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1.
Croat Med J ; 63(2): 156-165, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35505649

RESUMO

AIM: To assess serotype distribution, antibiotic resistance, and vaccine coverage against Streptococcus pneumoniae causing invasive infections in Croatian adults from 2005 to 2019. METHODS: In this retrospective study, invasive pneumococcal strains were collected through a microbiological laboratory network with country coverage >95%. Capsular typing was performed with the Quellung reaction. In vitro susceptibility testing was carried out according to the European Committee on Antimicrobial Susceptibility Twating guidelines. In macrolide-resistant isolates, the presence of ermB and mefA genes was evaluated. RESULTS: During the fifteen-year study period, 1123 invasive pneumococcal isolates were obtained. The most prevalent serotypes were 3, 14, 19A, 9V, 7F, and 23F, comprising 60% of all invasive pneumococcal isolates. Serotype 3 was the dominant serotype, with the highest prevalence in patients ≥65 years of age. Penicillin susceptibility, increased exposure was 18.6%, mostly associated with serotypes 14 and 19A. Resistance to penicillin was low (<1%). Macrolide resistance was 23%, mostly associated with serotypes 14, 19A, and 19F. The coverage with 13-valent conjugate vaccine (PCV13) and 23-valent polysaccharide vaccine (PPV23) was 80.2% and 93.6%, respectively. CONCLUSIONS: The incidence of invasive pneumococcal disease in adults is highest in patients ≥65 years of age. Penicillin susceptibility, increased exposure and macrolide resistance were mostly associated with serotypes 14 and 19A. PCV13 and PPV23 provide very high serotype coverage. Future studies should evaluate the effects of the 10-valent vaccine, introduced in the Croatian National Immunization Program in June 2019, on serotype distribution and antibiotic resistance rates.


Assuntos
Antibacterianos , Streptococcus pneumoniae , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Croácia/epidemiologia , Farmacorresistência Bacteriana/genética , Humanos , Macrolídeos/farmacologia , Testes de Sensibilidade Microbiana , Penicilinas/farmacologia , Estudos Retrospectivos , Sorogrupo , Sorotipagem , Streptococcus pneumoniae/genética
2.
Proc Natl Acad Sci U S A ; 119(18): e2117310119, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35486701

RESUMO

SignificanceMicrobial resistance to ß-lactam antibiotics mediated by ß-lactamase-catalyzed hydrolysis is a major global health concern. Penam sulfones, which are structurally related to penicillins, inhibit clinically important serine ß-lactamases (SBLs) by forming transiently stable covalent complexes, thereby protecting ß-lactam antibiotics from hydrolysis. The characterization of these complexes and mechanisms of SBL inhibition is important for development of new SBL inhibitors (SBLi). Studies on the mechanism of the new SBLi enmetazobactam employing mass spectrometry and X-ray crystallography inform on its mode of action and also lead to reevaluation of mechanisms of current clinically important SBLi. In addition to insights into the mechanisms of transient SBL inhibition by penam sulfones, the results reveal potential for penam sulfone optimization to enable irreversible SBL inhibition.


Assuntos
Compostos Azabicíclicos , Inibidores de beta-Lactamases , Penicilinas , Sulfonas , Triazóis , Inibidores de beta-Lactamases/química , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/química
3.
Am Fam Physician ; 105(4): Online, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35426651
4.
PLoS One ; 17(4): e0264438, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35385475

RESUMO

OBJECTIVE: This study aimed to compare the efficacy of different antibiotic classes and dosages in preventing maternal infection after cesarean delivery. METHODS: Databases were searched for randomized controlled trials (RCTs) published between January 1980 and January 2021 on antibiotic use for the prevention of maternal infection after cesarean delivery. The outcomes were endometritis, febrile morbidity, and wound infection, reported as odds ratios (OR) and surface under the cumulative ranking curve analysis scores. RESULTS: A total of 31 RCTs met the inclusion criteria. In the network meta-analysis (NMA) for endometritis, pooled network OR values indicated that the following interventions were superior to placebo: cephalosporins (OR: 0.18, 95% credibility interval [CrI]: 0.07-0.45), penicillins (OR: 0.19, 95% CrI: 0.07-0.50), penicillins (multiple doses) (OR: 0.20, 95% CrI: 0.05-0.65), combination therapies (OR: 0.22, 95% CrI: 0.09-0.54), and cephalosporins (multiple doses) (OR: 0.25, 95% CrI: 0.08-0.74). In the NMA for febrile morbidity, placebo was more effective than the other interventions. In the NMA for wound infection, pooled network OR values indicated that the following interventions were superior to placebo: penicillin (OR: 0.14, 95% CrI: 0.05-0.37), cephalosporins (OR: 0.19, 95% CrI: 0.08-0.41), cephalosporins (multiple doses) (OR: 0.20, 95% CrI: 0.06-0.58), combination therapies (OR: 0.29, 95% CrI: 0.13-0.57), macrolides (OR: 0.33, 95% CrI: 0.15-0.74), and penicillins (multiple doses) (OR: 0.40, 95% CrI: 0.17-0.91). CONCLUSIONS: Compared with placebo, a single dose of commonly used antibiotics may prevent maternal infection after cesarean delivery. However, the incidence of febrile morbidity was not reduced.


Assuntos
Endometrite , Infecção dos Ferimentos , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Cesárea/efeitos adversos , Endometrite/tratamento farmacológico , Feminino , Febre/tratamento farmacológico , Febre/etiologia , Febre/prevenção & controle , Humanos , Metanálise em Rede , Penicilinas/uso terapêutico , Gravidez , Infecção dos Ferimentos/tratamento farmacológico
5.
Immunol Allergy Clin North Am ; 42(2): 375-389, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35469624

RESUMO

Penicillin allergy can be risk stratified in the hospital or outpatient setting to identify low-, moderate-, and high-risk phenotypes. Following ascertainment of risk, dedicated penicillin allergy testing strategies can be deployed successfully for each risk type-direct oral challenge (low risk), skin testing and oral challenge (moderate risk), and specialist review and/or skin testing (high risk).


Assuntos
Hipersensibilidade a Drogas , Penicilinas , Hipersensibilidade a Drogas/diagnóstico , Humanos , Penicilinas/efeitos adversos , Testes Cutâneos
6.
Immunol Allergy Clin North Am ; 42(2): 433-452, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35469628

RESUMO

Drug allergies are reported in approximately 10% of children and carry significant health and economic impacts. However, only a minority of these reported drug allergies are established on diagnostic workup. Classically, drug allergies were diagnosed by skin prick and/or intradermal tests. However, recent data reveal that a direct ingestion challenge is often an appropriate diagnostic strategy in cases of reported nonsevere reactions to penicillin derivatives in children. This article will review the prevalence, diagnosis, and management of the main culprits of pediatric drug allergies: antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). We will also review severe cutaneous adverse reactions to drugs in children.


Assuntos
Hipersensibilidade a Drogas , Antibacterianos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Criança , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/terapia , Humanos , Penicilinas/efeitos adversos , Testes Cutâneos
8.
Nat Commun ; 13(1): 2143, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440126

RESUMO

Boron neutron capture therapy (BNCT) is an attractive approach to treat invasive malignant tumours due to binary heavy-particle irradiation, but its clinical applications have been hindered by boron delivery agents with low in vivo stability, poor biocompatibility, and limited application of combinational modalities. Here, we report boronsome, a carboranyl-phosphatidylcholine based liposome for combinational BNCT and chemotherapy. Theoretical simulations and experimental approaches illustrate high stability of boronsome. Then positron emission tomography (PET) imaging with Cu-64 labelled boronsome reveals high-specific tumour accumulation and long retention with a clear irradiation background. In particular, we show the suppression of tumour growth treated with boronsome with neutron irradiation and therapeutic outcomes are further improved by encapsulation of chemotherapy drugs, especially with PARP1 inhibitors. In sum, boronsome may be an efficient agent for concurrent chemoradiotherapy with theranostic properties against malignancies.


Assuntos
Terapia por Captura de Nêutron de Boro , Neoplasias , Boro/uso terapêutico , Compostos de Boro , Terapia por Captura de Nêutron de Boro/métodos , Radioisótopos de Cobre , Humanos , Lipossomos , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Penicilinas
9.
Biomed Res Int ; 2022: 4230788, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372567

RESUMO

Antibiotic resistance is one of the significant problems globally; there is an increase in resistance with introducing every new class of antibiotics. Further, this has become one of the reasons for arising of new resistance mechanisms in Acinetobacter baumannii. In this study, we have screened natural compounds as a possible inhibitor against the NDM-1 ß-lactamase enzyme from A. baumannii using a combination of in silico methods and in vitro evaluation. The database of natural compounds was screened against NDM-1 protein, using Glide docking, followed by QM-polarised ligand docking (QPLD). When the screened hits were validated in vitro, withaferin A and mangiferin had good IC50 values in reducing the activity of NDM-1 enzymes, and their fractional inhibitory concentration index (FICI) was ascertained in combination with imipenem. The withaferin A and mangiferin-NDM-1 docking complexes were analyzed for structural stability by molecular dynamic simulation analysis using GROMACS for 100 ns. The molecular properties of the natural compounds were then calculated using density functional theory (DFT). Withaferin A and mangiferin showed promising inhibitory activity and can be a natural compound candidate inhibitor synergistically used along with carbapenems against NDM-1 producing A. baumannii.


Assuntos
Acinetobacter baumannii , Inibidores de beta-Lactamases , Acinetobacter baumannii/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Penicilinas , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/metabolismo
11.
Int J Antimicrob Agents ; 59(4): 106567, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35288257

RESUMO

An increasing proportion of penicillin-susceptible Staphylococcus aureus (PSSA) has been reported over the last years. The aim of this retrospective study was to compare penicillin G with cloxacillin in the treatment of PSSA bloodstream infections. The primary outcome was the mortality rate after 90 days and the secondary outcome was the development of treatment complications of varying severity. Medical records from patients with PSSA bacteraemia during 2018-2020 were reviewed. Patient outcome was ranked on an ordinal scale according to severity: (i) alive at 90 days without any complications; (ii) adverse events not requiring treatment; (iii) change or addition of antibiotics owing to treatment failure or adverse events; (iv) relapse within 90 days; and (v) death within 90 days. The outcome ranking scale was dichotomised at every level and was analysed by logistic regression and a propensity score-weighted analysis. A total of 316 patients received cloxacillin and 68 patients received penicillin G as final treatment. Mortality rates did not differ significantly between the treatment groups (cloxacillin 19% vs. penicillin G 13%; P = 0.24), but patients treated with cloxacillin had an increased odds of having any complication compared with patients treated with penicillin G (odds ratio = 2.43, 95% confidence interval 1.30-4.53; P = 0.005). A propensity score analysis confirmed the results. Mortality rates in PSSA bacteraemia did not differ between treatment groups but cloxacillin treatment increased the overall odds of treatment complications.


Assuntos
Bacteriemia , Infecções Estafilocócicas , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Cloxacilina/uso terapêutico , Humanos , Penicilina G , Penicilinas/efeitos adversos , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Resultado do Tratamento
12.
Allergy Asthma Proc ; 43(2): 163-167, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35317894

RESUMO

Background: Penicillin is the most common reported drug allergy. Previous literature suggests that there is increased prevalence of penicillin drug allergy in female patients in the outpatient setting. However, this is poorly described in the inpatient setting. Objective: This study was performed to determine whether female sex is an independent risk factor for penicillin allergy in the inpatient setting. Methods: A retrospective review of electronic medical records (January 1, 2001-December 31, 2017) was performed for patients with a history of penicillin allergy who underwent penicillin skin testing (PST). Each chart review included the age at initial skin testing, sex, medications, and medical co-morbidities. The study was approved by the institutional review board. Results: 30,883 patients underwent PST with 29,354 and 1,529 occurring in the outpatient and inpatient setting respectively. 170 patients tested positive with a ≥ 5x5 wheal. Of the 170 positive patients, 122 were female (72%) and 48 were male (28%). 15 patients tested positive in the inpatient setting. Of the 1506 adult patients tested in the inpatient setting, 809 were female and 697 were male. 12 females (92.3%) and 1 one male (7.7%) tested positive with a ≥ 5x5 wheal (OR-10.5; 95% CI-1.4-80.8; p-value=0.02). 23 pediatric patients were tested in the inpatient setting. Two pediatric male patients were positive and no female pediatric patients tested positive (OR-1.7; 95% CI-0.5-5.9; p-value=0.5). Conclusion: In the inpatient setting, adult females are 10 times more likely to have a positive PST compared to males. Female sex may be a potential risk factor for objective penicillin drug allergy in the inpatient setting.


Assuntos
Hipersensibilidade a Drogas , Penicilinas , Adulto , Antibacterianos/efeitos adversos , Criança , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia , Feminino , Humanos , Pacientes Internados , Masculino , Penicilinas/efeitos adversos , Fatores de Risco , Testes Cutâneos/efeitos adversos
13.
JAMA Netw Open ; 5(3): e222117, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35285918

RESUMO

Importance: Penicillin allergy labels influence clinical decision-making, yet most children who are labeled do not have type 1 hypersensitivity allergic reactions and instead have a history of predictable adverse reactions or unspecified illness symptoms while receiving penicillin for viral infections. Studies describing penicillin allergy labeling in the pediatric outpatient setting are lacking. Objective: To describe the epidemiology and factors associated with penicillin allergy labels across 2 large US pediatric primary care networks. Design, Setting, and Participants: This retrospective, longitudinal birth cohort study was conducted in 90 primary care pediatric practices serving a diverse population of children across Houston, Texas, Austin, Texas, Philadelphia, Pennsylvania, and parts of New Jersey. Participants were children born between January 2010 and June 2020 who had a health care visit in the first 14 days of life and at least 2 additional visits in the first year of life at one of 90 primary care pediatric practices. Censoring criteria were additionally applied to exclude data from children no longer seeking health care in the 90 clinics over time. Statistical analysis was performed from February to May 2021. Exposures: Basic patient demographics, health care utilization, penicillin exposure, and primary clinic location. Main Outcomes and Measures: Addition of penicillin allergy label in the electronic medical record. Results: Among 334 465 children in the birth cohort, 164 173 (49.1%) were female; 72 831 (21.8%) were Hispanic, 59 598 (17.8%) were non-Hispanic Black, and 148 534 (44.4%) were non-Hispanic White; the median (IQR) age at censoring was 3.8 (1.7-6.6) years; 18 015 (5.4%) were labeled as penicillin allergic, but the prevalence of penicillin allergy labeling ranged from 0.9% to 10.2% across practices. Children were labeled at a median (IQR) age of 1.3 (0.9-2.3) years. Non-Hispanic White children were more likely to be labeled compared with non-Hispanic Black children after controlling for potential confounders (adjusted odds ratio, 1.7 [95% CI, 1.6-1.8]). There were 6797 allergic children (37.7%) labeled after receiving 1 penicillin prescription and 1423 (7.9%) labeled after receiving 0 penicillin prescriptions. Conclusions and Relevance: In this cohort study of more than 330 000 children, penicillin allergy labeling was common and varied widely across practices. Children were labeled early in life, and almost half were labeled after receiving 1 or 0 penicillin prescriptions. These findings raise questions regarding the validity of penicillin allergy labels. Future work exploring the fidelity of and outcomes associated with penicillin allergy-labeling in children is warranted.


Assuntos
Hipersensibilidade a Drogas , Registros Eletrônicos de Saúde , Antibacterianos/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Hipersensibilidade a Drogas/epidemiologia , Feminino , Humanos , Lactente , Masculino , Penicilinas/efeitos adversos , Philadelphia , Atenção Primária à Saúde , Estudos Retrospectivos
14.
PLoS Biol ; 20(3): e3001579, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35263322

RESUMO

Understanding how antibiotic use drives resistance is crucial for guiding effective strategies to limit the spread of resistance, but the use-resistance relationship across pathogens and antibiotics remains unclear. We applied sinusoidal models to evaluate the seasonal use-resistance relationship across 3 species (Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae) and 5 antibiotic classes (penicillins, macrolides, quinolones, tetracyclines, and nitrofurans) in Boston, Massachusetts. Outpatient use of all 5 classes and resistance in inpatient and outpatient isolates in 9 of 15 species-antibiotic combinations showed statistically significant amplitudes of seasonality (false discovery rate (FDR) < 0.05). While seasonal peaks in use varied by class, resistance in all 9 species-antibiotic combinations peaked in the winter and spring. The correlations between seasonal use and resistance thus varied widely, with resistance to all antibiotic classes being most positively correlated with use of the winter peaking classes (penicillins and macrolides). These findings challenge the simple model of antibiotic use independently selecting for resistance and suggest that stewardship strategies will not be equally effective across all species and antibiotics. Rather, seasonal selection for resistance across multiple antibiotic classes may be dominated by use of the most highly prescribed antibiotic classes, penicillins and macrolides.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Escherichia coli/genética , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Penicilinas , Estações do Ano
15.
Pediatrics ; 149(3)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35229120

RESUMO

BACKGROUND AND OBJECTIVES: Cefazolin, a first-generation cephalosporin, is the most commonly recommended antibiotic for perioperative prophylaxis to reduce surgical site infections. Children with a reported penicillin allergy often receive an alternative antibiotic because of a common misunderstanding of the cross-reactivity between these antibiotics. This use of alternative antibiotics in surgical populations have been associated with increased infections, antibiotic resistance, and health care costs. We aimed to increase the percentage of patients with nonsevere penicillin-class allergies who receive cefazolin for antibiotic prophylaxis. METHODS: A multidisciplinary team conducted this quality improvement initiative, with a series of 3 plan-do-study-act cycles aimed at children with nonsevere penicillin-class allergies undergoing surgical procedures that require antibiotic prophylaxis. The primary outcome measure was the percentage of surgical encounters among patients with nonsevere penicillin-class allergies who received cefazolin as antibiotic prophylaxis. Statistical process control charts were used to measure improvement over time. RESULTS: Approximately 400 children were involved in this project. There was special cause variation and a shift in the center line from 60% to 80% of eligible patients receiving cefazolin for antibiotic prophylaxis, which was sustained for the duration of the project. In the last month, 90% of eligible patient received cefazolin, surpassing our goal of 85%. This improvement has been sustained in the 5 months after project completion. We had no cases of severe allergic reactions in the operating room. CONCLUSIONS: Our multidisciplinary education-focused interventions were associated with a significant increase in the use of cefazolin for perioperative antibiotic prophylaxis in patient with penicillin allergies.


Assuntos
Cefazolina , Hipersensibilidade a Drogas , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/efeitos adversos , Cefazolina/uso terapêutico , Criança , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/prevenção & controle , Humanos , Penicilinas/efeitos adversos , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/prevenção & controle
17.
Microbiol Spectr ; 10(2): e0182221, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35357224

RESUMO

Streptococcus pneumoniae is one of the leading causes of meningitis in children. In Japan, since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), the number of pneumococcal meningitis due to non-PCV13 serotypes in children has increased. To clarify the clinical outcomes, serotype distributions, and antimicrobial susceptibility of isolated S. pneumoniae strains from pediatric pneumococcal meningitis, we clinically and bacteriologically analyzed 34 cases of pediatric pneumococcal meningitis that were reported after the PCV13 introduction era in Japan. The median age at diagnosis was 1 year (range: 3 months-13 years). Ten (29.4%) patients had underlying diseases. Twenty-nine (85.3%) patients had received at least one dose of any pneumococcal vaccine. Of the 34 patients with pneumococcal meningitis, 6 had sequelae, and 4 died. Nine (26.5%) strains were resistant to penicillin; five (15%) strains to meropenem, with an MIC of 0.5 µg/mL. All strains were susceptible to vancomycin and linezolid. Daptomycin's MIC50 was 0.064 µg/mL and MIC90 was 0.094 µg/mL. Among the tested strains, only four were PCV13 serotypes. Penicillin-resistant S. pneumoniae was isolated from 30.0% of the patients with sequelae and death. Particularly, the proportion of serotype 10A in the sequelae and deceased cases was significantly higher than that in the complete recovery cases. We should carefully monitor the serotype and drug susceptibility of S. pneumoniae strains isolated from patients with meningitis after the PCV13 era and reconsider the treatment strategy to prepare against further drug-resistant pneumococcal strains. IMPORTANCE We analyzed 34 cases of pediatric pneumococcal meningitis that were reported after the 13-valent pneumococcal conjugate vaccine (PCV13) introduction era in Japan. Our study revealed that pneumococcal meningitis in children was mainly caused by non-PCV13 serotypes; all cases with sequelae and death were caused by non-PCV13 serotypes. Moreover, all serotypes of penicillin resistant Streptococcus pneumoniae strains (26.5%; 9/34) were non-PCV13 serotypes. We also analyzed antimicrobial susceptibilities of glycopeptides, linezolid (LZD), and daptomycin (DAP) of isolated S. pneumoniae strains. All tested strains were susceptible to vancomycin, teicoplanin, LZD, and DAP. Especially. DAP demonstrated the best outcome among the tested antibiotics, with MIC90 of 0.094 µg/mL. Pneumococcal meningitis in children continues to persist and is difficult to control with the current conjugate vaccines. Therefore, it is important to monitor the serotype and antimicrobial susceptibility of S. pneumoniae strains isolated from patients with meningitis and accordingly reconsider the treatment strategy.


Assuntos
Daptomicina , Meningite Pneumocócica , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , Daptomicina/uso terapêutico , Humanos , Lactente , Japão/epidemiologia , Linezolida/uso terapêutico , Meningite Pneumocócica/tratamento farmacológico , Meningite Pneumocócica/epidemiologia , Meningite Pneumocócica/prevenção & controle , Penicilinas/uso terapêutico , Vacinas Pneumocócicas , Sorogrupo , Streptococcus pneumoniae , Vacinas Conjugadas/uso terapêutico , Vancomicina/uso terapêutico
18.
Org Biomol Chem ; 20(13): 2651-2660, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35293422

RESUMO

1,2,3-Triazolylidene MIC M-complexes (M = Au, Pd, Pt) having 2-azetidinones and penicillin G substituents at the triazole ring were prepared by CuAAC on 2-azetidinones having a terminal alkyne tethered at N1, followed by alkylation of the 1,2,3-triazole ring and transmetallation [Au(I), Pd(II) and Pt(II)]. The Au-MIC complexes efficiently catalyze the regioselective cycloisomerization of enynes, while the Pt-MIC complexes were efficient catalysts in hydrosilylation reactions.


Assuntos
Complexos de Coordenação , Metano/análogos & derivados , Penicilinas , Triazóis , beta-Lactamas
19.
Ann Allergy Asthma Immunol ; 128(5): 568-574, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35123076

RESUMO

BACKGROUND: Penicillin allergy in pregnancy is associated with increased morbidity and the use of less effective antibiotics. Penicillin allergy evaluation in pregnancy is now recommended as per obstetrical guidelines but remains infrequent. OBJECTIVE: We studied pregnant women who underwent penicillin allergy evaluation in an allergy clinic to assess the effectiveness and safety of penicillin skin testing (PST) and incremental drug challenge (IDC) in pregnancy. METHODS: Index drug reactions, PST, and IDC results were reviewed. Antibiotic use, pregnancy outcomes, and pregnancy complications were compared with a control cohort of pregnant women with penicillin allergy who did not undergo allergy evaluation before delivery. RESULTS: Penicillin allergy was evaluated in 136 women. Culprit drugs included penicillin (37%), amoxicillin (30%), and unknown (20%). Index reactions occurred greater than 5 years ago in 91%, and these reactions were cutaneous or unknown in 92%. Of the 133 patients who underwent skin testing, 131 (99%) had negative or equivocal results and proceeded to incremental challenge. All 131 women passed penicillin IDC. Of the 69 women who ultimately used intrapartum beta-lactam antibiotics, all but 1 patient tolerated them. Women who underwent penicillin allergy evaluation did not have an increased risk of cesarean delivery or other pregnancy complications when compared with women without penicillin allergy evaluation. CONCLUSION: PST and IDC can be safely conducted in pregnant women. When evaluated as low risk, most women tolerate IDC and can receive penicillin intrapartum without adverse reactions or negative pregnancy outcomes.


Assuntos
Hipersensibilidade a Drogas , Complicações Infecciosas na Gravidez , Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/tratamento farmacológico , Feminino , Humanos , Masculino , Penicilinas/efeitos adversos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Gestantes , Testes Cutâneos/métodos
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