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Medicina (Kaunas, Lithuania) Mar 2023Acute otitis media (AOM) in children is one of the leading causes of health care visits and antibiotic prescriptions worldwide. The overall aim of the current study is... (Review)
Review
Acute otitis media (AOM) in children is one of the leading causes of health care visits and antibiotic prescriptions worldwide. The overall aim of the current study is twofold: 1. to analyze and discuss the antibiotic prescription patterns in AOM in children without complications or risk factors and 2. to assess to what extent the watchful-waiting approach is a real practice or a mere desideratum. We performed an electronic search in the PubMed and Embase databases from 2013 to 2023 to capture original research studies investigating antibiotic prescribing patterns for AOM in children. Among the 12 papers included in the analysis, the antibiotic prescription rate ranged from 44.8% to 98%. Our study reveals similarities regarding the use of amoxicillin as a first-line antibiotic in pediatric AOM, but also discrepancies in the watchful-waiting approach attitude and in the choice of second or third-line antimicrobial agents. The proportion of cases managed with the watchful-waiting approach ranged from 7.5% (Australia) to 55.2% (Finland). Denmark was the only country reporting penicillin V as a first-choice regimen for children with AOM, which fulfils the guidelines' recommendations. The most unsatisfying rate of amoxicillin use was recorded in Japan, contrary to the recommendations of local guidelines. The use of quinolones was reported in two out of twelve studies, with the highest proportion in Japan, where tosufloxacin was used in 21.4% of the total number of cases. The duration of the antibiotic regimens was analyzed in three out of twelve papers. Since global antibiotic overuse contributes to the emergence of antibiotic resistant bacteria, new strategies are needed to increase the rate of watchful waiting and to promote the judicious use of antibiotics.
Topics: Child; Humans; Infant; Watchful Waiting; Acute Disease; Otitis Media; Amoxicillin; Anti-Bacterial Agents
PubMed: 36984521
DOI: 10.3390/medicina59030520 -
Open Forum Infectious Diseases Dec 2021This healthy volunteer study aimed to explore phenoxymethylpenicillin (penicillin-V) pharmacokinetics (PK) to support the planning of large dosing studies in adults....
This healthy volunteer study aimed to explore phenoxymethylpenicillin (penicillin-V) pharmacokinetics (PK) to support the planning of large dosing studies in adults. Volunteers were dosed with penicillin-V at steady state. Total and unbound penicillin-V serum concentrations were determined, and a base population PK model was fitted to the data.
PubMed: 34934774
DOI: 10.1093/ofid/ofab573 -
British Journal of Clinical Pharmacology Aug 2017In vitro studies have demonstrated that formation of reactive oxygen species (ROS) contributes to the effect of bactericidal antibiotics. The formation of ROS is not... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
In vitro studies have demonstrated that formation of reactive oxygen species (ROS) contributes to the effect of bactericidal antibiotics. The formation of ROS is not restricted to bacteria, but also occurs in mammalian cells. Oxidative stress is linked to several diseases. This study investigates whether antibiotic drugs induce oxidative stress in healthy humans as a possible mechanism for adverse reactions to the antibiotic drugs.
METHODS
This study contains information from two randomised, controlled trials. Participants underwent 1 week treatment with clarithromycin, trimethoprim, phenoxymethylpenicillin (penicillin V), or placebo. Oxidative modifications were measured as 24-h urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and plasma levels of malondialdehyde before and after treatment as a measurement of DNA oxidation, RNA oxidation, and lipid peroxidation, respectively.
RESULTS
Clarithromycin significantly increased urinary excretion of 8-oxodG by 22.0% (95% confidence interval (CI): 3.6-40.4%) and 8-oxoGuo by 14.9% (95% CI: 3.7-26.1%). Further, we demonstrated that trimethoprim significantly lowered urinary excretion of 8-oxodG by 21.7% (95% CI: 5.8-37.6%), but did not influence urinary excretion of 8-oxoGuo. Penicillin V did not influence urinary excretion of 8-oxodG or 8-oxoGuo. None of the antibiotic drugs influenced plasma levels of malondialdehyde.
CONCLUSION
Clarithromycin significantly increases oxidative nucleic acid modifications. Increased oxidative modifications might explain some of clarithromycin's known adverse reactions. Trimethoprim significantly lowers DNA oxidation but not RNA oxidation. Penicillin V had no effect on oxidative nucleic acid modifications.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Anti-Bacterial Agents; Biomarkers; Clarithromycin; DNA; Deoxyguanosine; Guanosine; Healthy Volunteers; Humans; Lipid Peroxidation; Male; Malondialdehyde; Oxidation-Reduction; Oxidative Stress; Penicillin V; Placebos; RNA; Reactive Oxygen Species; Trimethoprim; Young Adult
PubMed: 28185274
DOI: 10.1111/bcp.13261 -
The FEBS Journal Jun 2016Mycobacterium tuberculosis is a human respiratory pathogen that causes the deadly disease tuberculosis. The rapid global spread of antibiotic-resistant M. tuberculosis...
UNLABELLED
Mycobacterium tuberculosis is a human respiratory pathogen that causes the deadly disease tuberculosis. The rapid global spread of antibiotic-resistant M. tuberculosis makes tuberculosis infections difficult to treat. To overcome this problem new effective antimicrobial strategies are urgently needed. One promising target for new therapeutic approaches is PonA1, a class A penicillin-binding protein, which is required for maintaining physiological cell wall synthesis and cell shape during growth in mycobacteria. Here, crystal structures of the transpeptidase domain, the enzymatic domain responsible for penicillin binding, of PonA1 from M. tuberculosis in the inhibitor-free form and in complex with penicillin V are reported. We used site-directed mutagenesis, antibiotic profiling experiments, and fluorescence thermal shift assays to measure PonA1's sensitivity to different classes of β-lactams. Structural comparison of the PonA1 apo-form and the antibiotic-bound form shows that binding of penicillin V induces conformational changes in the position of the loop β4'-α3 surrounding the penicillin-binding site. We have also found that binding of different antibiotics including penicillin V positively impacts protein stability, while other tested β-lactams such as clavulanate or meropenem resulted in destabilization of PonA1. Our antibiotic profiling experiments indicate that the transpeptidase activity of PonA1 in both M. tuberculosis and M. smegmatis mediates tolerance to specific cell wall-targeting antibiotics, particularly to penicillin V and meropenem. Because M. tuberculosis is an important human pathogen, these structural data provide a template to design novel transpeptidase inhibitors to treat tuberculosis infections.
DATABASE
Structural data are available in the PDB database under the accession numbers 5CRF and 5CXW.
Topics: Binding Sites; Crystallography, X-Ray; Drug Resistance, Microbial; Humans; Mutagenesis, Site-Directed; Mycobacterium tuberculosis; Penicillin V; Penicillin-Binding Proteins; Peptidyl Transferases; Tuberculosis; beta-Lactams
PubMed: 27101811
DOI: 10.1111/febs.13738 -
Journal of Dental Research Sep 2019Dentists prescribe a large portion of all oral antibiotics, and these are associated with a risk of adverse drug reactions (ADRs). The aim of this study was to quantify...
Dentists prescribe a large portion of all oral antibiotics, and these are associated with a risk of adverse drug reactions (ADRs). The aim of this study was to quantify the risk of ADRs associated with oral antibiotics commonly prescribed by dentists. NHS Digital Prescribing data and Yellow Card Drug Analysis data for 2010 to 2017 were abstracted to quantify dental antibiotic prescribing in England, and the rate and types of ADRs associated with them. During the period of study, the mean number of actively practicing dentists in England was 23,624. Amoxicillin accounted for 64.8% of dental antibiotic prescribing and had the lowest reported rate of fatal ADRs (0.1/million prescriptions) and overall ADRs (21.5/million prescriptions). Indeed, amoxicillin was respectively 6 and 3 times less likely to cause an ADR than the other penicillins, penicillin V and amoxicillin + clavulanic acid, and appears to be very safe in patients with no history of penicillin allergy. In contrast, clindamycin, which is often used in patients with penicillin allergy, had the highest rate of fatal (2.9/million prescriptions) and overall (337.3/million prescriptions) ADRs, with (formerly ) infections pivotal to its ADR profile. Other amoxicillin alternatives, clarithromycin and metronidazole, while significantly worse than amoxicillin, were 3 and nearly 5 times less likely to cause an ADR than clindamycin. Ranked from least to most likely to cause an ADR, antibiotics most commonly prescribed were as follows: amoxicillin < cephalosporins < erythromycin < tetracyclines < azithromycin < metronidazole < amoxicillin + clavulanic acid < clarithromycin < penicillin V < clindamycin. This study confirmed the high level of safety associated with use of amoxicillin by dentists and the significantly worse rates of fatal and nonfatal ADRs associated with other penicillins and alternatives to amoxicillin for those who are penicillin allergic. In particular, clindamycin had the highest rate of fatal and nonfatal ADRs of any of the antibiotics commonly prescribed by dentists.
Topics: Administration, Oral; Adverse Drug Reaction Reporting Systems; Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Clindamycin; Dentists; England; Humans; Metronidazole; Penicillins
PubMed: 31314998
DOI: 10.1177/0022034519863645 -
BMJ (Clinical Research Ed.) Feb 2016To evaluate if oral fluoroquinolone use is associated with an increased risk of serious arrhythmia.
OBJECTIVE
To evaluate if oral fluoroquinolone use is associated with an increased risk of serious arrhythmia.
DESIGN
Bi-national cohort study, linking register data on filled prescriptions, cases of serious arrhythmia, and patient characteristics.
SETTING
Denmark, 1997-2011; Sweden, 2006-13.
PARTICIPANTS
The study cohort was derived from a source population of all Danish and Swedish adults, aged 40 to 79 years. 909,656 courses of fluoroquinolone use (ciprofloxacin 82.6%, norfloxacin 12.1%, ofloxacin 3.2%, moxifloxacin 1.2%, and other fluoroquinolones 0.9%) and 909,656 courses of penicillin V use, matched 1:1 on propensity score, were included.
MAIN OUTCOME MEASURE
The main outcome was risk of serious arrhythmia (fatal and non-fatal), comparing courses of fluoroquinolone use with courses of penicillin V use (an antibiotic with no pro-arrhythmic effect). The risk period of interest was current use, defined as days 0-7 of treatment. Subgroup analyses were conducted according to country, sex, age, underlying cardiovascular disease, concomitant use of drugs known to increase the risk of torsades de pointes, fluoroquinolone type, and levels of arrhythmia risk score.
RESULTS
144 cases of serious arrhythmia occurred during follow-up, 66 among current fluoroquinolone users (incidence rate 3.4 per 1000 person years) and 78 among current penicillin users (4.0 per 1000 person years); comparing oral fluoroquinolone treatment with penicillin V, the rate ratio was 0.85 (95% confidence interval 0.61 to 1.18). Compared with penicillin V, the absolute risk difference was -13 (95% confidence interval -35 to 16) cases of serious arrhythmia per 1,000,000 courses of fluoroquinolones. The risk of serious arrhythmia was not statistically significantly increased in any of the subgroups, including analyses by fluoroquinolone type.
CONCLUSIONS
Contrary to previous reports, oral fluoroquinolone treatment was not associated with an increased risk of serious arrhythmia in the general adult populations of Denmark and Sweden. Given the statistical power of the study, even small increases in relative and absolute risk could be ruled out. Since ciprofloxacin was the most commonly used fluoroquinolone in our study, we cannot exclude that intraclass differences influence the risk of serious arrhythmia associated with other less frequently used fluoroquinolones.
Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Arrhythmias, Cardiac; Denmark; Epidemiologic Methods; Fluoroquinolones; Humans; Middle Aged; Penicillin V; Sweden
PubMed: 26920666
DOI: 10.1136/bmj.i843 -
MSphere Jun 2018Various species have been reported to deconjugate bile acids in the gastrointestinal tract (GIT) through the action of bile salt hydrolase (BSH) proteins. This function...
Various species have been reported to deconjugate bile acids in the gastrointestinal tract (GIT) through the action of bile salt hydrolase (BSH) proteins. This function contributes to altering the gut microbiota composition and bile metabolism and detoxification and to lowering cholesterol levels. Here, we investigated the BSH repertoire across 170 sequenced species. We used hidden Markov models to distinguish between BSH and closely related penicillin-V acylase (PVA) proteins. Even though BSH and PVA proteins have very different target substrates, they share high sequence similarity and are often misannotated. We determined that 82/170 (48.24%) species encoded PVA proteins, 39/170 (22.94%) species encoded BSH proteins, and 8/170 (4.71%) species encoded both BSH and PVA proteins, while 57/170 (33.53%) species encoded neither. Mapping the occurrence of BSH-encoding species onto a phylogenetic tree revealed that BSH-encoding lactobacilli primarily adopt the vertebrate-adapted lifestyle but not the environmental or plant-associated subsets. Phylogenetic analysis of the BSH sequences revealed two distinct clades, several conserved motifs, and the presence of six previously reported active-site residues. These data will guide future mechanistic studies of BSH activity and contribute to the development and selection of BSH-encoding strains with therapeutic potential. Bile acids play an integral role in shaping the gut microbiota and host physiology by regulating metabolic signaling, weight gain, and serum cholesterol and liver triglyceride levels. Given these important roles of bile acids, we investigated the presence of bile salt hydrolase (BSH) in genomes representing 170 different species, determined strain- and species-specific patterns of occurrences, and expanded on the diversity of the BSH repertoire in this genus. While our data showed that 28% of species encode BSH proteins, these species are associated mainly with vertebrate-adapted niches, demonstrating selective pressure on lactobacilli to evolve to adapt to specific environments. These new data will allow targeted selection of specific strains of lactobacilli and BSH proteins for future mechanistic studies to explore their therapeutic potential for treating metabolic disorders.
Topics: Adaptation, Biological; Amidohydrolases; Genetic Variation; Genotype; Lactobacillus; Penicillin Amidase; Phylogeny; Sequence Homology
PubMed: 29848760
DOI: 10.1128/mSphere.00140-18 -
Environmental Science and Pollution... Sep 2022Although antibiotic exposure in the general population has been well documented by a biomonitoring approach, epidemiologic data on the relationships between urinary...
Although antibiotic exposure in the general population has been well documented by a biomonitoring approach, epidemiologic data on the relationships between urinary antibiotic burden in the elderly with blood pressure (BP) are still lacking. The current study revealed thirty-four antibiotics in urine specimens from 990 elderly patients in Lu'an City, China, with detection frequencies ranging from 0.2 to 35.5%. Among the elderly, the prevalence of hypertension was 72.0%, and 12 antibiotics were detected in more than 10% of individuals with hypertension. The elderly with hypertension had the maximum daily exposure (5450.45 μg/kg/day) to fluoroquinolones (FQs). Multiple linear regression analyses revealed significant associations of BP and pulse pressure (PP) with exposure to specific antibiotics. The estimated β values (95% confidence interval) of associations with systolic blood pressure (SBP) in the right arm were 4.42 (1.15, 7.69) for FQs, 4.26 (0.52, 8.01) for the preferred as human antibiotics (PHAs), and 3.48 (0.20, 6.77) for the mixtures (FQs + tetracyclines [TCs] (tertile 3 vs. tertile 1)), respectively. Increased concentrations of TCs were associated with decreased diastolic BP (DBP; tertile 3: -1.75 [-3.39, -0.12]) for the right arm. Higher levels of FQs (tertile 3: 4.28 [1.02, 7.54]), PHAs (tertile 3: 4.25 [0.49, 8.01]), and FQs + TCs (tertile 3: 3.99 [0.71, 7.26]) were associated with increased SBP, and an increase in DBP for FQs (tertile 3: 1.82 [0.22, 3.42]) was shown in the left arm. Also, higher urinary concentrations of FQs (tertile 3: 3.18 [0.53, 5.82]), PHAs (tertile 3: 3.42 [0.40, 6.45]), and FQs + TCs (tertile 3: 3.06 [0.40, 5.72]) were related to increased PP, whereas a decline in PP for TCs (tertile 2: -2.93 [-5.60, -0.25]) in the right arm. And increased concentrations of penicillin V (tertile 3: 5.31 [1.53, 9.10]) and FQs + TCs (tertile 3: 2.84 [0.19, 5.49]) were related to higher PP in the left arm. By utilizing restricted cubic splines, our current study revealed a potential nonlinear dose-response association between FQ exposure and hypertension risk. In conclusion, this investigation is the first to present antibiotic exposure using a biomonitoring approach, and informs understanding of impacts of antibiotic residues, as emerging hazardous pollutants, on the hypertension risk in the elderly.
Topics: Aged; Anti-Bacterial Agents; Blood Pressure; Fluoroquinolones; Humans; Hypertension; Penicillin V; Tetracyclines
PubMed: 35513617
DOI: 10.1007/s11356-022-20613-3 -
Waste Management (New York, N.Y.) Mar 2020Penicillin V mycelial residue (PMR) is a byproduct of the pharmaceutical industry and may be disposed through land application after alkaline-thermal treatment. However,...
Penicillin V mycelial residue (PMR) is a byproduct of the pharmaceutical industry and may be disposed through land application after alkaline-thermal treatment. However, the efficacy of alkaline-thermally treated PMR in soil amelioration and the potential contamination risk caused by introduced penicillin V are poorly understood. In this study, soil pH, the contents of organic matter, available phosphorus, available potassium were measured to study the effect of alkaline-thermally treated PMR on soil fertility; the numbers of culturable microorganisms and the activities of enzymes, which not only reflect the decomposing ability of organic matter but also monitor the ecological suppression in soil ecosystem, were also investigated; moreover, the persistence of introduced penicillin V and the variation of antibiotic resistance genes (ARGs) in soil were examined to evaluate the resulting antibiotic resistance risk. The results indicated that the pH and the content of available potassium in amended soil with treated PMR profoundly improved. In addition, the culturable microorganisms and enzymes were not inhibited throughout the incubation of treated PMR in soil. The stability of treated PMR in soil relatively completed after 43 days. More importantly, the penicillin V derived by treated PMR rapidly depleted within 3 days, which suggested a relatively low environmental persistence. The treated PMR did not enrich the ARGs detected in soil, demonstrating that the addition of treated PMR might not trigger the antibiotic resistance risk in the short-term in soil. In conclusion, our results concluded that alkaline-thermally treated PMR is available for soil application.
Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Ecosystem; Genes, Bacterial; Penicillin V; Soil; Soil Microbiology; Soil Pollutants
PubMed: 32088571
DOI: 10.1016/j.wasman.2020.02.008 -
Photodiagnosis and Photodynamic Therapy Dec 2020This study used Electron Cryo-tomography (ECT) and fluorescent images to evaluate antimicrobial photodynamic therapy (aPDT) on the envelope architecture of a...
This study used Electron Cryo-tomography (ECT) and fluorescent images to evaluate antimicrobial photodynamic therapy (aPDT) on the envelope architecture of a Gram-negative bacteria and the effects of combined therapy of aPDT and antibiotics. Standard and clinical suspension of Escherichia coli were submitted to photodynamic treatment with methylene blue solution (100μM) and a 100 mW LED emitting at 660 nm with 3 and 18 J of energy. As a control group, a suspension of E. coli was submitted to penicillin V for 60 min at 30 °C, to compare the damage in cell wall structure. After treatment, ECT images were collected and E. coli biofilms were grown in glass-cover slides and stained with live/dead staining for fluorescence analysis before and after treatments. Bacteria were also submitted to disc diffusion and MIC tests with Ampicillin, Amoxicillin + Clavulanic acid, Clindamycin and Erythromycin. For in vivo experiment Galleria mellonella larvae were infected with E. coli and treated with antibiotics, aPDT or combined therapy. ECT images presented damage to cell walls and vesicles structures inside and outside the bacteria and fluorescent images showed dose dependent effect of aPDT. Antibiotic or aPDT alone did not improve the survival of caterpillars, but the combined therapy significantly increased survival curve. ECT and fluorescent images shows that aPDT seems to promote micro-damages to cell envelope and causes the production of membrane vesicles permeabilizing cell membranes. The results showed that pre-treating bacterial cells with a photosensitizer and light make them more susceptible to antibiotics and could be an alternative to local infection treatment by resistant bacteria.
Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Escherichia coli; Photochemotherapy; Photosensitizing Agents
PubMed: 32980553
DOI: 10.1016/j.pdpdt.2020.102029