Changes in the phenotypic susceptibility of Mannheimia haemolytica isolates to macrolide antimicrobials during the early feeding period following metaphylactic tulathromycin use in western Canadian feedlot calves.

Cattle at high-risk for bovine respiratory disease on entry to western Canadian feedlots are often treated metaphylactically with antimicrobials from the macrolide class. High levels of resistance to macrolides have been reported in Mannheimia haemolytica isolates from clinical samples, but it is less clear whether this trend extends to the broader feedlot population. The objective was to describe near-term [< 40 days on feed (DOF)] changes in the recovery and susceptibility of M. haemolytica isolates from healthy feedlot calves after metaphylactic exposure to tulathromycin. Eight cohorts of 100 calves (n = 800) were sampled via deep nasopharyngeal swab at entry processing (i.e., before metaphylaxis, at 1 DOF) and again at 13 DOF. Ten calves from each cohort (n = 80) were randomly sampled a third time at 36 DOF. Recovery of M. haemolytica isolates across all cohorts increased over the study period, from 33% (95% CI: 26.5 to 40.2%) at 1 DOF to 75% (95% CI: 71.4 to 78.3%) at 36 DOF. A significant shift in the minimum inhibitory concentration (MIC) distribution of tulathromycin from 1 DOF (MIC90 ≤ 8 µg/mL) to 13 DOF (MIC90 > 64 µg/mL) was observed. A subset of 36 isolates from 13 DOF screened for macrolide resistance genes via multiplex polymerase chain reaction all harbored the msrE and mphE genes. Recovery of M. haemolytica at 13 and 36 DOF did not decline in response to metaphylactic use of tulathromycin; conversely, we inferred the potential for rapid inter-pen spread of a macrolide-resistant clone by 13 DOF in 6 of 8 pens under selective pressure from antimicrobial use.

Changements dans la sensibilité phénotypique des isolats de Mannheimia haemolytica aux a ntibiotiques de la classe des macrolides au début de la période d'alimentation après l'utilisation m étaphylactique de tulathromycine chez les veaux des parcs d'engraissement de l'Ouest canadien. Les bovins à risque élevé de maladies respiratoires bovines à leur entrée dans les parcs d'engraissement de l'Ouest canadien sont souvent traités métaphylactiquement avec des antimicrobiens de la classe des macrolides. Des taux élevés de résistance aux macrolides ont été signalés chez les isolats de Mannheimia haemolytica provenant d'échantillons cliniques, mais il est moins clair si cette tendance s'étend à la population plus large des parcs d'engraissement. L'objectif était de décrire les changements à court terme [< 40 jours d'alimentation (DOF)] dans la récupération et la sensibilité des isolats de M. haemolytica provenant de veaux sains en parc d'engraissement après une exposition métaphylactique à la tulathromycine. Huit cohortes de 100 veaux (n = 800) ont été échantillonnées via un prélèvement nasopharyngé profond lors du traitement d'entrée (i.e., avant la métaphylaxie, à 1 DOF) et à nouveau à 13 DOF. Dix veaux de chaque cohorte (n = 80) ont été échantillonnés au hasard une troisième fois à 36 DOF. La récupération des isolats de M. haemolytica dans toutes les cohortes a augmenté au cours de la période d'étude, passant de 33 % (IC 95 % : 26,5 à 40,2 %) à 1 DOF à 75 % (IC 95 % : 71,4 à 78,3 %) à 36 DOF. Un changement significatif dans la distribution de la concentration minimale inhibitrice (MIC) de la tulathromycine de 1 DOF (MIC90 ≤ 8 µg/mL) à 13 DOF (MIC90 > 64 µg/mL) a été observé. Un sous-ensemble de 36 isolats de 13 DOF criblés pour les gènes de résistance aux macrolides via une réaction d'amplification en chaîne par polymérase multiplex hébergeaient tous les gènes msrE et mphE. L'isolement de M. haemolytica à 13 et 36 DOF n'a pas diminué en réponse à l'utilisation métaphylactique de la tulathromycine; à l'inverse, nous avons suggéré le potentiel de propagation rapide entre les enclos d'un clone résistant aux macrolides par 13 DOF dans 6 des 8 enclos sous la pression sélective de l'utilisation d'antimicrobiens.(Traduit par Dr Serge Messier).

Eltrombopag in pediatric chronic and refractory ITP: data from a retrospective multicenter study from Lebanon.

About 20% to 30% of pediatric patients with immune thrombocytopenia (ITP) develop chronic or refractory disease lasting 12 months or more that can be challenging to treat. Eltrombopag is being used after failure of previous lines of therapy with good results at tertiary healthcare centers in Lebanon, a developing country with available multidisciplinary treatment modalities. This is a retrospective multicenter observational study that analyzed data on pediatric patients with chronic or refractory ITP who were given eltrombopag as second- or third-line therapy in 6 large referral hospitals in Beirut (country capital located in mid Lebanon), South, North, and Mount Lebanon between October 2016 and May 2020. The primary end point of the study was a proportion of patients achieving platelet counts of ≥ 50 × 109/L for at least 6 weeks without requiring rescue therapy during the observation period. Data from 36 patients treated for chronic and refractory ITP, 20 (55.6%) males and 16 (44.4%) females, were analyzed. The median age at the eltrombopag dose was 11 years (2-18 years). All the patients had failure of the first-line therapy with steroids, 3 patients received eltrombopag as second-line therapy, and the remaining patients had failure of at least 2 previous lines of therapy, including steroids. The primary end point was achieved in 21 (58.3%) of 36 patients. The treatment was discontinued in 3 patients due to no response. Hepatotoxicity and all other adverse events (headache, weakness, and diarrhea) were mild and transient. All the patients who achieved the target platelet count of ≥ 50 × 109/L maintained the response for the treatment duration, which was a minimum of 5 months up to 3 years, with median/mean observation periods of 12 months and 14 months, respectively. This study confirms the findings of randomized controlled trials that eltrombopag as second- or third-line therapy in pediatric patients with chronic and refractory ITP is effective and safe, reinforcing its role in the real-world management of these patients.