Intramammary treatment of clinical mastitis quarters with ceftiofur does not cause anbiotic residues in adjacent untreated quarters.

The study was carried out in dairy cows to elucidate whether treatment of clinical mastitis quarters with Spectramast® LC (ceftiofur hydrochloride, 125 mg, Zoetis) created a reason for discarding milk from adjacent untreated healthy quarters. The antibiotic was infused once daily in the affected mammary quarter for four days. Forty-nine cows were evaluated after diagnosis of clinical mastitis in three or fewer udder quarters. In all cases, quarters that did not receive treatment had milk samples collected one day after the end of treatment. All milk samples from untreated quarters were below the maximum permissible limit for the presence of antibiotic residues after analysis with the BetaStar S Combo test. Pharmacokinetic and pharmacodynamic characteristics may explain this finding. We conclude that it is feasible to use milk from untreated quarters of animals that have been treated with Spectramast® LC. We also reiterate the need to carry out tests with other pharmacological bases, and that the results found in this experiment cannot be extrapolated to other drugs.Dairy cattle have considerable importance in the development of the Brazilian economy, being directly linked to economic and social progress. In the first half of 2020, 12.1 billion liters of milk were produced in Brazil and in 2019, there was a new record of 25.01 billion liters produced (IBGE, 2020). This production comes from a wide variety of production systems, coming from smallholder farmers as well as from large companies that use the latest technologies available on the market. Dairy production is a complex activity. For one to obtain economical success, several aspects must be monitored. Maintaining the health of animals is a top priority, and the literature suggests that various diseases are a common challenge for dairy producers. Mastitis is the main disease that affects dairy cows, responsible for considerable economic loss and significant zootechnical and productive challenges (Ruegg, ). It is considered the second leading cause of cow culling in dairy herds, behind reproductive problems. Mastitis is characterized by infection of the mammary gland and may or may not occur with inflammation, generating changes in the mammary tissue and properties of the milk. It is classifield into clinical or subclinical mastitis, according to presence or absence of clinical signs, and into contagious or environmental based on the causative agent (Correa et al., ).

Improved efficiency in the management of newborns with infectious risk factors by the sepsis risk calculator and clinical observation.

OBJECTIVE: To evaluate the efficiency of the sepsis risk calculator and the serial clinical observation in the management of late preterm and term newborns with infectious risk factors. METHOD: Single-center, observational, two-phase cohort study comparing the rates of neonates born ≥35 weeks' gestation, ≥2000 g birthweight, and without major congenital anomalies, who were screened and/or received antibiotics for early-onset neonatal sepsis risk at our center during two periods, before (January/2018-June/2019) and after (July/2019-December/2020) the implementation of the sepsis risk calculator. RESULTS: A total of 1796 (Period 1) and 1867 (Period 2) patients with infectious risk factors were included. During the second period, tests to rule out sepsis were reduced by 34.0 % (RR, 95 %CI): 0.66 (0.61, 0.71), blood cultures by 13.1 %: 0.87 (0.77, 0.98), hospital admissions by 13.5 %: 0.86 (0.76, 0.98) and antibiotic administration by 45.9 %: 0.54 (0.47, 0.63). Three cases of early-onset neonatal sepsis occurred in the first period and two in the second. Clinical serial evaluation would have detected all true cases. CONCLUSIONS: The implementation of a sepsis risk calculator in the management of newborns ≥35 weeks GA, ≥2000 g birthweight, without major congenital anomalies, with infectious risk factors is safe and adequate to reduce laboratory tests, blood cultures, hospital admissions, and antibiotics administration. Serial clinical observation, in addition, could be instrumental to achieve or even improve this goal.

Improved efficiency in the management of newborns with infectious risk factors by the sepsis risk calculator and clinical observation

Abstract Objective To evaluate the efficiency of the sepsis risk calculator and the serial clinical observation in the management of late preterm and term newborns with infectious risk factors. Method Single-center, observational, two-phase cohort study comparing the rates of neonates born ≥35 weeks' gestation, ≥2000 g birthweight, and without major congenital anomalies, who were screened and/or received antibiotics for early-onset neonatal sepsis risk at our center during two periods, before (January/2018-June/2019) and after (July/2019-December/2020) the implementation of the sepsis risk calculator. Results A total of 1796 (Period 1) and 1867 (Period 2) patients with infectious risk factors were included. During the second period, tests to rule out sepsis were reduced by 34.0 % (RR, 95 %CI): 0.66 (0.61, 0.71), blood cultures by 13.1 %: 0.87 (0.77, 0.98), hospital admissions by 13.5 %: 0.86 (0.76, 0.98) and antibiotic administration by 45.9 %: 0.54 (0.47, 0.63). Three cases of early-onset neonatal sepsis occurred in the first period and two in the second. Clinical serial evaluation would have detected all true cases. Conclusions The implementation of a sepsis risk calculator in the management of newborns ≥35 weeks GA, ≥2000 g birthweight, without major congenital anomalies, with infectious risk factors is safe and adequate to reduce laboratory tests, blood cultures, hospital admissions, and antibiotics administration. Serial clinical observation, in addition, could be instrumental to achieve or even improve this goal.

Crude Mortality Associated With the Empirical Use of Polymyxins in Septic Patients in a Setting of High Prevalence of Carbapenem-Resistant Gram-negative Bacteria: Retrospective Analysis of a Cohort.

BACKGROUND: Our aim in this retrospective cohort study was to assess the impact on mortality of the empirical use of polymyxin as therapy for carbapenem-resistant gram-negative bacteria (CR-GNB) in septic patients. The study was performed at a tertiary academic hospital in Brazil, from January 2018 to January 2020, the pre-coronavirus disease 2019 period. METHODS: We included 203 patients with suspected sepsis. The first doses of antibiotics were prescribed from a "sepsis antibiotic kit", which contained a selection of drugs, including polymyxin, with no preapproval policy. We developed a logistic regression model to assess risk factors associated with 14-day crude mortality. Propensity score for polymyxin was used to control biases. RESULTS: Seventy (34%) of 203 patients had infections with at least 1 multidrug-resistant organism isolated from any clinical culture. Polymyxins in monotherapy or in combination therapy were prescribed to 140 of the 203 (69%) patients. The overall 14-day mortality rate was 30%. The 14-day crude mortality was associated with age (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 1.01-1.05; P = .01), SOFA (sepsis-related organ failure assessment) score value (aOR, 1.2; 95% CI, 1.09-1.32; P < .001), CR-GNB infection (aOR, 3.94; 95% CI, 1.53-10.14; P = .005), and time between suspected sepsis and antibiotic administration (aOR, 0.73; 95% CI, .65-.83; P < .001). The empirical use of polymyxins was not associated with decreased crude mortality (aOR, 0.71; 95% CI, .29-1.71; P = .44). CONCLUSIONS: Empirical use of polymyxin for septic patients in a setting with high CR-GNB prevalence was not associated with decreased crude mortality.

Therapeutic efficacy of enrofloxacin in treatment of Francisella orientalis infections in juvenile Nile tilapia (Oreochromis niloticus L.).

Outbreaks of infections by Francisella orientalis represent one of the main obstacles to Nile tilapia (Oreochromis niloticus L.) farming. It is responsible for acute mortality in fingerlings and juveniles. The main control measure available is oral antibiotic therapy. This study compared the therapeutic efficacy of the antibiotics enrofloxacin and oxytetracycline, the most commonly used antimicrobial, against francisellosis in juvenile Nile tilapia (O. niloticus). Fish were challenged with a virulent isolate of F. orientalis and treated with medicated feed containing one of two doses of oxytetracycline (100 or 300 mg/kg of live weight (LW)) or 10 mg/kg of LW of enrofloxacin. The positive and negative control groups received feed without antibiotics; the negative control group was unchallenged. The results showed that enrofloxacin at a dose of 10 mg/kg of LW is effective against francisellosis in juvenile Nile tilapia (O. niloticus). Treatment with oxytetracycline did not eliminate the pathogen from the infected host, and the surviving fish became carriers. Enrofloxacin was able to cure the fish of infection with F. orientalis. This study suggests that enrofloxacin is a better option for treating francisellosis in Nile tilapia (O. niloticus L.). It controls mortality and avoids the carrier state in the fish, thus reducing the possibility of recurrence in the affected batches.

Advances and perspectives for antimicrobial peptide and combinatory therapies.

Antimicrobial peptides (AMPs) have shown cell membrane-directed mechanisms of action. This specificity can be effective against infectious agents that have acquired resistance to conventional drugs. The AMPs' membrane-specificity and their great potential to combat resistant microbes has brought hope to the medical/therapeutic scene. The high death rate worldwide due to antimicrobial resistance (AMR) has pushed forward the search for new molecules and product developments, mainly antibiotics. In the current scenario, other strategies including the association of two or more drugs have contributed to the treatment of difficult-to-treat infectious diseases, above all, those caused by bacteria. In this context, the synergistic action of AMPs associated with current antibiotic therapy can bring important results for the production of new and effective drugs to overcome AMR. This review presents the advances obtained in the last 5 years in medical/antibiotic therapy, with the use of products based on AMPs, as well as perspectives on the potentialized effects of current drugs combined with AMPs for the treatment of bacterial infectious diseases.

Uso de antibióticos para instalación de implantes óseo integrados / Antibiotics for osseointegrated dental implants

Introducción: La extracción de dientes permanentes se puede deber a varias razones, como la caries dental, enfermedad periodontal, entre otras. Frente a este problema, surgen los implantes dentales, definidos como un dispositivo protésico aloplástico implantado en el tejido óseo, proporcionando retención y soporte para una prótesis dental fija o removible. A pesar de la alta tasa de éxito, existen fracasos en implantología, a causa de una infección postoperatoria. Es por esto, que se han incluido dentro del tratamiento distintos regímenes de terapias antibióticas, sin embargo, actualmente su efectividad para evitar complicaciones peri y postoperatorias es controversial. Métodos: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metaanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Resultados y conclusiones: Identificamos 23 revisiones sistemáticas que en conjunto incluyeron 16 estudios primarios, de los cuales, 9 corresponden a ensayos aleatorizados. Concluimos que la terapia antibiótica pre operatoria en comparación a placebo probablemente reduce el fracaso de los implantes y de las prótesis, sin embargo, puede generar poca o nula diferencia en las infecciones postoperatorias. Por otro lado, no está claro si el tratamiento de terapia antibiótica (perioperatoria y postoperatoria) en comparación a placebo reduce el fracaso de los implantes y de infección postoperatoria, debido a que la certeza de la evidencia existente es muy baja.

Introduction: The extraction of permanent teeth can be due to various reasons, such as dental caries, periodontal disease, among others. Faced with this problem, dental implants arise, defined as an alloplastic prosthetic device implanted in bone tissue, providing retention and support for a fixed or removable dental prosthesis. Despite the high success rate, there are failures in implantology, due to postoperative infection. For this reason, different antibiotic therapy regimens have been included in the treatment; however, their effectiveness in avoiding perioperative and postoperative complications remains controversial. Methods: A search was performed using Epistemonikos, the biggest database for systematic reviews in health, which is maintained by screening of multiple sources of information, including MEDLINE, EMBASE, Cochrane, among others. Data from systematic reviews were extracted, and analysis of the primary studies was performed, including a meta-analysis and a summary of findings table using GRADE approach. Results and conclusions: We identified 23 systematic reviews that together included 16 primary studies, of which 9 correspond to randomized clinical trials. We conclude that antibiotic prophylaxis compared to placebo probably reduces implant and prosthetic failure, however, it may make little or no difference in postoperative infections. On the other hand, it is not clear whether antibiotic therapy treatment (perioperative and postoperative) compared to placebo reduces implant failure and postoperative infection, because the certainty of the existing evidence is very low.

¿Son útiles los antimicrobianos en pacientes con trabajo de parto prematuro, espontáneo, membranas intactas e infección bacteriana ascendente? Una revisión narrativa / Are antibiotics useful in patients with preterm and spontaneous labor, intact membranes and ascendant bacterial infection? A narrative review

El parto prematuro (PP) es la principal causa de morbilidad/mortalidad perinatal y frecuentemente es espontáneo, con membranas intactas (MI). La infección intrauterina es su causa más común en un hospital público de Chile. Existe evidencia que la infección bacteriana ascendente desde la vagina es responsable de la infección/inflamación intraamniótica, del PP y de los resultados adversos maternos y perinatales. Esta revisión narrativa incluye ensayos controlados aleatorizados (ECAs), publicados en PubMed, Cochrane, Embase, Scielo, Science Direct, Wiley Online Library, sobre los mecanismos que intervienen en el ascenso de la infección vaginal, los factores infecciosos que participan en el resultado adverso materno-perinatal y la eficacia de los antimicrobianos en estos casos. Estos trabajos no recomiendan usar antimicrobianos profilácticos porque producen daño a corto y largo plazo en los hijos. Pero este resultado tiene sesgo porque no se evaluó la presencia de infección/inflamación subclínica, lo que disminuye el grado de recomendación. También existen ECAs, que erradican la infección/inflamación intraamniótica, reducen la morbilidad/mortalidad neonatal, pero son trabajos aislados, obtenidos de subanálisis, con bajo nivel de evidencia. Se requieren revisiones sistemáticas y metaanális de ECAs con estudio de infección/inflamación subclínica para evaluar si son útiles los antimicrobianos en el PP espontáneo con MI.

Preterm labor (PL) is the leading cause of perinatal morbidity/ mortality and is frequently spontaneous with intact membranes (IM). Intrauterine infection is its most common cause in a public hospital in Chile. There is evidence that ascending bacterial infection from the vagina is responsible for intraamniotic infection/inflammation, PL, and adverse maternal and perinatal outcomes. This narrative review includes randomized controlled trials (RCTs), published in PubMed, Cochrane, Embase, Scielo, Science Direct, Wiley Online Library on the mechanisms involved in the rise of vaginal infection, the infectious factors involved in adverse maternal-perinatal outcomes, and the efficacy of antibiotics in these cases. They do not recommend the use of prophylactic antibiotics because they cause short and long-term damage to children. But this result is biased because the presence of subclinical infection/inflammation was not evaluated, which lowers the degree of recommendation. There are also RCTs that eradicate intra-amniotic infection/inflammation, reduce neonatal morbidity/ mortality, but they are isolated studies, obtained from subanalyses, with a low level of evidence. Systematic reviews and meta-analyses of RCTs with subclinical infection/inflammation study are required to assess whether antibiotics are useful in spontaneous PL with IM.

Eficácia in sílico do florfenicol no tratamento de pododermatite infecciosa por Fusobacterium necrophorum em ovelhas / In sílico efficacy of florfenicol in the treatment of Fusobacterium necrophorum infectious pododermatitis in sheep

Objetivou-se comparar o efeito in silico do florfenicol nas doses de 20 e 30 mg/Kg em ovinos pelas vias intravenosa (IV) e intramuscular (IM), usando a modelagem PK/PD. Realizou-se uma simulação de Monte Carlo com base nos dados de concentração plasmática de um estudo publicado anteriormente. Calculou-se a área sob a curva (ASC) e as taxas de eficácia do florfenicol para os efeitos bacteriostático, bactericida e de erradicação bacteriológica. A dose de 20 mg/Kg IV demonstrou efeitos de erradicação de 100, 93 e 0% para CIM de 0,5, 1 e acima, respectivamente. O efeito bacteriostático foi de 99 e 90% para CIM de 4 e 2 µg/ml, enquanto o bactericida foi de 14% para CIM de 2 µg/ml. A dose de 30 mg/Kg IV apresentou 100% de erradicação para CIM de 1 µg/mL e 100% de efeito bactericida para CIM de 2 µg/mL. Há 100% de efeito bacteriostático em CIM de 4 µg/ml. As doses de 20 e 30 mg/Kg IM mostraram 100% de erradicação para CIM até 1 µg/mL e 0% para CIM maiores. O efeito bacteriostático foi mantido em 100% para uma CIM de 4 µg/mL em ambas as doses. Este estudo mostra o efeito de erradicação bacteriológica do florfenicol nas doses de 20 e 30 mg/Kg, IV e IM. Recomenda-se que seja feito um estudo de eficácia in vivo com a dose de 30mg/Kg IM em ovinos infectados por F. necrophorum com MIC superior a 2 µg/mL.

We aimed to compare the in silico effect of florfenicol at doses of 20 and 30 mg/Kg in sheep by intravenous (IV) and intramuscular (IM) routes, using PK/PD modeling. We performed a Monte Carlo simulation based on plasma concentration data from a previously published study. We calculated the area under the curve (AUC) and the efficacy rates of florfenicol to bacteriostatic, bactericidal, and bacteriological eradication effects. The dose of 20 mg/Kg IV demonstrated 100, 93, and 0% eradication effects for MICs of 0.5, 1, and above, respectively. The bacteriostatic effect was 99 and 90% for MIC of 4 and 2 µg/ml, while the bactericide was 14% for MIC of 2 µg/ml. The 30 mg/Kg IV dose showed 100% eradication for MIC of 1 µg/mL and 100% bactericidal effect for MIC of 2 µg/mL. There is a 100% of bacteriostatic effect at MIC of 4 µg/ml. Doses of 20 and 30 mg/Kg IM showed 100% eradication for MIC up to 1 µg/mL and 0% for MIC above. The bacteriostatic effect was maintained at 100% for a MIC of 4 µg/mL at both doses. This study shows the bacteriological eradication effect of florfenicol at doses of 20 and 30 mg/Kg, IV, and IM. Therefore, we recommend an in vivo efficacy study with a dose of 30mg/Kg IM in sheep infected with F. necrophorum with MIC greater than two µg/mL.

Efectividad de la antibioticoterapia sistémica precoz en pacientes con endoftalmitis postraumática / Effectiveness of the early systemic antibiotic therapy in patients with postraumatic endophthalmitis

Introducción: La endoftalmitis postraumática se define como una marcada inflamación de los fluidos y tejidos de las cavidades intraoculares, provocada por la invasión y replicación de microorganismos después de un traumatismo ocular a globo abierto, lo cual puede ocasionar la pérdida de la visión. Objetivo: Evaluar la efectividad de la terapia antibiótica sistémica precoz en pacientes con endoftalmitis postraumática. Métodos: Se efectuó un estudio cuasiexperimental de 72 pacientes con traumatismo ocular a globo abierto, ingresados en el Centro Oftalmológico del Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba, desde enero del 2017 hasta mayo del 2019. Se realizó un muestreo aleatorio simple; los pacientes se distribuyeron en 2 grupos: uno de control con 28 integrantes, a los cuales se le administró el tratamiento farmacológico habitual y otro de estudio con 44, quienes además de lo anterior recibieron terapia antibiótica sistémica. Resultados: Predominaron los pacientes masculinos, con edades entre 45 y 54 años (29,5 %); 72,7 % no mostraron antecedentes personales de interés y el trauma ocular ocurrió con más frecuencia en un ambiente rural (77,8 %). La zona 1 fue la más afectada (65,3 %); en 39,3 % de los pacientes la evolución del trauma fue menor de 6 horas, pero en el grupo que no recibió la terapéutica sistémica precoz y presentó endoftalmitis (10,7 %) este tiempo fue mayor, la reparación ocurrió tardíamente. Conclusiones: La terapia antibiótica sistémica precoz fue efectiva en la mayoría de los pacientes que recibieron este tratamiento contra la endoftalmitis postraumática.

Introduction: Postraumatic endophthalmitis is defined as a marked inflammation of the fluids and tissues of the intraocular cavities, caused by the invasion and replication of microorganisms after an ocular traumatism on open globe, that can cause loss of the vision. Objective: To evaluate the effectiveness of the early systemic antibiotic therapy in patients with postraumatic endophthalmitis. Method: A quasi-experiment study of 72 patients with ocular traumatism on open globe was carried out, they were admitted in the Ophthalmologic Center of Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba, from January, 2017 to May, 2019. A simple random sampling was carried out; patients were distributed in 2 groups: one of control with 28 members, that received the habitual pharmacological treatment and a study group with 44 members who received systemic antibiotic therapy besides the above-mentioned. Results: Male patients prevailed, aged between 45 and 54 years (29.5 %); 72.7 % didn't show personal history of interest and the ocular trauma happened with more frequency in a rural atmosphere (77.8 %). The area 1 was the most affected (65.3 %); in 39.3 % of the patients the clínical course of trauma was less than 6 hours, but in the group that didn't receive the early systemic therapy and presented endophthalmitis (10,7 %) this time was higher, the repair happened belatedly. Conclusions: The early systemic antibiotic therapy was effective in most of the patients that received this treatment against the postraumatic endophthalmitis.

Infecciones del sitio quirúrgico en un hospital de enseñanza. Estudio observacional / Surgical site infections in a teaching hospital. Observacional study

Objetivo: determinar el número de pacientes que desarrollaron una infección postquirúrgica, posibles agentes etiológicos y complicaciones.Métodos : se realizó un estudio retrospectivo observacional que incluye a todos los supervivientes de las cirugías electivas y de emergencia de los servicios de Cirugía I, II y III del Hospital Universitario de Caracas durante el año 2019. Los datos fueron recopilados a través de la revisión de historias médicas. 48 historias cumplieron los criterios de inclusión, en estas se analizaron distintas variables como: días de hospitalización, síntomas, resultados de laboratorio, cultivos microbiológicos y tratamientos. A partir de estas se elaboraron tablas de frecuencia y análisis bivariado (Chi-cuadrado de Pearson) con el programa IBM SPSS Statistics 26.Resultados : la prevalencia de las infecciones postoperatorias fue de 4,69% CI 95% = (2,79-7,16%) en los servicios de Cirugía (I, II y III) del hospital durante el año 2019, la mayoría ocurrieron tras cirugías de emergencia (87,50%) tales como: apendicectomías (45,83%) y colecistectomías (10,41%). Solo al 22,91% de estos pacientes se les realizó cultivo microbiológico donde se encontró:E. coli (10,50%), Enterococcus sp. y Klebsiella pneumoniae (6,24%), Morganella morganii (2,1%) y Streptococcus pneumoniae (2,1%). Conclusión : las infecciones del sitio quirúrgico siguen siendo una de las principales causas de morbi-mortalidad y aumento de la estadía hospitalaria en los servicios de cirugía, son de diversa etiología bacteriana y están mayormente asociadas a cirugías abdominales, de emergencia(AU)

Objective: to determine the number of patients that developed a surgical site infection (SSI), possible etiologic agents and complications.Methods : an observational and retrospective study that includes every patient that underwent and survived a surgical procedure at the general surgery I, II and III services at the University Hospital of Caracas between January and December 2019. The study data were collected through the review of the medical records. 48 medical records that met the inclusion criteria and different variables were analyzed, including: days of hospitalization, symptoms, laboratory results, microbiological cultures and treatments. From those variables, frequency tables and bivariate analysis (Pearson's Chi-Square) were created with the IBM SPSS Statistics 26 program.Results : the SSI prevalence was 4,69% CI 95%= (2,79-7,16%) including the three surgery services (I, II and III) at the University Hospital of Caracas during 2019. Most of these occurred after emergency surgeries (87,50%) among which stand out: appendectomy (45,83%) and cholecystectomies (10,41%). Microbiological cultures were performed only in 22,91% of these patients and the following bacteria were isolated:E. coli (10,50%), Enterococcus sp. plus Klebsiella pneumoniae (6,24%), Morganella morganii (2,1%) and Streptococcus pneumoniae (2,1%). Conclusion : Surgical Site Infection (SSI) continues to be one of the main causes of morbimortality and increased hospital stay in surgical services in the hospital. These infections have a diverse bacterial etiology and are mostly associated with abdominal or emergency surgeries(AU)

Farm microbiological milk culture: study case on cow performance, financial and economic aspects / Cultivo microbiológico de leite na fazenda: estudo de caso sobre desempenho de vacas, aspectos financeiros e econômicos

This study evaluated the use of microbiological culture of milk from cows with clinical mastitis (CM), and the performance and economic results after implementing this procedure. The 18-month data were obtained from a farm in Minas Gerais State, Brazil, with an average daily production of 23.1 L of milk from cows milked twice daily under a semi-intensive regime. After a case of CM was identified, a milk sample from the affected quarter was collected and sent to the farm's laboratory. First, a bi-plate containing selective growth medium was used for isolation of Gram-positive and negative bacteria (Plate 1). Subsequently, a tri-plate with selective growth medium was used for isolation of Gram-positive and negative bacteria, and bacteria of the genus Streptococcus (Plate 2). Finally, a tri-plate containing three chromogenic culture media capable of identifying 18 bacterial species was used (Plate 3). Clinical cases of mastitis were treated once a day based on the results of the microbiological culture. Two economic scenarios were evaluated (scenarios 1 and 2). Scenario 1 compared the situation if all cases of CM were treated (not using on-farm culture) vs. the use of on-farm culture (real data) and the generated savings for one year. Data from 1,582 lactations of 1,227 cows were evaluated, with 1,917 cases of CM from 636 cows recorded. The average annual incidence of CM was 48.2%. Of all cases evaluated, 76.8% were classified as grade 1 mastitis; 20% as grade 2, and 3.2% as grade 3. The incidence of new clinical cases of mastitis was 4.17% per month. From the samples analyzed on the three plates, 27.8% of the cases received a recommendation to not be treated and 72.2% received a recommendation of treatment. However, only 18.6% were not treated, making a total of 81.4% treated cases. Of the clinical cases that did not receive intramammary antibiotic therapy, 84.3% had a clinical cure. Conversely, the clinical cure rate reached 84% for the cases that received intramammary antibiotic therapy. In scenario 1, the total operational cost of the clinical case decreased by 10.3% after the implementation of the on-farm culture, with an 18.4% reduction in the use of antibiotics. In scenario 2, there was a 5.5% reduction in the cost of the clinical case and an 11.8% reduction in the use of antibiotics. Thus, the implementation of on-farm culture and the applied methodology, enhanced treatment accuracy of CM cases, reducing the total operating cost of the case and the use of antibiotics on the farm.

O objetivo deste estudo foi avaliar a utilização da cultura microbiológica de leite de vacas com mastite clínica (MC), os resultados zootécnicos e econômicos após implementação desse procedimento. Dados de 18 meses foram obtidos em uma fazenda em Minas Gerais com produção média de 23,1 L de leite/vaca/dia, em duas ordenhas diárias em regime semi-intensivo. Após a identificação da MC, uma amostra de leite do quarto afetado foi coletada e encaminhada para laboratório da fazenda. Primeiramente foi utilizada placa bipartida em meio de cultura seletivo para crescimento de bactérias Gram-positivas e negativas (Placa 1), seguindo-se para a utilização da placa tri-partida com meios de cultura seletivos para crescimento de bactérias Gram-positivas e negativas e bactérias do gênero Streptococcus (Placa 2) e posteriormente para placa tripartida, contendo três meios de cultura cromogênicos, capazes de identificar 18 espécies bacterianas (Placa 3). Foram avaliados dados de 1.227 vacas em 1.582 lactações, sendo registrados 1.917 casos de MC. Os casos clínicos de mastite foram tratados uma vez ao dia com base nos resultados da cultura microbiológica. Foram realizadas duas avaliações financeiras (cenário 1 e 2). O cenário 1 comparou a situação se todos os casos de MC fossem tratados (ausência de cultura na fazenda), comparado com a utilização da cultura na fazenda (dados reais) e as economias de recursos geradas durante o período de um ano. O cenário 2 utilizou os resultados reais após a economia de recursos gerados pela cultura, seguindo a recomendação ideal de tratamento. Foram avaliados 1.917 casos de MC (636 animais), totalizando incidência média anual de 48,2%. Do total dos casos avaliados, 76,8% foram classificados como mastite grau 1; 20% grau 2 e 3,2% grau 3. A incidência de novos casos clínicos de mastite foi de 4,17% ao mês. Das amostras analisadas nas três placas, 27,8% dos casos receberam a recomendação de não serem tratados e 72,2% de tratamento. Entretanto, apenas 18,6% realmente não foram tratados, totalizando 81,4% de tratamentos. Dos casos clínicos que não receberam antibioticoterapia intramamária, 84,3% apresentaram cura clínica. Já os casos que passaram por antibioticoterapia intramamária, a taxa de cura clínica foi de 84,0%. No primeiro cenário, após a implementação da cultura na fazenda, o custo operacional total do caso clínico reduziu em 10,3%, com redução de 18,4% de utilização de antibióticos. Já no segundo cenário, houve redução de 5,5% no custo do caso clínico e redução de 11,8% na utilização de antibióticos. A implementação da cultura na fazenda e a metodologia aplicada, promoveu maior assertividade dos tratamentos dos casos de MC, com redução do custo operacional total do caso e da utilização de antibióticos na propriedade.

Características microbiológicas de los pacientes con úlcera del pie diabético / Microbiologic characteristics of patients with diabetic foot ulceration

RESUMEN Introducción: Las infecciones de las úlceras del pie diabético son comunes, complejas, de alto costo y constituyen la principal causa de amputación no traumática de las extremidades inferiores. Objetivo: Identificar los microorganismos aislados para estimar tanto la sensibilidad a los antibióticos como la coincidencia entre el tratamiento empírico y los resultados microbiológicos en pacientes con úlceras del pie diabético. Métodos: Se realizó una investigación descriptiva-retrospectiva. La población de estudio estuvo constituida por 210 pacientes ingresados en el Hospital Universitario Clínico Quirúrgico "Comandante Faustino Pérez Hernández" de Matanzas entre junio de 2017 y junio de 2020. Las variables de salida fueron la frecuencia y el tipo de germen, la cantidad de gérmenes por úlcera, la sensibilidad para cada tipo de antibiótico, y el porcentaje de coincidencia entre el tratamiento empírico y el resultado microbiológico. Resultados: Se identificaron 259 gérmenes y se observaron 1,23 gérmenes por úlcera. El 62,5 por ciento de los gérmenes encontrados fueron Gram negativos, pero el germen más representado fue el Staphylococcus aureus. El 58,8 por ciento de los Staphylococcus aureus se mostraron resistentes a la meticillin. La vancomicina y el linezolid resultaron efectivos en el 100 por ciento de los Gram positivos. La amikacina fue el antibiótico más efectivo para los Gram negativos. Se observó coincidencia entre el tratamiento empírico y el resultado del antibiograma en el 27,6 por ciento de los pacientes. Conclusiones: Resulta necesario un apropiado diagnóstico microbiológico de las úlceras del pie diabético para identificar los gérmenes presentes en las lesiones y diseñar algoritmos de terapia antimicrobiana adecuados(AU)

ABSTRACT Introduction: Diabetic foot ulcer infections are common, complex, high cost and are the leading cause of non-traumatic lower extremity amputation. Objective: To identify the microorganisms isolated to estimate both the sensitivity to antibiotics and the coincidence between empirical treatment and microbiological results in patients with diabetic foot ulcers. Methods: A descriptive-retrospective investigation was performed. The study population consisted of 210 patients admitted to the University Hospital "Comandante Faustino Pérez Hernández" of Matanzas between June 2017 and June 2020. The output variables were the frequency and type of germ, the number of germs per ulcer, the sensitivity for each type of antibiotic, and the percentage of coincidence between the empirical treatment and the microbiological result. Results: A total of 259 germs were identified and 1.23 germs per ulcer were observed. The 62.5 percent of the germs found were Gram negative, but the most represented germ was Staphylococcus aureus. Of the Staphylococcus aureus, 58.8 percentwere resistant to methicillin. Vancomycin and linezolid were effective in 100 percent of Gram positives. Amikacin was the most effective antibiotic for Gram-negatives. Agreement between empirical treatment and antibiogram result was observed in 27.6 percent of patients. Conclusions: An appropriate microbiological diagnosis of diabetic foot ulcers is necessary to identify the germs present in the lesions and to design adequate antimicrobial therapy algorithms(AU)

Beneficios de los antibióticos en la rotura prematura de membranas de pretérmino y factores que intervienen en la eficacia del tratamiento: revisión narrativa / Benefits of antibiotics in preterm premature rupture of membranes and factors involved in the efficacy of the treatment: narrative review

Resumen El parto prematuro es la principal causa de morbilidad y de mortalidad perinatal, y hasta un tercio de los casos presentan rotura prematura de membranas. La infección intrauterina que asciende desde la vagina es su principal causa en un hospital público de Chile. Esta revisión narrativa mediante búsqueda en PubMed, Cochrane, Embase, Scielo, Science Direct y Wiley Online Library incluye estudios publicados sobre los diferentes factores infecciosos que intervienen en el resultado adverso perinatal y la eficacia de los antibióticos en la rotura prematura de membranas de pretérmino. Además, contiene recomendaciones de sociedades científicas sobre el uso de antibióticos en estos casos. Los ensayos concluyen que los antimicrobianos prolongan el embarazo, disminuyen la corioamnionitis clínica y reducen variadas morbilidades neonatales, pero no reducen la mortalidad perinatal ni las secuelas tardías en la infancia. Los resultados adversos obstétricos, especialmente los neonatales, y las secuelas dependen de la existencia de invasión microbiana de la cavidad amniótica o de infección cérvico-vaginal, de la virulencia de los microorganismos aislados, del compromiso inflamatorio/infeccioso de la placenta (corioamnionitis histológica, funisitis) y de la respuesta inflamatoria fetal. Para mejorar los resultados adversos obstétricos neonatales en la rotura prematura de membranas de pretérmino, los esquemas de antibióticos deben ser eficaces, cubriendo el amplio espectro microbiológico existente y actuando sobre los factores infecciosos implicados en la gravedad de la infección. Además, deben administrarse de manera intensiva y prolongada hasta el parto.

Abstract Preterm birth is the leading cause of perinatal morbidity and mortality, and up to a third of them have premature rupture of membranes. Intrauterine infection that rises from the vagina is its main cause in a public hospital in Chile. This narrative review by searching PubMed, Cochrane, Embase, Scielo, Science Direct and Wiley Online Library includes published studies of the different infectious factors involved in perinatal adverse outcome and of the efficacy of antibiotics in preterm premature rupture of membranes. It also contains recommendations from scientific societies on the use of antibiotics in these cases. These trials conclude that antimicrobials prolong pregnancy, decrease clinical chorioamnionitis, and reduce various neonatal morbidities, but do not reduce perinatal mortality or infant sequelae. Obstetric and especially neonatal adverse outcomes in these patients depend on the existence of microbial invasion of the amniotic cavity and/or cervicovaginal infection, of the virulence of the isolated microorganisms, of inflammatory/infectious involvement of the placenta (histological chorioamnionitis, funisitis) and fetal inflammatory response. To improve adverse neonatal obstetric outcomes in preterm premature rupture of membranes, antibiotic regimens must be effective, covering the wide existing microbiological spectrum and acting on infectious factors responsible for the severity of the infection. In addition, they must be administered aggressively and for a long time until delivery.

Is combined rather than single antibiotic therapy actually reasonable in patients with acute calculous cholecystitis?

SUMMARY OBJECTIVE Acute calculous cholecystitis (AC) is a frequently encountered emergency surgery disease and its standard treatment is cholecystectomy. In patients with high risk in surgery, antibiotic treatment (AT) is important. In routine clinical practices, antibiotics are frequently used either as single or in combination in the treatment of AC. This study examined whether or not combined antibiotic treatment (CAT) had superiority over single antibiotic treatment (SAT) in AC. METHODS Patients with cholecystitis who received treatment in the period of 2016-2019 were retrospectively examined. The treatment procedures applied, patient findings, and laboratory data were analyzed using relevant statistical software. The patients were categorized into groups based on the treatment approaches applied, and the effects of SAT and CAT on infection parameters were analyzed. RESULTS In all, 184 patients received treatment for AC, with a mean age of 57.7, and the female-to-male ratio was 77:107. Of these, 139 patients received SAT and 45 received CAT. No significant difference was found in terms of effectiveness between the SAT and CAT in the patients who received early cholecystectomy treatment and those who received medical treatment with noninvasive intervention. CONCLUSIONS In patients with AC, antibiotics are commonly used either as single or in combination for prophylaxis and therapeutic purposes. As no significant difference was observed between single and combined use in terms of treatment effectiveness and hospitalization duration, CAT is not recommended due to its possibility of allergic side effects, toxicity, and cost-increasing effects.

Delayed reduction of Anaplasma marginale parasitemia and packed cell volume normalization despite prolonged enrofloxacin treatment of cattle co-infected with Trypanosoma vivax.

Although co-infections of Trypanosoma vivax, Anaplasma spp., and Babesia spp. have been reported, knowledge gaps remain that need to be addressed. The present study evaluated the efficacy of enrofloxacin (7.5 mg/kg) against A. marginale in naturally infected cattle and cattle experimentally co-infected with T. vivax by observation of the variation in A. marginale parasitemia and packed cell volume (PCV) for 39 days. Bovines were distributed into two groups, each with six calves: T01 = animals immunosuppressed with dexamethasone and with latent anaplasmosis; T02 = animals immunosuppressed with dexamethasone, with latent anaplasmosis and experimentally co-infected with T. vivax on day 0 (D0). Animals of both groups were immunosuppressed with dexamethasone and received enrofloxacin (7.5 mg/kg) whenever mean values of parasitemia for A. marginale were ≥ 5% per group. Cattle of group T02 were also treated with isometamidium chloride (0.5 mg/kg) on D25. On D17 and D22 to D28 of the study, there was a higher (P ≤ 0.05) A. marginale parasitemia in animals of T02 than in those of T01. Animals of T01 required one enrofloxacin treatment to decrease A. marginale parasitemia, while those from T02 needed five treatments. From D5 to D37 of study, the mean values of PCV for calves from T02 were lower (P ≤ 0.05) than that for calves from T01. In conclusion, bovines co-infected T. vivax needed four more treatments with enrofloxacin to reduce A. marginale parasitemia and keep PCV values within reference standards.

Modelagem farmacocinética/farmacodinâmica do florfenicol para o tratamento da adenite equina por meio da simulação de Monte Carlo / Pharmacokinetic/pharmacodynamic modeling of florfenicol for the treatment of equine adenitis using Monte Carlo simulation

O objetivo deste trabalho foi avaliar a eficácia do florfenicol na dose usualmente empregada em equinos de 22 mg/kg pelas vias intravenosa, intramuscular e oral para o tratamento de adenite equina por Streptococcus equi. subsp. equi, usando a modelagem farmacocinética/farmacodinâmica (PK/PD ­ Pharmacokinetic/Pharmacodynamic) e a simulação de Monte Carlo. Foi realizada uma simulação de Monte Carlo a partir dos parâmetros PK, logo depois, efetuou-se a modelagem PK/PD para determinar as taxas de eficácia do antimicrobiano para o tratamento dessa infecção bacteriana, de acordo com o valor da concentração inibitória mínima (CIM), em um intervalo de CIM de 0,125 ­ 4 µg/mL. Pela via intravenosa, a probabilidade de erradicação bacteriana foi de 100% para CIM até 0,5 µg/mL e efeito bacteriostático com probabilidades de 99% e 80% para CIMs de 2 e 4 µg/mL, respectivamente. Já pelas vias intramuscular e oral a probabilidade de se atingir o índice de erradicação bacteriológica foi de 100% para CIM de até 0,5 µg/mL, contudo, atinge valores de 80% e 81%, respectivamente, para CIM de 1 µg/mL considerando o efeito bactericida (p<0,01). Portanto, através desse estudo é evidenciado a eficácia do florfenicol até a CIM de 0,5 µg/mL para as três vias de administração citadas, entretanto, para CIMs superiores a esse valor, é imprescindível o ajuste da dose farmacológica, evitando falhas na terapêutica e possível resistência microbiana.

The objective of this study was to evaluate the efficacy of florfenicol at the dose usually used in horses of 22 mg/kg by intravenous, intramuscular and oral routes for the treatment of equine adenitis caused by Streptococcus equi. subsp. equi, using Pharmacokinetic/Pharmacodynamic (PK/PD) modeling and Monte Carlo simulation. A Monte Carlo simulation was performed from the PK parameters, then PK/PD modeling was performed to determine the antimicrobial efficacy rates for the treatment of this bacterial infection, according to the minimum inhibitory concentration (MIC) value, in a MIC range of 0.125 - 4 µg/mL. Intravenously, the probability of bacterial eradication was 100% for MICs up to 0.5 µg/mL, and the bacteriostatic effect was 99% and 80% for MICs of 2 and 4 µg/mL, respectively. However, for the intramuscular and oral routes, the probability of reaching the bacteriologic eradication index was 100% for MICs of up to 0.5 µg/mL, however, it reaches values of 80% and 81%, respectively, for MICs of 1 µg/mL considering the bactericidal effect (p<0.01). Therefore, through this study the efficacy of florfenicol is evidenced up to the MIC of 0.5 µg/mL for the three routes of administration cited, however, for MICs higher than this value, it is essential to adjust the pharmacological dose, avoiding failures in therapy and possible microbial resistance.

Treatment of patients with immunodeficiency: Medication, gene therapy, and transplantation

Abstract Objectives: To provide an overview of drug treatment, transplantation, and gene therapy for patients with primary immunodeficiencies. Source of data: Non-systematic review of the literature in the English language carried out at PubMed. Synthesis of data: The treatment of patients with primary immunodeficiencies aims to control their disease, especially the treatment and prevention of infections through antibiotic prophylaxis and/or immunoglobulin replacement therapy. In several diseases, it is possible to use specific medications for the affected pathway with control of the condition, especially in autoimmune or autoinflammatory processes associated with inborn immunity errors. In some diseases, treatment can be curative through hematopoietic stem cell transplantation (HSCT); more recently, gene therapy has opened new horizons through new technologies. Conclusions: Immunoglobulin replacement therapy remains the main therapeutic tool. Precision medicine with specific drugs for altered immune pathways is already a reality for several immune defects. Advances in the management of HSCT and gene therapy have expanded the capacity for curative treatments in patients with primary immunodeficiencies.

Modelagem farmacocinética/farmacodinâmica do florfenicol para o tratamento da adenite equina por meio da simulação de Monte Carlo / Pharmacokinetic/pharmacodynamic modeling of florfenicol for the treatment of equine adenitis using Monte Carlo simulation

O objetivo deste trabalho foi avaliar a eficácia do florfenicol na dose usualmente empregada em equinos de 22 mg/kg pelas vias intravenosa, intramuscular e oral para o tratamento de adenite equina por Streptococcus equi. subsp. equi, usando a modelagem farmacocinética/farmacodinâmica (PK/PD – Pharmacokinetic/Pharmacodynamic) e a simulação de Monte Carlo. Foi realizada uma simulação de Monte Carlo a partir dos parâmetros PK, logo depois, efetuou-se a modelagem PK/PD para determinar as taxas de eficácia do antimicrobiano para o tratamento dessa infecção bacteriana, de acordo com o valor da concentração inibitória mínima (CIM), em um intervalo de CIM de 0,125 – 4 μg/mL. Pela via intravenosa, a probabilidade de erradicação bacteriana foi de 100% para CIM até 0,5 μg/mL e efeito bacteriostático com probabilidades de 99% e 80% para CIMs de 2 e 4 μg/mL, respectivamente. Já pelas vias intramuscular e oral a probabilidade de se atingir o índice de erradicação bacteriológica foi de 100% para CIM de até 0,5 μg/mL, contudo, atinge valores de 80% e 81%, respectivamente, para CIM de 1 μg/mL considerando o efeito bactericida (p<0,01). Portanto, através desse estudo é evidenciado a eficácia do florfenicol até a CIM de 0,5 μg/mL para as três vias de administração citadas, entretanto, para CIMs superiores a esse valor, é imprescindível o ajuste da dose farmacológica, evitando falhas na terapêutica e possível resistência microbiana.

The objective of this study was to evaluate the efficacy of florfenicol at the dose usually used in horses of 22 mg/kg by intravenous, intramuscular and oral routes for the treatment of equine adenitis caused by Streptococcus equi. subsp. equi, using Pharmacokinetic/Pharmacodynamic (PK/PD) modeling and Monte Carlo simulation. A Monte Carlo simulation was performed from the PK parameters, then PK/PD modeling was performed to determine the antimicrobial efficacy rates for the treatment of this bacterial infection, according to the minimum inhibitory concentration (MIC) value, in a MIC range of 0.125 - 4 μg/mL. Intravenously, the probability of bacterial eradication was 100% for MICs up to 0.5 μg/mL, and the bacteriostatic effect was 99% and 80% for MICs of 2 and 4 μg/mL, respectively. However, for the intramuscular and oral routes, the probability of reaching the bacteriologic eradication index was 100% for MICs of up to 0.5 μg/mL, however, it reaches values of 80% and 81%, respectively, for MICs of 1 μg/mL considering the bactericidal effect (p<0.01). Therefore, through this study the efficacy of florfenicol is evidenced up to the MIC of 0.5 μg/mL for the three routes of administration cited, however, for MICs higher than this value, it is essential to adjust the pharmacological dose, avoiding failures in therapy and possible microbial resistance.

Antimicrobial stewardship in the outpatient parenteral antimicrobial therapy (OPAT) setting: the impact of prescription assessment by an infectious diseases specialist.

OBJECTIVE: In recent years, the use of outpatient parenteral antimicrobial therapy (OPAT) has increased, resulting in the need to ensure its rational and adequate utilization. This article describes the implementation of an antimicrobial stewardship program in the OPAT setting by a Health Maintenance Organization (HMO) and its results. METHOD: An infectious disease (ID) physician made routine assessments of all home care parenteral antimicrobial requests from February to December 2019. Information on diagnosis, renal function, weight, previous antimicrobials, and microbiology were gathered during remote evaluations. Prescription changes recommended by the ID specialist were not mandatory, but implemented by the primary provider as accepted. Antibiotic consumption data was analyzed from January 2018 to December 2019. An active screening was conducted for treatment failures: two or more treatment course requirements, or death within 15 days of the evaluation were reexamined. RESULTS: A total of 506 antimicrobial requests were assessed. The most frequent diagnoses were urinary tract infection, pneumonia, and orthopedic surgical site infection. Six percent of evaluations were not completed due to insufficient information and 12% were requests by the primary physician for initial antimicrobial guidance. Of the 416 completed prescriptions evaluations, 58% had suggested changes, including different antimicrobials (40%), treatment duration (25%), and route of administration (23%). There was an increase in use of teicoplanin and meropenem, and a decrease in ceftriaxone, ertapenem, cefepime, amikacin and daptomycin use. The HMO's overall parenteral antimicrobial outpatient consumption, which had shown an upward trend over the previous year, decreased after program initiation. No major adverse results were detected in patients' clinical outcomes; two treatment failures were detected and promptly corrected; no deaths attributed to antibiotic changes were detected. CONCLUSION: Outpatient antimicrobial stewardship, through remote assessment by an ID specialist, was effective and safe in the OPAT setting.