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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 -
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 -
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 -
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 -
Revue Medicale Suisse Oct 2022
Topics: Amoxicillin; Anti-Bacterial Agents; Humans
PubMed: 36226449
DOI: 10.53738/REVMED.2022.18.799.1887 -
European Journal of Pediatrics Nov 2022Streptococcus pneumoniae is the most common typical bacterial cause of pneumonia among children. The World Health Organization (WHO) recommends a 5-day Amoxicillin-based... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Streptococcus pneumoniae is the most common typical bacterial cause of pneumonia among children. The World Health Organization (WHO) recommends a 5-day Amoxicillin-based empiric treatment. However, longer treatments are frequently used. This study aimed to compare shorter and longer Amoxicillin regimens for children with uncomplicated community-acquired pneumonia (CAP). A search of PubMed, EMBASE, and Cochrane Central was conducted to identify randomized controlled trials (RCTs) comparing 5-day and 10-day courses of Amoxicillin for the treatment of CAP in children older than 6 months in an outpatient setting. Studies involving overlapping populations, lower-than-standard antibiotic doses, and hospitalized patients were excluded. The outcome of interest was clinical cure. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed using the Cochran Q test and I statistics. Two independent authors conducted the critical appraisal of the included studies according to the RoB-2 tool for assessing the risk of bias in randomized trials, and disagreements were resolved by consensus. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) tool to evaluate the certainty of evidence of our results. Three RCTs and 789 children aged from 6 months to 10 years were included, of whom 385 (48.8%) underwent a 5-day regimen. Amoxicillin-based therapy was used in 774 (98%) patients. No differences were found between 5-day and 10-day therapy regarding clinical cure (RR 1.01; 95% CI 0.98-1.05; p = 0.49; I = 0%). Subgroup analysis of children aged 6-71 months showed no difference in the rates of the same outcome (RR 1.01; 95% CI 0.98-1.05; p = 0.38; I = 0%). The GRADE tool suggested moderate certainty of evidence.
CONCLUSION
These findings suggest that a short course of Amoxicillin (5 days) is just as effective as a longer course (10 days) for uncomplicated CAP in children under 10 years old. Nevertheless, generalizations should be made with caution considering the socioeconomic settings of the studies included.PROSPERO Identifier: CRD42022328519.
WHAT IS KNOWN
• In the outpatient setting, a few international guidelines recommend a 10-day Amoxicillin course as first-line treatment for community-acquired pneumonia (CAP). • Recent trials have shown that shorter courses of Amoxicillin may be as effective as 10-day regimens in uncomplicated pneumonia.
WHAT IS NEW
• When comparing 5-day to 10-day Amoxicillin regimens, evidence suggests no significant difference in clinical cure rates for uncomplicated CAP in outpatient settings. • Generalizations should be made with caution considering the socioeconomic context of the population within the included studies.
Topics: Amoxicillin; Anti-Bacterial Agents; Child; Community-Acquired Infections; Drug Administration Schedule; Humans; Infant; Pneumonia
PubMed: 36066660
DOI: 10.1007/s00431-022-04603-8 -
Monographs in Oral Science 2021The systemic administration of antibiotics in conjunction with mechanical biofilm disruption results in reduced numbers of subgingival periodontal pathogens and improved... (Review)
Review
The systemic administration of antibiotics in conjunction with mechanical biofilm disruption results in reduced numbers of subgingival periodontal pathogens and improved clinical outcomes. Penicillins, tetracyclines, macrolides, quinolones, and nitroimidazoles were used in laboratory and clinical studies. The current literature was reviewed and studies investigating the effect of antibiotics on periodontal pathogens in biofilm models or in clinical trials were analyzed. While there is only a limited number of in vitro studies, numerous clinical studies reported microbiological outcomes. The combination of amoxicillin and metronidazole seems to provide superior antimicrobial effects when used in biofilm models or in clinical trials. In vitro studies using biofilm models showed that antibiotics alone have only limited effects on the bacterial load in biofilms but might be effective in reducing specific species. These results imply that mechanical biofilm disruption is indicated to allow antibiotics to be effective. Clinical trials also demonstrated that the combination therapy of amoxicillin and metronidazole might result in more superior microbiological effects than amoxicillin or metronidazole alone. The results of clinical studies investigating azithromycin are contrary. While it seems to be appropriate to use in chronic periodontitis (comparable to the new classification: stage 3 or 4, grade B generalized periodontitis), there was no superior effect observed in aggressive periodontitis (comparable to the new classification: stage 3 or 4, grade C generalized periodontitis). Doxycycline cannot be recommended for chronic periodontitis (stage 3 or 4, grade B) patients. Antibiotics as drugs come with side effects. Common adverse effects of antibiotics are opportunistic yeast infection and gastrointestinal complications (e.g., nausea, diarrhea, and colitis). The development of resistance suggests a role for microbiological analysis and antibiotic susceptibility testing in the selection of systemic periodontal antibiotic therapy.
Topics: Amoxicillin; Anti-Bacterial Agents; Biofilms; Doxycycline; Humans; Metronidazole
PubMed: 33427226
DOI: 10.1159/000510188 -
The Journal of Pediatrics Jun 2018
Topics: Amoxicillin; Humans; Otitis Media
PubMed: 29550231
DOI: 10.1016/j.jpeds.2018.02.012 -
Revue Medicale Suisse Jun 2022
Topics: Amoxicillin; Calcitonin; Humans; Procalcitonin; Protein Precursors
PubMed: 35735157
DOI: 10.53738/REVMED.2022.18.787.1283 -
The Lancet. Gastroenterology &... Jan 2024We previously showed rising primary antibiotic resistance of Helicobacter pylori during 1990-2015 in the Asia-Pacific region. However, whether primary antibiotic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We previously showed rising primary antibiotic resistance of Helicobacter pylori during 1990-2015 in the Asia-Pacific region. However, whether primary antibiotic resistance continues to rise is unknown. Therefore, we aimed to assess the latest prevalence of H pylori antibiotic resistance in this region.
METHODS
We did an updated systematic review and meta-analysis of observational studies and randomised controlled trials published in PubMed, Embase, and Cochrane Library between Jan 1, 1990, and July 12, 2023. Studies investigating primary H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline in individuals naive to eradication therapy in the Asia-Pacific region (as defined by the UN geoscheme) were eligible for inclusion. There were no language restrictions. Studies that focused on specific subpopulations (eg, children) were excluded. Using a standardised extraction form, two authors independently reviewed and extracted summary data from all eligible articles. The updated prevalence of antibiotic resistance was generated by meta-analysis under a random-effects model and subgroup analyses were done by countries and periods of study. Between-study variability was assessed by use of I. The study is registered in PROSPERO, CRD42022339956.
FINDINGS
A total of 351 studies, including 175 new studies and 176 studies from our previous analysis, were included in this meta-analysis. The overall prevalence of primary antibiotic resistance of H pylori between 1990 and 2022 was 22% (95% CI 20-23; I=96%) for clarithromycin, 52% (49-55; I=99%) for metronidazole, 26% (24-29; I=96%) for levofloxacin, 4% (3-5; I=95%) for tetracycline, and 4% (3-5; I=95%) for amoxicillin. Prevalence varied considerably between countries and across study periods. From 1990 to 2022, the prevalence of primary resistance increased for clarithromycin, metronidazole, and levofloxacin but remained stable for amoxicillin and tetracycline. The latest primary resistance prevalences were 30% (95% CI 28-33; I=93%) for clarithromycin, 61% (55-66; I=99%) for metronidazole, 35% (31-39; I=95%) for levofloxacin, 4% (2-6; I=96%) for tetracycline, and 6% (4-8; I=96%) for amoxicillin in the Asia-Pacific region.
INTERPRETATION
Treatment guidelines should be adapted in response to the rising primary resistance of key antibiotics for H pylori eradication. A global policy to control and monitor the antibiotic resistance of H pylori is urgently needed.
FUNDING
Ministry of Health and Welfare of Taiwan, National Science and Technology Council of Taiwan, and National Taiwan University.
TRANSLATION
For the Chinese translation of the abstract see Supplementary Materials section.
Topics: Child; Humans; Clarithromycin; Metronidazole; Levofloxacin; Helicobacter pylori; Helicobacter Infections; Anti-Bacterial Agents; Amoxicillin; Tetracycline; Drug Resistance, Microbial; Asia
PubMed: 37972625
DOI: 10.1016/S2468-1253(23)00281-9