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Clinical Microbiology and Infection :... Jul 2020Amoxicillin has been in use since the 1970s; it is the most widely used penicillin both alone and in combination with the β-lactamase clavulanic acid. (Review)
Review
BACKGROUND
Amoxicillin has been in use since the 1970s; it is the most widely used penicillin both alone and in combination with the β-lactamase clavulanic acid.
OBJECTIVES
In this narrative review, we re-examine the properties of oral amoxicillin and clavulanic acid and provide guidance on their use, with emphasis on the preferred use of amoxicillin alone.
SOURCES
Published medical literature (MEDLINE database via Pubmed).
CONTENT
While amoxicillin and clavulanic acid have similar half-lives, clavulanic acid is more protein bound and even less heat stable than amoxicillin, with primarily hepatic metabolism. It is also more strongly associated with gastrointestinal side effects, including Clostridium difficile infection, and, thus, in oral combination formulations, limits the maximum daily dose of amoxicillin that can be given. The first ratio for an amoxicillin-clavulanic acid combination was set at 4:1 due to clavulanic acid's high affinity for β-lactamases; ratios of 2:1, 7:1, 14:1 and 16:1 are currently available in various regions. Comparative effectiveness data for the different ratios are scarce. Amoxicillin-clavulanic acid is often used as empiric therapy for many of the World Health Organization's Priority Infectious Syndromes in adults and children, leading to extensive consumption, when some of these syndromes could be handled with a delayed antibiotic prescription approach or amoxicillin alone.
IMPLICATIONS
Using available epidemiological and pharmacokinetic data, we provide guidance on indications for amoxicillin versus amoxicillin-clavulanic acid and on optimal oral administration, including choice of combination ratio. More data are needed, particularly on heat stability, pharmacodynamic effects and emergence of resistance in 'real-world' clinical settings.
Topics: Administration, Oral; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Drug Dosage Calculations; Drug Stability; Humans; Practice Guidelines as Topic
PubMed: 31811919
DOI: 10.1016/j.cmi.2019.11.028 -
Digestion 2022Helicobacter pylori eradication treatments are widely performed to improve gastric mucosal inflammation, promote ulcer healing, and reduce the incidence of gastric... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Helicobacter pylori eradication treatments are widely performed to improve gastric mucosal inflammation, promote ulcer healing, and reduce the incidence of gastric cancer. However, there are several issues associated with H. pylori eradication treatment. First, various treatment regimens are currently used worldwide, and the standard treatment varies with region and country. Second, the antimicrobial resistance of H. pylori is increasing due to indiscriminate antibiotic use. Finally, gut microbiota dysbiosis is potentially induced by H. pylori treatment.
SUMMARY
Based on current international guidelines and a network meta-analysis comparing the effects of various treatment regimens, nonbismuth quadruple therapies for 10-14 days and vonoprazan-based triple therapy for 7 days are the currently recommended H. pylori treatment regimens. These regimens show good eradication rates of approximately 90%, even in areas where antimicrobial-resistant strains are highly prevalent. However, these regimens still have inherent drawbacks that may promote further increases in antimicrobial resistance and induce gut microbiota dysbiosis because of the empiric use of multiple antibiotics. Key Message: The ideal concept for the present and future H. pylori eradication treatment involves "a simple, cost-effective strategy that fosters compliance without having a negative impact on the gut microbiota or contributing to future antimicrobial resistance." One interesting possibility that may fulfill this concept is a dual therapy involving vonoprazan and amoxicillin. This is the simplest treatment regimen that provides acceptable eradication rates, improves safety and tolerability, and minimizes the potential for increasing antimicrobial resistance or causing gut microbiota dysbiosis.
Topics: Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Proton Pump Inhibitors
PubMed: 34662879
DOI: 10.1159/000519413 -
JAMA Sep 2023Acute sinusitis is one of the most common indications for antibiotic prescribing in children, with an estimated 4.9 million such prescriptions in the US annually.... (Comparative Study)
Comparative Study
IMPORTANCE
Acute sinusitis is one of the most common indications for antibiotic prescribing in children, with an estimated 4.9 million such prescriptions in the US annually. Consensus does not exist regarding the optimal empirical antibiotic.
OBJECTIVE
To compare amoxicillin-clavulanate vs amoxicillin for the treatment of acute sinusitis in outpatient children.
DESIGN, SETTING, AND PARTICIPANTS
Cohort study of children and adolescents aged 17 years or younger with a new outpatient diagnosis of acute sinusitis and a same-day new prescription dispensation of amoxicillin-clavulanate or amoxicillin in a nationwide health care utilization database. Propensity score matching was used to mitigate confounding.
EXPOSURE
A new prescription dispensation of amoxicillin-clavulanate or amoxicillin.
MAIN OUTCOMES AND MEASURES
Treatment failure, defined as an aggregate of a new antibiotic dispensation, emergency department or inpatient encounter for acute sinusitis, or inpatient encounter for a sinusitis complication, was assessed 1 to 14 days after cohort enrollment. Adverse events were evaluated, including gastrointestinal symptoms, hypersensitivity and skin reactions, acute kidney injury, and secondary infections.
RESULTS
The cohort included 320 141 patients. After propensity score matching, there were 198 942 patients (99 471 patients per group), including 100 340 (50.4%) who were female, 101 726 (51.1%) adolescents aged 12 to 17 years, 52 149 (26.2%) children aged 6 to 11 years, and 45 067 (22.7%) children aged 0 to 5 years. Treatment failure occurred in 1.7% overall; 0.01% had serious failure (an emergency department or inpatient encounter). There was no difference in the risk of treatment failure between the amoxicillin-clavulanate and amoxicillin groups (relative risk [RR], 0.98 [95% CI, 0.92-1.05]). The risk of gastrointestinal symptoms (RR, 1.15 [95% CI, 1.05-1.25]) and yeast infections (RR, 1.33 [95% CI, 1.16-1.54]) was higher with amoxicillin-clavulanate. After patients were stratified by age, the risk of treatment failure after amoxicillin-clavulanate was an RR of 0.98 (95% CI, 0.86-1.12) for ages 0 to 5 years; RR was 1.06 (95% CI, 0.92-1.21) for 6 to 11 years; and RR was 0.87 (95% CI, 0.79-0.95) for 12 to 17 years. The age-stratified risk of adverse events after amoxicillin-clavulanate was an RR of 1.23 (95% CI, 1.10-1.37) for ages 0 to 5 years; RR was 1.19 (95% CI, 1.04-1.35) for 6 to 11 years; and RR was 1.04 (95% CI, 0.95-1.14) for 12 to 17 years.
CONCLUSIONS AND RELEVANCE
In children with acute sinusitis who were treated as outpatients, there was no difference in the risk of treatment failure between those who received amoxicillin-clavulanate compared with amoxicillin, but amoxicillin-clavulanate was associated with a higher risk of gastrointestinal symptoms and yeast infections. These findings may help inform decisions for empirical antibiotic selection in acute sinusitis.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cohort Studies; Mycoses; Sinusitis; Treatment Failure
PubMed: 37721610
DOI: 10.1001/jama.2023.15503 -
Antimicrobial Agents and Chemotherapy Feb 2019Amoxicillin is widely used to treat bacterial infections in neonates. However, considerable intercenter variability in dosage regimens of antibiotics exists in clinical...
Amoxicillin is widely used to treat bacterial infections in neonates. However, considerable intercenter variability in dosage regimens of antibiotics exists in clinical practice. The pharmacokinetics of amoxicillin has been described in only a few preterm neonates. Thus, we aimed to evaluate the population pharmacokinetics of amoxicillin through a large sample size covering the entire age range of neonates and young infants and to establish evidence-based dosage regimens based on developmental pharmacokinetics-pharmacodynamics. This is a prospective, multicenter, pharmacokinetic study using an opportunistic sampling design. Amoxicillin plasma concentrations were determined using high-performance liquid chromatography. Population pharmacokinetic analysis was performed using NONMEM. A total of 224 pharmacokinetic samples from 187 newborns (postmenstrual age range, 28.4 to 46.3 weeks) were available for analysis. A two-compartment model with first-order elimination was used to describe population pharmacokinetics. Covariate analysis showed that current weight, postnatal age, and gestational age were significant covariates. The final model was further validated for predictive performance in an independent cohort of patients. Monte Carlo simulation demonstrated that for early-onset sepsis, the currently used dosage regimen (25 mg/kg twice daily [BID]) resulted in 99.0% of premature neonates and 87.3% of term neonates achieving the pharmacodynamic target (percent time above MIC), using a MIC breakpoint of 1 mg/liter. For late-onset sepsis, 86.1% of premature neonates treated with 25 mg/kg three times a day (TID) and 79.0% of term neonates receiving 25 mg/kg four times a day (QID) reached the pharmacodynamic target, using a MIC breakpoint of 2 mg/liter. The population pharmacokinetics of amoxicillin was assessed in neonates and young infants. A dosage regimen was established based on developmental pharmacokinetics-pharmacodynamics.
Topics: Amoxicillin; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Female; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Models, Theoretical; Prospective Studies
PubMed: 30509939
DOI: 10.1128/AAC.02336-18 -
The Journal of Pediatrics Dec 2022The objective of the study was to compare the antibiotic treatment failure and recurrence rates between antibiotic agents (amoxicillin, amoxicillin-clavulanate,...
OBJECTIVES
The objective of the study was to compare the antibiotic treatment failure and recurrence rates between antibiotic agents (amoxicillin, amoxicillin-clavulanate, cefdinir, and azithromycin) for children with uncomplicated acute otitis media (AOM).
STUDY DESIGN
We completed a retrospective cohort study of children 6 months-12 years of age with uncomplicated AOM identified in a nationwide claims database. The primary exposure was the antibiotic agent, and the primary outcomes were treatment failure and recurrence. Logistic regression was used to estimate ORs, and analyses were stratified by primary exposure, patient age, and antibiotic duration.
RESULTS
Among the 1 051 007 children included in the analysis, 56.6% were prescribed amoxicillin, 13.5% were prescribed amoxicillin-clavulanate, 20.6% were prescribed cefdinir, and 9.3% were prescribed azithromycin. Most prescriptions (93%) were for 10 days, and 98% were filled within 1 day of the medical encounter. Treatment failure and recurrence occurred in 2.2% (95% CI: 2.1, 2.2) and 3.3% (3.2, 3.3) of children, respectively. Combined failure and recurrence rates were low for all agents including amoxicillin (1.7%; 1.7, 1.8), amoxicillin-clavulanate (11.3%; 11.1, 11.5), cefdinir (10.0%; 9.8, 10.1), and azithromycin (9.8%; 9.6, 10.0).
CONCLUSIONS
Despite microbiologic changes in AOM etiology, treatment failure and recurrence were uncommon for all antibiotic agents and were lower for amoxicillin than for other agents. These findings support the continued use of amoxicillin as a first-line agent for AOM when antibiotics are prescribed.
Topics: Child; Humans; Infant; Amoxicillin; Azithromycin; Cefdinir; Retrospective Studies; Acute Disease; Treatment Outcome; Anti-Bacterial Agents; Otitis Media; Amoxicillin-Potassium Clavulanate Combination
PubMed: 35944719
DOI: 10.1016/j.jpeds.2022.07.053 -
Swiss Dental Journal 2017Non-surgical periodontal therapy is often performed as a combinational approach using supplemental systemic amoxicillin and metronidazole. Better clinical outcomes, less...
Non-surgical periodontal therapy is often performed as a combinational approach using supplemental systemic amoxicillin and metronidazole. Better clinical outcomes, less need for periodontal surgery and limited systemic complications are arguments to justify such an approach. However, combination therapy with systemic antibiotic treatment is still a matter of debate due to emerging antibiotic resistance patterns. In this case report, a 61-year-old women suffering from an acute pancreatitis following systemic antibiotic combinational treatment as part of a non-surgical periodontal therapy is described. Following adequate symptomatic treatment during a hospitalization of three days, the patient recovered and periodontal conditions improved significantly thereafter. This case report illustrates a rare, but potentially serious complication when prescribing systemic combinational antibiotics in non-surgical periodontal therapy. Adequate history taking and timely diagnosis of pancreatitis if developing is important to provide relevant treatment and to avoid pancreatitis-associated complications.
Topics: Amoxicillin; Biofilms; Combined Modality Therapy; Dental Scaling; Female; Humans; Metronidazole; Middle Aged; Pancreatitis, Acute Necrotizing; Periodontitis; Referral and Consultation
PubMed: 28480950
DOI: No ID Found -
BMJ Clinical Evidence Dec 2011Acute sinusitis is defined pathologically, by transient inflammation of the mucosal lining of the paranasal sinuses lasting less than 4 weeks. Clinically, it is... (Review)
Review
INTRODUCTION
Acute sinusitis is defined pathologically, by transient inflammation of the mucosal lining of the paranasal sinuses lasting less than 4 weeks. Clinically, it is characterised by nasal congestion, rhinorrhoea, facial pain, hyposmia, sneezing, and, if more severe, additional malaise and fever. It affects 1% to 5% of the adult population each year in Europe.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with clinically diagnosed acute sinusitis, and in people with radiologically or bacteriologically confirmed acute sinusitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (amoxicillin, amoxicillin-clavulanic acid [co-amoxiclav], doxycycline, cephalosporins, macrolides; different doses, long-course regimens), antihistamines, decongestants (xylometazoline, phenylephrine, pseudoephedrine), saline nasal washes, steam inhalation, and topical corticosteroids (intranasal).
Topics: Acute Disease; Administration, Oral; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Double-Blind Method; Evidence-Based Medicine; Humans; Macrolides; Sinusitis
PubMed: 22189346
DOI: No ID Found -
Clinical Infectious Diseases : An... Oct 2022Amoxicillin is a broad-spectrum antibiotic used to treat a variety of gram-positive and gram-negative infections, such as infections of the ear, nose, and throat,...
Evaluation of Amoxicillin and Amoxicillin-Clavulanate (Augmentin) for Antimicrobial Postexposure Prophylaxis Following Bacillus anthracis Inhalational Exposure in Cynomolgus Macaques.
Amoxicillin is a broad-spectrum antibiotic used to treat a variety of gram-positive and gram-negative infections, such as infections of the ear, nose, and throat, genitourinary tract, skin, and lower respiratory tract; gonorrhea; and Helicobacter pylori. The prophylactic benefit of both amoxicillin and Augmentin (amoxicillin-clavulanate for use against β-lactamase-expressing bacteria) was evaluated for inhalation anthrax in cynomolgus macaques in 2 studies. A pilot study on amoxicillin-clavulanate that used a portion of the study animals demonstrated empirically that dosing twice a day was efficacious. In a subsequent study on both amoxicillin and amoxicillin-clavulanate that used the remaining study animals, the animals were treated orally every 12 hours on days 1-28 postchallenge and followed for an additional 60 days (total of 88 days from day of aerosol challenge to when the animals were culled). The animals from each treatment arm of the 2 studies were completely protected. All untreated animals succumbed to the infection. The degree of protection observed in this study suggests that both amoxicillin and amoxicillin-clavulanate, administered prophylactically over a period of 28 days after a lethal exposure to Bacillus anthracis spores, is sufficient for full protection.
Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Bacillus anthracis; Macaca; Pilot Projects; beta-Lactamases
PubMed: 36251552
DOI: 10.1093/cid/ciac572 -
BMC Microbiology Aug 2023The microbiome of the human gut serves a role in a number of physiological processes, but can be altered through effects of age, diet, and disturbances such as...
BACKGROUND
The microbiome of the human gut serves a role in a number of physiological processes, but can be altered through effects of age, diet, and disturbances such as antibiotics. Several studies have demonstrated that commonly used antibiotics can have sustained impacts on the diversity and the composition of the gut microbiome. The impact of the two most overused antibiotics, azithromycin, and amoxicillin, in the human microbiome has not been thoroughly described. In this study, we recruited a group of individuals and unrelated controls to decipher the effects of the commonly used antibiotics amoxicillin and azithromycin on their gut microbiomes.
RESULTS
We characterized the gut microbiomes by metagenomic sequencing followed by characterization of the resulting microbial communities. We found that there were clear and sustained effects of the antibiotics on the gut microbial community with significant alterations in the representations of Bifidobacterium species in response to azithromycin (macrolide antibiotic). These results were supported by significant increases identified in putative antibiotic resistance genes associated with macrolide resistance. Importantly, we did not identify these trends in the unrelated control individuals. There were no significant changes observed in other members of the microbial community.
CONCLUSIONS
As we continue to focus on the role that the gut microbiome plays and how disturbances induced by antibiotics might affect our overall health, elucidating members of the community most affected by their use is of critical importance to understanding the impacts of common antibiotics on those who take them. Clinical Trial Registration Number NCT05169255. This trial was retrospectively registered on 23-12-2021.
Topics: Humans; Anti-Bacterial Agents; Amoxicillin; Azithromycin; Metagenomics; Macrolides; Drug Resistance, Bacterial
PubMed: 37528343
DOI: 10.1186/s12866-023-02949-z -
Chinese Medical Journal Jan 2023Bismuth-containing quadruple therapy (BQT) has long been recommended for Helicobacter pylori ( H. pylori ) eradication in China. Meanwhile, in the latest national... (Review)
Review
Bismuth-containing quadruple therapy (BQT) has long been recommended for Helicobacter pylori ( H. pylori ) eradication in China. Meanwhile, in the latest national consensus in China, dual therapy (DT) comprising an acid suppressor and amoxicillin has also been recommended. In recent years, the eradication rate of H. pylori has reached >90% using DT, which has been used not only as a first-line treatment but also as a rescue treatment. Compared with BQT, DT has great potential for H. pylori eradication; however, it has some limitations. This review summarizes the development of DT and its application in H. pylori eradication. The H. pylori eradication rates of DT were comparable to or even higher than those of BQT or standard triple therapy, especially in the first-line treatment. The incidence of adverse events associated with DT was lower than that with other therapies. Furthermore, there were no significant differences in the effects of dual and quadruple therapies on gastrointestinal microecology. In the short term, H. pylori eradication causes certain fluctuations in the gastrointestinal microbiota; however, in the long term, the gastrointestinal microbiota eventually returns to its normal state. In the penicillin-naïve population, patients receiving DT have a high eradiation rate, better compliance, lower incidence of adverse reactions, and lower primary and secondary resistance to amoxicillin. These findings suggest the safety, efficacy, and potential of DT for H. pylori eradication.
Topics: Humans; Helicobacter Infections; Anti-Bacterial Agents; Helicobacter pylori; Proton Pump Inhibitors; Drug Therapy, Combination; Amoxicillin; Treatment Outcome
PubMed: 36805362
DOI: 10.1097/CM9.0000000000002565