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1.
Sci Total Environ ; 806(Pt 1): 150509, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34582861

RESUMO

Temperature and pH are important factors affecting the hydrolysis of ß-lactam antibiotics in water environments. However, the determination of hydrolysis kinetics and pathways is experimentally challenging, particularly in low temperature aqueous solutions because of time and cost constraints. In this study, an equation was employed to correct the Gibbs energy calculated in aqueous solutions by density functional theory methods to predict the effect of temperature on the hydrolysis kinetics and pathways of penicillin G. The results indicate that the most likely hydrolysis mechanism involves the opening of the ß-lactam ring of anionic penicillin G protonated at the ß-lactam oxygen atom with the participation of the carboxyl group and a water molecule. The results also suggest that the carboxyl group of ß-lactam antibiotics was crucial for the hydrogen transfer. The predicted rate constants were of the same order of magnitude as the experimental values obtained under comparable pH and temperature conditions. Therefore, the quantum chemical methodology described herein can be potentially employed to determine pH- and temperature-based two-dimensional hydrolysis rate models, which can enable the prediction of the ß-lactam antibiotics persistence in frigid waters.


Assuntos
Penicilinas , beta-Lactamas , Concentração de Íons de Hidrogênio , Hidrólise , Cinética , Temperatura
2.
BMJ Case Rep ; 14(11)2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753720

RESUMO

A 24-year-old fit and well Caucasian man was referred to acute hospital via his General Practitioner with chest pain, palpitations, shortness of breath and an antecedent sore throat. Investigations revealed pericardial and pleural effusions, pericardial thickening on MRI, mild mitral regurgitation on echocardiogram and a raised Antistreptolysin O (ASO) titre.He was treated as acute rheumatic fever (ARF) with a prolonged course of penicillin, supportive therapy with bisoprolol and colchicine with lansoprazole cover. The patient made a full recovery and subsequent cardiac MRI showed resolution of all changes.


Assuntos
Derrame Pleural , Febre Reumática , Adulto , Dor no Peito , Ecocardiografia , Humanos , Masculino , Penicilinas/uso terapêutico , Febre Reumática/complicações , Febre Reumática/diagnóstico , Febre Reumática/tratamento farmacológico , Adulto Jovem
3.
Int J Med Inform ; 156: 104611, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34653809

RESUMO

BACKGROUND: The penicillin adverse drug reaction (ADR) label is common in electronic health records (EHRs). However, there is significant misclassification between allergy and intolerance within the EHR and most patients can be delabelled after an immunologic assessment. Machine learning natural language processing may be able to assist with the categorisation and risk stratification of penicillin ADRs. OBJECTIVE: The aim of this study was to use text entered into an EHR to derive and evaluate machine learning models to classify penicillin ADRs and assess the risk of true allergy. METHODS: Machine learning natural language processing was applied to free-text penicillin ADR data extracted from a public health system EHR. The model was developed by training on labelled dataset. ADR entries were split into training and testing datasets and used to develop and test a variety of machine learning models. These were compared to categorisation with a simple algorithm using keyword search. RESULTS: The best performing model for the classification of penicillin ADRs as being consistent with allergy or intolerance was the artificial neural network (AUC 0.994, sensitivity 0.99, specificity 0.96). The artificial neural network also achieved the highest AUC in the classification of high- or low-risk of true allergy (AUC 0.988, sensitivity 0.99, specificity 0.99). All ADR labels were able to be classified using these machine learning models, whereas a small proportion were unclassifiable using the simple algorithm as they contained no keywords. CONCLUSION: Machine learning natural language processing performed similarly to expert criteria in classifying and risk stratifying penicillin ADRs labels. These models outperformed simpler algorithms in their ability to interpret free-text data contained in the EHR. The automated evaluation of penicillin ADR labels may allow real-time risk stratification to facilitate delabelling and improve the specificity of prescribing alerts.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Processamento de Linguagem Natural , Algoritmos , Automação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Registros Eletrônicos de Saúde , Humanos , Aprendizado de Máquina , Penicilinas/efeitos adversos , Medição de Risco
4.
BMC Infect Dis ; 21(1): 1083, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34670500

RESUMO

BACKGROUND: Penicillin allergy prevalence is internationally reported to be around 10%. However, the majority of patients who report a penicillin allergy do not have a clinically significant hypersensitivity. Few patients undergo evaluation, which leads to overuse of broad-spectrum antibiotics. The objective of this study was to monitor prevalence and implement screening and testing of hospitalized patients. METHODS: All patients admitted to the medical department in a local hospital in Oslo, Norway, with a self-reported penicillin allergy were screened using an interview algorithm to categorize the reported allergy as high-risk or low-risk. Patients with a history of low-risk allergy underwent a direct graded oral amoxicillin challenge to verify absence of a true IgE-type allergy. RESULTS: 257 of 5529 inpatients (4.6%) reported a penicillin allergy. 191 (74%) of these patients underwent screening, of which 86 (45%) had an allergy categorized as low-risk. 54 (63%) of the low-risk patients consented to an oral test. 98% of these did not have an immediate reaction to the amoxicillin challenge, and their penicillin allergy label could thus be removed. 42% of the patients under treatment with antibiotics during inclusion could switch to treatment with penicillins immediately after testing, in line with the national recommendations for antibiotic use. CONCLUSIONS: The prevalence of self-reported penicillin allergy was lower in this Norwegian population, than reported in other studies. Screening and testing of hospitalized patients with self-reported penicillin allergy is a feasible and easy measure to de-label a large proportion of patients, resulting in immediate clinical and environmental benefit. Our findings suggest that non-allergist physicians can safely undertake clinically impactful allergy evaluations.


Assuntos
Hipersensibilidade a Drogas , Penicilinas , Amoxicilina/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Humanos , Penicilinas/efeitos adversos , Projetos Piloto , Testes Cutâneos
5.
J Chromatogr A ; 1658: 462605, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34662823

RESUMO

The presence of antibiotics in the aquatic environment is becoming one of the main research focus of scientists and policy makers. Proof of that is the inclusion of four antibiotics, amongst which is amoxicillin, in the EU Watch List (WL) (Decision 2020/1161/EU)) of substances for water monitoring. The accurate quantification of amoxicillin in water at the sub-ppb levels required by the WL is troublesome due to its physicochemical properties. In this work, the analytical challenges related to the determination of amoxicillin, and six related penicillins (ampicillin, cloxacillin, dicloxacillin, penicillin G, penicillin V and oxacillin), have been carefully addressed, including sample treatment, sample stability, chromatographic analysis and mass spectrometric detection by triple quadrupole. Given the low recoveries obtained using different solid-phase extraction cartridges, we applied the direct injection of water samples using a reversed-phase chromatographic column that allowed working with 100% aqueous mobile phase. Matrix effects were evaluated and corrected using the isotopically labelled internal standard or correction factors based on signal suppression observed in the analysis of spiked samples. The methodology developed was satisfactorily validated at 50 and 500 ng L - 1 for the seven penicillins studied, and it was applied to different types of water matrices, revealing the presence of ampicillin in one surface water sample and cloxacillin in three effluent wastewater samples.


Assuntos
Amoxicilina , Água , Ampicilina/análise , Cromatografia Líquida de Alta Pressão , União Europeia , Penicilinas/análise , Extração em Fase Sólida
6.
Molecules ; 26(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34641579

RESUMO

Spiro compounds provide attractive targets in drug discovery due to their inherent three-dimensional structures, which enhance protein interactions, aid solubility and facilitate molecular modelling. However, synthetic methodology for the spiro-functionalisation of important classes of penicillin and cephalosporin ß-lactam antibiotics is comparatively limited. We report a novel method for the generation of spiro-cephalosporin compounds through a Michael-type addition to the dihydrothiazine ring. Coupling of a range of catechols is achieved under mildly basic conditions (K2CO3, DMF), giving the stereoselective formation of spiro-cephalosporins (d.r. 14:1 to 8:1) in moderate to good yields (28-65%).


Assuntos
Cefalosporinas/síntese química , Compostos de Espiro/síntese química , Catecóis/química , Estrutura Molecular , Penicilinas/química
7.
PLoS One ; 16(9): e0257004, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34534230

RESUMO

AIM: To investigate the epidemiology of S. aureus and MRSA nasal carriage among people with diabetes at the Korle Bu Teaching Hospital in Accra, including the prevalence, predictors of carriage, and antibiotic resistance. METHODOLOGY: This study was cross-sectional, involving 300 diabetes patients and 106 non-diabetic individuals. Swab specimens of the nares were obtained from the participants and bacteriologically-cultured. Identification and characterization of S. aureus and MRSA were based on standard bacteriological methods; antimicrobial susceptibility testing was by the Kirby-Bauer method. RESULTS: The prevalence of staphylococcal carriage, the diabetes group relative to the non-diabetes group, were 31.0% and 10.4% (S. aureus), and 3.3% and 0.0% (MRSA). Presence of diabetes predisposed to S. aureus carriage, but not MRSA nor coagulase-negative staphylococci (CoNS) carriage (OR = 3.88; p < 0.0001). Colonization with CoNS was protective of S. aureus (OR = 0.039, p < 0.001) and MRSA (OR = 0.115, p = 0.043) colonization among the diabetics. The antimicrobial resistance patterns recorded among the S. aureus isolated from the diabetic individuals relative to the non-diabetics were as follows: penicillin (95% vs. 91%), tetracycline (37% vs. 27%), cotrimoxazole (30% vs. 36%), erythromycin (17% vs. 0%), norfloxacin (13% vs. 0%), clindamycin (12% vs. 0%), gentamicin (9% vs. 0%), fusidic acid (10% vs. 9%), linezolid (4% vs. 0%), and rifampicin (5% vs. 0%). The proportion of multidrug resistant S. aureus was 41% (n = 38) in the diabetes group and 0% in the non-diabetes group; this difference was statistically significant (p = 0.01). CONCLUSIONS: The presence of diabetes predisposed the participants to S. aureus carriage by almost four folds, but not MRSA carriage. Colonization with CoNS was protective of S. aureus and MRSA carriage in the diabetes group. Finally, linezolid remains a good therapeutic agent for anti-MRSA therapy.


Assuntos
Complicações do Diabetes/microbiologia , Diabetes Mellitus/microbiologia , Farmacorresistência Bacteriana Múltipla , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/microbiologia , Adolescente , Adulto , Antibacterianos/uso terapêutico , Portador Sadio , Clindamicina/uso terapêutico , Estudos Transversais , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Eritromicina/uso terapêutico , Feminino , Ácido Fusídico/uso terapêutico , Gentamicinas/uso terapêutico , Humanos , Linezolida/uso terapêutico , Masculino , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Cavidade Nasal/microbiologia , Norfloxacino/uso terapêutico , Penicilinas/uso terapêutico , Rifampina/uso terapêutico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Tetraciclina/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
8.
J Pharm Biomed Anal ; 206: 114377, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34563978

RESUMO

The evaluation of true penicillin allergy is significant to reduce its occurrence and the overdiagnosis before anti-infective treatment. However, the currently available methods with high specificity still face the problem of low sensitivity, thereby easily leading to false negatives. Herein, an alkyne responsive surface-enhanced Raman scattering (SERS) immunosensor is reported for ultrasensitive detection of penicillin allergen penicilloyl protein (P-protein) by using Au-Ag alloy nanoparticles@(antibody + alkyne probe) (as SERS immunoprobe) together with Ag nanofilm modified by antibody (as SERS capture substrate). The SERS immunoassay integrates the interference-free Raman response of high wavenumber region (2212 cm-1) and specific capture antibody with high affinity to selectively recognize P-protein from complicated sample. Meanwhile, the target-induced near-field coupling effect between localized surface plasmon resonances of individual SERS immunoprobe and capture substrate enables the detection of P-protein as low as pg/mL level, and the limit of detection can reach 0.329 pg/mL that is about 6 orders of magnitude lower than the limit defined protein residue (causing penicillin allergy). With the ultrasensitivity and specific selectivity, the proposed SERS immunoassay platform can precisely evaluate the content of P-protein in blood sample or penicillin drugs. It will be a potential tool to monitor allergic reaction to penicillin and better understand the mechanism of penicillin hypersensitivity.


Assuntos
Técnicas Biossensoriais , Hipersensibilidade , Nanopartículas Metálicas , Alcinos , Ouro , Humanos , Imunoensaio , Penicilinas , Prata , Análise Espectral Raman
9.
Environ Pollut ; 290: 118075, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34492529

RESUMO

Combining hydrothermal treatment and composting is an effective method to dispose of penicillin fermentation residue (PFR), but the safety and related mechanism are still unclear. In this study, penicillin solution was hydrothermally treated to decipher its degradation mechanism, and then hydrothermally treated PFR (HT-PFR) was mixed with bulking agents at ratios of 2:0 (CK), 2:1.5 (T1), and 2:5 (T2) to determine the absolute abundance of antibiotic resistance genes (ARGs) and the succession of bacterial community. Results showed that penicillin was degraded to several new compounds without the initial lactam structure after hydrothermal treatment. During composting, temperature and pH of the composts increased with the raising of HT-PFR proportion, except the pH at days 2. After 52 days of composting, the absolute copies of ARGs (blaTEM, blaCMY2, and blaSFO) and the relative abundance of bacteria related to pathogens were reduced significantly (P < 0.05). Especially, the total amount of ARGs in the samples of CK and T1 were decreased to equal level (around 5 log10 copies/g), which indicated that more ARGs were degraded in the latter by the composting process. In the CK samples, Bacteroidetes and Proteobacteria accounted for ~69.8% of the total bacteria, but they were gradually replaced by Firmicutes with increasing proportions of HT-PFR, which can be caused by the high protein content in PFR. Consisting with bacterial community, more gram-positive bacteria were observed in T1 and T2, and most of them are related to manganese oxidation and chitinolysis. As composting proceeded, bacteria having symbiotic or pathogenic relationships with animals and plants were reduced, but those related to ureolysis and cellulolysis were enriched. Above all, hydrothermal treatment is effective in destroying the lactam structure of penicillin, which makes that most ARGs and pathogenic bacteria are eliminated in the subsequent composting.


Assuntos
Compostagem , Animais , Antibacterianos/farmacologia , Bactérias/genética , Resistência Microbiana a Medicamentos/genética , Fermentação , Genes Bacterianos , Esterco , Penicilinas
10.
BMJ Open ; 11(9): e049481, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580096

RESUMO

INTRODUCTION: Alternatives to carbapenems are needed in the treatment of third-generation cephalosporin-resistant Enterobacterales (3GCR-E). Temocillin is a suitable candidate, but comparative randomised studies are lacking. The objective is to investigate if temocillin is non-inferior to carbapenems in the targeted treatment of bacteraemia due to 3GCR-E. METHODS AND ANALYSIS: Multicentre, open-label, randomised, controlled, pragmatic phase 3 trial. Patients with bacteraemia due to 3GCR-E will be randomised to receive intravenously temocillin (2 g three times a day) or carbapenem (meropenem 1 g three times a day or ertapenem 1 g once daily). The primary endpoint will be clinical success 7-10 days after end of treatment with no recurrence or death at day 28. Adverse events will be collected; serum levels of temocillin will be investigated in a subset of patients. For a 10% non-inferiority margin, 334 patients will be included (167 in each study arm). For the primary analysis, the absolute difference with one-sided 95% CI in the proportion of patients reaching the primary endpoint will be compared in the modified intention-to-treat population. ETHICS AND DISSEMINATION: The study started after approval of the Spanish Regulatory Agency and the reference institutional review board. Data will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04478721.


Assuntos
Bacteriemia , Meropeném , Penicilinas , Bacteriemia/tratamento farmacológico , Cefalosporinas/farmacologia , Ensaios Clínicos Fase III como Assunto , Enterobacteriaceae/efeitos dos fármacos , Humanos , Meropeném/uso terapêutico , Estudos Multicêntricos como Assunto , Penicilinas/uso terapêutico , Ensaios Clínicos Pragmáticos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Am J Case Rep ; 22: e932467, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34379615

RESUMO

BACKGROUND Neurosyphilis is a bacterial infection of the brain and the spinal cord, caused by Treponema pallidum. Its nonspecific clinical presentation includes cognitive impairment and motor and/or sensory function compromise. Neurosyphilis infections in patients with HIV have increased over the past few years and many cases of neurosyphilis manifest in patients with HIV who have low CD4 T-cell counts and high viral loads (VL). However, there is extremely limited acknowledgement in the literature about neurosyphilis presentations in patients with HIV who have normal CD4 counts. CASE REPORT We present a neurosyphilis and HIV coinfection in a patient with a normal CD4 count and an undetectable VL. A 69-year-old woman with a medical history of HIV was on a prescribed antiretroviral treatment regimen. She presented in the Emergency Room in an unresponsive state, although this had been preceded by a period of rapidly progressive cognitive decline. Her brain computed tomography scan without contrast was unremarkable. Laboratory test results were within normal limits, except for a positive result for the microhemagglutination assay for Treponema pallidum antibodies and rapid plasma regain (RPR) test, which was highly suggestive of neurosyphilis as a presumed diagnosis. She showed remarkable clinical improvement after the initiation of conventional treatment for neurosyphilis, which is a 14-day regimen of intravenous penicillin G. CONCLUSIONS Given the broad neurological manifestations of neurosyphilis and its increasing incidence in patients with HIV, it is important to consider neurosyphilis in the differential diagnosis after ruling out other causes of encephalopathy, especially in patients with an undetectable VL and a normal CD4 count.


Assuntos
Infecções por HIV , Neurossífilis , Idoso , Contagem de Linfócito CD4 , Feminino , HIV , Infecções por HIV/complicações , Humanos , Neurossífilis/complicações , Neurossífilis/diagnóstico , Neurossífilis/tratamento farmacológico , Penicilinas , Carga Viral
12.
Ned Tijdschr Geneeskd ; 1652021 07 08.
Artigo em Holandês | MEDLINE | ID: mdl-34346594

RESUMO

In this Commentary on a British study of congenital malformations after use of macrolide antibiotics by pregnant women with data from general practitioners, the importance of high-quality healthcare databases for pharmacovigilance is emphasized. The authors of the British study compared three groups during the study period January 1990 through June 2016: 104,605 children from mothers treated during pregnancy with a macrolide or penicillin, a group of 53,735 siblings, and 82,314 children whose mothers were treated with a macrolide before conception. A significantly increased risk of 55% of congenital malformations was seen for use of macrolides during the first semester in comparison to use of penicillins, especially cardiovascular malformations. Although this well-performed study is the largest up till now, some potential limitations are discussed such as potential exposure and outcome misclassification, as well as confounding by indication.


Assuntos
Macrolídeos , Gestantes , Antibacterianos/efeitos adversos , Criança , Atenção à Saúde , Feminino , Humanos , Macrolídeos/efeitos adversos , Penicilinas , Gravidez
13.
J Allergy Clin Immunol Pract ; 9(8): 2947-2956, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34366093

RESUMO

In the western world, up to 10% of the general population and more than 15% of hospitalized patients report penicillin allergy. After a comprehensive evaluation, more than 95% of patients who report a penicillin allergy can subsequently tolerate this antibiotic. Traditionally, the most widely accepted protocol to evaluate beta-lactam (BL) allergy consisted of skin testing (ST) followed by a drug provocation test (DPT) in ST-negative patients. DPT is the gold standard for proving or excluding BL allergy and is considered the final and definitive step in the evaluation. Recently, studies have been published that support the use of direct DPTs without preceding ST for both pediatric and adult patients who report a low-risk historical reaction to BLs. However, these studies use various risk-stratification criteria to determine eligibility for a direct DPT. A standardized protocol for DPT is also lacking. In this review, we assess the current literature and evidence for performing direct DPT in the pediatric and adult populations. On the basis of this evidence, we also present risk-based algorithms for the evaluation of BL allergy in pediatric and adult populations based on a description of the historical reaction.


Assuntos
Hipersensibilidade a Drogas , beta-Lactamas , Adulto , Antibacterianos/efeitos adversos , Criança , Hipersensibilidade a Drogas/diagnóstico , Humanos , Penicilinas/efeitos adversos , Testes Cutâneos , beta-Lactamas/efeitos adversos
14.
Sci Rep ; 11(1): 16768, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408224

RESUMO

Increasing incidence of type 1 diabetes is supposed to be induced by environmental factors. Microbiome modulated by antibiotics seems to serve as one of the environmental factors which could influence the development of T1DM. Mitochondria, as autochthonous environmental bacteria living in our cells, and other bacteria share many common enzymes including beta-lactamases and it is supported by evidence that some beta-lactamase inhibitors are able to interact with counterpart enzymes. Thus, antibiotics may utilize two different pathways influencing the development of T1DM; one through modulation of microbiome and a second one via the interaction of mitochondrial enzymes. Data of consumption of penicillin (both narrow and broad spectrum) and beta-lactamase inhibitors in 30 European countries were collected from the database of the European Centre for Disease Prevention and Control. These data were correlated with the prevalence reported by the International Diabetes Federation (2019) referring to type 1 diabetes in Europe. No correlation was found between total penicillin consumption or use of broad spectrum penicillin and the prevalence of type 1 diabetes. Nevertheless, broad spectrum penicillin, in combination with beta-lactamase inhibitor, was in inverse correlation with the prevalence of type 1 diabetes (r = - 0.573, p = 0.001). On the other hand, narrow spectrum penicillin was in positive correlation with type 1 diabetes (r = 0.523, p = 0.003). Prevalence of type 1 diabetes showed an inverse correlation with the use of beta-lactamase inhibitors and a positive one with that of narrow spectrum penicillin. Such a detailed analysis has not so far been provided referring to the penicillin group. In the background of this association either microbiomal or direct mitochondrial effects can be supposed.


Assuntos
Diabetes Mellitus Tipo 1 , Penicilinas , Inibidores de beta-Lactamases , Adolescente , Adulto , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Lactente , Masculino , Penicilinas/administração & dosagem , Penicilinas/efeitos adversos , Prevalência , Adulto Jovem , Inibidores de beta-Lactamases/administração & dosagem , Inibidores de beta-Lactamases/efeitos adversos
15.
Appl Microbiol Biotechnol ; 105(18): 6909-6920, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34463802

RESUMO

From the previous transcriptome analysis (Hirasawa et al. Biotechnol J 13:e1700612, 2018), it was found that expression of genes whose expression is regulated by stress-responsive transcriptional regulators was altered during penicillin-induced glutamic acid production in Corynebacterium glutamicum. Therefore, we investigated whether stress treatments, such as copper and iron addition, could induce glutamic acid production in C. glutamicum and found that the addition of copper did induce glutamic acid production in this species. Moreover, we also determined that glutamic acid production levels upon copper addition in a gain-of-function mutant strain of the mechanosensitive channel, NCgl1221, involved in glutamic acid export, were comparable to glutamic acid levels produced upon penicillin addition and biotin limitation in the wild-type strain. Furthermore, disruption of the odhI gene, which encodes a protein responsible for the decreased activity of the 2-oxoglutarate dehydrogenase complex during glutamic acid production, significantly diminished glutamic acid production induced by copper. These results indicate that copper can induce glutamic acid production and this induction requires OdhI like biotin limitation and penicillin addition, but a gain-of-function mutation in the NCgl1221 mechanosensitive channel is necessary for its high-level glutamic acid production. However, a significant increase in odhI transcription was not observed with copper addition in both wild-type and NCgl1221 gain-of-function mutant strains. In addition, disruption of the csoR gene encoding a copper-responsive transcriptional repressor enhanced copper-induced glutamic acid production in the NCgl1221 gain-of-function mutant, indicating that unidentified CsoR-regulated genes may contribute to copper-induced glutamic acid production in C. glutamicum. KEY POINTS: • Copper can induce glutamic acid production by Corynebacterium glutamicum. • Copper-induced glutamic acid production requires OdhI protein. • Copper-induced glutamic acid production requires a gain-of-function mutation in the mechanosensitive channel NCgl1221, which is responsible for the production of glutamic acid.


Assuntos
Corynebacterium glutamicum , Proteínas de Bactérias/genética , Cobre , Corynebacterium glutamicum/genética , Ácido Glutâmico , Penicilinas
16.
BMC Pediatr ; 21(1): 327, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315435

RESUMO

BACKGROUND: Infectious morbidity and mortality in the first week of life is commonly caused by early-onset neonatal Group B streptococcus (GBS) disease. This infection is spread from GBS positive mothers to neonates by vertical transmission during delivery and results in serious illness for newborns. Intrapartum prophylactic antibiotics have decreased the incidence of early-onset neonatal GBS disease by 80%. Patients labeled with a penicillin allergy (PcnA) alternatively receive either vancomycin or clindamycin but effectiveness is controversial. We evaluated the influence of a reported PcnA label versus no PcnA label on inpatient maternal and neonatal outcomes. METHODS: Our goal was to examine the relationship between a PcnA label, maternal and neonatal outcomes, and hospital costs. We collected retrospective data with institutional IRB approval from 2016 - 2018 for hospitalized patients who were GBS positive, pregnant at time of admission, ≥ 18 years of age, received antibiotic prophylaxis for GBS, were labeled as PcnA or non-PcnA, and completed a vaginal delivery. Patient characteristics and maternal/neonatal outcomes were examined. Statistical tests included calculations of means, medians, proportions, Mann-Whitney, two-sample t-tests, Chi-squared or Fisher's Exact tests, and generalized linear and logistic regression models. Significance was set at p < 0.05. RESULTS: Most PcnA patients were white, older, had a higher median body mass index and mean heart rate, and a greater proportion used tobacco than non-PcnA patients. In regression analyses, PcnA hospitalized patients received a shorter duration of antibiotic treatment than non-PcnA patients [incidence rate ratio (IRR): 0.45, 95% CI: 0.38-0.53]. PcnA patients were also more likely to have their baby's hospital LOS be > 48 h [adjusted odds ratio (AOR): 1.35, 95% CI: 1.07-1.69] even though the PcnA mothers' LOS was not different from non-PcnA mothers. Cost of care, mortality, intensive care, median parity, mean gravidity, and miscarriage were similar between the groups. CONCLUSIONS: In hospitalized obstetric patients, a PcnA label was associated with a shorter maternal course of antibiotic treatment and a longer neonatal LOS. Further prospective studies are needed to clarify the underlying reasons for these outcomes.


Assuntos
Hipersensibilidade a Drogas , Complicações Infecciosas na Gravidez , Infecções Estreptocócicas , Antibacterianos/efeitos adversos , Antibioticoprofilaxia , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/prevenção & controle , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Mães , Penicilinas/efeitos adversos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/prevenção & controle , Estudos Retrospectivos , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus agalactiae
17.
BMC Infect Dis ; 21(1): 679, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256734

RESUMO

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.


Assuntos
Amoxicilina/farmacologia , Cefotaxima/farmacologia , Testes de Sensibilidade Microbiana/métodos , Penicilinas/farmacologia , Pneumonia Pneumocócica , Streptococcus pneumoniae , Administração Oral , Antibacterianos/farmacologia , Cefalosporinas/classificação , Cefalosporinas/farmacologia , Humanos , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , beta-Lactamas/farmacologia
18.
BMJ Case Rep ; 14(7)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34257106

RESUMO

Actinomycosis is a subacute-to-chronic bacterial infection caused by gram-positive, filamentous, non-acid-fast, facultative anaerobic bacteria. It is a normal commensal bacterium found in the oral cavity and the lower reproductive tract of women. We present a case of primary actinomycosis of the breast. A postmenopausal woman, complicated by penicillin allergy, presented with a left breast lump clinically simulating malignancy. The first line of treatment for actinomycosis is penicillin. Due to a penicillin allergy, the patient was initially treated with doxycycline. However, doxycycline was discontinued due to tremors, and was replaced by clindamycin. The patient had a good clinical response with resolution of the abscess.


Assuntos
Actinomicose , Hipersensibilidade a Drogas , Actinomicose/diagnóstico , Actinomicose/tratamento farmacológico , Antibacterianos/efeitos adversos , Clindamicina , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/etiologia , Feminino , Humanos , Penicilinas/efeitos adversos
19.
Inorg Chem ; 60(15): 11081-11089, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34242020

RESUMO

A CuI-TbIII heterometallic MOF, namely 1·DMF, was obtained via a coordination assembly process of isonicotinic acid with CuI and TbIII. 1·DMF can be switched to 1·MeOH in methanol with a luminescent emission response. Meanwhile, 1·MeOH exhibits a reversible single-crystal transformation to 1·DMF after immersion in DMF. Both MOFs have superior physicochemical stability. The 1·DMF-based biosensor has a remarkable sensing performance toward penicillin.


Assuntos
Cobre/química , Luminescência , Compostos Organometálicos/química , Penicilinas/análise , Térbio/química , Teoria da Densidade Funcional , Modelos Moleculares , Conformação Molecular , Penicilinas/química
20.
J Antimicrob Chemother ; 76(12 Suppl 2): ii60-ii67, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312656

RESUMO

OBJECTIVES: The quality of antibiotic consumption in the community can be assessed using 12 drug-specific quality indicators (DSQIs) developed by the European Surveillance of Antimicrobial Consumption (ESAC) project. We compared quality in 2009 and 2017 in the EU/European Economic Area (EEA) and evaluated the impact of using different DDD values (ATC/DDD indices 2011 and 2019) for the 2009 quality assessment using these DSQIs and a joint scientific opinion (JSO) indicator. METHODS: We calculated the 12 DSQIs and the JSO indicator for 2017 and for 2009 for EU/EEA countries able to deliver values. For each of the indicators we grouped the 2017 and 2009 indicator values into four quartiles. To evaluate changes in quality between 2009 and 2017, we used the quartile distribution of the 2009 indicator values in 30 EU/EEA countries as benchmarks. In addition, we compared the quality assessment for 2009 using the ATC/DDD indices 2011 and 2019. RESULTS: In 2017, a difference in the quality of antibiotic consumption in the community between northern and southern EU/EEA countries remained, but also several eastern EU/EEA countries shifted towards lower quality. Quality of antibiotic consumption decreased between 2009 and 2017 in particular indicator values for penicillin, quinolone, relative ß-lactam and broad- versus narrow-spectrum antibiotic consumption, and seasonal variation. Using different ATC/DDD indices did not substantially change countries' ranking based on their DSQI values. CONCLUSIONS: The quality of antibiotic consumption in the community as measured by the DSQIs further decreased between 2009 and 2017, especially in Southern and Eastern European countries. A continuous effort to improve antibiotic consumption is essential to reduce antibiotic consumption in general and the use of broad-spectrum antibiotics in particular.


Assuntos
Antibacterianos , Quinolonas , Antibacterianos/uso terapêutico , Uso de Medicamentos , Europa (Continente) , União Europeia , Humanos , Penicilinas
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