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The Science of the Total Environment Jul 2022Antibiotics play a role in preventing and treating infectious diseases and also contribute to other health risks for humans. With the overuse of antibiotics, they are... (Review)
Review
Antibiotics play a role in preventing and treating infectious diseases and also contribute to other health risks for humans. With the overuse of antibiotics, they are widely distributed in the environment. Long-term exposure to multiple antibiotics may occur in humans through medication and dietary intake. Therefore, it is critical to estimate daily intake and health risk of antibiotics based on urinary biomonitoring. This review compares the strengths and weaknesses of current analytical methods to determine antibiotics in urine samples, discusses the urinary concentration profiles and hazard quotients of individual antibiotics, and overviews correlations of antibiotic exposure with the risk of diseases. Liquid chromatography-tandem mass spectrometry is most applied to simultaneously determine multiple types of antibiotics at trace levels. Solid-phase extraction with a hydrophilic-lipophilic balance adsorbent is commonly used to extract antibiotics in urine samples. Fifteen major antibiotics with relatively higher detection frequencies and concentrations include sulfaclozine, trimethoprim, erythromycin, azithromycin, penicillin V, amoxicillin, oxytetracycline, chlortetracycline, tetracycline, doxycycline, ofloxacin, enrofloxacin, ciprofloxacin, norfloxacin, and florfenicol. Humans can be easily at microbiological effect-based risk induced by florfenicol, ciprofloxacin, azithromycin, and amoxicillin. Positive associations were observed between specific antibiotic exposure and obesity, allergic diseases, and mental disorders. Overall, the accessible, automated, and environmentally friendly methods are prospected for simultaneous determinations of antibiotics at trace level in urine. To estimate human exposure to antibiotics more accurately, knowledge gaps need to be filled up, including the transformation between parent and metabolic antibiotics, urinary excretion proportions of antibiotics at low-dose exposure and pharmacokinetic data of antibiotics in humans, and the repeated sampling over a long period in future research is needed. Longitudinal studies about antibiotic exposure and the risk of diseases in different developmental windows as well as in-depth research on the pathogenic mechanism of long-term, low-dose, and joint antibiotic exposure are warranted.
Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; Biological Monitoring; Ciprofloxacin; Humans
PubMed: 35339554
DOI: 10.1016/j.scitotenv.2022.154775 -
Environmental Research Nov 2022The presence of emerging pollutants, and specifically antibiotics, in agricultural soils has increased notably in recent decades, causing growing concern as regards...
The presence of emerging pollutants, and specifically antibiotics, in agricultural soils has increased notably in recent decades, causing growing concern as regards potential environmental and health issues. With this in mind, the current study focuses on evaluating the toxicity exerted by three antibiotics (amoxicillin, trimethoprim, and ciprofloxacin) on the growth of soil bacterial communities, when these pollutants are present at different doses, and considered in the short, medium, and long terms (1, 8 and 42 days of incubation). Specifically, the research was carried out in 12 agricultural soils having different physicochemical characteristics and was performed by means of the leucine (H) incorporation method. In addition, changes in the structure of soil microbial communities at 8 and 42 days were studied in four of these soils, using the phospholipids of fatty acids method for this. The main results indicate that the most toxic antibiotic was amoxicillin, followed by trimethoprim and ciprofloxacin. The results also show that the toxicity of amoxicillin decreases with time, with values of Log IC ranging from 0.07 ± 0.05 to 3.43 ± 0.08 for day 1, from 0.95 ± 0.07 to 3.97 ± 0.15 for day 8, and from 2.05 ± 0.03 to 3.18 ± 0.04 for day 42, during the incubation period. Regarding trimethoprim, 3 different behaviors were observed: for some soils the growth of soil bacterial communities was not affected, for a second group of soils trimethoprim toxicity showed dose-response effects that remained persistent over time, and, finally, for a third group of soils the toxicity of trimethoprim increased over time, being greater for longer incubation times (42 days). As regards ciprofloxacin, this antibiotic did not show a toxicity effect on the growth of soil bacterial communities for any of the soils or incubation times studied. Furthermore, the principal component analysis performed with the phospholipids of fatty acids results demonstrated that the microbial community structure of these agricultural soils, which persisted after 42 days of incubation, depended mainly on soil characteristics and, to a lesser extent, on the dose and type of antibiotic (amoxicillin, trimethoprim or ciprofloxacin). In addition, it was found that, in this research, the application of the three antibiotics to soils usually favored the presence of fungi and Gram-positive bacteria.
Topics: Amoxicillin; Anti-Bacterial Agents; Bacteria; Ciprofloxacin; Environmental Pollutants; Fatty Acids; Phospholipids; Soil; Soil Microbiology; Soil Pollutants; Trimethoprim
PubMed: 35872321
DOI: 10.1016/j.envres.2022.113916 -
Saudi Journal of Gastroenterology :... 2023Vonoprazan-amoxicillin (VA) dual therapy has recently been proposed to eradicate Helicobacter pylori (H. pylori) with controversial results. We, therefore, conducted a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vonoprazan-amoxicillin (VA) dual therapy has recently been proposed to eradicate Helicobacter pylori (H. pylori) with controversial results. We, therefore, conducted a meta-analysis to assess the effect of this therapy for H. pylori eradication.
METHODS
We searched PubMed, Embase, Cochrane Library, and Web of Science database from inception until November 2022, collecting randomized controlled trials (RCTs) comparing VA dual therapy with other regimens for H. pylori eradication. Pooled relative risks (RRs) were calculated using random effects model.
RESULTS
Five RCTs were ultimately included. Compared with the vonoprazan-amoxicillin-clarithromycin (VAC) triple therapy, the eradication rate of VA dual therapy was lower in intention-to-treat (ITT) analysis (n = 3 RCTs, RR = 0.94, 95% CI: 0.88-0.99, P = 0.03), but there was no significant difference between them in the per-protocol (PP) analysis (RR = 0.96, 95% CI: 0.91-1.01, P = 0.11). For clarithromycin-resistant H. pylori strains, the eradication rate of VA dual therapy was significantly higher than that of the VAC triple therapy (n = 2 RCTs, RR = 1.20, 95% CI: 1.03-1.39, P = 0.02). Compared with the PPI-based triple therapy (PAC), VA dual therapy had a superior eradication rate (n = 2 RCTs, ITT analysis: RR = 1.13, 95% CI: 1.04-1.23, P = 0.003; PP analysis: pooled RR = 1.14, 95% CI: 1.06-1.22, P = 0.0004). Compared with VAC or PAC triple therapy, VA dual therapy has a similar incidence of total adverse events and compliance.
CONCLUSIONS
VA dual therapy had a similar effect compared to VAC triple therapy and was superior to PAC triple therapy. Future RCTs are needed to ascertain the optimal dosage and duration of vonoprazan and amoxicillin, and the effect of VA dual therapy compared with the mainstream regimens recommended by current guidelines.
Topics: Humans; Amoxicillin; Clarithromycin; Anti-Bacterial Agents; Helicobacter pylori; Helicobacter Infections; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Drug Therapy, Combination; Treatment Outcome
PubMed: 37602635
DOI: 10.4103/sjg.sjg_153_23 -
Journal of the Pediatric Infectious... Mar 2024Acute otitis media (AOM) is the most common reason children are prescribed antibiotics. Bacteria that produce beta-lactamase are an increasingly frequent cause of AOM...
BACKGROUND
Acute otitis media (AOM) is the most common reason children are prescribed antibiotics. Bacteria that produce beta-lactamase are an increasingly frequent cause of AOM and may be resistant to amoxicillin, the currently recommended treatment for AOM. We aimed to evaluate the clinical outcomes of children treated with amoxicillin for AOM and assessed whether outcomes vary by infecting pathogen or beta-lactamase production.
METHODS
205 children 6-35 months old diagnosed with AOM and prescribed amoxicillin were included. Bacterial culture and qualitative multiplex real-time polymerase chain reaction were performed on nasopharyngeal swabs collected at enrollment. Parents completed surveys assessing symptoms, antibiotic adherence, and potential adverse events. The primary outcome was treatment failure with amoxicillin. Secondary outcomes included recurrence, symptom improvement, resolution, and adverse drug events (ADE).
RESULTS
8 children (5.4%) experienced treatment failure and 14 (6.8%) had recurrence. By day 5, 152 (74.1%) children had symptom improvement and 97 (47.3%) had resolution. Parents reported ADE for 56 (27.3%) children. Among 149 children who did not take any amoxicillin before enrollment, 98 (65.8%) had one or more beta-lactamase-producing bacteria. Common bacterial otopathogens were Moraxella catarrhalis (79, 53.0%), Streptococcus pneumoniae (51, 34.2%), Haemophilus influenzae (30, 20.1%), and Staphylococcus aureus (21, 14.1%). Treatment failure did not differ between children that did (5, 5.1%) and did not (3, 5.9%) have beta-lactamase-producing otopathogens (p = .05).
CONCLUSIONS
Among children diagnosed with AOM treated with amoxicillin, treatment failure was uncommon and did not differ by pathogen or beta-lactamase production. These data support guidance recommending amoxicillin despite an increasing prevalence of beta-lactamase-producing bacteria.
Topics: Child; Humans; Infant; Amoxicillin; Otitis Media; Anti-Bacterial Agents; Amoxicillin-Potassium Clavulanate Combination; beta-Lactamases; Acute Disease
PubMed: 38314853
DOI: 10.1093/jpids/piae010 -
International Journal of Oral and... Sep 2022The aim of this systematic review was to determine whether antibiotics, compared to placebo, can prevent infection or dry socket after third molar surgery. A systematic... (Meta-Analysis)
Meta-Analysis Review
The aim of this systematic review was to determine whether antibiotics, compared to placebo, can prevent infection or dry socket after third molar surgery. A systematic review and network meta-analysis (NMA) was performed following registration of the protocol (CRD42021276266). Four databases and the grey literature were searched, and papers were selected based on the PICOS question. RoB 2 and GRADE were used to evaluate the risk of bias and certainty of the evidence, respectively. The NMA was performed using Stata. Of 58 randomized clinical trials identified, 34 were included in the NMA. Patients treated with amoxicillin (relative risk (RR) 0.56, 95% confidence interval (CI) 0.38-0.84; low quality of evidence) and those treated with metronidazole (RR 0.51, 95% CI 0.31-0.84; low quality of evidence) showed a lower risk of infection and dry socket when compared to patients given a placebo. Postoperative amoxicillin (750 mg) and amoxicillin plus clavulanate (500 mg + 125 mg, or 2000 mg + 125 mg), and preoperative metronidazole (800 mg) are useful to prevent infection or dry socket when compared to placebo. The low rate of infection after third molar surgery, the correct concept of antibiotic prophylaxis, and antibiotic resistance must be taken into account when choosing to treat healthy patients undergoing third molar surgery with antibiotics.
Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Antibiotic Prophylaxis; Dry Socket; Humans; Metronidazole; Molar, Third; Network Meta-Analysis
PubMed: 35527115
DOI: 10.1016/j.ijom.2022.04.001 -
Current Opinion in Allergy and Clinical... Aug 2015The aim of the present review was to discuss recent advances supporting a role of drug metabolism, and particularly of the generation of reactive metabolites, in... (Review)
Review
PURPOSE OF REVIEW
The aim of the present review was to discuss recent advances supporting a role of drug metabolism, and particularly of the generation of reactive metabolites, in hypersensitivity reactions to drugs.
RECENT FINDINGS
The development of novel mass-spectrometry procedures has allowed the identification of reactive metabolites from drugs known to be involved in hypersensitivity reactions, including amoxicillin and nonsteroidal antiinflammatory drugs such as aspirin, diclofenac or metamizole. Recent studies demonstrated that reactive metabolites may efficiently bind plasma proteins, thus suggesting that drug metabolites, rather than - or in addition to - parent drugs, may elicit an immune response. As drug metabolic profiles are often determined by variability in the genes coding for drug-metabolizing enzymes, it is conceivable that an altered drug metabolism may predispose to the generation of reactive drug metabolites and hence to hypersensitivity reactions. These findings support the potential for the use of pharmacogenomics tests in hypersensitivity (type B) adverse reactions, in addition to the well known utility of these tests in type A adverse reactions.
SUMMARY
Growing evidence supports a link between genetically determined drug metabolism, altered metabolic profiles, generation of highly reactive metabolites and haptenization. Additional research is required to developing robust biomarkers for drug-induced hypersensitivity reactions.
Topics: Amoxicillin; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Proteins; Drug Hypersensitivity; Humans; Mass Spectrometry; Pharmacogenetics
PubMed: 26110676
DOI: 10.1097/ACI.0000000000000174 -
Critical Reviews in Analytical Chemistry May 2017Bacterial infections are the second leading cause of global mortality. Considering this fact, it is extremely important studying the antimicrobial agents. Amoxicillin is... (Review)
Review
Bacterial infections are the second leading cause of global mortality. Considering this fact, it is extremely important studying the antimicrobial agents. Amoxicillin is an antimicrobial agent that belongs to the class of penicillins; it has bactericidal activity and is widely used in the Brazilian health system. In literature, some analytical methods are found for the identification and quantification of this penicillin, which are essential for its quality control, which ensures maintaining the product characteristics, therapeutic efficacy and patient's safety. Thus, this study presents a brief literature review on amoxicillin and the analytical methods developed for the analysis of this drug in official and scientific papers. The major analytical methods found were high-performance liquid chromatography (HPLC), ultra-performance liquid chromatography (U-HPLC), capillary electrophoresis and iodometry and diffuse reflectance infrared Fourier transform. It is essential to note that most of the developed methods used toxic and hazardous solvents, which makes necessary industries and researchers choose to develop environmental-friendly techniques to provide enhanced benefits to environment and staff.
Topics: Amoxicillin; Anti-Bacterial Agents; Bacterial Infections; Chromatography, High Pressure Liquid; Green Chemistry Technology; Humans; Streptococcus
PubMed: 28080135
DOI: 10.1080/10408347.2017.1281097 -
Clinical and Experimental Allergy :... Aug 2019Amoxicillin is the most common antibiotic prescribed in children with increasing use over time. While up to 10% of children are labelled as amoxicillin allergic, most... (Review)
Review
Amoxicillin is the most common antibiotic prescribed in children with increasing use over time. While up to 10% of children are labelled as amoxicillin allergic, most children can tolerate amoxicillin after allergy evaluation. It is well documented that the label of amoxicillin allergy in children is associated with adverse health outcomes such as antibiotic-resistant infections. However, it remains controversial how best to assess children for amoxicillin allergy. While in general it is recommended that skin testing be done prior to drug provocation test in the evaluation of amoxicillin allergy, there is increasing evidence that drug provocation testing could be done in lower risk children without skin testing prior. The goal of this article as a narrative review is to review the strengths and limitations of skin testing prior to drug provocation test in children who have a history of either immediate or non-immediate, reactions to amoxicillin.
Topics: Amoxicillin; Anti-Bacterial Agents; Child; Child, Preschool; Drug Hypersensitivity; Female; Humans; Male; Skin Tests
PubMed: 31141238
DOI: 10.1111/cea.13443 -
The Journal of Antimicrobial... Mar 2023In the randomized controlled trial PANTHEM, the prophylactic effect of oral amoxicillin or clindamycin is investigated in patients receiving chronic haemodialysis (HD).... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
In the randomized controlled trial PANTHEM, the prophylactic effect of oral amoxicillin or clindamycin is investigated in patients receiving chronic haemodialysis (HD). However, data on plasma concentrations of these antibiotics during HD are sparse. This study aims to determine if the plasma concentration of amoxicillin and clindamycin is sufficient during HD after oral administration of amoxicillin and clindamycin at three different time intervals prior to the HD procedure.
METHODS
Adult patients receiving chronic HD were investigated twice with an interval of at least 7 days starting with either a tablet of 500/125 mg amoxicillin/clavulanic acid or a tablet of 600 mg clindamycin. Patients were randomized to take the antibiotics either 30, 60 or 120 min prior to the HD procedure. Plasma antibiotic concentrations were measured at start, midway and at the end of HD. A lower threshold was set at 2.0 mg/L for amoxicillin and at 1.0 mg/L for clindamycin. In addition, a population pharmacokinetic (PK) analysis was performed, assessing PTA.
RESULTS
In the amoxicillin cohort (n = 37), 84% of patients and 95% of all plasma amoxicillin concentrations were above or at the threshold throughout the dialysis procedure. In the clindamycin cohort (n = 33), all concentrations were above the threshold throughout the dialysis procedure. Further, in all patients, the mean plasma concentration of both amoxicillin and clindamycin across the HD period was well above the threshold. Finally, the PK model predicted a high PTA in the majority of patients.
DISCUSSION
In patients on chronic HD, oral administration of amoxicillin/clavulanic acid (500/125 mg) or clindamycin (600 mg) within 30-120 min prior to HD leads to a sufficient prophylactic plasma concentration across the HD period.
Topics: Adult; Humans; Amoxicillin; Clindamycin; Anti-Bacterial Agents; Amoxicillin-Potassium Clavulanate Combination; Renal Dialysis
PubMed: 36640129
DOI: 10.1093/jac/dkad002 -
Evidence-based Dentistry Jun 2022Design A multicentre, prospective, randomised, placebo-controlled, double-blinded clinical trial reported the early implant failure and postoperative infections of... (Review)
Review
Design A multicentre, prospective, randomised, placebo-controlled, double-blinded clinical trial reported the early implant failure and postoperative infections of healthy or relatively healthy patients receiving 2 grams of amoxicillin one hour preoperatively from their scheduled dental implant placement. The registration of the study protocol in EudraCT and Clinical Trials.gov (#NCT03412305) followed the ethical principles of the Declaration of Helsinki and the CONSORT guidelines for clinical trials.Case selection Several trial drugs expired before recruiting the intended 1,000 patients calculated based on previous trials reporting 2% and 5% early implant loss, with and without antibiotic prophylaxis. Thus, the study cohort (age >18 years, not planned for immediate loading, not requiring substantial bone augmentation, with an absence of severe diseases or immunosuppression or immunodeficiency) received 757 implants in total between November 2014 and April 2018, consisting of the prophylactic antibiotic therapy group (patients n = 235) and the placebo group (patients n = 235), with a fair sex distribution and a mean age of 57.4 ± 13.9 years. A computer-generated list of random numbers assisted the randomisation (test or control group) with a block-size six. For the clinical procedures, bone augmentation was limited to autogenous bone chips and bone debris. One- and two-stage surgery protocols were used in maxillary or mandibular single or multiple dental implants. The utilised implant systems were Straumann SLA (Straumann Implants, Switzerland), Astra Tech Dental Implant Systems (Dentsply Sirona, Sweden), Nobel Biocare (Sweden) and Southern Implants (Ltd, South Africa). Chlorhexidine 0.2% was prescribed preoperatively and/or postoperatively. Implant failure was the main measured outcome, whereas postoperative infections and adverse events were the secondary outcomes postoperatively assessed at 7-14-day (first follow-up) and 3-6-month (second follow-up) intervals.Data analysis The sample size calculation (type one error: 0.05; power: 80%) estimated 500 patients in each group. Proportional differences and relative risk (RR) with a 95% confidence interval (CI) were calculated. Implant failure was the dependent variable for the multiple logistic regression (MLR) model examining the indicator variables smoking (yes or no), and age (<50 years; 50-64; and ≥65), as well as the independent variables bone augmentation (yes or no), number of implants (1, 2-3 and ≥4), and treatment group (antibiotic prophylaxis or placebo). P-values <0.05 or 95% CIs for ratios not including one were deemed statistically significant. The analyses were carried out using statistical software for data science (STATA).Results Overall, six (2.5%) and seven patients (3.0%) from the amoxicillin and placebo groups had implant failures, respectively. Thus, the intergroup difference was not significant (RR: 0.85; 95% CI: 0.29-2.48, p = 0.75). Absolute risk reduction was 0.46%, with a number needed to treat (NNT) of 219. In other words, one in every 219 patients will benefit from receiving prophylactic antibiotics. In addition, no variable was associated with implant failure. Two (0.8%) and five patients (2.1%) from the amoxicillin and placebo groups, respectively, had postoperative infections at the first follow-up interval. Thus, the intergroup difference was not significant (RR: 0.29; 95% CI: 0.08-2.01, p = 0.25). Five (2.1%) and seven patients (3.0%) from the amoxicillin and placebo groups, respectively, had postoperative infections at the second follow-up interval. Thus, the intergroup difference was not significant (RR: 0.70; 95% CI: 0.23-2.18, p = 0.54). No adverse events were reported.Conclusion Prophylactic antibiotic treatment for dental implant surgery to prevent implant loss may not be appropriate. Each dose must be prescribed based on evidence-based guidelines to avoid overuse and misuse of antibiotics promoting resistant bacteria.
Topics: Adult; Aged; Amoxicillin; Antibiotic Prophylaxis; Dental Implants; Dental Restoration Failure; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Postoperative Complications; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 35750737
DOI: 10.1038/s41432-022-0266-7