is still prescribed in Iran. Recent studies have shown high rates of H. pylori eradication in patients treated with levofloxacin. The main purpose of this study was to compare the effect of levofloxacin with clarithromycin on the eradication of H. pylori infection in the Iranian population.
METHODS
A comprehensive meta-analysis was done for relevant cohort studies and clinical trials to compare the therapeutic effects of levofloxacin and clarithromycin in the Iranian population. We pooled the data using odds ratio (OR) and corresponding 95% confidence interval (CI) to determine the clinical efficacy of levofloxacin versus clarithromycin to treat H. pylori infection. Heterogeneity and publication bias were also measured for the included studies.
RESULTS
Thirteen studies were included in the quantitative synthesis. The eradication rate was significantly higher in patients receiving levofloxacin compared with clarithromycin (75.2% vs. 66.3%; OR = 1.76, 95% CI 1.40-2.20). Additionally, in the subgroup analyses it was confirmed that the cure rate was relatively higher in levofloxacin-treated cases. However, there was significant heterogeneity and publication bias, thus the results should be interpreted with caution.
CONCLUSION
We found that the success of levofloxacin treatment was significantly higher than clarithromycin. Therefore, it is suggested that clarithromycin-based triple therapy be replaced by levofloxacin-based triple therapy in countries with high resistance to clarithromycin such as Iran. Nevertheless, the findings of this study need to be approved with a larger investigation on the Iranian population.
Topics: Anti-Bacterial Agents; Clarithromycin; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Iran; Levofloxacin
PubMed: 34788690
DOI: 10.1016/j.jgar.2021.10.019 -
Therapeutics and Clinical Risk... 2021The US Food and Drug Administration issued safety warnings about neuropathy in 2013 and dysglycemia in 2018 caused by fluoroquinolone use, mainly based on case reports... (Review)
Review
INTRODUCTION
The US Food and Drug Administration issued safety warnings about neuropathy in 2013 and dysglycemia in 2018 caused by fluoroquinolone use, mainly based on case reports and case series. We conducted this systematic review to evaluate the safety of fluoroquinolones in diabetic patients by investigating their dysglycemic and neuropathic effects.
METHODS
PubMed, Scopus, and Google Scholar were searched for randomized controlled trials and observational studies published from inception till September 2019 evaluating the safety of fluoroquinolones. Efficacy studies of fluoroquinolones reporting these adverse effects were also included. Primary outcomes were hypoglycemia, hyperglycemia, and neuropathy among patients with or without diabetes and treated with fluoroquinolones compared with placebo or other antibiotics. The Cochrane Collaboration tool for randomized controlled trials and modified Newcastle-Ottawa quality-assessment scale were used for assessment of the included studies.
RESULTS AND DISCUSSION
A total of 725 studies were identified in the initial search. After screening of titles and abstracts and full-text review, 16 articles fulfilled the inclusion criteria. The sampled patients were aged 30-78 years. Hyperglycemia was reported in 1,588 patients that received fluoroquinolone among eight studies with 4,663 patients, and hypoglycemia was reported in 2,179 patients that received fluoroquinolones among eleven studies with 6,208 patients. Dysglycemia was not generally associated with diabetes mellitus per se. Nevertheless, patients with more comorbidities, especially those with chronic kidney disease, receiving antidiabetics and/or steroids had more glycemic events when treated with fluoroquinolones.
CONCLUSION
Moxifloxacin was found to be associated the most and ciprofloxacin the least with dysglycemia. fluoroquinolones must be used with great caution among diabetic patients who have comorbidities and are receiving antidiabetics and/or steroids. Further evidence is required from studies on neuropathy caused by fluoroquinolones.
PubMed: 34675522
DOI: 10.2147/TCRM.S284171 -
Gastroenterologia Y Hepatologia May 2022Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last...
Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last iteration of Spanish consensus guidelines on H. pylori infection was conducted in 2016. Recent changes in therapeutic schemes along with increasing supporting evidence were key for developing the V Spanish Consensus Conference (May 2021). Fourteen experts performed a systematic review of the scientific evidence and developed a series of recommendations that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. An eradication therapy, when prescribed empirically, is considered acceptable when it reliably achieves, or preferably surpass, 90% cure rates. Currently, only quadruple therapies (with or without bismuth) and generally lasting 14 days, accomplish this goal in first- and second-line therapies. A non-bismuth quadruple concomitant regimen (proton pump inhibitor, clarithromycin, amoxicillin, and metronidazole) or a quadruple bismuth-based combination (proton pump inhibitor, bismuth, tetracycline, and metronidazole), are recommended as first-line regimens. Rescue therapies after eradication failure and management of H. pylori infection in peptic ulcer disease were also reviewed.
Topics: Amoxicillin; Anti-Bacterial Agents; Bismuth; Clarithromycin; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Peptic Ulcer; Proton Pump Inhibitors
PubMed: 34629204
DOI: 10.1016/j.gastrohep.2021.07.011 -
Annals of Palliative Medicine Sep 2021The efficacy of levofloxacin and ciprofloxacin in the treatment of urinary tract infection is not clear yet. This study perform a meta-analysis to explore the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy of levofloxacin and ciprofloxacin in the treatment of urinary tract infection is not clear yet. This study perform a meta-analysis to explore the differences between the two against urinary tract infection (UTI).
METHODS
A computerized literature search was conducted of the databases of PubMed, Medline, Embase, and the Cochrane Library. All the retrieved literatures were randomized comparative studies of levofloxacin and ciprofloxacin. The included studies were screened according to the standard of nanofiltration. The risk of bias was assessed with RevMan 5.3.5 software. The treatment effect index and incidence of adverse reactions index were established and compared via meta-analysis.
RESULTS
A total of 5 studies were included, involving 2,877 patients overall. The results showed that levofloxacin was more effective than ciprofloxacin, but the difference between the 2 drugs was not statistically significant [odds ratio (OR) =1.18, 95% confidence interval (CI): 0.94 to 1.46, P=0.15]. There was also no statistical significance in the rate of adverse reactions between the 2 drugs (OR =0.91, 95% CI: 0.78 to 1.07, P=0.27).
DISCUSSION
In the treatment of UTI, the efficacy and safety of levofloxacin and ciprofloxacin are similar statistically. If bacterial resistance is discovered after the treatment of one of the drugs, the other drug might become an alternative.
Topics: Ciprofloxacin; Humans; Levofloxacin; Urinary Tract Infections
PubMed: 34628902
DOI: 10.21037/apm-21-2042 -
Antibiotics (Basel, Switzerland) Sep 2021The emergence of multidrug-resistant poses a public healthcare threat, particularly in low- and middle-income countries. Recently, the World Health Organization has... (Review)
Review
The emergence of multidrug-resistant poses a public healthcare threat, particularly in low- and middle-income countries. Recently, the World Health Organization has classified clarithromycin-resistant as high priority in the research and discovery of novel antibiotics. This study was aimed to systematically review the prevalence of primary antibiotic resistance in in Southeast Asian countries (SEAC) and to review current studies of antimicrobial peptides against . We systematically searched through electronic databases of studies conducted on antimicrobial resistance of in SEA countries. Furthermore, we searched articles that conducted studies on antimicrobial peptides, naturally occurring host's defense molecules, against . After a series of screening processes, 15 studies were included in our systematic review. Our analysis revealed that primary resistance of to metronidazole, clarithromycin, and levofloxacin were high in SEAC, although the primary resistance to amoxicillin and tetracycline remains low. Multidrug-resistant are emerging in SE Asian countries. The antimicrobial peptides show promising antibacterial and antibiofilm activity against drug-resistant . The research and discovery of antimicrobial peptides against in SEAC will help in limiting the spread of antimicrobial resistance of .
PubMed: 34572643
DOI: 10.3390/antibiotics10091061