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JAC-antimicrobial Resistance Feb 2023The intestinal microbiota functions as a reservoir of antibiotic resistance.
BACKGROUND
The intestinal microbiota functions as a reservoir of antibiotic resistance.
OBJECTIVES
To evaluate penicillin V (phenoxymethylpenicillin) effects on the faecal microbiota with focus on beta-lactam resistance.
METHODS
We included 31 primary care patients with group A streptococcal pharyngotonsillitis treated with penicillin V for 5 (800 mg × 4) or 10 days (1000 mg × 3). Twenty-nine patients contributed with three faecal swab samples each. The faecal specimens were collected at the start of penicillin V treatment, after the last dose and at follow-up 7-9 days after completed treatment. Samples were inoculated semiquantitatively on selective screening agar plates to study beta-lactam resistance, species shifts among Enterobacterales and enterococci, and colonization with spp. and . Representative colonies were identified using MALDI-TOF. Results were analysed by non-parametric statistical methods.
RESULTS
An increase in the proportion of patients colonized with ampicillin-resistant Enterobacterales, from 52% to 86% ( = 0.007), and Enterobacterales with decreased susceptibility to third-generation cephalosporins, from 32% to 52% ( = 0.034), was observed between the first and second samples. This increase was no longer significant at follow-up. New colonization with ampicillin-resistant Enterobacterales species and non-Enterobacterales Gram-negative species was observed, and persisted at follow-up.
CONCLUSIONS
Following treatment with penicillin V, we observed decreased susceptibility to ampicillin and third-generation cephalosporins, and prolonged colonization with non- Gram-negative species. These findings challenge the perception that penicillin V has limited ecological effect on the intestinal microbiota, and emphasizes the importance of avoiding even narrow-spectrum antimicrobials when possible.
PubMed: 36816747
DOI: 10.1093/jacamr/dlad006 -
Microbial Cell Factories Jun 2021Biodegradation of antibiotics is a promising method for the large-scale removal of antibiotic residues in the environment. However, the enzyme that is involved in the...
BACKGROUND
Biodegradation of antibiotics is a promising method for the large-scale removal of antibiotic residues in the environment. However, the enzyme that is involved in the biodegradation process is the key information to be revealed.
RESULTS
In this study, the beta-lactamase from Ochrobactrum tritici that mediates the biodegradation of penicillin V was identified and characterized. When searching the proteins of Ochrobactrum tritici, the β-lactamase (OtLac) was identified. OtLac consists of 347 amino acids, and predicted isoelectric point is 7.0. It is a class C β-lactamase according to BLAST analysis. The coding gene of OtLac was amplified from the genomic DNA of Ochrobactrum tritici. The OtLac was overexpressed in E. coli BL21 (DE3) and purified with Ni column affinity chromatography. The biodegradation ability of penicillin V by OtLac was identified in an in vitro study and analyzed by HPLC. The optimal temperature for OtLac is 32 ℃ and the optimal pH is 7.0. Steady-state kinetics showed that OtLac was highly active against penicillin V with a Km value of 17.86 μM and a kcat value of 25.28 s respectively.
CONCLUSIONS
OtLac demonstrated biodegradation activity towards penicillin V potassium, indicating that OtLac is expected to degrade penicillin V in the future.
Topics: Anti-Bacterial Agents; Biodegradation, Environmental; Catalysis; Cloning, Molecular; DNA, Bacterial; Fermentation; Hydrogen-Ion Concentration; Kinetics; Ochrobactrum; Penicillins; Recombinant Fusion Proteins; Temperature; beta-Lactamases
PubMed: 34120587
DOI: 10.1186/s12934-021-01606-2 -
Bioconjugate Chemistry Sep 2017The conjugation of antibiotics with polymers is rarely done, but it might be a promising alternative to low-molecular-weight derivatization. The two penicillins...
The conjugation of antibiotics with polymers is rarely done, but it might be a promising alternative to low-molecular-weight derivatization. The two penicillins penicillin G (PenG) and penicillin V (PenV) were attached to the end groups of different water-soluble poly(2-oxazoline)s (POx) via their carboxylic acid function. This ester group was shown to be more stable against hydrolysis than the β-lactam ring of the penicillins. The conjugates are still antimicrobially active and up to 20 times more stable against penicillinase catalyzed hydrolysis. The antibiotic activity of the conjugates against Staphylococcus aureus in the presence of penicillinase is up to 350 times higher compared with the free antibiotics. Conjugates with a second antimicrobial function, a dodecyltrimethylammonium group (DDA-X), at the starting end of the PenG and PenV POx conjugates are more antimicrobially active than the conjugates without DDA-X and show high activity in the presence of penicillinase. For example, the conjugates DDA-X-PEtOx-PenG and DDA-X-PEtOx-PenV are 200 to 350 times more active against S. aureus in the presence of penicillinase and almost as effective as the penicillinase stable cloxacollin (Clox) under these conditions. These conjugates show even greater activity compared to cloxacollin without this enzyme present. Further, both conjugates kill Escherichia coli more effectively than PenG and Clox.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Stability; Escherichia coli; Escherichia coli Infections; Humans; Hydrolysis; Oxazoles; Penicillinase; Penicillins; Staphylococcal Infections; Staphylococcus aureus
PubMed: 28817271
DOI: 10.1021/acs.bioconjchem.7b00424 -
American Family Physician May 2020In 2019, regular surveillance of 110 English-language research journals identified 254 studies that met the criteria to become POEMs (patient-oriented evidence that... (Review)
Review
In 2019, regular surveillance of 110 English-language research journals identified 254 studies that met the criteria to become POEMs (patient-oriented evidence that matters). Physician members of the Canadian Medical Association rated these POEMs for their relevance to patients in their practices. This article summarizes the clinical questions and bottom-line answers from the top 20 POEMs of 2019. Taking blood pressure medications at night results in a large mortality reduction over six years compared with morning dosing. Automated devices are the best way to measure blood pressure. Nonfasting lipid profiles are preferred over fasting lipid profiles, and nonfasting and fasting lipid profiles are equally effective at predicting risk. The benefit of statins for primary prevention in people 75 years and older is uncertain at best. Aspirin has no net benefit for primary prevention of cardiovascular disease and has no effect on cancer outcomes. An Italian study found fecal immunochemical testing over five biennial screening cycles has a similar colorectal cancer yield as screening colonoscopy, whereas a meta-analysis found that taking aspirin, an anticoagulant, or a nonsteroidal anti-inflammatory drug has no impact on the positive predictive value of fecal immunochemical testing. Regarding infections, a meta-analysis showed that patients presenting with symptoms of acute respiratory tract infection are unlikely to have pneumonia if vital signs and the lung examination findings are normal. For streptococcal pharyngitis (strep throat), penicillin V at a dosage of 800 mg four times a day for five days is at least as effective as a dosage of 1,000 mg three times a day for 10 days. A primary care study in the United Kingdom reinforced that clinicians should counsel parents of children with lower respiratory tract symptoms to be patient, because these infections can take three weeks or more to fully resolve. Among direct oral anticoagulants, apixaban has the lowest bleeding risk, and cotreating with a proton pump inhibitor significantly reduces bleeding risk. Single ibuprofen doses from 400 to 800 mg significantly reduce acute pain to a similar degree. The two-dose recombinant zoster vaccine is much more effective than the single-dose live, attenuated vaccine but with a greater risk of injection site pain. Exercise helps reduce the risk of falls in older adults. Practice guidelines from 2019 on antithrombotics for atrial fibrillation, the management of type 2 diabetes mellitus, and screening for breast cancer were judged to be especially relevant.
Topics: Humans; Periodicals as Topic; Physicians, Primary Care; Primary Health Care; Research
PubMed: 32412223
DOI: No ID Found -
Health Science Reports Nov 2022Penicillin V prophylaxis protects children living with sickle cell disease (SCD) from bacteria infections especially . However, the uptake of penicillin V prophylaxis is...
BACKGROUND AND AIMS
Penicillin V prophylaxis protects children living with sickle cell disease (SCD) from bacteria infections especially . However, the uptake of penicillin V prophylaxis is difficult to assess and often poor among SCD patients. Therefore, this study sought to investigate oral penicillin V prophylaxis adherence among SCD children using urine assay and self-reported methods and the associated factors.
METHODS
The study employed an analytical cross-sectional design in the assessment of penicillin V prophylaxis adherence using both urine assay and self-reported methods. Multiple logistic regression analysis was used to determine the factors associated with penicillin V prophylaxis adherence. A value < 0.05 was considered statistically significant.
RESULTS
Among the 421 SCD patients recruited, penicillin V prophylaxis adherence was observed to be 30.0% and 68.0% for the objective and subjective methods of assessment, respectively. For the objective method of assessment, being cared for by grandparents increased the odds of penicillin V adherence (adjusted odds ratio [aOR] = 3.68, confidence interval [CI] = 1.03-13.15). However, SCD patients within the ages of 10-14 years (aOR = 0.36, CI = 0.17-0.80), >14 years (aOR = 0.17, CI = 0.05-0.61), SCD patient cared for by married caregivers/parents (aOR = 0.32, CI = 0.14-0.72), SCD patient cared for by divorced caregivers/parents (aOR = 0.23, CI = 0.07-0.75), SCD patients taking homemade (herbal) preparations for the treatment of SCD (aOR = 0.42, CI = 0.21-0.83), and inappropriate intake of penicillin V prophylaxis (aOR = 0.27, CI = 0.11-0.67) reduced the odds of penicillin V adherence. For the subjective method of assessment, taking homemade preparation (herbal) for the treatment of SCD (aOR = 0.52, CI = 0.30-0.89) and inappropriate intake of penicillin V (aOR = 0.32, CI = 0.17-0.60) reduced the odds of penicillin V adherence.
CONCLUSION
This study reports a relatively low adherence rate of penicillin V prophylaxis among children living with SCD. Educating and counseling both SCD patients and/or caregivers on the need to be adherent to penicillin V prophylaxis could prevent complications that may arise from nonadherence.
PubMed: 36439045
DOI: 10.1002/hsr2.953 -
JAMA Dermatology Nov 2018Controversies about the choice of antibiotic agent and treatment modality exist in the management of erythema migrans in early cutaneous Lyme borreliosis (LB). (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Controversies about the choice of antibiotic agent and treatment modality exist in the management of erythema migrans in early cutaneous Lyme borreliosis (LB).
OBJECTIVE
To conduct a network meta-analysis (NMA) of all randomized clinical trials on various antibiotic agents and treatment modalities in early cutaneous LB.
DATA SOURCES
Electronic searches in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were conducted from inception until July 2017. The reference lists of the included studies were hand searched, authors were contacted, and ongoing trials were searched at ClinicalTrials.gov.
STUDY SELECTION
One reviewer screened the titles and abstracts of the 9975 reports identified by the electronic searches. Full-text copies of 161 potentially relevant articles were obtained, and 2 reviewers independently assessed those articles for inclusion. Adults with a physician-confirmed early localized skin infection who were treated with antibiotics of any dose or duration were included.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data on study, patient, and intervention characteristics. Network meta-analyses on treatment effects and adverse outcomes were calculated with a frequentist approach using the R package netmeta. The Grading of Recommendations Assessment, Development and Evaluation guidance for NMA was used to assess the certainty of evidence.
MAIN OUTCOMES AND MEASURES
Treatment effects for response to treatment (resolution of symptoms) and treatment-related adverse events.
RESULTS
Overall, 19 studies (2532 patients) were included. The mean patient age ranged between 37 and 56 years, and the percentage of female patients ranged from 36% to 60%. The antibiotics investigated were doxycycline, cefuroxime axetil, ceftriaxone, amoxicillin, azithromycin, penicillin V, and minocycline. Pooled effect sizes from NMAs did not suggest any significant differences in treatment response by antibiotic agent (eg, amoxicillin vs doxycycline odds ratio, 1.26; 95% CI, 0.41-3.87), dose, or duration (eg, doxycycline, 200 mg/d for 3 weeks, vs doxycycline, 200 mg/d for 2 weeks, odds ratio, 1.28; 95% CI, 0.49-3.34). Treatment failures were rare at both 2 months (4%; 95% CI, 2%-5%) and 12 months (2%, 95% CI, 1%-3%) after treatment initiation. There were also no differences in the effect sizes among antibiotic agents and treatment modalities for treatment-related adverse outcomes, which were generally mild to moderate. Certainty of evidence was categorized as low and very low mostly because of imprecision, indirectness, and study limitations (high risk of bias) of the included studies.
CONCLUSIONS AND RELEVANCE
This NMA suggests that neither the antibiotic agent nor treatment modality contributed to comparative effectiveness or drug-related adverse outcomes. This finding is relevant for physicians treating patients with LB and for patient decision making.
Topics: Anti-Bacterial Agents; Global Health; Humans; Incidence; Lyme Disease; Network Meta-Analysis; Skin Diseases, Bacterial
PubMed: 30285069
DOI: 10.1001/jamadermatol.2018.3186 -
ACS Omega Nov 2020Penicillin V acylase (PVA, EC 3.5.1.11) hydrolyzes the side chain of phenoxymethylpenicillin (Pen V) and finds application in the manufacture of the pharmaceutical...
Penicillin V acylase (PVA, EC 3.5.1.11) hydrolyzes the side chain of phenoxymethylpenicillin (Pen V) and finds application in the manufacture of the pharmaceutical intermediate 6-aminopenicillanic acid (6-APA). Here, we report the scale-up of cultivation of whole cells expressing a highly active PVA from and their encapsulation in polyvinyl alcohol-poly(ethylene glycol) Lentikats hydrogels. A biocatalytic process for the hydrolysis of 2% (w/v) Pen V was set up in a 2 L reactor using the Lentikats-immobilized whole cells, with a customized setup to enable continuous downstream processing of the reaction products. The biocatalytic reaction afforded complete conversion of Pen V for 10 reaction cycles, with an overall 90% conversion up to 50 cycles. The bioprocess was further scaled up to the pilot-scale at 10 L, enabling complete conversion of Pen V to 6-APA for 10 cycles. The 6-APA and phenoxy acetic acid products were recovered from downstream processing with isolated yields of 85-90 and 87-92%, respectively. Immobilization in Lentikats beads improved the stability of the whole cells on storage, maintaining 90-100% activity and similar conversion efficiency after 3 months at 4 °C. The robust PVA biocatalyst can be employed in a continuous process to provide a sustainable route for bulk 6-APA production from Pen V.
PubMed: 33225127
DOI: 10.1021/acsomega.0c02813 -
Journal of Oral and Maxillofacial... Apr 2016We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the effectiveness of a single dose of preoperative antibiotic administered perorally,... (Review)
Review
PURPOSE
We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the effectiveness of a single dose of preoperative antibiotic administered perorally, intravenously, intramuscularly, or topically for preventing infection and alveolar osteitis in lower third molar surgical extraction applying osteotomy.
MATERIALS AND METHODS
The Medline, Cochrane Library, and Embase databases were searched for RCTs until August 2015. The primary outcome measure was postoperative inflammatory reactions, with a subgroup analysis of surgical site infection (SSI) and alveolar osteitis. A risk-of-bias assessment of the included trials was done according to the Cochrane guidelines.
RESULTS
A total of 53 RCTs were identified; however, only 10 could be included in the present review. A meta-analysis of the 10 trials showed a statistically significant reduction in SSI and alveolar osteitis when antibiotics had been used (odds ratio [OR] = 0.30; 95% confidence interval [CI], 0.19 to 0.47; P ≤ .00001). A subgroup meta-analysis of 6 trials showed that preoperative administration of antibiotics perorally or intravenously significantly reduced the incidence of SSI (OR = 0.19; 95% CI, 0.08 to 0.45; P = .0002). A meta-analysis of 5 trials showed that 2 g of preoperative oral amoxicillin was able to reduce the incidence of SSI and the difference was statistically significant (OR = 0.22; 95% CI, 0.08 to 0.59; P = .002). Seven trials reported on alveolar osteitis, 6 studies on oral use, 2 studies on amoxicillin, 2 on metronidazole, 2 on penicillin V, and 1 on the intravenous use of penicillin. The pooled results showed that preoperative antibiotics significantly reduced the prevalence of alveolar osteitis (OR = 0.35; 95% CI, 0.13 to 0.96; P = .04). The subgroup analysis showed that penicillin V was effective in reducing the incidence of alveolar osteitis (OR = 0.1; 95% CI, 0.03 to 0.30; P ≤ .0001).
CONCLUSIONS
A single oral dose of 2 g of amoxicillin before lower third molar osteotomy surgical extraction significantly decreased the incidence of SSI. A single dose of 0.8 g of penicillin V before lower third molar osteotomy surgical extraction significantly decreased the incidence of alveolar osteitis.
Topics: Administration, Intravenous; Administration, Oral; Administration, Topical; Anti-Bacterial Agents; Antibiotic Prophylaxis; Dry Socket; Humans; Injections, Intramuscular; Molar, Third; Osteotomy; Surgical Wound Infection; Tooth Extraction
PubMed: 26706491
DOI: 10.1016/j.joms.2015.11.017 -
Microorganisms Apr 2023Beta (β)-lactam antibiotic is an industrially important molecule produced by /. Penicillin is a building block for 6-aminopenicillanic acid (6-APA), an important active...
Beta (β)-lactam antibiotic is an industrially important molecule produced by /. Penicillin is a building block for 6-aminopenicillanic acid (6-APA), an important active pharmaceutical intermediate (API) used for semi-synthetic antibiotics biosynthesis. In this investigation, we isolated and identified , P. rubens, P. brocae, P. citrinum, Aspergillus fumigatus, A. sydowii, Talaromyces tratensis, Scopulariopsis brevicaulis, P. oxalicum, and P. dipodomyicola using the internal transcribed spacer (ITS) region and the β-tubulin () gene for precise species identification from Indian origin. Furthermore, the gene distinguished between complex species of and to a certain extent which partially failed by the ITS region. In addition, these species were distinguished by metabolic markers profiled by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Secalonic acid, Meleagrin, and Roquefortine C were absent in . The crude extract evaluated for PenV production by antibacterial activities by well diffusion method against NCIM-2079. A high-performance liquid chromatography (HPLC) method was developed for simultaneous detection of 6-APA, phenoxymethyl penicillin (PenV), and phenoxyacetic acid (POA). The pivotal objective was the development of an indigenous strain portfolio for PenV production. Here, a library of 80 strains of / was screened for PenV production. Results showed 28 strains capable of producing PenV in a range from 10 to 120 mg/L when 80 strains were screened for its production. In addition, fermentation parameters, precursor concentration, incubation period, inoculum size, pH, and temperature were monitored for the improved PenV production using promising strain BIONCL P45. In conclusion, / strains can be explored for the industrial-scale PenV production.
PubMed: 37317105
DOI: 10.3390/microorganisms11051132 -
Applied Microbiology and Biotechnology Mar 2017Virulence pathways in gram-negative pathogenic bacteria are regulated by quorum sensing mechanisms, through the production and sensing of N-acylhomoserine lactone (AHL)...
Virulence pathways in gram-negative pathogenic bacteria are regulated by quorum sensing mechanisms, through the production and sensing of N-acylhomoserine lactone (AHL) signal molecules. Enzymatic degradation of AHLs leading to attenuation of virulence (quorum quenching) could pave the way for the development of new antibacterials. Penicillin V acylases (PVAs) belong to the Ntn hydrolase superfamily, together with AHL acylases. PVAs are exploited widely in the pharmaceutical industry, but their role in the natural physiology of their native microbes is not clearly understood. This report details the characterization of AHL degradation activity by homotetrameric PVAs from two gram-negative plant pathogenic bacteria, Pectobacterium atrosepticum (PaPVA) and Agrobacterium tumefaciens (AtPVA). Both the PVAs exhibited substrate specificity for degrading long-chain AHLs. Exogenous addition of these enzymes into Pseudomonas aeruginosa greatly diminished the production of elastase and pyocyanin and biofilm formation and increased the survival rate in an insect model of acute infection. Subtle structural differences in the PVA active site that regulate specificity for acyl chain length have been characterized, which could reflect the evolution of AHL-degrading acylases in relation to the environment of the bacteria that produce them and also provide strategies for enzyme engineering. The potential for using these enzymes as therapeutic agents in clinical applications and a few ideas about their possible significance in microbial physiology have also been discussed.
Topics: Acyl-Butyrolactones; Agrobacterium tumefaciens; Bacterial Proteins; Biofilms; Catalytic Domain; Cloning, Molecular; Escherichia coli; Gene Expression Regulation, Bacterial; Hydrolysis; Models, Molecular; Pancreatic Elastase; Pectobacterium; Penicillin Amidase; Protein Conformation; Pseudomonas aeruginosa; Pyocyanine; Quorum Sensing; Recombinant Proteins; Substrate Specificity; Virulence
PubMed: 27933456
DOI: 10.1007/s00253-016-8031-5