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Medicine Dec 2022It is estimated that up to 90% of head and neck infections have an odontogenic origin, which are considered among the most common in the oral cavity and maxillofacial...
BACKGROUND
It is estimated that up to 90% of head and neck infections have an odontogenic origin, which are considered among the most common in the oral cavity and maxillofacial region. Bacterial resistance has been 1 of the main problems related to the treatment of this type of infection in recent years. The frequency of this resistance is increasing, which is mainly due to patient self-medication and the mutations that bacteria present. Therefore, the objective of this study is to analyze the antimicrobial resistance of antibiotics commonly administered for the treatment of odontogenic infections.
METHOD
To carry out the study, PubMed, ScienceDirect, and Scopus databases were reviewed using the keywords "odontogenic infection", "pharmacological treatment", and "microbial resistance. Studies whose main objective was the pharmacological treatment of odontogenic infections were selected. Exclusions were review-type studies, systematic reviews, or in vitro or animal model studies. For the analysis of risk of bias, the Checklist for Analytical Cross-Sectional Studies of the Joanna Briggs Institute was used. The search and analysis of the studies was carried out by 2 researchers independently.
RESULTS
A total of 13 studies were included in this review. The mean age was 39.6 years; the location of the infection in the study subjects was in the submandibular and vestibular spaces; there were periodontal, periapical, and dentoalveolar lesions; the main microorganisms identified were Streptococcus, Staphylococcus, Prevotella, Peptostreptococcus, Clostridium, and Klebsiella; and finally, the main microorganisms identified for bacterial resistance were penicillin, clindamycin and amoxicillin.
CONCLUSION
The health professional is obliged to update their knowledge to avoid such antibiotic resistance and thus provide better patient care.
Topics: Humans; Anti-Bacterial Agents; Cross-Sectional Studies; Drug Resistance, Bacterial; Bacterial Infections; Amoxicillin; Microbial Sensitivity Tests; Review Literature as Topic
PubMed: 36550913
DOI: 10.1097/MD.0000000000031345 -
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 -
The Journal of Antimicrobial... Sep 2023Pharmacokinetic (PK) data underlying paediatric penicillin dosing remain limited, especially in critical care.
The Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA): investigating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin pharmacokinetics from birth to adolescence.
BACKGROUND
Pharmacokinetic (PK) data underlying paediatric penicillin dosing remain limited, especially in critical care.
OBJECTIVES
The primary objective of the Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA) was to characterize PK profiles of commonly used penicillins using data obtained during routine care, to further understanding of PK variability and inform future evidence-based dosing.
METHODS
NAPPA was a multicentre study of amoxicillin, co-amoxiclav, benzylpenicillin, flucloxacillin and piperacillin/tazobactam. Patients were recruited with informed consent. Antibiotic dosing followed standard of care. PK samples were obtained opportunistically or at optimal times, frozen and analysed using UPLC with tandem MS. Pharmacometric analysis was undertaken using NONMEM software (v7.3). Model-based simulations (n = 10 000) tested PTA with British National Formulary for Children (BNFC) and WHO dosing. The study had ethical approval.
RESULTS
For the combined IV PK model, 963 PK samples from 370 participants were analysed simultaneously incorporating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin data. BNFC high-dose regimen simulations gave these PTA results (median fT>MIC at breakpoints of specified pathogens): amoxicillin 100% (Streptococcus pneumoniae); benzylpenicillin 100% (Group B Streptococcus); flucloxacillin 48% (MSSA); and piperacillin 100% (Pseudomonas aeruginosa). Oral population PK models for flucloxacillin and amoxicillin enabled estimation of first-order absorption rate constants (1.16 h-1 and 1.3 h-1) and bioavailability terms (62.7% and 58.7%, respectively).
CONCLUSIONS
NAPPA represents, to our knowledge, the largest prospective combined paediatric penicillin PK study undertaken to date, and the first paediatric flucloxacillin oral PK model. The PTA results provide evidence supportive of BNFC high-dose IV regimens for amoxicillin, benzylpenicillin and piperacillin.
Topics: Infant, Newborn; Humans; Child; Adolescent; Piperacillin; Floxacillin; Amoxicillin; Prospective Studies; Anti-Bacterial Agents; Penicillins; Microbial Sensitivity Tests
PubMed: 37531085
DOI: 10.1093/jac/dkad196 -
MBio Feb 2022Mycobacterium abscessus () infections are a growing menace to the health of many patients, especially those suffering from structural lung disease and cystic fibrosis....
Mycobacterium abscessus () infections are a growing menace to the health of many patients, especially those suffering from structural lung disease and cystic fibrosis. With multidrug resistance a common feature and a growing understanding of peptidoglycan synthesis in , it is advantageous to identify potent β-lactam and β-lactamase inhibitor combinations that can effectively disrupt cell wall synthesis. To improve existing therapeutic regimens to address serious infections, we evaluated the ability of durlobactam (DUR), a novel diazobicyclooctane β-lactamase inhibitor to restore susceptibilities in combination with β-lactams and provide a biochemical rationale for the activity of this compound. In cell-based assays, susceptibility of subsp. isolates to amoxicillin (AMOX), imipenem (IMI), and cefuroxime (CXM) was significantly enhanced with the addition of DUR. The triple drug combinations of CXM-DUR-AMOX and IMI-DUR-AMOX were most potent, with MIC ranges of ≤0.06 to 1 μg/mL and an MIC/MIC of ≤0.06/0.25 μg/mL, respectively. We propose a model by which this enhancement may occur, DUR potently inhibited the β-lactamase Bla with a relative Michaelis constant ( ) of 4 × 10 ± 0.8 × 10μM and acylation rate (/) of 1 × 10 M s. Timed mass spectrometry captured stable formation of carbamoyl-enzyme complexes between DUR and Ldt and d,d-carboxypeptidase, potentially contributing to the intrinsic activity of DUR. Molecular modeling showed unique and favorable interactions of DUR as a Bla inhibitor. Similarly, modeling showed how DUR might form stable Michaelis-Menten complexes with Ldt and d,d-carboxypeptidase. The ability of DUR combined with amoxicillin or cefuroxime and imipenem to inactivate multiple targets such as d,d-carboxypeptidase and Ldt supports new therapeutic approaches using β-lactams in eradicating . Durlobactam (DUR) is a potent inhibitor of Bla and provides protection of amoxicillin and imipenem against hydrolysis. DUR has intrinsic activity and forms stable acyl-enzyme complexes with Ldt and Ldt. The ability of DUR to protect amoxicillin and imipenem against Bla and its intrinsic activity along with the dual β-lactam target redundancy can explain the rationale behind the potent activity of this combination.
Topics: Humans; beta-Lactams; beta-Lactamase Inhibitors; Anti-Bacterial Agents; Mycobacterium abscessus; Cefuroxime; Microbial Sensitivity Tests; Imipenem; Amoxicillin; beta-Lactamases
PubMed: 35073757
DOI: 10.1128/mbio.03529-21 -
Molecules (Basel, Switzerland) Mar 2020This work aimed to develop accurate, quick, and practical tools for the detection of residues of penicillin G antibiotic in biological and non-biological samples. The...
This work aimed to develop accurate, quick, and practical tools for the detection of residues of penicillin G antibiotic in biological and non-biological samples. The assays were developed based on the binding mechanism of -lactam to penicillin-binding proteins; samples of different concentrations of penicillin G were incubated with in vitro expressed 6X-Histidine-tagged soluble penicillin-binding protein (PBP2x*) of (), whereby penicillin G in samples specifically binds to PBP2x*. The fluorescent-labeled -lactam analogue Bocillin FL was used as a competent substrate, and two different routes estimated the amounts of the penicillin G. The first route was established based on the differences in the concentration of non-bounded Bocillin FL molecules within the reactions while using a real-time polymerase chain reaction (PCR)-based method for fluorescence detection. The second route depended on the amount of the relative intensity of Bocillin FL bounded to Soluble PBP-2x*, being run on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-page), visualized by a ChemiDoc-It2 Imager, and quantified based on the fluorescence affinity of the competent substrate. While both of the methods gave a broad range of linearity and high sensitivity, the on column based real-time method is fast, non-time consuming, and highly sensitive. The method identified traces of antibiotic in the range 0.01-0.2 nM in addition to higher accuracy in comparison to the SDS-based detection method, while the sensitivity of the SDS-based method ranged between 0.015 and 2 µM). Thus, the on column based real time assay is a fast novel method, which was developed for the first time based on the binding inhibition of a fluorescence competitor material and it can be adapted to screen traces of penicillin G in any biological and environmental samples.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Biosensing Techniques; Boron Compounds; Microbial Sensitivity Tests; Penicillin-Binding Proteins; Penicillins; Streptococcus pneumoniae; beta-Lactams
PubMed: 32164217
DOI: 10.3390/molecules25051248 -
Microbiology Spectrum Dec 2021Lyme disease (LD) is a heavy public health burden. The most common manifestations of LD include erythema migrans (EM), Lyme neuroborreliosis (LNB), and Lyme arthritis... (Meta-Analysis)
Meta-Analysis
Lyme disease (LD) is a heavy public health burden. The most common manifestations of LD include erythema migrans (EM), Lyme neuroborreliosis (LNB), and Lyme arthritis (LA). The efficacy and safety of antibiotics for treating LD is still controversial. Thus, we performed a network meta-analysis (NMA) to obtain more data and tried to solve this problem. We searched studies in the databases of Embase and PubMed from the date of their establishments until 22 April 2021. Odds ratios (ORs) were used to assess dichotomous outcomes. A total of 31 randomized controlled trials (RCTs) involving 2,748 patients and 11 antibiotics were included. Oral amoxicillin (1.5 g/day), oral azithromycin (0.5 g/day), injectable ceftriaxone, and injectable cefotaxime were effective for treating LD (range of ORs, 1.02 to 1,610.43). Cefuroxime and penicillin were safe for treating LD (range of ORs, 0.027 to 0.98). Amoxicillin was effective for treating EM (range of ORs, 1.18 to 25.66). Based on the results, we thought oral amoxicillin (1.5 g/day), oral azithromycin (0.5 g/day), injectable ceftriaxone, and injectable cefotaxime were effective for treating LD. Cefuroxime and penicillin were safe for treating LD. Amoxicillin was effective for treating EM. We did not observe evidence proving the advantage of doxycycline in efficacy and safety for treating LD, LA, LNB, and EM of children or adults. We did not have sufficient data to prove the significant difference of efficacy for treating LA and LNB in adults and LD in children, the significant difference of safety of oral drugs for treating LD, and the significant difference of safety of drugs for treating EM. Some previous studies investigated the efficacy and safety of antibiotics for treating Lyme disease (LD). However, due to technical limitations, several questions regarding the routes of drug administration and the dosages of drug are still unclear, which might be causing problems for clinicians. Hence, we performed network meta-analysis (NMA) to quantitatively analyze the clinical data published during the last 40 years. Here, we demonstrate the evidence regarding the efficacy and safety of antibiotics commonly used for treating LD in adults and children. We found that amoxicillin, azithromycin, ceftriaxone, and cefotaxime were effective for treating LD, but we did not observe significant efficacy and safety of doxycycline for treating LD.
Topics: Administration, Oral; Adult; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Borrelia burgdorferi; Borrelia burgdorferi Group; Cefotaxime; Ceftriaxone; Child; Doxycycline; Humans; Injections; Lyme Disease; Network Meta-Analysis; Penicillins
PubMed: 34756070
DOI: 10.1128/Spectrum.00761-21 -
BMC Cardiovascular Disorders Feb 2022Ethiopia has a high acute rheumatic fever (ARF) and rheumatic heart disease (RHD) prevalence, and to our knowledge, there are no data on the status of secondary...
BACKGROUND
Ethiopia has a high acute rheumatic fever (ARF) and rheumatic heart disease (RHD) prevalence, and to our knowledge, there are no data on the status of secondary prevention in children with RHD. This study describes the status of secondary RHD prevention.
METHODS
A multicenter, prospective study was performed on children aged 5-17 years with RHD in Ethiopia. Good adherence was defined as at least 80% completion of benzathine penicillin (BPG) or oral Amoxicillin within the previous year. The primary outcome measure was adherence to prophylaxis, expressed as a proportion. Socio-demographics, severity of RHD, and ARF recurrence were evaluated.
RESULTS
A total of 337 children with a mean age of 12.9 ± 2.6 years were included. The majority (73%) had severe aortic/mitral disease. Participants were on BPG (80%) or Amoxicillin (20%) prophylaxis. Female sex (P = 0.04) use of BPG (0.03) and shorter mean duration of prophylaxis in months (48.5 ± 31.5 vs. 60.7 ± 33, respectively, P < 0.008) predicted good adherence. Running out of medications (35%), interrupted follow-up (27%), and the COVID-19 pandemic (26%) were the most common reasons for missing prophylaxis. Recurrence of ARF was higher in participants on Amoxicillin compared with BPG (40% vs. 16%, P < 0.001) and in those with poor adherence compared with good adherence (36.8% vs. 17.9%, respectively, P = 0.005). Type and duration of prophylaxis (OR 0.5, CI = 0.24, 0.9, P = 0.02; OR = 1.1, CI = 1.1, 1.2, P = 0.04, respectively), and sex (OR = 1.9, CI = 1.1, 3.4, P = 0.03) were independent predictors of poor adherence.
CONCLUSION
Poor adherence is prevalent in Ethiopian children living with RHD. Amoxicillin is a suboptimal option for prophylaxis as its use is associated with lower adherence and a higher rate of ARF recurrence.
Topics: Adolescent; Amoxicillin; Anti-Bacterial Agents; Child; Child, Preschool; Ethiopia; Female; Humans; Male; Medication Adherence; Penicillin G Benzathine; Prevalence; Prospective Studies; Recurrence; Rheumatic Heart Disease; Risk Assessment; Risk Factors; Secondary Prevention; Time Factors; Treatment Outcome
PubMed: 35109807
DOI: 10.1186/s12872-022-02473-4 -
Pediatrics Oct 2022Necrotizing enterocolitis (NEC) is a severe intestinal inflammatory disease and a leading cause of morbidity and mortality in NICUs. Management of NEC is variable...
OBJECTIVES
Necrotizing enterocolitis (NEC) is a severe intestinal inflammatory disease and a leading cause of morbidity and mortality in NICUs. Management of NEC is variable because of the lack of evidence-based recommendations. It is widely accepted that standardization of patient care leads to improved outcomes. This quality improvement project aimed to decrease variation in the evaluation and management of NEC in a Level IV NICU.
METHODS
A multidisciplinary team investigated institutional variation in NEC management and developed a standardized guideline and electronic medical record tools to assist in evaluation and management. Retrospective baseline data were collected for 2 years previously and prospectively for 3.5 years after interventions. Outcomes included the ratio of observed-to-expected days of antibiotics and nil per os (NPO) on the basis of the novel guidelines and the percentage of cases treated with piperacillin/tazobactam. Balancing measures were death, surgery, and antifungal use.
RESULTS
Over 5.5 years, there were 124 evaluations for NEC. Special cause variation was noted in the observed-to-expected antibiotic and NPO days ratios, decreasing from 1.94 to 1.18 and 1.69 to 1.14, respectively. Piperacillin/tazobactam utilization increased from 30% to 91%. There were no increases in antifungal use, surgery, or death.
CONCLUSIONS
Variation in evaluation and management of NEC decreased after initiation of a guideline and supporting electronic medical record tools, with fewer antibiotic and NPO days without an increase in morbidity or mortality. A quality improvement approach can benefit patients and decrease variability, even in diseases with limited evidence-based standards.
Topics: Anti-Bacterial Agents; Antifungal Agents; Enterocolitis, Necrotizing; Female; Fetal Diseases; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intensive Care Units, Neonatal; Piperacillin; Retrospective Studies; Tazobactam
PubMed: 36164852
DOI: 10.1542/peds.2022-056616 -
Scientific Reports Jul 2023The dysbiotic biofilm of periodontitis may function as a reservoir for opportunistic human pathogens of clinical relevance. This study explored the virulence and...
The dysbiotic biofilm of periodontitis may function as a reservoir for opportunistic human pathogens of clinical relevance. This study explored the virulence and antimicrobial susceptibility of staphylococci isolated from the subgingival biofilm of individuals with different periodontal conditions. Subgingival biofilm was obtained from 142 individuals with periodontal health, 101 with gingivitis and 302 with periodontitis, and cultivated on selective media. Isolated strains were identified by mass spectrometry. Antimicrobial susceptibility was determined by disk diffusion. The mecA and virulence genes were surveyed by PCR. Differences among groups regarding species, virulence and antimicrobial resistance were examined by Chi-square, Kruskal-Wallis or Mann-Whitney tests. The overall prevalence of subgingival staphylococci was 46%, especially in severe periodontitis (> 60%; p < 0.01). S. epidermidis (59%) and S. aureus (22%) were the predominant species across groups. S. condimenti, S. hominis, S. simulans and S. xylosus were identified only in periodontitis. High rates of resistance/reduced sensitivity were found for penicillin (60%), amoxicillin (55%) and azithromycin (37%), but multidrug resistance was observed in 12% of the isolates. Over 70% of the mecA + strains in periodontitis were isolated from severe disease. Higher detection rates of fnB + isolates were observed in periodontitis compared to health and gingivitis, whereas luxF/luxS-pvl + strains were associated with sites with deep pockets and attachment loss (p < 0.05). Penicillin-resistant staphylococci is highly prevalent in the subgingival biofilm regardless of the periodontal status. Strains carrying virulence genes related to tissue adhesion/invasion, inflammation and cytotoxicity support the pathogenic potential of these opportunists in the periodontal microenvironment.
Topics: Humans; Staphylococcus; Anti-Bacterial Agents; Staphylococcus aureus; Virulence; Drug Resistance, Bacterial; Periodontitis; Amoxicillin; Staphylococcus epidermidis; Gingivitis; Microbial Sensitivity Tests
PubMed: 37463947
DOI: 10.1038/s41598-023-38599-4 -
Environmental Science and Pollution... Dec 2022Farms utilizing sewage sludge and manure in their agronomic plant production are recognized as potential hotspots for environmental release of antibiotics and the...
Farms utilizing sewage sludge and manure in their agronomic plant production are recognized as potential hotspots for environmental release of antibiotics and the resulting promotion of antibiotic resistance. As part of the circular economy, the use of biogas digestates for soil fertilizing is steadily increasing, but their potential contribution to the spreading of pharmaceutical residues is largely unknown. Digestates can be produced from a variety of biowaste resources, including sewage sludge, manure, food waste, and fish ensilage. We developed a method for the detection of 17 antibiotics and 2 steroid hormones and applied the method to detect pharmaceutical residues in digestates from most municipal biogas plants in Norway, covering a variety of feedstocks. The detection frequency and measured levels were overall low for most compounds, except a few incidents which cause concern. Specifically, relatively high levels of amoxicillin, penicillin G, ciprofloxacin, and prednisolone were detected in different digestates. Further, ipronidazole was detected in four digestates, although no commercial pharmaceutical products containing ipronidazole are currently registered in Norway. A simplified risk assessment showed a high risk for soil microorganisms and indicates the tendency for antibiotic-resistant bacteria for penicillin G and amoxicillin. For prednisolone and ipronidazole; however, no toxicity data is available for reliable risk assessments.
Topics: Animals; Biofuels; Manure; Sewage; Anti-Bacterial Agents; Food; Ipronidazole; Refuse Disposal; Soil; Steroids; Amoxicillin; Prednisolone; Pharmaceutical Preparations; Anaerobiosis
PubMed: 35796924
DOI: 10.1007/s11356-022-21479-1