scholarly journals Resistance against macrocyclic lactones in Psoroptes ovis in cattle

2020 ◽  
Author(s):  
Wouter van Mol ◽  
Nathalie De Wilde ◽  
Stijn Casaert ◽  
Zhenzhen Chen ◽  
Marieke Vanhecke ◽  
...  

Abstract Background Psoroptic mange is an important disease in beef cattle, and Belgian Blue cattle are particularly susceptible. Treatment failure of macrocyclic lactones against Psoroptes ovis has been reported, but clear evidence of in vivo resistance is still lacking. This study was conducted to investigate the efficacy of macrocyclic lactone products in 16 beef farms in Belgium and The Netherlands in vivo and in vitro . Methods On each farm a group of animals (n= 7-14) with psoroptic mange was treated with two subcutaneous injections of a macrocyclic lactone product with 7-10 days interval (15 farms) or a single injection with a long-acting macrocyclic lactone (1 farm). In vivo efficacy was assessed by the reduction in mite counts and clinical index (estimated proportion of the body surface affected by lesions), the proportion of the animals with negative mite counts after the first treatment round and the number of treatment rounds needed to obtain zero mites counts in all animals. A mite population from a given farm was categorized as sensitive when the mite count reduction after the first treatment round >95% and the lower limit of the uncertainty interval >90%. Resistance was detected when both parameters were below the threshold. Resistance was suspected when only one was below its threshold. In vitro knock-down and mortality was evaluated in a contact test. Results The proportion of the animals with negative mite counts after the first treatment round varied from 0-80%. All farms needed two or more rounds of treatments to obtain zero mite counts on all animals. Clinical index had a high variation and only started to reduce after the second treatment round. Mite populations from three farms were categorized as sensitive, one as suspected resistant and the other 12 as resistant. No correlation was found between in vitro lethal dose 50 and knock-down dose 50 values and any parameter of in vivo efficacy. Conclusions Unambiguous treatment failure was detected on 12/16 beef farms, confirming the presence of macrocyclic lactone resistance on Belgian Blue beef farms. In vitro parameters could not discriminate the farms based on their in vivo sensitivity. The mean reduction in mite counts and the lower limit of the confidence interval are proposed as most useful parameters to identify acaricide resistance.

2019 ◽  
Author(s):  
Wouter van Mol ◽  
Nathalie De Wilde ◽  
Stijn Casaert ◽  
Zhenzhen Chen ◽  
Marieke Vanhecke ◽  
...  

Abstract Background Psoroptic mange is an important disease in beef cattle, and Belgian Blue cattle are particularly susceptible. Treatment failure of macrocyclic lactones against Psoroptes ovis has been reported, but clear evidence of in vivo resistance is still lacking. This study was conducted to investigate ML efficacy in 16 beef farms in Belgium and The Netherlands in vivo and in vitro.Methods On each farm a group of animals (n= 7-14) with clinical psoroptic mange was treated with two subcutaneous injections of a macrocyclic lactone with 7-10 days interval (15 farms) or a single injection with a long-acting macrocyclic lactone (1 farm). In vivo efficacy was assessed by the reduction in mite counts and clinical index (part of the body affected by lesions), the cure rate after the first treatment round and the number of treatment rounds needed to cure all animals. In vitro knock-down and mortality was evaluated in a contact test.Results Cure rates after the first treatment round varied from 0-80%. All farms needed two or more rounds of treatments to obtain full efficacy. Clinical index had a high variation and only started to reduce after the second treatment round. Only three farms were categorized as susceptible with a mean mite count reduction>95% and a lower limit of the uncertainty interval>90%. One farm had a mean reduction>95%, but its lower limit of the confidence interval was <90%. All other farms had mean reductions<95% and lower limits of their uncertainty intervals<90%. No correlation was found between in vitro lethal dose 50 and knock-down dose 50 values and any parameter of in vivo efficacy.Conclusion Unambiguous treatment failure was detected on 12/16 beef farms, confirming the presence of macrocyclic lactone resistance in Belgian Blue beef farms. In vitro parameters could not discriminate the farms based on their in vivo susceptibility. The mean reduction in mite counts and the lower limit of the confidence interval stood out as most useful parameter to identify acaricide resistance.


2020 ◽  
Author(s):  
Wouter van Mol ◽  
Nathalie De Wilde ◽  
Stijn Casaert ◽  
Zhenzhen Chen ◽  
Marieke Vanhecke ◽  
...  

Abstract Background Psoroptic mange is an important disease in Belgian Blue cattle. Treatment failure of macrocyclic lactones against Psoroptes ovis has been reported, but clear evidence of in vivo resistance is lacking. This study assessed the efficacy of macrocyclic lactone products on 16 beef farms in Belgium and the Netherlands in vivo and in vitro . Methods On each farm a group of animals ( n = 7–14) with psoroptic mange was treated with two subcutaneous injections of a macrocyclic lactone product with 7–10 days interval (15 farms) or a single injection with a long-acting macrocyclic lactone (1 farm). In vivo efficacy was assessed by the reduction in mite counts, clinical index (proportion of the body surface affected by lesions), the proportion of the animals with negative mite counts after the first treatment round and the number of treatment rounds needed to obtain zero mites counts in all animals. A mite population was categorized as sensitive when the mite count reduction after the first treatment round > 95% and the lower limit of the uncertainty interval > 90%. Resistance was detected when both parameters were below their threshold and suspected when one parameter was too low. In vitro knockdown and mortality were evaluated in a contact test. Results The proportion of the animals with negative mite counts after the first treatment round varied from 0 to 80%. All farms needed two or more treatments rounds to obtain zero mite counts on all animals. Clinical index only started to reduce after the second treatment round. Mite populations from three farms were categorized as sensitive, one as suspected resistant and 12 as resistant. No correlation was found between in vitro lethal dose 50 and knockdown dose 50 values and in vivo efficacy parameters. Conclusions Unambiguous treatment failure was detected on 12 out of 16 farms, confirming the presence of macrocyclic lactone resistance on Belgian Blue beef farms. In vitro parameters could not discriminate the farms based on their in vivo sensitivity. The mean reduction in mite counts and the lower limit of the confidence interval are proposed as parameters to identify acaricide resistance.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pierre Santucci ◽  
Daniel J. Greenwood ◽  
Antony Fearns ◽  
Kai Chen ◽  
Haibo Jiang ◽  
...  

AbstractTo be effective, chemotherapy against tuberculosis (TB) must kill the intracellular population of the pathogen, Mycobacterium tuberculosis. However, how host cell microenvironments affect antibiotic accumulation and efficacy remains unclear. Here, we use correlative light, electron, and ion microscopy to investigate how various microenvironments within human macrophages affect the activity of pyrazinamide (PZA), a key antibiotic against TB. We show that PZA accumulates heterogeneously among individual bacteria in multiple host cell environments. Crucially, PZA accumulation and efficacy is maximal within acidified phagosomes. Bedaquiline, another antibiotic commonly used in combined TB therapy, enhances PZA accumulation via a host cell-mediated mechanism. Thus, intracellular localisation and specific microenvironments affect PZA accumulation and efficacy. Our results may explain the potent in vivo efficacy of PZA, compared to its modest in vitro activity, and its critical contribution to TB combination chemotherapy.


2021 ◽  
Author(s):  
L Giacani ◽  
A Haynes ◽  
M Vall Mayans ◽  
M Ubals Cazorla ◽  
C Nieto ◽  
...  

Author(s):  
Jerzy Karczewski ◽  
Christine M Brown ◽  
Yukari Maezato ◽  
Stephen P Krasucki ◽  
Stephen J Streatfield

Abstract Objectives To evaluate the efficacy of a novel lantibiotic, CMB001, against MRSA biofilms in vitro and in an in vivo experimental model of bacterial infection. Methods Antibacterial activity of CMB001 was measured in vitro after its exposure to whole blood or to platelet-poor plasma. In vitro efficacy of CMB001 against a Staphylococcus aureus biofilm was studied using scanning electron microscopy. The maximum tolerable dose in mice was determined and a preliminary pharmacokinetic analysis for CMB001 was performed in mice. In vivo efficacy was evaluated in a neutropenic mouse thigh model of infection. Results CMB001 maintained its antibacterial activity in the presence of blood or plasma for up to 24 h at 37°C. CMB001 efficiently killed S. aureus within the biofilm by causing significant damage to the bacterial cell wall. The maximum tolerable dose in mice was established to be 10 mg/kg and could be increased to 30 mg/kg in mice pretreated with antihistamines. In neutropenic mice infected with MRSA, treatment with CMB001 reduced the bacterial burden with an efficacy equivalent to that of vancomycin. Conclusions CMB001 offers potential as an alternative treatment option to combat MRSA. It will be of interest to evaluate the in vivo efficacy of CMB001 against infections caused by other pathogens, including Clostridioides difficile and Acinetobacter baumannii, and to expand its pharmacokinetic/pharmacodynamic parameters and safety profile.


2005 ◽  
Vol 20 (1) ◽  
pp. 61 ◽  
Author(s):  
Yun Sil Chang ◽  
Jong Hee Hwang ◽  
Hyuk Nam Kwon ◽  
Chang Won Choi ◽  
Sun Young Ko ◽  
...  

1999 ◽  
Vol 289 (4) ◽  
pp. 445-456 ◽  
Author(s):  
Joachim W. Fluhr ◽  
Bettina Bösch ◽  
Max Gloor ◽  
Ulrich Hoffler

2009 ◽  
Vol 53 (12) ◽  
pp. 5022-5025 ◽  
Author(s):  
M. Mar Rodríguez ◽  
F. Javier Pastor ◽  
Enrique Calvo ◽  
Valentina Salas ◽  
Deanna A. Sutton ◽  
...  

ABSTRACT A broth microdilution method was used to evaluate the in vitro activities of seven antifungal agents against 15 clinical strains of Rhizopus microsporus. Amphotericin B (AMB) and posaconazole (POS) were the most active drugs. In a model of disseminated R. microsporus infection in immunosuppressed mice, we studied the efficacy of POS administered once or twice daily against four of the strains previously tested in vitro and compared it with that of liposomal AMB (LAMB). LAMB was the most effective treatment for the two strains with intermediate susceptibility to POS. For the two POS-susceptible strains, LAMB and POS at 20 mg/kg of body weight twice a day orally showed similar efficacies. The in vivo efficacy of POS administered twice a day orally correlated with the in vitro susceptibility data and the serum drug concentrations.


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