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Objectives: The cross-reactivity problem between cephalosporins and penicillins has mainly been evaluated in the context of patients allergic to penicillins. However, we have little data regarding the opposite aspect of the problem, i.e. the cross-reactivity in subjects primarily sensitized to cephalosporins. This prospective study aims to evaluate the cross-reactivity to penicillins and some other cephalosporins in patients with immediate allergic reactions to cephalosporins. Methods: The study included 21 children with immediate allergic reactions to at least one cephalosporin. Skin testing was performed with a panel of minor and major determinant mixtures of penicillins and three commonly used cephalosporins (cephazoline, cefuroxime and ceftriaxone). Results: The children had used 5.14±4.91 (1-15) times any beta-lactam antibiotic in the previous year and the most common cephalosporins accused were ceftriaxone (42.92%), and cefuroxime, cefazolin, cefixime, cefprozil and cefotaxime (9.5% each). Skin tests were positive for any cephalosporin in 14 (66.7%) subjects and penicillin allergens in 15 (71.4%) subjects. Totally, 85.7% of children with a positive allergy history to cephalosporins were found to be sensitive to either penicillin or any one of three cephalosporins. Conclusion: There seems to be a high risk of adverse reactions to penicillins and other cephalosporins in children with a history of type I hypersensitivity reaction to cephalosporins. Therefore, skin testing with both cephalosporins and penicillins should be performed in patients with a history of cephalosporin allergy.
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OBJECTIVES: To estimate risk factors for acute kidney injury (AKI) and the effect of AKI on mortality in Staphylococcus aureus bacteraemia, while taking into account recurrent AKI episodes, competing risks, time-varying variables, and time-varying effects. METHODS: We performed an unplanned analysis using data from a multicentre cohort study of patients with Staphylococcus aureus bacteraemia (SAB). The primary outcome was cumulative incidence of AKI, according to Kidney Disease Improving Global Outcomes definitions. RESULTS: We included 453 patients in this study of whom 194 (43%) patients experienced one or more AKI episodes. Age (hazard ratio (HR) 1.013, 95% CI 1.001-1.024), Charlson comorbidity index (HR 1.07, 95% CI 1.01-1.14), prior chronic kidney disease (HR 1.76, 95% CI 1.28-2.42), septic shock (HR 3.28, 95% CI 2.31-4.66), persistent bacteraemia (HR 1.53, 95% CI 1.08-2.17), and vancomycin therapy (HR 1.80, 95% CI 1.05-3.09) were independently associated with AKI, but flucloxacillin, cefazolin, rifampicin, and aminoglycoside therapy were not. After adjustment for confounders and immortal time bias, AKI was associated with an increased risk of 90-day mortality (HR 4.26, 95% CI 2.91-6.23). DISCUSSION: The incidence of AKI in SAB is high and a substantial proportion of patients develop recurrent episodes of AKI after recovery. AKI is specifically linked to the use of vancomycin and not to anti-staphylococcal penicillins. The clinical outcome of patients with SAB complicated by AKI is worse than previously estimated.
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PURPOSE: Critically ill patients are vulnerable to penicillin allergy labels that may be incorrect. The validity of skin testing in intensive care units (ICUs) is uncertain. Many penicillin allergy labels are low risk, and validated tools exist to identify those amenable to direct oral challenge. This pilot randomised controlled trial explored the feasibility, safety, and validity of direct enteral challenge for low-risk penicillin allergy labels in critical illness. METHODS: Consenting patients with a low-risk penicillin allergy label (PAL) (PEN-FAST risk assessment score < 3) in four ICUs (Melbourne, Australia) were randomised 1:1 to penicillin (250 mg amoxicillin or implicated penicillin) direct enteral challenge versus routine care (2-h post-randomisation observation for each arm). Repeat challenge was performed post -ICU in the intervention arm. Patients were reviewed at 24 h and 5 days after each challenge/observation. RESULTS: We screened 533 patients. 130 (24.4%) were eligible and 80/130 (61.5%) enrolled (age median 64.5 years (interquartile range, IQR 53.5, 74), PEN-FAST median 1 (IQR 0,1)), with 40 (50%) randomised to direct enteral challenge. A positive challenge rate of 2.5% was identified. No antibiotic-associated serious adverse events were identified. 32/40 (80%) received a repeat challenge (zero positive). Post-randomisation, 13 (32%) of the intervention arm and 4 (10%) of the control arm received penicillin (odds ratio, OR 4.33 [1.27, 14.78] p = 0.019). CONCLUSION: These findings support the safety, validity, and feasibility of direct enteral challenge for critically ill patients with PEN-FAST assessed low-risk penicillin allergy. The absence of false negative results was confirmed by subsequent negative repeat challenges. A relatively low recruitment to screened ratio suggests that more inclusive eligibility criteria and integration of allergy assessment into routine ICU processes are needed to optimise allergy delabelling in critical illness.
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Enfermedad Crítica , Hipersensibilidad a las Drogas , Estudios de Factibilidad , Unidades de Cuidados Intensivos , Penicilinas , Humanos , Persona de Mediana Edad , Masculino , Proyectos Piloto , Femenino , Anciano , Penicilinas/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Unidades de Cuidados Intensivos/estadística & datos numéricos , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Administración Oral , Medición de Riesgo/métodos , Pruebas Cutáneas/métodosRESUMEN
Introducción: Las reacciones alérgicas son uno de los problemas de seguridad más graves asociadas al uso de medicamentos, siendo la alergia a los antibióticos betalactámicos la más prevalente. Las pruebas de alergia a las penicilinas pueden ayudar a identificar pacientes hospitalizados y ambulatorios que podrían tolerar y usar de manera segura este grupo de antibióticos y evitar rótulos que limiten el uso de antibióticos betalactámicos por tiempo indefinido. Objetivo: Identificar las herramientas disponibles en la literatura para valorar el antecedente de alergia a las penicilinas y proponer una herramienta que consolide la información extraída. Metodología: Revisión estructurada en PubMed/MEDLINE entre 1 junio 2015 hasta 30 noviembre 2022, utilizando los términos MeSH: (((skin tests[MeSH Terms]) OR (skin irritancy tests[MeSH Terms])) AND (penicillins[All Fields])) AND (drug hypersensitivity[MeSH Terms]). Publicaciones en inglés y español con acceso a texto completo y estudios realizados en humanos, sobre herramientas disponibles para evaluar la alergia a penicilinas fueron incluidos. Resultados: Se identificaron201 artículos, de los cuales se incluyeron 108. Dentro de las herramientas para evaluar la alergia a las penicilinas se identificaron: a) pruebas in vivo: pruebas cutáneas, pruebas de provocación oral, pruebas del parche; y b) pruebas in vitro: pruebas de IgE específica, determinación de triptasa, histamina. De los 1181 pacientes reportados con alergia a las penicilinas, sólo el 2 % de ellos se confirmó la presencia de alergia. Conclusión: Las pruebas cutáneas y de provocación oral sumado a algunas combinaciones in vivo/in vitro, fueron las herramientas más utilizadas para evaluar la alergia a las penicilinas. (AU)
Introduction: Allergic reactions are one of the most serious safety problems associated with the use of medications, with allergy to beta-lactam antibiotics being the most prevalent. In fact, the American Academy of Allergy, Asthma and Immunology (AAAAI) states that penicillin allergy testing can help identify inpatients and outpatients who could safely tolerate and use this group of antibiotics and avoid labels that limit the use of beta-lactam antibiotics indefinitely. Objective: To identify the tools available in the literature to assess the history of allergy to penicillins and propose a tool that consolidates the information extracted. Methodology: Structured review on PubMed/MEDLINE between June 1, 2015 until November 30, 2022; using the search terms MeSH: (((skin tests[MeSH Terms]) OR (skin irritancy tests[MeSH Terms])) AND (penicillins[All Fields])) AND (drug hypersensitivity[MeSH Terms]). Papers in English and Spanish with access to full text and human trials, regarding available tools used to evaluate penicillin allergies were included. Results: A total of 201 articles were identified, of which after an independent evaluation, 108 were included. Among the tools to evaluate penicillin allergy, in vivo tests were identified: skin tests, oral provocation tests, patch tests and in vitro tests: specific IgE tests, determination of tryptase, histamine, T lymphocytes and basophilic activation tests. Of the patients (1181) reported with penicillin allergy, 905 (77 %) had their allergy assessed with skin testing or oral challenge tests, and only 2 % of them had a confirmed allergic reaction. Conclusion: Skin tests and oral provocation tests added to some in vivo/in vitro combinations were the most used tools to evaluate penicillin allergy. (AU)
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Hipersensibilidad a las Drogas , Penicilinas , Pruebas Cutáneas , beta-LactamasRESUMEN
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.
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Inhibidores de beta-Lactamasas , beta-Lactamas , Inhibidores de beta-Lactamasas/farmacología , beta-Lactamas/farmacología , Doripenem , Agar , Cromatografía Liquida , Espectrometría de Masas en Tándem , Antibacterianos/farmacología , Penicilinas , Ácido Clavulánico/farmacología , Imipenem/farmacología , Agua , Pruebas de Sensibilidad MicrobianaRESUMEN
PURPOSE: Antistaphylococcal penicillins and cefazolin have been used as first line therapy in Methicillin-susceptible Staphylococcus aureus bloodstream infection. While efficacy of both regimens seems to be similar, the compounds may differ with regard to tolerability. This study aims to describe the clinical use of cefazolin and flucloxacillin, focussing on discontinuation or change of anti-infective agent due to adverse events. METHODS: This observational prospective study was conducted at two German tertiary care centres with an internal recommendation of flucloxacillin for MSSA-BSI in one, and of cefazolin in the other centre. Adverse events were registered weekly under treatment and at a 90-day follow-up. Descriptive analysis was complemented by a propensity score analysis comparing adverse events (stratified rank-based test applied to the sum of Common Terminology Criteria for adverse events ratings per patient). RESULTS: Of 71 patients included, therapy was initiated with flucloxacillin in 56 (79%), and with cefazolin in 15 (21%). The propensity score analysis indicates a statistically significant difference concerning the severity of adverse events between the treatment groups in favour of cefazolin (p = 0.019). Adverse events led to discontinuation of flucloxacillin in 7 individuals (13% of all patients receiving flucloxacillin). Clinical outcome was not different among treatment groups. CONCLUSION: Using cefazolin rather than flucloxacillin as a first line agent for treatment of MSSA-BSI is supported by these clinical data.
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Antibacterianos , Cefazolina , Floxacilina , Infecciones Estafilocócicas , Staphylococcus aureus , Humanos , Cefazolina/uso terapéutico , Floxacilina/uso terapéutico , Masculino , Femenino , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Persona de Mediana Edad , Estudios Prospectivos , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Anciano , Staphylococcus aureus/efectos de los fármacos , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Adulto , Anciano de 80 o más Años , AlemaniaRESUMEN
The term Hoigné's syndrome denotes a mimicker of anaphylaxis, which occurs immediately after the parenteral administration of a drug and is likely caused by non-thrombotic pulmonary and systemic drug micro-embolization. It has so far been documented uniquely in case reports and small case series. Because this condition has never been systematically evaluated, we performed a structured literature review (pre-registered as CRD42023392962). The search was carried out in Excerpta Medica, National Library of Medicine, and Google Scholar. Cases with features consistent with anaphylaxis, urticaria, angioedema, asthma, syncope, anxiety, or panic attack triggered by needle phobia, and local anesthetic systemic toxicity were excluded. For the final analysis, we retained reports published between 1951 and 2021, which presented 247 patients with Hoigné's syndrome: 37 children and 211 adults with a male: female ratio of 2.1 : 1.0. The patients presented within 1 min after parenteral administration of a drug (intramuscular penicillin in 90 % of the cases) with chest discomfort, shortness of breath, fear of death, psychomotor agitation, and auditory or visual hallucinations and impairment. Recovery occurred within 30 min. The diagnosis of Hoigné's syndrome was also established in five patients 66-91 years of age with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the aforementioned symptoms. It was therefore speculated that pulmonary drug micro-embolization induced a lethal cardiovascular compromise in these individuals. Histologic investigations supporting this hypothesis were performed in only one case. The diagnosis of Hoigné's pulmonary drug micro-embolization was established also in five patients with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the afore mentioned symptoms. Histologic investigations supporting this hypothesis were performed in only one case. In conclusion, Hoigné's syndrome is an uncommon non-immune-mediated reaction. This report seeks to promote broader awareness and knowledge regarding this alarming mimicker of anaphylaxis. Diagnosis relies solely on clinical evaluation.
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Anafilaxia , Humanos , Anafilaxia/diagnóstico , Anafilaxia/etiología , Anafilaxia/terapia , Diagnóstico Diferencial , Masculino , Femenino , Anciano , Adulto , Anciano de 80 o más Años , Síndrome , Niño , Penicilinas/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/terapiaRESUMEN
Introduction: Penicillin allergy labels (PAL) are common in the hospital setting and are associated with worse clinical outcomes. Desensitization can be a useful strategy for allergic patients when alternative options are suboptimal or not available. The aim was to compare clinical outcomes of patients with PAL managed with antibiotic desensitization vs. those who received alternative non-beta-lactam antibiotic treatments. Methods: A retrospective 3:1 case-control study was performed between 2015-2022. Cases were adult PAL patients with infection who required antibiotic desensitization; controls were PAL patients with infection managed with an alternative antibiotic treatment. Cases and controls were adjusted for age, sex, infection source, and critical or non-critical medical services. Results: Fifty-six patients were included: 14 in the desensitization group, 42 in the control group. Compared to the control group, desensitized PAL patients had more comorbidities, with a higher Charlson index (7.4 vs. 5; p = 0.00) and more infections caused by multidrug-resistant (MDR) pathogens (57.1% vs. 28.6%; p = 0.05). Thirty-day mortality was 14.3% in the desensitized group, 28.6% in the control group (p = 0.24). Clinical cure occurred in 71.4% cases and 54.8% controls (p = 0.22). Four control patients selected for MDR strains after alternative treatment; selection of MDR strains did not occur in desensitized patients. Five controls had antibiotic-related adverse events, including Clostridioides difficile or nephrotoxicity. No antibiotic-related adverse events were found in the study group. In multivariate analysis, no differences between groups were observed for main variables. Conclusion: Desensitization was not associated with worse clinical outcomes, despite more severe patients in this group. Our study suggests that antibiotic desensitization may be a useful Antimicrobial Stewardship tool for the management of selected PAL patients.
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Background: Penicillin allergy is self-reported by 3-10% of patients admitted to hospital. The label is wrong in 90% of the cases and has severe health implications. Penicillin-delabeling can reverse the negative effects of the label, and pathways adapted to local practice are needed. No tools are available in Norway for penicillin delabeling outside an allergy clinic. Objective: To create and validate the first penicillin delabeling pathway applicable outside an allergy clinic in Norway. Methods: An interdisciplinary taskforce created a penicillin allergy delabeling program (PAD) adapted to the Norwegian health care system. This was validated in a prospective, single-center study. Very low-risk and low-risk patients underwent a direct oral penicillin challenge and high-risk patients were referred for allergologic evaluation. Results: One-hundred forty-nine patients declaring penicillin allergy were included. Seventy-four (50%) were very-low- and low risk patients suitable for a direct oral penicillin challenge resulting in only 1 mild reaction. Sixty high-risk patients were eligible for an oral penicillin challenge after allergologic evaluation; 3 patients reacted non-severely. Conclusion: We have created and demonstrated feasibility of the first penicillin delabeling program (PAD) applicable in a hospital setting outside an allergy clinic in Norway. Our data suggest this is safe and beneficial, with 49% patients delabeled through a direct oral penicillin challenge, performed without any serious adverse events, and an overall 87% delabeling rate.
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INTRODUCTION: The drug allergy alert system reduces the frequency of adverse drug events, although it is subjected to collateral effects, since 80-90% of alerts are not real, and a large percentage of alerts are overridden (46.2-96.2%). We reviewed how the alert system is used at University Hospital Fundación Alcorcon (HUFA). METHODS: Data were obtained from the drug allergy alert and the alert overriding notification forms (both in the period 2011-20). We also recorded drug allergy diagnoses at HUFA, drug consumption in primary care in 2016. We calculated the incidence of drug allergy alert activation, temporal trends in use, and correlations between the number of drugs in several datasets. RESULTS: We collected 15,535 alerts. NSAIDs and penicillins were the drugs with the highest number of drug allergy alerts (36.55% and 26.91%, respectively). A correlation was found between the number of drug alerts and the type of drug allergy in HUFA in 2016. Only 6.83% of the alerts were removed, and, of these, 21.77% were reactivated. Approximately 100 overrides were recorded per year from 2016 (6.8% of 8,434 activated alerts during 2014-2020). CONCLUSIONS: The number of drug allergy alerts recorded via the drug allergy alert system of HUFA correlates with the distribution of drug allergy diagnoses in the hospital, although many of the alerts could be false positives (as per current published evidence). We detected a very low frequency of removed alerts (6.83%), a relevant frequency of reactivations (one quarter), and a very low frequency of overrides (6.8%).
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Hipersensibilidad a las Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Sistemas de Entrada de Órdenes Médicas , Humanos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/epidemiología , HospitalesRESUMEN
OBJECTIVE: The objective of this study was to assess the results of a clinical guideline for the treatment and early discharge of patients with complicated acute appendicitis in terms of infectious complications and hospital stay. MATERIALS AND METHODS: A guideline for appendicitis treatment according to severity was created. Complicated appendicitis cases were treated with ceftriaxone-metronidazole for 48h, with discharge being approved if certain clinical and blood test criteria were met. A retrospective analytical study comparing the incidence of postoperative intra-abdominal abscess (IAA) and surgical site infection (SSI) in patients under 14 years of age to whom the new guideline was applied (Group A) vs. the historical cohort (Group B, treated with gentamicin-metronidazole for 5 days) was carried out. A prospective cohort study to assess which antibiotic therapy (amoxicillin-clavulanic acid or cefuroxime-metronidazole) proved more effective in patients meeting early discharge criteria was also conducted. RESULTS: 205 patients under 14 years of age were included in Group A, whereas 109 patients were included in Group B. IAA was present in 14.3% of patients from Group A vs. 13.8% from Group B (p= 0.83), while SSI was present in 1.9% of patients from Group A vs. 8.25% from Group B (p= 0.008). Early discharge criteria were met by 62.7% of patients from Group A. Median hospital stay decreased from 6 to 3 days. At discharge, 57% of patients received amoxicillin-clavulanic acid, whereas 43% received cefuroxime-metronidazole, with no differences being found in terms of SSI (p= 0.24) or IAA (p= 0.12). CONCLUSIONS: Early discharge reduces hospital stay without increasing the risk of postoperative infectious complications. Amoxicillin-clavulanic acid is a safe option for at-home oral antibiotic therapy.
OBJETIVO: El objetivo de este estudio es evaluar los resultados en términos de complicaciones infecciosas y estancia hospitalaria de la instauración de una guía clínica para el tratamiento y alta precoz en pacientes con apendicitis aguda complicada. MATERIAL Y METODOS: Se elaboró una guía para el tratamiento de las apendicitis en función de su grado de severidad. Las complicadas se trataron con ceftriaxona-metronidazol durante 48 h, siendo alta si cumplen ciertos criterios clínicos y analíticos. Se realizó un estudio analítico retrospectivo comparando la incidencia de abscesos intraabdominales postquirúrgicos (AIA) e infección del sitio quirúrgico (ISQ) en pacientes menores de 14 años sometidos a la nueva guía (Grupo A), respecto a una cohorte histórica (Grupo B), en la que la pauta de tratamiento era gentamicina-metronidazol 5 días. Además, se realizó un estudio de cohortes prospectivas para evaluar qué antibioterapia (amocilina-clavulánico o cefuroxima-metronidazol) es más eficaz en los pacientes que cumplen criterios de alta precoz. RESULTADOS: Se incluyeron 205 pacientes menores de 14 años en el Grupo A y 109 en el Grupo B. Presentaron AIA un 14,3% en el grupo A, frente al 13,8% en el B (p= 0,83); e ISQ un 1,9% y un 8,25% respectivamente (p= 0,008). Cumplieron criterios de alta precoz el 62,7% de los pacientes del Grupo A. La mediana de estancia disminuyó a de 6 a 3 días. Al alta, el 57% recibieron amoxicilina-clavulánico y el 43% cefuroxima-metronidazol, sin hallarse diferencias en términos de ISQ (p= 0,24) ni de AIA (p= 0,12). CONCLUSIONES: El alta precoz disminuye la estancia hospitalaria sin aumentar el riesgo de complicaciones infecciosas postquirúrgicas. La amoxicilina-clavulánico es una opción segura para la antibioterapia oral domiciliaria.
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Apendicitis , Metronidazol , Humanos , Metronidazol/uso terapéutico , Cefuroxima/uso terapéutico , Apendicitis/complicaciones , Apendicitis/tratamiento farmacológico , Apendicitis/cirugía , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Alta del Paciente , Estudios Retrospectivos , Estudios Prospectivos , Antibacterianos , Infección de la Herida Quirúrgica/epidemiología , Apendicectomía/métodos , Resultado del TratamientoRESUMEN
Objetivo: El objetivo de este estudio es evaluar los resultados entérminos de complicaciones infecciosas y estancia hospitalaria de lainstauración de una guía clínica para el tratamiento y alta precoz enpacientes con apendicitis aguda complicada.Material y métodos: Se elaboró una guía para el tratamiento delas apendicitis en función de su grado de severidad. Las complicadas setrataron con ceftriaxona-metronidazol durante 48h, siendo alta si cumplen ciertos criterios clínicos y analíticos. Se realizó un estudio analíticoretrospectivo comparando la incidencia de abscesos intraabdominalespostquirúrgicos (AIA) e infección del sitio quirúrgico (ISQ) en pacientesmenores de 14 años sometidos a la nueva guía (Grupo A), respecto a unacohorte histórica (Grupo B), en la que la pauta de tratamiento era gentamicina-metronidazol 5 días. Además, se realizó un estudio de cohortesprospectivas para evaluar qué antibioterapia (amocilina-clavulánico ocefuroxima-metronidazol) es más eficaz en los pacientes que cumplencriterios de alta precoz. Resultados: Se incluyeron 205 pacientes menores de 14 años en elGrupo A y 109 en el Grupo B. Presentaron AIA un 14,3% en el grupoA, frente al 13,8% en el B (p= 0,83); e ISQ un 1,9% y un 8,25% respectivamente (p= 0,008). Cumplieron criterios de alta precoz el 62,7%de los pacientes del Grupo A. La mediana de estancia disminuyó a de6 a 3 días. Al alta, el 57% recibieron amoxicilina-clavulánico y el 43%cefuroxima-metronidazol, sin hallarse diferencias en términos de ISQ(p= 0,24) ni de AIA (p= 0,12).Conclusiones: El alta precoz disminuye la estancia hospitalariasin aumentar el riesgo de complicaciones infecciosas postquirúrgicas.La amoxicilina-clavulánico es una opción segura para la antibioterapiaoral domiciliaria.(AU)
Objective: The objective of this study was to assess the results of aclinical guideline for the treatment and early discharge of patients withcomplicated acute appendicitis in terms of infectious complicationsand hospital stay. Materials and methods: A guideline for appendicitis treatmentaccording to severity was created. Complicated appendicitis caseswere treated with ceftriaxone-metronidazole for 48h, with dischargebeing approved if certain clinical and blood test criteria were met. Aretrospective analytical study comparing the incidence of postoperative intra-abdominal abscess (IAA) and surgical site infection (SSI) inpatients under 14 years of age to whom the new guideline was applied(Group A) vs. the historical cohort (Group B, treated with gentamicinmetronidazole for 5 days) was carried out. A prospective cohort study toassess which antibiotic therapy (amoxicillin-clavulanic acid or cefuroxime-metronidazole) proved more effective in patients meeting earlydischarge criteria was also conducted.Results: 205 patients under 14 years of age were included in GroupA, whereas 109 patients were included in Group B. IAA was presentin 14.3% of patients from Group A vs. 13.8% from Group B (p=0.83),while SSI was present in 1.9% of patients from Group A vs. 8.25%from Group B (p=0.008). Early discharge criteria were met by 62.7%of patients from Group A. Median hospital stay decreased from 6 to 3days. At discharge, 57% of patients received amoxicillin-clavulanic acid,whereas 43% received cefuroxime-metronidazole, with no differencesbeing found in terms of SSI (p=0.24) or IAA (p=0.12). Conclusions: Early discharge reduces hospital stay without increas-ing the risk of postoperative infectious complications. Amoxicillin-clavulanic acid is a safe option for at-home oral antibiotic therapy.(AU)
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Humanos , Masculino , Femenino , Niño , Apendicitis/complicaciones , Apendicitis/tratamiento farmacológico , Tiempo de Internación , Ceftriaxona/administración & dosificación , Metronidazol/administración & dosificación , Absceso Abdominal , Pediatría , Cirugía General , Estudios Retrospectivos , Estudios de Cohortes , Alta del PacienteRESUMEN
BACKGROUND: Conflicting international guidelines exist on the management of sore throat by antibiotics. OBJECTIVES: To assess with the Appraisal of Guidelines for Research and Evaluation II (AGREE) instrument the quality of guidelines for uncomplicated acute group A beta-haemolytic streptococcal (GABHS) sore-throat. To make a sensitivity analysis restricted to guidelines with a rigour of development score higher than 60% and to describe their recommendations on scores, tests, and antibiotic therapy, including their justification. METHODS: A guideline literature review of acute GABHS sore throat, published between January 2000 and December 2019 in primary care and secondary care. The PubMed database, the Canadian Medical Association Infobase on Clinical Practice Guidelines and the International Network Guidelines were used. The quality of guidelines was assessed using the AGREE II instrument. The guidelines were classified into 2 categories: high-quality guidelines had to rate >60% for the rigour of development score, the others were classified as low-quality guidelines. RESULTS: Significant heterogeneity between the 15 guidelines concerned the scores of the 6 assessment domains. Among them, 6 guidelines presented a score above 60% with regards to the rigor of development domain and used a systematic literature search method, citing meta-analyses of recent randomised clinical trials. Most of the 6 high-quality guidelines no longer recommended the systematic use of diagnostic scores and tests, nor antibiotic therapy to prevent acute rheumatic fever or loco-regional complications, except for high-risk patients. CONCLUSION: Major discrepancies emphasise the need for only high-quality guidelines, based on adequately assessed evidence. Restricted antibiotic prescriptions to severe cases or high-risk patients would avoid antibiotic resistance.
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OBJECTIVES: Evaluate the impact of an allergy history-guided algorithm for optimizing perioperative cefazolin use in patients with reported beta-lactam allergy undergoing cesarean delivery. METHODS: The Allergy Clarification for Cefazolin Evidence-based Prescribing Tool (ACCEPT) was developed through consensus by allergists, anesthesiologists, and infectious diseases specialists, and implemented over a 2-month period (December 1, 2018, to January 31, 2019). A segmented regression on monthly cefazolin use was conducted during the baseline (January 1 to November 30, 2018) and intervention (February 1 to December 31, 2019) periods to evaluate the impact of ACCEPT on the monthly use of perioperative cefazolin in patients with reported beta-lactam allergy undergoing cesarean delivery. The frequency of perioperative allergic reactions and surgical site infections was collected during both periods. RESULTS: Of the 3128 eligible women who underwent a cesarean delivery, 282 (9%) reported a beta-lactam allergy. The most common beta-lactam allergens were penicillin (64.3%), amoxicillin (16.0%), and cefaclor (6.0%). The most frequently reported allergic reactions were rash (38.1%), hives (21.4%), and unknown (11.6%). Use of cefazolin increased from 52% (baseline) to 87% during the intervention period. Segmented regression analysis confirmed a statistically significant increase following implementation (incidence rate ratio 1.62, 95% CI 1.19-2.21, P = 0.002). There was 1 perioperative allergic reaction in the baseline period and 2 during the intervention period. Cefazolin use remained high (92%) 2 years after algorithm implementation. CONCLUSIONS: Implementation of a simple allergy history-guided algorithm in obstetrical patients with reported beta-lactam allergy resulted in a sustained increase in perioperative cefazolin prophylaxis.
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Hipersensibilidad a las Drogas , Hipersensibilidad , Embarazo , Humanos , Femenino , Cefazolina/uso terapéutico , Antibacterianos/uso terapéutico , beta-Lactamas/uso terapéutico , Hipersensibilidad a las Drogas/epidemiología , Hipersensibilidad a las Drogas/prevención & control , Profilaxis Antibiótica/métodos , Hipersensibilidad/complicaciones , Hipersensibilidad/tratamiento farmacológicoRESUMEN
INTRODUCTION: The rising numbers of multiple drug-resistant (MDR) pathogens and the consequent antibacterial therapy failure that resulted in severe medical conditions push to illustrate new molecules with extended activity against the resistant strains. In this manner, chemical derivatization of known antibiotics is proposed to save efforts in drug discovery, and penicillins serve as an ideal in this regard. METHOD: Seven synthesized 6-aminopenicillanic acid-imine derivatives (2a-g) were structure elucidated using FT-IR, 1H NMR, 13C NMR, and MS spectroscopy. In silico molecular docking and ADMET studies were made. The analyzed compounds obeyed Lipinski's rule of five and showed promising in vitro bactericidal potential when assayed against E. coli, E. cloacae, P. aeruginosa, S. aureus, and A. baumannii. MDR strains using disc diffusion and microplate dilution techniques. RESULT: The MIC values were 8 to 32 µg/mL with more potency than ampicillin, explained by better membrane penetration and more ligand-protein binding capacity. The 2g entity was active against E. coli. This study was designed to find new active penicillin derivatives against MDR pathogens. CONCLUSION: The products showed antibacterial activity against selected MDR species and good PHK, PHD properties, and low predicted toxicity, offering them as future candidates that require further preclinical assays.
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With the growing incidence of multi-drug resistant organisms, delabelling incorrect antibiotic allergies has become an integral part of antimicrobial stewardship worldwide. For example, around 90% of penicillin allergy labels are found to be inaccurate following a full allergy work-up, which deprive patients the use of effective first-line penicillin antibiotics and increase the risk of antimicrobial resistance with the use of other extended spectrum non-penicillin antimicrobials. Significant numbers of adult and paediatric patients over time are labelled with multiple penicillin and non-penicillin antibiotic allergies often during inappropriate antimicrobial use, resulting in a label of "multiple antibiotic allergy". In contrast to delabelling penicillin allergy where oral direct provocation tests can be used for low-risk, mild reactions, and sensitivity/specificity/positive and negative predictive values of skin tests have been demonstrated, diagnostic tests for multiple antibiotic allergy often require the use of a combination of in-vivo and in-vitro tests across different antimicrobial classes for evaluation. Shared decision making with patients and informed consent are also needed when prioritising which drugs to delabel first, balancing the risks, benefits of testing vs. interim use of alternative antibiotics. Similar to delabelling penicillin allergy, the cost-effectiveness of delabelling multiple drug allergies is unknown.
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In clinical microbiology, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) is frequently employed for rapid microbial identification. However, rapid identification of antimicrobial resistance (AMR) in Escherichia coli based on a large amount of MALDI-TOF MS data has not yet been reported. This may be because building a prediction model to cover all E. coli isolates would be challenging given the high diversity of the E. coli population. This study aimed to develop a MALDI-TOF MS-based, data-driven, two-stage framework for characterizing different AMRs in E. coli. Specifically, amoxicillin (AMC), ceftazidime (CAZ), ciprofloxacin (CIP), ceftriaxone (CRO), and cefuroxime (CXM) were used. In the first stage, we split the data into two groups based on informative peaks according to the importance of the random forest. In the second stage, prediction models were constructed using four different machine learning algorithms-logistic regression, support vector machine, random forest, and extreme gradient boosting (XGBoost). The findings demonstrate that XGBoost outperformed the other four machine learning models. The values of the area under the receiver operating characteristic curve were 0.62, 0.72, 0.87, 0.72, and 0.72 for AMC, CAZ, CIP, CRO, and CXM, respectively. This implies that a data-driven, two-stage framework could improve accuracy by approximately 2.8%. As a result, we developed AMR prediction models for E. coli using a data-driven two-stage framework, which is promising for assisting physicians in making decisions. Further, the analysis of informative peaks in future studies could potentially reveal new insights. IMPORTANCE Based on a large amount of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) clinical data, comprising 37,918 Escherichia coli isolates, a data-driven two-stage framework was established to evaluate the antimicrobial resistance of E. coli. Five antibiotics, including amoxicillin (AMC), ceftazidime (CAZ), ciprofloxacin (CIP), ceftriaxone (CRO), and cefuroxime (CXM), were considered for the two-stage model training, and the values of the area under the receiver operating characteristic curve (AUC) were 0.62 for AMC, 0.72 for CAZ, 0.87 for CIP, 0.72 for CRO, and 0.72 for CXM. Further investigations revealed that the informative peak m/z 9714 appeared with some important peaks at m/z 6809, m/z 7650, m/z 10534, and m/z 11783 for CIP and at m/z 6809, m/z 10475, and m/z 8447 for CAZ, CRO, and CXM. This framework has the potential to improve the accuracy by approximately 2.8%, indicating a promising potential for further research.
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Antibacterianos , Escherichia coli , Antibacterianos/farmacología , Ceftriaxona/farmacología , Ceftazidima , Cefuroxima , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Ciprofloxacina , AmoxicilinaRESUMEN
OBJECTIVE: Growing evidence is highlighting the inefficacy of clindamycin as an effective substitute to amoxicillin in patients self-reporting a penicillin allergy. The hypothesis is that implant failure is higher in these patients, when compared to patients receiving penicillin. To test this hypothesis, a systematic review and meta-analysis was undertaken and a protocol for delabeling penicillin allergic patients was presented. MATERIALS AND METHODS: A systematic review was undertaken by searching across three different databases, namely PubMed, Scopus and Web of Science. RESULTS: Out of 572 results, four studies were eligible to be included. Fixed-effects meta-analysis showed a higher number of failed implants in patients who were administered clindamycin, because of a self-reported allergy to penicillin. Results showed that these patients are over three times more likely (OR = 3.30, 95% C.I. 2.58-4.22, p-value < .00001) to undergo implant failure with an average cumulative proportion of 11.0% (95% C.I. 3.5-22.0%) versus 3.8% (95% C.I. 1.2-7.7%) of patients not requiring clindamycin and administered amoxicillin. A protocol for penicillin allergy delabeling is proposed. CONCLUSIONS: Current evidence is still limited and based on retrospective observational studies, it is difficult to state if penicillin allergy, clindamycin administration or a combination of both is responsible for the current trends and reported findings.