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EBioMedicine Jun 2024Accurate prediction of the optimal dose for β-lactam antibiotics in neonatal sepsis is challenging. We aimed to evaluate whether a reliable clinical decision support...
BACKGROUND
Accurate prediction of the optimal dose for β-lactam antibiotics in neonatal sepsis is challenging. We aimed to evaluate whether a reliable clinical decision support system (CDSS) based on machine learning (ML) can assist clinicians in making optimal dose selections.
METHODS
Five β-lactam antibiotics (amoxicillin, ceftazidime, cefotaxime, meropenem and latamoxef), commonly used to treat neonatal sepsis, were selected. The CDSS was constructed by incorporating the drug, patient, dosage, pharmacodynamic, and microbiological factors. The CatBoost ML algorithm was used to build the CDSS. Real-world studies were used to evaluate the CDSS performance. Virtual trials were used to compare the CDSS-optimized doses with guideline-recommended doses.
FINDINGS
For a specific drug, by entering the patient characteristics and pharmacodynamic (PD) target (50%/70%/100% fraction of time that the free drug concentration is above the minimal inhibitory concentration [fT > MIC]), the CDSS can determine whether the planned dosing regimen will achieve the PD target and suggest an optimal dose. The prediction accuracy of all five drugs was >80.0% in the real-world validation. Compared with the PopPK model, the overall accuracy, precision, recall, and F1-Score improved by 10.7%, 22.1%, 64.2%, and 43.1%, respectively. Using the CDSS-optimized doses, the average probability of target concentration attainment increased by 58.2% compared to the guideline-recommended doses.
INTERPRETATION
An ML-based CDSS was successfully constructed to assist clinicians in selecting optimal β-lactam antibiotic doses.
FUNDING
This work was supported by the National Natural Science Foundation of China; Distinguished Young and Middle-aged Scholar of Shandong University; National Key Research and Development Program of China.
PubMed: 38917512
DOI: 10.1016/j.ebiom.2024.105221 -
PloS One 2024Antibiotic self-medication is one of the common causes of antibiotic resistance of bacterial organisms. The COVID-19 pandemic introduced a new paradigm shift and...
BACKGROUND
Antibiotic self-medication is one of the common causes of antibiotic resistance of bacterial organisms. The COVID-19 pandemic introduced a new paradigm shift and significantly influenced healthcare behaviors, including an increase in antibiotic self-medication, which contributes to antibiotic resistance. This study was aimed at determining the prevalence of antibiotic self-medication and the possible associated factors during the peak of the COVID-19 pandemic among adult residents of Tema in Ghana from April to July 2021.
METHODS
Using a cross-sectional design, 400 adults were randomly selected and surveyed using a researcher-assisted questionnaire. Data were analyzed with IBM® SPSS® Statistics Version 22.0, considering associations significant at a 95% confidence interval (p < 0.05).
RESULTS
Of the 400 respondents, (76%) 304 had practiced antibiotic self-medication within the previous 12 months during the COVID-19 pandemic. Significant factors associated with antibiotic self-medication included gender, age, marital status, education, occupation, and National Health Insurance Scheme subscription. Convenience and avoiding long hospital queues were primary non-medical reasons for antibiotic self-medication, while previous successful experience, easy access to antibiotics, treating symptoms, prophylaxis, and fear of hospital infection were the medical reasons for antibiotic self-medication. Commonly self-administered antibiotics were azithromycin (34%), amoxicillin/clavulanic acid (22%), and metronidazole (16%) for perceived respiratory tract and gastrointestinal tract infections.
CONCLUSIONS
The high prevalence of antibiotic self-medication observed during the COVID-19 pandemic underscores the need for enhanced public education and stricter enforcement of regulations governing antibiotic sales. The non-medical and medical factors of convenience, avoiding long hospital queues, previous successful experience, easy access to antibiotics, treating symptoms, prophylaxis, and fear of hospital infection which motivated antibiotic self-medication practices require the implementation of antimicrobial stewardship interventions.
Topics: Humans; Self Medication; Male; Female; Adult; Cross-Sectional Studies; COVID-19; Anti-Bacterial Agents; Middle Aged; Ghana; Young Adult; SARS-CoV-2; Surveys and Questionnaires; Pandemics; Aged; Adolescent
PubMed: 38917123
DOI: 10.1371/journal.pone.0305602 -
Microbiology Spectrum Jun 2024The aim of the present study was first to isolate from gastric biopsy specimens and to test their antibiotic susceptibility. Second, it was to evaluate the efficacy of...
The aim of the present study was first to isolate from gastric biopsy specimens and to test their antibiotic susceptibility. Second, it was to evaluate the efficacy of the standard triple therapy from patients of the west central region of Colombia. positive patients received standard triple therapy with proton pump inhibitor (PPI) (40 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxicillin (1 g b.i.d.) for 14 days. Thereafter, antibiotic susceptibility of the isolates was assessed by E-Test. From 94 patients enrolled, 67 were positive for by histology or culture. Overall resistance to metronidazole, levofloxacin, rifampicin, clarithromycin, and amoxicillin was 81%, 26.2%, 23.9%, 19%, and 9.5%, respectively. No resistance was found for tetracycline. A total of 54 patients received standard triple therapy, 48 attended follow-ups testing, and of them, 30 had resistance test reports. Overall eradication rate was 81.2%. Second-line treatment was given to eight patients, four of whom were followed up with a 13C urea breath test (UBT) and remained positive for . Eradication was significantly higher in patients with clarithromycin susceptible than in resistant strains (95.6% vs 42.8% = 0.001). The updated percentages of resistance to clarithromycin in this geographical area had increased, so this value must be considered when choosing the treatment regimen.IMPORTANCEAntibiotic resistance in has increased worldwide, as has resistance to multiple antimicrobials (MDRs), which seriously hampers the successful eradication of the infection. The ideal success rate in eradicating infection (≥90%) was not achieved in this study (81.2%). This is the first time that MDR is reported (14.3%) in the region; the resistance to clarithromycin increased over time (3.8%-19%), and levofloxacin (26.2%) and rifampicin (23%) resistant isolates were detected for the first time. With these results, strain susceptibility testing is increasingly important, and the selection of treatment regimen should be based on local antibiotic resistance patterns.
PubMed: 38916348
DOI: 10.1128/spectrum.00401-24 -
Scientific Reports Jun 2024Antibiotic resistance among bacteria is recognized as the primary factor contributing to the failure of treatment. In this research, our objective was to examine the...
Antibiotic resistance among bacteria is recognized as the primary factor contributing to the failure of treatment. In this research, our objective was to examine the prevalence of antibiotic resistance in H. pylori bacteria in Palestine. We enlisted 91 individuals suffering from dyspepsia, comprising 49 females and 42 males. These participants underwent esophagogastroduodenoscopy procedures with gastric biopsies. These biopsies were subsequently subjected to microbiological assessments and tested for their susceptibility to various antimicrobial drugs. Among the 91 patients, 38 (41.7%) exhibited the presence of H. pylori. Notably, Ciprofloxacin displayed the highest efficacy against H. pylori, followed by Levofloxacin, Moxifloxacin, and Amoxicillin, with resistance rates of 0%, 0%, 2.6%, and 18.4%, respectively. On the contrary, Metronidazole and Clarithromycin demonstrated the lowest effectiveness, with resistance percentages of 100% and 47.4%, respectively. The outcomes of this investigation emphasize that H. pylori strains within the Palestinian patient group exhibit substantial resistance to conventional first-line antibiotics like clarithromycin and metronidazole. However, alternative agents such as fluoroquinolones and amoxicillin remain efficacious choices. Consequently, we recommend favoring quinolone-based treatment regimens for H. pylori infections and adopting a more judicious approach to antibiotic usage among the Palestinian population.
Topics: Humans; Helicobacter pylori; Female; Male; Helicobacter Infections; Cross-Sectional Studies; Anti-Bacterial Agents; Adult; Prevalence; Middle Aged; Drug Resistance, Bacterial; Hospitals, University; Microbial Sensitivity Tests; Amoxicillin; Clarithromycin; Metronidazole; Levofloxacin
PubMed: 38914675
DOI: 10.1038/s41598-024-63982-0 -
European Journal of Pharmaceutical... Jun 2024The escalating challenges of Helicobacter pylori-induced gastric complications, driven by rising antibiotic resistance and persistent cancer risks, underscore the demand...
The escalating challenges of Helicobacter pylori-induced gastric complications, driven by rising antibiotic resistance and persistent cancer risks, underscore the demand for innovative therapeutic strategies. This study addresses this urgency through the development of tailored semi-interpenetrating polymer networks (semi-IPN) serving as gastroretentive matrices for amoxicillin (AMOX). They are biodegradable, absorb significant volume of simulated gastric fluid (swelling index > 360%) and exhibit superporous microstructures, remarkable mucoadhesion, and buoyancy. The investigation includes assessment at pH 1.2 for comparative analysis with prior studies and, notably, at pH 5.0, reflecting the acidic environment in H. pylori-infected stomachs. The semi-IPN demonstrated gel-like structures, maintaining integrity throughout the 24-hour controlled release study, and disintegrating upon completing their intended function. Evaluated in gastroretentive drug delivery system performance, AMOX release at pH 1.2 and pH 5.0 over 24 hours (10%-100%) employed experimental design methodology, elucidating dominant release mechanisms. Their mucoadhesive, buoyant, three-dimensional scaffold stability, and gastric biodegradability make them ideal for accommodating substantial AMOX quantities. Furthermore, exploring the inclusion of the potassium-competitive acid blocker (P-CAB) vonoprazan (VONO) in AMOX-loaded formulations shows promise for precise and effective drug delivery. This innovative approach has the potential to combat H. pylori infections, thereby preventing the gastric cancer induced by this pathogen.
PubMed: 38909691
DOI: 10.1016/j.ejps.2024.106840 -
BMC Oral Health Jun 2024Isaacs' syndrome, also known as neuromyotonia or peripheral nerve hyperexcitability, is a rare disorder that affects the peripheral nervous system. Clinical findings...
BACKGROUND
Isaacs' syndrome, also known as neuromyotonia or peripheral nerve hyperexcitability, is a rare disorder that affects the peripheral nervous system. Clinical findings include cramps, fasciculations, and myokymia; however, there are few reports of dental treatment for trismus.
CASE PRESENTATION
A patient with trismus due to Isaacs' syndrome experienced swelling and pain in the gingiva surrounding his right lower first molar. He was diagnosed with chronic apical periodontitis by a dentist near his home. However, the patient was informed that dental treatment and medication could not be administered because of the presence of Isaacs' syndrome, and he visited the Geriatric Dentistry and Perioperative Oral Care Center at Kyushu University Hospital 2 weeks later. The patient's painless mouth-opening distance (between incisors) was 20 mm at that time, and medication, including amoxicillin capsules and acetaminophen, was administered because the dental extraction forceps or endodontic instruments were difficult to insert into the oral cavity for treatment. Two months after his initial visit, the patient visited us complaining of pain in the same area. However, he had recently undergone plasmapheresis treatment in neurology to alleviate limited mouth opening and systemic myalgia, resulting in a pain-free mouth-opening distance of approximately 35 mm. During this temporary period in which he had no restriction in mouth opening, we performed tooth extraction and bridge restoration on the mandibular right first molar and created an oral appliance for sleep bruxism.
CONCLUSIONS
Plasmapheresis therapy transiently reduced trismus, rendering dental interventions feasible, albeit temporarily. This case report underscores the importance of close collaboration between neurologists and dentists who encounter similar cases while furnishing valuable insights to inform dental treatment planning.
Topics: Humans; Male; Trismus
PubMed: 38909199
DOI: 10.1186/s12903-024-04485-2 -
An evaluation of endodontic sealers and an antibiotic to assess their antimicrobial effect against .Biomaterial Investigations in Dentistry 2024This study aimed to compare the antimicrobial effect of three endodontic sealers (AH Plus, Mineral trioxide aggregate [MTA] Fillapex, and BioRoot RCS) with and without...
OBJECTIVE
This study aimed to compare the antimicrobial effect of three endodontic sealers (AH Plus, Mineral trioxide aggregate [MTA] Fillapex, and BioRoot RCS) with and without amoxicillin against .
METHODOLOGY
Amoxicillin, equivalent to 10% of the sealers' total weight, was mixed with the sealers. Another batch was prepared without amoxicillin. The direct contact test (DCT) and the agar diffusion test were used to assess the antibacterial effect. Results were analysed using one-way analysis of variance (ANOVA), the F-test, and the Kruskal-Wallis test.
RESULTS
AH Plus significantly suppressed without the addition of amoxicillin in the DCT (p = 0.011), while in the agar diffusion test, BioRoot RCS had a larger inhibition zone than the control (p < 0.001). When amoxicillin was added to the sealers, AH Plus (p = 0.003) and MTA Fillapex (p = 0.042) reduced growth. In contrast, all three sealers showed larger inhibition zones than the control (p = 0.001), with AH Plus displaying a larger inhibition zone than MTA Fillapex (p = 0.042) and BioRoot RCS (p = 0.032).
CONCLUSIONS
It was thus concluded that the addition of amoxicillin to endodontic sealers enhances their antimicrobial activity against .
PubMed: 38903776
DOI: 10.2340/biid.v11.40646 -
Frontiers in Nutrition 2024Managing severe acute malnutrition (SAM) involves an outpatient therapeutic program (OTP), targeting more than 80% of SAM children where the quality of primary...
BACKGROUND
Managing severe acute malnutrition (SAM) involves an outpatient therapeutic program (OTP), targeting more than 80% of SAM children where the quality of primary healthcare remains poor. Treatment success and recovery from SAM remain poor and could be affected by many factors, where such evidence is limited in East Hararghe. This study assessed the predictors of time to recovery from SAM in eastern Ethiopia.
METHODS
A retrospective cohort study was conducted on 402 records of SAM children under 5 years of age enrolled on OTP at 12 health posts retrieved from 2020 to 2021. We used the Kaplan-Meir estimate along with the -value of the log-rank test and the survival curve to compare the time to recovery across categories. A multivariable Cox proportional hazard model was fitted to identify predictors of time to recovery from SAM. A -value below 0.05 was used to declare statistical significance.
RESULTS
A total of 402 records were reviewed, and the cure rate from SAM was 89.6% [95% confidence interval (CI), 87-93]. Moreover, a death rate of 0.7%, a default rate of 9.5%, and a non-responder rate of 0.2% were obtained with a median length of stay of 7 weeks. The median time to recovery was significantly shorter for children from shorter distances from OTP sites with edema, amoxicillin, ( < 0.05). Edema at admission [adjusted hazard ratio (AHR) = 1.74; 95% CI: 1.33-2.29], without diarrhea (AHR = 1.51; 95% CI: 1.18-1.94), taking amoxicillin (AHR = 1.55; 95% CI: 1.19-2.02), shorter travel time to the OTP site (AHR = 1.44; 95% CI: 1.13-1.85), breastfeeding (AHR = 1.60; 95% CI: 1.27-2.02), adequacy of ready-to-use therapeutic food (RUTF) (AHR = 1.22; 95% CI: 0.90-1.65), and new admission (AHR = 1.62; 95% CI: 0.84-3.10) were important predictors of recovery from SAM.
CONCLUSION
Recovery from SAM was found to be acceptable in comparison with the Sphere Standards and is predicted by edema, diarrhea, distance from the OTP site, amoxicillin, and RUTF adequacy. These allow for focused interventions that address the identified factors for better recovery from SAM.
PubMed: 38903630
DOI: 10.3389/fnut.2024.1275943 -
Research Square May 2024The uptake and elimination of beta-lactam antibiotics in the human body are facilitated by the proton-coupled peptide transporters PepT1 (SLC15A1) and PepT2 (SLC15A2)....
The uptake and elimination of beta-lactam antibiotics in the human body are facilitated by the proton-coupled peptide transporters PepT1 (SLC15A1) and PepT2 (SLC15A2). The mechanism by which SLC15 family transporters recognize and discriminate between different drug classes and dietary peptides remains unclear, hampering efforts to improve antibiotic pharmacokinetics through targeted drug design and delivery. Here, we present cryo-EM structures of the mammalian proton-coupled peptide transporter, PepT2, in complex with the widely used beta-lactam antibiotics cefadroxil, amoxicillin and cloxacillin. Our structures, combined with pharmacophore mapping, molecular dynamics simulations and biochemical assays, establish the mechanism of antibiotic recognition and the important role of protonation in drug binding and transport.
PubMed: 38903084
DOI: 10.21203/rs.3.rs-4435259/v1 -
World Journal of Clinical Cases Jun 2024() eradication rates have fallen globally, likely in large part due to increasing antibiotic resistance to traditional therapy. In areas of high clarithromycin and...
BACKGROUND
() eradication rates have fallen globally, likely in large part due to increasing antibiotic resistance to traditional therapy. In areas of high clarithromycin and metronidazole resistance such as ours, Maastricht VI guidelines suggest high dose amoxicillin dual therapy (HDADT) can be considered, subject to evidence for local efficacy. In this study we assess efficacy of HDADT therapy for eradication in an Irish cohort.
AIM
To assess the efficacy of HDADT therapy for eradication in an Irish cohort as both first line, and subsequent therapy for patients diagnosed with .
METHODS
All patients testing positive for in a tertiary centre were treated prospectively with HDADT (amoxicillin 1 g and esomeprazole 40 mg × 14 d) over a period of 8 months. Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy. A delta-over-baseline > 4% was considered positive. Patient demographics and treatment outcomes were recorded, analysed and controlled for basic demographics and prior treatment.
RESULTS
One hundred and ninety-eight patients were identified with infection, 10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing. In all 139 were included in the analysis, 55% ( = 76) were female, mean age was 46.6 years. Overall, 93 (67%) of patients were treatment-naïve and 46 (33%) had received at least one previous course of treatment. The groups were statistically similar. Self-reported compliance with HDADT was 97%, mild side-effects occurred in 7%. There were no serious adverse drug reactions. Overall the eradication rate for our cohort was 56% (78/139). Eradication rates were worse for those with previous treatment [43% (20/46) 62% (58/93), = 0.0458, odds ratio = 2.15]. Age and Gender had no effect on eradication status.
CONCLUSION
Overall eradication rates with HDADT were disappointing. Despite being a simple and possibly better tolerated regime, these results do not support its routine use in a high dual resistance country. Further investigation of other regimens to achieve the > 90% eradication target is needed.
PubMed: 38899284
DOI: 10.12998/wjcc.v12.i16.2773