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Bone Concentration of Ampicillin/Sulbactam: A Pilot Study in Patients with Osteonecrosis of the Jaw.International Journal of Environmental... Nov 2022Osteonecrosis of the jaw (ONJ) occurs typically after irradiation of the head and neck area or after the intake of antiresorptive agents. Both interventions can lead to...
Osteonecrosis of the jaw (ONJ) occurs typically after irradiation of the head and neck area or after the intake of antiresorptive agents. Both interventions can lead to compromised bone perfusion and can ultimately result in infection and necrosis. Treatment usually consists of surgical necrosectomy and prolonged antibiotic therapy, usually through beta-lactams such as ampicillin/sulbactam. The poor blood supply in particular raises the question as to whether this form of antibiosis can achieve sufficient concentrations in the bone. Therefore, we investigated the antibiotic concentration in plasma and bone samples in a prospective study. Bone samples were collected from the necrosis core and in the vital surrounding bone. The measured concentrations in plasma for ampicillin and sulbactam were 126.3 ± 77.6 and 60.2 ± 35.0 µg/mL, respectively. In vital bone and necrotic bone samples, the ampicillin/sulbactam concentrations were 6.3 ± 7.8/1.8 ± 2.0 µg/g and 4.9 ± 7.0/1.7 ± 1.7 µg/g, respectively. These concentrations are substantially lower than described in the literature. However, the concentration seems sufficient to kill most bacteria, such as and , which are mostly present in the biofilm of ONJ. We, therefore, conclude that intravenous administration of ampicillin/sulbactam remains a valuable treatment in the therapy of ONJ. Nevertheless, increasing resistance of towards beta-lactam antibiotics have been reported and should be considered.
Topics: Humans; Sulbactam; Pilot Projects; Prospective Studies; Ampicillin; Anti-Bacterial Agents; Osteonecrosis; Escherichia coli
PubMed: 36429636
DOI: 10.3390/ijerph192214917 -
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 -
The Turkish Journal of Pediatrics 2023Acute otitis media (AOM) is the inflammation of the middle ear. It constitutes one of the most frequent infections which affects children and usually occurs between 6 to... (Review)
Review
BACKGROUND
Acute otitis media (AOM) is the inflammation of the middle ear. It constitutes one of the most frequent infections which affects children and usually occurs between 6 to 24 months of age. AOM can emerge due to viruses and/or bacteria. The aim of the current systematic review is to assess in children between 6 months and 12 years of age with AOM, the efficacy of any antimicrobial agent or placebo compared with amoxicillinclavulanate, to measure the resolution of AOM or symptoms.
METHODS
The medical databases PubMed (MEDLINE) and Web of Science were used. Data extraction and analysis were performed by two independent reviewers. Eligibility criteria were set, and only randomised control trials (RCTs) were included. Critical appraisal of the eligible studies was performed. Pooled analysis was conducted using the Review Manager v. 5.4.1 software (RevMan).
RESULTS
Twelve RCTs were totally included. Three (25.0%) RCTs studied the impact of azithromycin, two (16.7%) investigated the impact of cefdinir, two (16.7%) investigated placebo, three (25.0%) studied quinolones, one (8.3%) investigated cefaclor and one (8.3%) studied penicillin V, compared to amoxicillin-clavulanate. In five (41.7%) RCTs, amoxicillin-clavulanate proved to be superior to azithromycin, cefdinir, placebo, cefaclor and penicillin V, while in seven (58.3%) RCTs its efficacy was comparable with other antimicrobials or placebo. The rates of AOM relapse after treatment with amoxicillin-clavulanate were comparable to those of other antimicrobials or placebo. However, amoxicillin-clavulanate was more effective in eradicating Streptococcus pneumoniae from the culture, when compared to cefdinir. The results of the meta-analysis were not evaluated due to substantial heterogeneity between studies.
CONCLUSIONS
Amoxicillin-clavulanate should be the treatment of choice for children between 6 months and 12 years of age with AOM.
Topics: Child; Humans; Infant; Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Cefaclor; Cefdinir; Otitis Media; Penicillin V; Treatment Outcome
PubMed: 37395955
DOI: 10.24953/turkjped.2022.893 -
Critical Care (London, England) Jun 2023In recent years, numerous dosing studies have been conducted to optimize therapeutic antibiotic exposures in patients with serious infections. These studies have led to...
BACKGROUND
In recent years, numerous dosing studies have been conducted to optimize therapeutic antibiotic exposures in patients with serious infections. These studies have led to the inclusion of dose optimization recommendations in international clinical practice guidelines. The last international survey describing dosing, administration and monitoring of commonly prescribed antibiotics for critically ill patients was published in 2015 (ADMIN-ICU 2015). This study aimed to describe the evolution of practice since this time.
METHODS
A cross-sectional international survey distributed through professional societies and networks was used to obtain information on practices used in the dosing, administration and monitoring of vancomycin, piperacillin/tazobactam, meropenem and aminoglycosides.
RESULTS
A total of 538 respondents (71% physicians and 29% pharmacists) from 409 hospitals in 45 countries completed the survey. Vancomycin was mostly administered as an intermittent infusion, and loading doses were used by 74% of respondents with 25 mg/kg and 20 mg/kg the most favoured doses for intermittent and continuous infusions, respectively. Piperacillin/tazobactam and meropenem were most frequently administered as an extended infusion (42% and 51%, respectively). Therapeutic drug monitoring was undertaken by 90%, 82%, 43%, and 39% of respondents for vancomycin, aminoglycosides, piperacillin/tazobactam, and meropenem, respectively, and was more frequently performed in high-income countries. Respondents rarely used dosing software to guide therapy in clinical practice and was most frequently used with vancomycin (11%).
CONCLUSIONS
We observed numerous changes in practice since the ADMIN-ICU 2015 survey was conducted. Beta-lactams are more commonly administered as extended infusions, and therapeutic drug monitoring use has increased, which align with emerging evidence.
Topics: Humans; Adult; Anti-Bacterial Agents; Vancomycin; Meropenem; Cross-Sectional Studies; Piperacillin, Tazobactam Drug Combination; Surveys and Questionnaires; Intensive Care Units; Aminoglycosides; Critical Illness; Piperacillin
PubMed: 37331935
DOI: 10.1186/s13054-023-04527-1 -
BMC Infectious Diseases Jul 2021Oral beta-lactam antimicrobials are not routinely tested against Streptococcus pneumoniae due to presumed susceptibility based upon penicillin minimum inhibitory...
BACKGROUND
Oral beta-lactam antimicrobials are not routinely tested against Streptococcus pneumoniae due to presumed susceptibility based upon penicillin minimum inhibitory concentration (MIC) testing. Currently, Clinical and Laboratory Standards Institute provides comments to use penicillin MIC ≤0.06 to predict oral cephalosporin susceptibility. However, no guidance is provided when cefotaxime MIC is known, leading to uncertainty with interpretation. The purpose of this study was to evaluate cefotaxime and penicillin MICs and their respective correlation to oral beta-lactam categorical susceptibility patterns.
METHODS
249 S. pneumoniae isolates were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-ToF) and then tested by broth microdilution method to penicillin, cefotaxime, amoxicillin, cefdinir, cefpodoxime, and cefuroxime.
RESULTS
Using Clinical and Laboratory Standards Institute (CLSI) non-meningitis breakpoints for cefotaxime, 240/249 isolates were classified as susceptible. Of the cefotaxime susceptible isolates, 23% of the isolates are misrepresented as cefdinir susceptible. Amoxicillin correlated well with penicillin MIC breakpoints with only 1 discordant isolate out of 249.
CONCLUSION
The correlation between amoxicillin and penicillin creates a very reliable predictor to determine categorical susceptibility. However oral cephalosporins were not well predicted by either penicillin or cefotaxime leading to the possible risk of treatment failures. Caution should be used when transitioning to oral cephalosporins in cefotaxime susceptible isolates, especially with higher cefotaxime MICs.
Topics: Administration, Oral; Amoxicillin; Anti-Bacterial Agents; Cefotaxime; Cephalosporins; Humans; Microbial Sensitivity Tests; Penicillins; Pneumonia, Pneumococcal; Streptococcus pneumoniae; beta-Lactams
PubMed: 34256734
DOI: 10.1186/s12879-021-06341-y -
BMJ Open Quality Jul 2022Patients with self-reported antibiotic allergies have a higher cost of care, more frequent infections with resistant bacteria and worse health outcomes than patients...
BACKGROUND
Patients with self-reported antibiotic allergies have a higher cost of care, more frequent infections with resistant bacteria and worse health outcomes than patients without antibiotic allergies. Ultimately, less than 5% of patients who report a penicillin allergy have a clinically significant immune-mediated hypersensitivity reaction when tested. As 10%-30% of the population of pregnant patients are colonised for group B (GBS) and guidelines recommend penicillin as the treatment of choice for GBS, current recommendations support penicillin allergy testing in pregnant patients who report an allergy.
METHODS AND INTERVENTION
In this quality improvement project, nursing staff used an algorithm outlining inclusion and exclusion criteria to determine which patients were eligible to have penicillin allergy testing completed. Penicillin allergy testing consisted of a skin test using benzylpenicilloyl polylysine (Pre-Pen), penicillin G potassium, amoxicillin and alkaline hydrolysis mix (penicilloate) as a prick skin test, followed by intradermal skin test and finally an oral challenge with either amoxicillin or penicillin. Patient outcomes were analysed to evaluate the impact of the intervention.
RESULTS
Of the 1266 patients receiving prenatal care during the intervention, 236 (19%) reported a history of penicillin allergy, and 212 if these were eligible for testing. 150 of the eligible patients were offered penicillin allergy testing. 101 patients (67%) completed testing and 49 (33%) declined testing. Seven patients (7%) had positive penicillin allergy testing, while 94 patients (93%) had negative penicillin allergy testing and were immediately de-labelled as penicillin allergic. Seventeen of the de-labelled patients subsequently tested positive for GBS colonisation, and all received intrapartum penicillin without adverse events.
CONCLUSIONS
Pursuing penicillin allergy testing for pregnant patients with reported penicillin allergy is a safe and feasible approach, allowing for allergy de-labelling and safe, guideline-driven antimicrobial therapy during subsequent labour and delivery hospitalisations. Cost-effectiveness of the allergy testing and impact on later episodes of care should be further investigated.
Topics: Amoxicillin; Anti-Bacterial Agents; Drug Hypersensitivity; Female; Humans; Penicillins; Pregnancy; Skin Tests
PubMed: 35906008
DOI: 10.1136/bmjoq-2022-001859 -
Research in Social & Administrative... Aug 2023Antimicrobial resistance (AMR) is a global healthcare challenge that governments and health systems are tackling primarily through antimicrobial stewardship (AMS). This...
Antimicrobial resistance (AMR) is a global healthcare challenge that governments and health systems are tackling primarily through antimicrobial stewardship (AMS). This should, improve antibiotic use, avoid inappropriate prescribing, reduce prescription numbers, aligning with national/international AMS targets. In primary care in the United Kingdom (UK) antibiotics are mainly prescribed for patients with urinary and respiratory symptoms (22.7% and 46% of all antibiotic prescriptions respectively). This study aimed to capture the time-series trends (2014-2022) for commonly prescribed antibiotics for respiratory and urinary tract infections in primary care in England. Trends for Amoxicillin, Amoxicillin sodium, Trimethoprim, Clarithromycin, Erythromycin, Erythromycin ethylsuccinate, Erythromycin stearate, Doxycycline hyclate, Doxycycline monohydrate and Phenoxymethylpenicillin (Penicillin V) were determined. In doing so providing evidence regarding meeting UK antibiotic prescribing rate objectives (a 15% reduction in human antibiotic use 2019-2024). Time series trend analysis of 62,949,272 antibiotic prescriptions from 6,370 General Practices in England extracted from the National Health Service (NHS) Business Services Authority web portal were explored. With additional investigation of prescribing rate trends by quintiles of the Index of Multiple Deprivation (IMD). Overall, there is a downwards trend in antibiotic prescribing for those explored. There is an association between IMD, geographical location, and higher antibiotic prescribing levels (prescribing hot spots). England has a well-documented North-South divide of health inequalities, this is reflected in antibiotic prescribing. The corona virus pandemic (COVID-19) impacted on AMS, with a rise in doxycycline and trimethoprim prescriptions notable in higher IMD areas. Since then, prescribing appears to have returned to pre-pandemic levels in all IMDs and continued to decline. AMS efforts are being adhered to in primary care in England. This study provides further evidence of the link between locality and poorer health outcomes (reflected in higher antibiotic prescribing). Further work is required to address antibiotic use in hot spot areas.
Topics: Humans; Anti-Bacterial Agents; State Medicine; COVID-19; Amoxicillin; Doxycycline; Inappropriate Prescribing; Penicillin V; Trimethoprim; Erythromycin; Primary Health Care; Practice Patterns, Physicians'
PubMed: 37183105
DOI: 10.1016/j.sapharm.2023.05.001 -
Revista Medica de Chile Mar 2021National rates of HIV, gonorrhoeae and syphilis have increased in Chile in recent years, but it is not known if syphilis among pregnant women (PW) is also escalating.
BACKGROUND
National rates of HIV, gonorrhoeae and syphilis have increased in Chile in recent years, but it is not known if syphilis among pregnant women (PW) is also escalating.
AIM
To explore syphilis rates among PW in a southern Chilean region and to describe clinical features of mothers and offspring.
PATIENTS AND METHODS
We selected PW with positive VDRL or T. pallidum micro-he-magglutination (MHA-TP) reactive tests, referred to a high-risk obstetrical pathology center between 2011 and 2019. Clinical information of mothers and their offspring was obtained from their medical records.
RESULTS
Syphilis rates among PW increased from 0.4 to 7.2 per 1,000 live births in the reference center from 2013 to 2019, along with a national and regional increase in both sexes. Twenty-nine cases of PW with syphilis were identified with a median age of 28 years (interquartile range 23-32). Seventeen percent had a history of drug abuse, and 14% had previous sexually transmitted diseases. In seven cases (24%), the diagnosis occurred at delivery. Three percent of patients had a primary syphilis, 14% a secondary syphilis, 24% an early latent syphilis, and 59% a latent syphilis. All cases except one case were treated with benzathine penicillin G and the remaining with erythromycin due to allergy suspicion. Penicillin desensitization was required in two cases (7%). Treatment timing was inadequate in 10 cases (34.5%). Of 19 patients with available serological follow-up, 10 (53%) showed a significant decrease in VDRL titers (≥ 2 dilutions) and two cases had re-infection. Two patients (7%) had an abortion, two had congenital syphilis (7%), and six had premature births (21%), totaling 35% of adverse-pregnancy outcomes.
CONCLUSIONS
Resurgence of syphilis among pregnant women is happening in southern Chile and is associated to adverse-pregnancy outcomes.
Topics: Adult; Chile; Female; Humans; Male; Penicillin G Benzathine; Pregnancy; Pregnancy Complications, Infectious; Pregnant Women; Syphilis; Syphilis, Congenital
PubMed: 34479313
DOI: 10.4067/s0034-98872021000300348 -
European Journal of Medical Research Aug 2023To evaluate the efficacy and safety of vonoprazan-amoxicillin (VA) dual therapy for radically eradicating Helicobacter pylori (H. pylori). (Meta-Analysis)
Meta-Analysis Review
AIM
To evaluate the efficacy and safety of vonoprazan-amoxicillin (VA) dual therapy for radically eradicating Helicobacter pylori (H. pylori).
METHODS
The PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched up to July 7, 2022, to identify clinical trials comparing the efficacy of VA dual therapy and triple therapy for H. pylori eradication. After evaluating the quality of the included studies, random effects models were conducted, and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to estimate the efficacy and safety of each approach.
RESULTS
Six publications (including four randomized controlled trials) involving 2019 patients were included in this meta-analysis. Overall, the eradication rate for VA dual therapy was 89.9%, while it was 85.2% for triple therapy based on other acid inhibitors. The eradication rate of H. pylori in the VA dual regimen group was higher than that in the PPI-based (omeprazole or lansoprazole) triple therapy group (RR = 1.15, 95% CI 1.07-1.23, p < 0.0001). However, the efficacy of VA dual therapy was comparable with VA-Clarithromycin (VAC) triple therapy (RR = 0.97, 95% CI 0.93-1.02). Besides, the incidence of adverse reactions in VA dual therapy was also lower than that in triple therapy (RR = 0.80, 95% CI 0.70-0.91, p = 0.0009).
CONCLUSION
Compared with PPI-based triple therapy, VA dual therapy showed a better therapeutic effect, safety and patient compliance rate for eradicating H. pylori, which should be used as a novel curative strategy in the future.
Topics: Humans; Amoxicillin; Helicobacter pylori; Anti-Bacterial Agents; Helicobacter Infections; Proton Pump Inhibitors; Drug Therapy, Combination; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37550781
DOI: 10.1186/s40001-023-01249-6 -
Experimental Biology and Medicine... Oct 2023Bacterial cell wall formation is essential for cellular survival and morphogenesis. The peptidoglycan (PG), a heteropolymer that surrounds the bacterial membrane, is a... (Review)
Review
Bacterial cell wall formation is essential for cellular survival and morphogenesis. The peptidoglycan (PG), a heteropolymer that surrounds the bacterial membrane, is a key component of the cell wall, and its multistep biosynthetic process is an attractive antibacterial development target. Penicillin-binding proteins (PBPs) are responsible for cross-linking PG stem peptides, and their central role in bacterial cell wall synthesis has made them the target of successful antibiotics, including β-lactams, that have been used worldwide for decades. Following the discovery of penicillin, several other compounds with antibiotic activity have been discovered and, since then, have saved millions of lives. However, since pathogens inevitably become resistant to antibiotics, the search for new active compounds is continuous. The present review highlights the ongoing development of inhibitors acting mainly in the transpeptidase domain of PBPs with potential therapeutic applications for the development of new antibiotic agents. Both the critical aspects of the strategy, design, and structure-activity relationships (SAR) are discussed, covering the main published articles over the last 10 years. Some of the molecules described display activities against main bacterial pathogens and could open avenues toward the development of new, efficient antibacterial drugs.
Topics: Penicillin-Binding Proteins; Anti-Bacterial Agents; beta-Lactams; Penicillins; Bacteria; Bacterial Proteins
PubMed: 38030964
DOI: 10.1177/15353702231208407