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1.
J Allergy Clin Immunol Pract ; 12(2): 451-457.e2, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38572700

RESUMO

BACKGROUND: About 10% of patients have a penicillin allergy label, but less than 5% of them are actually allergic. Unnecessary penicillin avoidance is associated with serious medical consequences. Given the growing number of these labels, it is imperative that our diagnostic strategy for penicillin allergy be as efficient as possible. The validity of traditionally used skin tests (STs) has been questioned, whereas drug provocation testing (DPT), the criterion standard, without previous ST appears very safe in most cases. OBJECTIVE: To evaluate the safety of direct DPT without consideration for ST results and the validity of ST in the diagnosis of penicillin allergy. METHODS: In this prospective cohort study without a control group, we recruited patients consulting an allergist for penicillin allergy. Patients underwent ST followed by DPT regardless of ST results. Patients with anaphylaxis to penicillin within the past 5 years or a severe delayed reaction were excluded, as were those with significant cardiorespiratory comorbidity. RESULTS: None of the 1002 recruited patients had a serious reaction to DPT. Ten (1.0%) had a mild immediate reaction, of whom only 1 (0.1%) was considered likely IgE-mediated. The positive and negative predictive values of ST for an immediate reaction were 3.6% and 99.1%, respectively. CONCLUSIONS: In a low-risk adult population reporting penicillin allergy, ST has very poor positive predictive value. Direct DPT without ST is safe and appears to be an ideal diagnostic strategy to remove penicillin allergy labels that could be implemented in first-line practice.


Assuntos
Anafilaxia , Hipersensibilidade a Drogas , Adulto , Humanos , Estudos Prospectivos , Penicilinas/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/complicações , Valor Preditivo dos Testes , Anafilaxia/induzido quimicamente , Testes Cutâneos/métodos , Antibacterianos/efeitos adversos
2.
BMJ Case Rep ; 17(4)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38569736

RESUMO

A healthy man in his late 20s was admitted to the emergency department due to a flare-up in his severe chronic stomatitis, along with flu-like symptoms. CXR showed multiple bilateral consolidations and subsequent CT revealed thrombosis of the left facial and internal jugular vein, together with septic embolism in both lungs. Blood cultures showed penicillin-susceptible Staphylococcus aureus The patient was diagnosed with Lemierre's syndrome, despite atypical bacteria and clinical presentation. During hospitalisation, he developed pulmonary empyema as a complication and was admitted for 4 weeks. During hospitalisation and after discharge, the patient was examined for multiple rheumatic, immunological and dermatological diseases, but no underlying cause for Lemierre's syndrome has been found. We present this case due to the rarity of its nature, with atypical clinical presentation and pathogen for Lemierre's syndrome, but with classic radiological findings.


Assuntos
COVID-19 , Síndrome de Lemierre , Infecções Estafilocócicas , Masculino , Humanos , Staphylococcus aureus , Síndrome de Lemierre/complicações , Síndrome de Lemierre/tratamento farmacológico , Síndrome de Lemierre/diagnóstico , Penicilinas/uso terapêutico , COVID-19/complicações , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico
3.
J Med Microbiol ; 73(4)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38567639

RESUMO

Background. Invasive Group B Streptococcus (GBS; Streptococcus agalactiae) remains a leading cause of infant morbidity and mortality. Intrapartum antibiotic prophylaxis (IAP) has been implemented in many countries with a reduction in early-onset disease, but an effective vaccine may further reduce the disease burden. Candidate vaccines targeting capsular polysaccharides and surface proteins are now in clinical trials.Methods. Using whole-genome sequencing and phenotypic antimicrobial susceptibility testing, we characterized sterile-site GBS isolates recovered from Western Australian infants between 2004 and 2020. Characteristics were compared between three time periods: 2004-2008, 2009-2015 and 2016-2020.Results. A total of 135 isolates were identified. The proportion of serotype III (22.7 % in Period 1 to 47.9 % in Period 3, P=0.04) and clonal complex 17 (13.6-39.6 %, P=0.01) isolates increased over time. Overall coverage of vaccines currently being trialled was >95 %. No isolates were penicillin resistant (MIC>0.25 mg l-1), but 21.5 % of isolates had reduced penicillin susceptibility (MIC>0.12 mg l-1) and penicillin MIC increased significantly over time (P=0.04). Clindamycin resistance increased over time to 45.8 % in the latest period.Conclusions. Based on comprehensive characterization of invasive infant GBS in Western Australia, we found that coverage for leading capsular polysaccharide and surface protein vaccine candidates was high. The demonstrated changes in serotype and molecular type highlight the need for ongoing surveillance, particularly with regard to future GBS vaccination programmes. The reduced susceptibility to IAP agents over time should inform changes to antibiotic guidelines.


Assuntos
Infecções Estreptocócicas , Vacinas , Lactente , Humanos , Streptococcus agalactiae , Infecções Estreptocócicas/tratamento farmacológico , Austrália Ocidental/epidemiologia , Austrália/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Penicilinas , Sorogrupo , Vacinas/uso terapêutico , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana
4.
Rev. esp. quimioter ; 37(2): 158-162, abr. 2024. tab, graf
Artigo em Inglês | IBECS | ID: ibc-231649

RESUMO

Objectives. We assessed the in vitro activity of delafloxacin and the synergy between cefotaxime and delafloxacin among cefotaxime non-susceptible invasive isolates of Streptococcus pneumoniae (CNSSP). Material and methods. A total of 30 CNSSP (cefotaxime MIC > 0.5 mg/L) were studied. Serotyping was performed by the Pneumotest-Latex and Quellung reaction. Minimum inhibitory concentrations (MICs) of delafloxacin, levofloxacin, penicillin, cefotaxime, erythromycin and vancomycin were determined by gradient diffusion strips (GDS). Synergistic activity of delafloxacin plus cefotaxime against clinical S. pneumoniae isolates was evaluated by the GDS cross method. Results. Delafloxacin showed a higher pneumococcal activity than its comparator levofloxacin (MIC50, 0.004 versus 0.75 mg/L and MIC90, 0.047 versus >32 mg/L). Resistance to delafloxacin was identified in 7/30 (23.3%) isolates, belonging to serotypes 14 and 9V. Synergy between delafloxacin and cefotaxime was detected in 2 strains (serotypes 19A and 9V). Antagonism was not observed. Addition of delafloxacin increased the activity of cefotaxime in all isolates. Delafloxacin susceptibility was restored in 5/7 (71.4%) strains. Conclusions. CNSSP showed a susceptibility to delafloxacin of 76.7%. Synergistic interactions between delafloxacin and cefotaxime were observed in vitro among CNSSP by GDS cross method. (AU)


Objetivos. Evaluamos la actividad in vitro de delafloxacino y la sinergia entre cefotaxima y delafloxacino entre aislados invasivos de Streptococcus pneumoniae no sensibles a cefotaxima (SPNSC). Material y métodos. Se estudiaron un total de 30 SPNSC (CIM de cefotaxima > 0,5 mg/L). El serotipado se realizó mediante la reacción Pneumotest-Latex y Quellung. Las concentraciones mínimas inhibitorias (CMI) de delafloxacino, levofloxacino, penicilina, cefotaxima, eritromicina y vancomicina se determinaron mediante tiras de difusión en gradiente (GDS). La actividad sinérgica de delafloxacino y cefotaxima frente aislados clínicos de S. pneumoniae se evaluó mediante el método cruzado GDS. Resultados. Delafloxacino mostró una mayor actividad neumocócica que su comparador levofloxacino (CIM50, 0,004 versus 0,75 mg/L y MIC90, 0,047 versus > 32 mg/L). Se identificó resistencia a delafloxacino en 7/30 (23,3%) aislados, pertenecientes a los serotipos 14 y 9V. Se detectó sinergia entre delafloxacino y cefotaxima en 2 cepas (serotipos 19A y 9V). No se observó antagonismo. La adición de delafloxacino aumentó la actividad de cefotaxima en todos los aislados. La sensibilidad a delafloxacino se restableció en 5/7 (71,4%) cepas. Conclusiones. SPNSC mostraron una susceptibilidad a delafloxacino del 76,7%. Se observaron interacciones sinérgicas in vitro entre delafloxacino y cefotaxima entre SPNSC mediante el método cruzado GDS. (AU)


Assuntos
Humanos , Streptococcus pneumoniae , Sinergismo Farmacológico , Cefotaxima , Levofloxacino , Penicilinas , Eritromicina , Vancomicina
5.
BMJ ; 384: q671, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490682

Assuntos
Penicilinas , Humanos
6.
PLoS Med ; 21(3): e1004301, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38484006

RESUMO

BACKGROUND: Antibiotic usage, contact with high transmission healthcare settings as well as changes in immune system function all vary by a patient's age and sex. Yet, most analyses of antimicrobial resistance (AMR) ignore demographic indicators and provide only country-level resistance prevalence values. This study aimed to address this knowledge gap by quantifying how resistance prevalence and incidence of bloodstream infection (BSI) varied by age and sex across bacteria and antibiotics in Europe. METHODS AND FINDINGS: We used patient-level data collected as part of routine surveillance between 2015 and 2019 on BSIs in 29 European countries from the European Antimicrobial Resistance Surveillance Network (EARS-Net). A total of 6,862,577 susceptibility results from isolates with age, sex, and spatial information from 944,520 individuals were used to characterise resistance prevalence patterns for 38 different bacterial species and antibiotic combinations, and 47% of these susceptibility results were from females, with a similar age distribution in both sexes (mean of 66 years old). A total of 349,448 isolates from 2019 with age and sex metadata were used to calculate incidence. We fit Bayesian multilevel regression models by country, laboratory code, sex, age, and year of sample to quantify resistant prevalence and provide estimates of country-, bacteria-, and drug-family effect variation. We explore our results in greater depths for 2 of the most clinically important bacteria-antibiotic combinations (aminopenicillin resistance in Escherichia coli and methicillin resistance in Staphylococcus aureus) and present a simplifying indicative index of the difference in predicted resistance between old (aged 100) and young (aged 1). At the European level, we find distinct patterns in resistance prevalence by age. Trends often vary more within an antibiotic family, such as fluroquinolones, than within a bacterial species, such as Pseudomonas aeruginosa. Clear resistance increases by age for methicillin-resistant Staphylococcus aureus (MRSA) contrast with a peak in resistance to several antibiotics at approximately 30 years of age for P. aeruginosa. For most bacterial species, there was a u-shaped pattern of infection incidence with age, which was higher in males. An important exception was E. coli, for which there was an elevated incidence in females between the ages of 15 and 40. At the country-level, subnational differences account for a large amount of resistance variation (approximately 38%), and there are a range of functional forms for the associations between age and resistance prevalence. For MRSA, age trends were mostly positive, with 72% (n = 21) of countries seeing an increased resistance between males aged 1 and 100 years and a greater change in resistance in males. This compares to age trends for aminopenicillin resistance in E. coli which were mostly negative (males: 93% (n = 27) of countries see decreased resistance between those aged 1 and 100 years) with a smaller change in resistance in females. A change in resistance prevalence between those aged 1 and 100 years ranged up to 0.51 (median, 95% quantile of model simulated prevalence using posterior parameter ranges 0.48, 0.55 in males) for MRSA in one country but varied between 0.16 (95% quantile 0.12, 0.21 in females) to -0.27 (95% quantile -0.4, -0.15 in males) across individual countries for aminopenicillin resistance in E. coli. Limitations include potential bias due to the nature of routine surveillance and dependency of results on model structure. CONCLUSIONS: In this study, we found that the prevalence of resistance in BSIs in Europe varies substantially by bacteria and antibiotic over the age and sex of the patient shedding new light on gaps in our understanding of AMR epidemiology. Future work is needed to determine the drivers of these associations in order to more effectively target transmission and antibiotic stewardship interventions.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Sepse , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Idoso , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Escherichia coli , Prevalência , Teorema de Bayes , Farmacorresistência Bacteriana , Bactérias , Sepse/tratamento farmacológico , Penicilinas/farmacologia , Testes de Sensibilidade Microbiana
9.
Cochrane Database Syst Rev ; 3: CD014959, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483067

RESUMO

BACKGROUND: Leptospirosis is a global zoonotic and waterborne disease caused by pathogenic Leptospira species. Antibiotics are used as a strategy for prevention of leptospirosis, in particular in travellers and high-risk groups. However, the clinical benefits are unknown, especially when considering possible treatment-associated adverse effects. This review assesses the use of antibiotic prophylaxis in leptospirosis and is an update of a previously published review in the Cochrane Library (2009, Issue 3). OBJECTIVES: To evaluate the benefits and harms of antibiotic prophylaxis for human leptospirosis. SEARCH METHODS: We identified randomised clinical trials through electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and other resources. We searched online clinical trial registries to identify unpublished or ongoing trials. We checked reference lists of the retrieved studies for further trials. The last date of search was 17 April 2023. SELECTION CRITERIA: We included ⁠⁠randomised clinical trials of any trial design, assessing antibiotics for prevention of leptospirosis, and with no restrictions on age, sex, occupation, or comorbidity of trial participants. We looked for trials assessing antibiotics irrespective of route of administration, dosage, and schedule versus placebo or no intervention. We also included trials assessing antibiotics versus other antibiotics using these criteria, or the same antibiotic but with another dose or schedule. DATA COLLECTION AND ANALYSIS: We followed Cochrane methodology. The primary outcomes were all-cause mortality, laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (inclusive of asymptomatic cases), clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation, clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (exclusive of asymptomatic cases), and serious adverse events. The secondary outcomes were quality of life and the proportion of people with non-serious adverse events. We assessed the risk of bias of the included trials using the RoB 2 tool and the certainty of evidence using GRADE. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean difference (MD), with their 95% confidence intervals (CI). We used a random-effects model for our main analyses and the fixed-effect model for sensitivity analyses. Our primary outcome analyses included trial data at the longest follow-up. MAIN RESULTS: We identified five randomised clinical trials comprising 2593 participants that compared antibiotics (doxycycline, azithromycin, or penicillin) with placebo, or one antibiotic compared with another. Four trials assessed doxycycline with different durations, one trial assessed azithromycin, and one trial assessed penicillin. One trial had three intervention groups: doxycycline, azithromycin, and placebo. Three trials assessed pre-exposure prophylaxis, one trial assessed postexposure prophylaxis, and one did not report this clearly. Four trials recruited residents in endemic areas, and one trial recruited soldiers who experienced limited time exposure. The participants' ages in the included trials were 10 to 80 years. Follow-up ranged from one to three months. Antibiotics versus placebo Doxycycline compared with placebo may result in little to no difference in all-cause mortality (RR 0.15, 95% CI 0.01 to 2.83; 1 trial, 782 participants; low-certainty evidence). Prophylactic antibiotics may have little to no effect on laboratory-confirmed leptospirosis, but the evidence is very uncertain (RR 0.56, 95% CI 0.25 to 1.26; 5 trials, 2593 participants; very low-certainty evidence). Antibiotics may result in little to no difference in the clinical diagnosis of leptospirosis regardless of laboratory confirmation (RR 0.76, 95% CI 0.53 to 1.08; 4 trials, 1653 participants; low-certainty evidence) and the clinical diagnosis of leptospirosis with laboratory confirmation (RR 0.57, 95% CI 0.26 to 1.26; 4 trials, 1653 participants; low-certainty evidence). Antibiotics compared with placebo may increase non-serious adverse events, but the evidence is very uncertain (RR 10.13, 95% CI 2.40 to 42.71; 3 trials, 1909 participants; very low-certainty evidence). One antibiotic versus another antibiotic One trial assessed doxycycline versus azithromycin but did not report mortality. Compared to azithromycin, doxycycline may have little to no effect on laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (RR 1.49, 95% CI 0.51 to 4.32; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), and on non-serious adverse events (RR 1.12, 95% CI 0.36 to 3.48; 1 trial, 137 participants), but the evidence is very uncertain. The certainty of evidence for all the outcomes was very low. None of the five included trials reported serious adverse events or assessed quality of life. One study is awaiting classification. Funding Four of the five trials included statements disclosing their funding/supporting sources, and the remaining trial did not include this. Three of the four trials that disclosed their supporting sources received the supply of trial drugs directly from the same pharmaceutical company, and the remaining trial received financial support from a governmental source. AUTHORS' CONCLUSIONS: We do not know if antibiotics versus placebo or another antibiotic has little or have no effect on all-cause mortality or leptospirosis infection because the certainty of evidence is low or very low. We do not know if antibiotics versus placebo may increase the overall risk of non-serious adverse events because of very low-certainty evidence. We lack definitive rigorous data from randomised trials to support the use of antibiotics for the prophylaxis of leptospirosis infection. We lack trials reporting data on clinically relevant outcomes.


Assuntos
Antibioticoprofilaxia , Leptospirose , Humanos , Antibioticoprofilaxia/efeitos adversos , Doxiciclina/efeitos adversos , Azitromicina/efeitos adversos , Qualidade de Vida , Antibacterianos/efeitos adversos , Penicilinas , Leptospirose/prevenção & controle
10.
Cochrane Database Syst Rev ; 3: CD014960, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483092

RESUMO

BACKGROUND: Leptospirosis is a disease transmitted from animals to humans through water, soil, or food contaminated with the urine of infected animals, caused by pathogenic Leptospira species. Antibiotics are commonly prescribed for the management of leptospirosis. Despite the widespread use of antibiotic treatment for leptospirosis, there seems to be insufficient evidence to determine its effectiveness or to recommend antibiotic use as a standard practice. This updated systematic review evaluated the available evidence regarding the use of antibiotics in treating leptospirosis, building upon a previously published Cochrane review. OBJECTIVES: To evaluate the benefits and harms of antibiotics versus placebo, no intervention, or another antibiotic for the treatment of people with leptospirosis. SEARCH METHODS: We identified randomised clinical trials following standard Cochrane procedures. The date of the last search was 27 March 2023. SELECTION CRITERIA: We searched for randomised clinical trials of various designs that examined the use of antibiotics for treating leptospirosis. We did not impose any restrictions based on the age, sex, occupation, or comorbidities of the participants involved in the trials. Our search encompassed trials that evaluated antibiotics, regardless of the method of administration, dosage, and schedule, and compared them with placebo or no intervention, or compared different antibiotics. We included trials regardless of the outcomes reported. DATA COLLECTION AND ANALYSIS: During the preparation of this review, we adhered to the Cochrane methodology and used Review Manager. The primary outcomes were all-cause mortality and serious adverse events (nosocomial infection). Our secondary outcomes were quality of life, proportion of people with adverse events considered non-serious, and days of hospitalisation. To assess the risk of bias of the included trials, we used the RoB 2 tool, and for evaluating the certainty of evidence we used GRADEpro GDT software. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), both accompanied by their corresponding 95% confidence intervals (CI). We used the random-effects model for all our main analyses and the fixed-effect model for sensitivity analyses. For our primary outcome analyses, we included trial data from the longest follow-up period. MAIN RESULTS: We identified nine randomised clinical trials comprising 1019 participants. Seven trials compared two intervention groups and two trials compared three intervention groups. Amongst the trials comparing antibiotics versus placebos, four trials assessed penicillin and one trial assessed doxycycline. In the trials comparing different antibiotics, one trial evaluated doxycycline versus azithromycin, one trial assessed penicillin versus doxycycline versus cefotaxime, and one trial evaluated ceftriaxone versus penicillin. One trial assessed penicillin with chloramphenicol and no intervention. Apart from two trials that recruited military personnel stationed in endemic areas or military personnel returning from training courses in endemic areas, the remaining trials recruited people from the general population presenting to the hospital with fever in an endemic area. The participants' ages in the included trials was 13 to 92 years. The treatment duration was seven days for penicillin, doxycycline, and cephalosporins; five days for chloramphenicol; and three days for azithromycin. The follow-up durations varied across trials, with three trials not specifying their follow-up periods. Three trials were excluded from quantitative synthesis; one reported zero events for a prespecified outcome, and two did not provide data for any prespecified outcomes. Antibiotics versus placebo or no intervention The evidence is very uncertain about the effect of penicillin versus placebo on all-cause mortality (RR 1.57, 95% CI 0.65 to 3.79; I2 = 8%; 3 trials, 367 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin or chloramphenicol versus placebo on adverse events considered non-serious (RR 1.05, 95% CI 0.35 to 3.17; I2 = 0%; 2 trials, 162 participants; very low-certainty evidence). None of the included trials assessed serious adverse events. Antibiotics versus another antibiotic The evidence is very uncertain about the effect of penicillin versus cephalosporin on all-cause mortality (RR 1.38, 95% CI 0.47 to 4.04; I2 = 0%; 2 trials, 348 participants; very low-certainty evidence), or versus doxycycline (RR 0.93, 95% CI 0.13 to 6.46; 1 trial, 168 participants; very low-certainty evidence). The evidence is very uncertain about the effect of cefotaxime versus doxycycline on all-cause mortality (RR 0.18, 95% CI 0.01 to 3.78; 1 trial, 169 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus doxycycline on serious adverse events (nosocomial infection) (RR 0.62, 95% CI 0.11 to 3.62; 1 trial, 168 participants; very low-certainty evidence) or versus cefotaxime (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of doxycycline versus cefotaxime on serious adverse events (nosocomial infection) (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus cefotaxime (RR 3.03, 95% CI 0.13 to 73.47; 1 trial, 175 participants; very low-certainty evidence), versus doxycycline (RR 2.80, 95% CI 0.12 to 67.66; 1 trial, 175 participants; very low-certainty evidence), or versus chloramphenicol on adverse events considered non-serious (RR 0.74, 95% CI 0.15 to 3.67; 1 trial, 52 participants; very low-certainty evidence). Funding Six of the nine trials included statements disclosing their funding/supporting sources and three trials did not mention funding source. Four of the six trials mentioning sources received funds from public or governmental sources or from international charitable sources, and the remaining two, in addition to public or governmental sources, received support in the form of trial drug supply directly from pharmaceutical companies. AUTHORS' CONCLUSIONS: As the certainty of evidence is very low, we do not know if antibiotics provide little to no effect on all-cause mortality, serious adverse events, or adverse events considered non-serious. There is a lack of definitive rigorous data from randomised trials to support the use of antibiotics for treating leptospirosis infection, and the absence of trials reporting data on clinically relevant outcomes further adds to this limitation.


Assuntos
Infecção Hospitalar , Leptospirose , Humanos , Antibacterianos/efeitos adversos , Doxiciclina/efeitos adversos , Azitromicina , Qualidade de Vida , Cloranfenicol , Penicilinas , Cefalosporinas/efeitos adversos , Cefotaxima , Leptospirose/tratamento farmacológico
11.
Drug Ther Bull ; 62(4): 51, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38527765

RESUMO

Overview of: Copaescu AM, Vogrin S, James F, et al. Efficacy of a clinical decision rule to enable direct oral challenge in patients with low-risk penicillin allergy: The PALACE randomized clinical trial. JAMA Intern Med 2023;183:944-52.


Assuntos
Hipersensibilidade a Drogas , Hipersensibilidade , Humanos , Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Penicilinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Testes Cutâneos
12.
Acta Derm Venereol ; 104: adv34879, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436430

RESUMO

Syphilis is currently a treatable disease, with a low incidence in most developed countries, although the prevalence has increased recently, especially among men-who-have-sex-with-men. In many of the least developed countries, however, syphilis is still a major health problem, although the problem is not comparable to the desperate situation worldwide less than 80 years ago. At that time, and for many centuries previously, syphilis dramatically affected the lives and health of individuals and threatened the well-being of many societies. This review examines the aetiology, transmission, and many manifestations of syphilis from a historical perspective, emphasizing morbidity, treatment, psychosocial and cultural manifestations, as well as ethical issues uncovered in the clinical search for knowledge about the manifestations of the disease.


Assuntos
Minorias Sexuais e de Gênero , Sífilis , Masculino , Humanos , Penicilinas/efeitos adversos , Homossexualidade Masculina , Pandemias , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Sífilis/epidemiologia
13.
BMC Genomics ; 25(1): 290, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500064

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) of Neisseria gonorrhoeae is a threat to public health as strains have developed resistance to antimicrobials available for the treatment of gonorrhea. Whole genome sequencing (WGS) can detect and predict antimicrobial resistance to enhance the control and prevention of gonorrhea. Data on the molecular epidemiology of N. gonorrhoeae is sparse in Zambia. This study aimed to determine the genetic diversity of N. gonorrhoeae isolated from patients attending sexually transmitted infection (STI) clinics in Lusaka, Zambia. METHODS: A cross-sectional study that sequenced 38 N. gonorrhoeae isolated from 122 patients with gonorrhea from 2019 to 2020 was conducted. The AMR profiles were determined by the E-test, and the DNA was extracted using the NucliSens easyMaG magnetic device. Whole genome sequencing was performed on the Illumina NextSeq550 platform. The Bacterial analysis pipeline (BAP) that is readily available at: https://cge.cbs.dtu.dk/services/CGEpipeline-1.1 was used for the identification of the species, assembling the genome, multi-locus sequence typing (MLST), detection of plasmids and AMR genes. Phylogeny by single nucleotide polymorphisms (SNPs) was determined with the CCphylo dataset. RESULTS: The most frequent STs with 18.4% of isolates each were ST7363, ST1921 and ST1582, followed by ST1583 (13%), novel ST17026 (7.9%), ST1588 (7.9%), ST1596 (5.3%), ST11181 (5.3%), ST11750 (2.6/%) and ST11241 (2.6%) among the 38 genotyped isolates. The blaTeM-1B and tetM (55%) was the most prevalent combination of AMR genes, followed by blaTeM-1B (18.4%), tetM (15.8%), and the combination of blaTeM-1B, ermT, and tetL was 2.6% of the isolates. The AMR phenotypes were predicted in ciprofloxacin, penicillin, tetracycline, azithromycin, and cefixime. The combination of mutations 23.7% was gryA (S91F), parC (E91G), ponA (L421) and rpsJ (V57M), followed by 18.4% in gyrA (S91F), ponA (L421P), rpsJ (V57M), and 18.4% in gyrA (D95G, S91F), ponA (L421P), and rpsJ (V57M). The combinations in gyrA (D95G, S91F) and rpsJ (V57M), and gyrA (D95G, S91F), parC (E91F), ponA (L421P) and rpsJ (V57M) were 13.2% each of the isolates. Plasmid TEM-1 (84.2%), tetM (15.8%), and gonococcal genetic island (GGI) was detected in all isolates. CONCLUSION: This study revealed remarkable heterogeneity of N. gonorrhoeae with blaTEM-1, tetM, ponA, gyrA, and parC genes associated with high resistance to penicillin, tetracycline, and ciprofloxacin demanding revision of the standard treatment guidelines and improved antimicrobial stewardship in Zambia.


Assuntos
Antibacterianos , Gonorreia , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Neisseria gonorrhoeae/genética , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Gonorreia/microbiologia , Tipagem de Sequências Multilocus , Zâmbia/epidemiologia , Estudos Transversais , Farmacorresistência Bacteriana/genética , Tetraciclina , Ciprofloxacina , Penicilinas , Testes de Sensibilidade Microbiana
14.
Int Tinnitus J ; 27(2): 211-216, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38507637

RESUMO

Dental caries are mainly occur owing to the presence and activity of bacterial agents. The present study was done to assess the prevalence and antibiotic resistance of bacterial strains isolated from the cases of dental caries. Fifty patients with approved dental carries were included in the study. Sampling from the site of dental caries was done using the sterile swab. Swabs were transferred to laboratory and subjected to microbial culture. Species identification of bacteria was done using biochemical test. Bacterial isolates were subjected to disk diffusion to assess their antimicrobial resistance. S. aureus (40%) harboured the highest rate of contamination, while S. oralis (16%) and E. aerogenes (10%) harbored the lowest. S. aureus and S. mutans (6%) harbored the highest distribution amongst the cases of mix infections, while S. aureus and S. oralis (2%) harbnored the lowest. S. aureus strains harbored the highest rate of resistance toward tetracycline (90%), penicillin (75%), ampicillin (75%), amoxicillin (60%), and erythromycin (60%). E. coli strains harbored the highest rate of resistance toward tetracycline (90%), gentamicin (80%), ampicillin (70%), and erythromycin (70%). S. mutans strains harbored the highest rate of resistance toward tetracycline (93.33%), ampicillin (86.66%), penicillin (80%), amoxicillin (80%), and erythromycin (80%). S. oralis strains harbored the highest rate of resistance toward tetracycline (100%), ampicillin (75%), penicillin (62.50%), and amoxicillin (62.50%). E. aerogenes strains harbored the highest rate of resistance toward tetracycline (80%), gentamicin (80%), and ampicillin (80%). S. aureus bacteria isolated from dental caries harbored the highest rate of MDR. Distribution of resistance against more than 3 antimicrobial agents amongst the S. aureus, E. coli, S. mutans, S. oralis, and E. aerogenes bacteria isolated from the cases of dental caries was 90%, 60%, 80%, 62.50%, and 80%, respectively. Application of disk diffuin can help practitioners to reduce the rate of resistance in bacteria responsible for dental caries.


Assuntos
Antibacterianos , Cárie Dentária , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Staphylococcus aureus , Prevalência , Cárie Dentária/epidemiologia , Cárie Dentária/tratamento farmacológico , Escherichia coli , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Eritromicina , Amoxicilina , Tetraciclina , Penicilinas , Gentamicinas
15.
17.
Antimicrob Agents Chemother ; 68(3): e0139923, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38329330

RESUMO

Non-clinical antibiotic development relies on in vitro susceptibility and infection model studies. Validating the achievement of the targeted drug concentrations is essential to avoid under-estimation of drug effects and over-estimation of resistance emergence. While certain ß-lactams (e.g., imipenem) and ß-lactamase inhibitors (BLIs; clavulanic acid) are believed to be relatively unstable, limited tangible data on their stability in commonly used in vitro media are known. We aimed to determine the thermal stability of 10 ß-lactams and 3 BLIs via LC-MS/MS in cation-adjusted Mueller Hinton broth at 25 and 36°C as well as agar at 4 and 37°C, and in water at -20, 4, and 25°C. Supplement dosing algorithms were developed to achieve broth concentrations close to their target over 24 h. During incubation in broth (pH 7.25)/agar, degradation half-lives were 16.9/21.8 h for imipenem, 20.7/31.6 h for biapenem, 29.0 h for clavulanic acid (studied in broth only), 23.1/71.6 h for cefsulodin, 40.6/57.9 h for doripenem, 46.5/64.6 h for meropenem, 50.8/97.7 h for cefepime, 61.5/99.5 h for piperacillin, and >120 h for all other compounds. Broth stability decreased at higher pH. All drugs were ≥90% stable for 72 h in agar at 4°C. Degradation half-lives in water at 25°C were >200 h for all drugs except imipenem (14.7 h, at 1,000 mg/L) and doripenem (59.5 h). One imipenem supplement dose allowed concentrations to stay within ±31% of their target concentration. This study provides comprehensive stability data on ß-lactams and BLIs in relevant in vitro media using LC-MS/MS. Future studies are warranted applying these data to antimicrobial susceptibility testing and assessing the impact of ß-lactamase-related degradation.


Assuntos
Inibidores de beta-Lactamases , beta-Lactamas , Inibidores de beta-Lactamases/farmacologia , beta-Lactamas/farmacologia , Doripenem , Ágar , Cromatografia Líquida , Espectrometria de Massas em Tandem , Antibacterianos/farmacologia , Penicilinas , Ácido Clavulânico/farmacologia , Imipenem/farmacologia , Água , Testes de Sensibilidade Microbiana
18.
J Antimicrob Chemother ; 79(3): 641-647, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305703

RESUMO

BACKGROUND: BaeS/BaeR is a two-component system of Escherichia coli that controls the expression of porins and efflux pumps. Its role in beta-lactam resistance is limited. OBJECTIVES: To study the role of baeS/baeR two-component system in temocillin resistance in E. coli. METHODS: E. coli strain BW25113 and single-gene deletion mutants related to two-component systems were collected from the KEIO collection. Double-gen deletion mutants were generated. Temocillin-resistant mutant frequencies were determined at 32 mg/L. E. coli BW25113 mutants were selected by selective pressure from serial passages. Biological costs were analysed by growth curves. Genomes of the generated mutants were sequenced. The expression level of the mdtA, mdtB, mdtC, acrD and tolC in the ΔbaeS mutant was determined by RT-PCR (with/without temocillin exposure). RESULTS: The frequency of temocillin mutants ranged from 2.12 × 10-8 to 4.51 × 10-8 in single-porin mutants. No mutants were recovered from E. coli BW25113 (>10-9). Selection of temocillin-resistant variants by serial passage yielded mutants up to 128 mg/L. Mutations were found in the baeS gene. Temocillin MICs ranged from 4 to 32 mg/L (highest MICs for ΔbaeS and ΔompR). The efflux pumps mdtA, mdtB, mdtC and acrD pumps were overexpressed 3-10-fold in the presence of temocillin in ΔbaeS compared to control. CONCLUSIONS: Mutations in the sensor histidine kinase, baeS, may be involved in temocillin resistance through the expression of the efflux pumps mdtABC and acrD. In addition, the low mutation rate may be a good predictor of temocillin activity.


Assuntos
Cadaverina/análogos & derivados , Proteínas de Escherichia coli , Escherichia coli , Penicilinas , Escherichia coli/genética , Transporte Biológico , Transativadores , Proteínas de Escherichia coli/genética
19.
J Phys Chem Lett ; 15(7): 1908-1913, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38345549

RESUMO

6-Aminopenicillanic acid is a penicillanic acid compound and is the active nucleus common to all penicillins. Using laser ablation techniques, we transformed the solid into the gas phase and characterized its conformational panorama by combining supersonic expansions and Fourier transform microwave techniques. Five conformers were determined, adopting different spatial configurations. Among them, the axial and equatorial forms, which are biologically relevant, have been observed. The structural similarity to d-Ala-d-Ala and the detection of both axial and equatorial forms could explain its potential as a penicillin core and its capability as an antibiotic.


Assuntos
Antibacterianos , Penicilinas , Conformação Molecular , Lasers
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